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Marco VINCETI

Professore Ordinario
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze Sede ex Sanità Pubblica

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Pubblicazioni

2024 - Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and exposure to selenium species: A cross-sectional study [Articolo su rivista]
Urbano, Teresa; Filippini, Tommaso; Malavolti, Marcella; Fustinoni, Silvia; Michalke, Bernhard; Wise, Lauren A.; Vinceti, Marco
abstract

Selenium is a trace element found in many chemical forms. Selenium and its species have nutritional and toxicologic properties, some of which may play a role in the etiology of neurological disease. We hypothesized that adherence to the Mediterranean-Dietary Approach to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet could influence intake and endogenous concentrations of selenium and selenium species, thus contributing to the beneficial effects of this dietary pattern. We carried out a cross-sectional study of 137 non-smoking blood donors (75 females and 62 males) from the Reggio Emilia province, Northern Italy. We assessed MIND diet adherence using a semiquantitative food frequency questionnaire. We assessed selenium exposure through dietary intake and measurement of urinary and serum concentrations, including speciation of selenium compound in serum. We fitted non-linear spline-based regression models to investigate the association between MIND diet adherence and selenium exposure concentrations. Adherence to the MIND diet was positively associated with dietary selenium intake and urinary selenium excretion, whereas it was inversely associated with serum concentrations of overall selenium and organic selenium, including serum selenoprotein P-bound selenium, the most abundant circulating chemical form of the metalloid. MIND diet adherence also showed an inverted U-shaped relation with inorganic selenium and particularly with its hexavalent form, selenate. Our results suggest that greater adherence to the MIND diet is non-linearly associated with lower circulating concentrations of selenium and of 2 potentially neurotoxic species of this element, selenoprotein P and selenate. This may explain why adherence to the MIND dietary pattern may reduce cognitive decline.

2024 - Adverse human health effects of climate change: an update [Articolo su rivista]
Filippini, Tommaso; Paduano, Stefania; Veneri, Federica; Barbolini, Giulia; Fiore, Gianluca; Vinceti, Marco
abstract

Background: The world is currently facing a process of climate change, which may adversely impact human health in many different ways. The safety of food, water and urban environments is endangered by the consequences of climate change. Sea level and temperature rise, along with more frequent and longer heat waves, represent only a few of the effects of climate change. The increased risk of extreme climate events (e.g., cyclones, droughts and floods) is another serious public health issue. These adverse effects are enhanced in areas and countries not having the capacity to effectively deal with climate change. Study design: We primarily aimed at summarizing the impacts of climate change on public health. A further aim was to identify the most concerning consequences of this phenomenon and the vulnerability factors that amplify the negative effects of climate change. Methods: PubMed and other literature databases were used as literature sources for this narrative review based on the search terms 'climate change' and 'diseases categories' up to January 2024, in order to assess the most recent and relevant scientific evidence about the relation between climate change and public health, identify knowledge gaps and priorities for future research. We also screened the websites of major agencies devoted to human health protection and environmental health. Results and conclusions: Climate change appears to induce a broad spectrum of generally adverse effects on public health. It may increase the risk of infectious diseases, psychiatric disorders, cancer and other diseases. Currently, we are not effectively counteracting this phenomenon, since pollutant and greenhouse gas emissions have been increasing alongside temperatures. A host of measures are required in order to prevent and fight climate change and related health effects. These include the adoption of a holistic approach and the collaboration of different kinds of expertise in order to design more effective strategies. Special attention should be paid to those who live in disadvantaged countries, and those who are more vulnerable to the adverse health consequences of climate change.

2024 - Age-specific prevalence of the different clinical presentations of AD and FTD in young-onset dementia [Articolo su rivista]
Zamboni, G.; Maramotti, R.; Salemme, S.; Tondelli, M.; Adani, G.; Vinceti, G.; Carbone, C.; Filippini, T.; Vinceti, M.; Pagnoni, G.; Chiari, A.
abstract

Background Studies have shown that the prevalence of all-variants Alzheimer's disease (AD) and frontotemporal dementia (FTD) both increase with age, even before the age of 65. However, it is not known whether their different clinical presentations all increase in prevalence with age in the same way.Methods We studied the prevalence of the different clinical presentations of young-onset AD and FTD by 5-year age groups in a population-based study identifying all dementia patients with a diagnosis of AD and FTD and symptoms onset before age 65 in the Modena province, Italy. By using regression models of cumulative occurrences, we also estimated age-specific prevalence and compared the growth curves of the clinical presentations.Results The prevalence of all-variants AD increased with age, from 18/1,000,000 in the 40-44 age group to 1411/1,000,000 in the 60-64 age group. The prevalence of all-variants FTD also increased with age, from 18/1,000,000 to 866/1,000,000. An estimation of age-specific prevalence functions of each clinical presentation showed that atypical non-amnestic AD and aphasic FTD grew the most in early ages, followed by the behavioural variant of FTD (bvFTD). Then, around the age of 60, amnestic AD took over and its age-specific prevalence continued to increase disproportionally compared to all the other clinical variants of AD and FTD, which, instead, started to decrease in prevalence.Conclusions Amnestic AD is the clinical presentation that increases the most with advancing age, followed by bvFTD, suggesting that there is a differential vulnerability to the effect of ageing within the same neurodegenerative disease.

2024 - Atrial Fibrillation and Other Cardiovascular Factors and the Risk of Dementia: An Italian Case–Control Study [Articolo su rivista]
Mazzoli, R.; Chiari, A.; Vitolo, M.; Garuti, C.; Adani, G.; Vinceti, G.; Zamboni, G.; Tondelli, M.; Galli, C.; Costa, M.; Salemme, S.; Boriani, G.; Vinceti, M.; Filippini, T.
abstract

: Dementia is a major neurologic syndrome characterized by severe cognitive decline, and it has a detrimental impact on overall physical health, leading to conditions such as frailty, changes in gait, and fall risk. Depending on whether symptoms occur before or after the age of 65, it can be classified as early-onset (EOD) or late-onset (LOD) dementia. The present study is aimed at investigating the role of cardiovascular factors on EOD and LOD risk in an Italian population. Using a case-control study design, EOD and LOD cases were recruited at the Modena Cognitive Neurology Centers in 2016-2019. Controls were recruited among caregivers of all the dementia cases. Information about their demographics, lifestyles, and medical history were collected through a tailored questionnaire. We used the odds ratio (OR) and 95% confidence interval (CI) to estimate the EOD and LOD risk associated with the investigated factors after adjusting for potential confounders. Of the final 146 participants, 58 were diagnosed with EOD, 34 with LOD, and 54 were controls. According to their medical history, atrial fibrillation was associated with increased disease risk (ORs 1.90; 95% CI 0.32-11.28, and 3.64; 95% CI 0.32-41.39 for EOD and LOD, respectively). Dyslipidemia and diabetes showed a positive association with EOD, while the association was negative for LOD. We could not evaluate the association between myocardial infarction and EOD, while increased risk was observed for LOD. No clear association emerged for carotid artery stenosis or valvular heart disease. In this study, despite the limited number of exposed subjects and the high imprecision of the estimates, we found positive associations between cardiovascular disease, particularly dyslipidemia, diabetes, and atrial fibrillation, and EOD.

2024 - Cadmium exposure and cardiovascular disease risk: A systematic review and dose-response meta-analysis [Articolo su rivista]
Verzelloni, Pietro; Urbano, Teresa; Wise, Lauren A.; Vinceti, Marco; Filippini, Tommaso
abstract

: Exposure to toxic metals is a global public health threat. Among other adverse effects, exposure to the heavy metal cadmium has been associated with greater risk of cardiovascular disease (CVD). Nonetheless, the shape of the association between cadmium exposure and CVD risk is not clear. This systematic review summarizes data on the association between cadmium exposure and risk of CVD using a dose-response approach. We carried out a literature search in PubMed, Web of Science, and Embase from inception to December 30, 2023. Inclusion criteria were: studies on adult populations, assessment of cadmium exposure, risk of overall CVD and main CVD subgroups as endpoints, and observational study design (cohort, cross-sectional, or case-control). We retrieved 26 eligible studies published during 2005-2023, measuring cadmium exposure mainly in urine and whole blood. In a dose-response meta-analysis using the one-stage method within a random-effects model, we observed a positive association between cadmium exposure and risk of overall CVD. When using whole blood cadmium as a biomarker, the association with overall CVD risk was linear, yielding a risk ratio (RR) of 2.58 (95 % confidence interval-CI 1.78-3.74) at 1 μg/L. When using urinary cadmium as a biomarker, the association was linear until 0.5 μg/g creatinine (RR = 2.79, 95 % CI 1.26-6.16), after which risk plateaued. We found similar patterns of association of cadmium exposure with overall CVD mortality and risks of heart failure, coronary heart disease, and overall stroke, whereas for ischemic stroke there was a positive association with mortality only. Overall, our results suggest that cadmium exposure, whether measured in urine or whole blood, is associated with increased CVD risk, further highlighting the importance of reducing environmental pollution from this heavy metal.

2024 - Changes in Cerebrospinal Fluid Concentrations of Selenium Species Induced by Tofersen Administration in Subjects with Amyotrophic Lateral Sclerosis Carrying SOD1 Gene Mutations [Articolo su rivista]
Vinceti, Marco; Urbano, Teresa; Filippini, Tommaso; Bedin, Roberta; Simonini, Cecilia; Sorarù, Gianni; Trojsi, Francesca; Michalke, Bernhard; Mandrioli, Jessica
abstract

: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting the brain and spinal cord motor neurons. On 25 April 2023, the drug tofersen, an antisense oligonucleotide, received the US Food and Drug Administration approval for treating ALS in adults carrying mutations of the SOD1 gene. We aimed at assessing whether cerebrospinal fluid concentrations of selenium, an element of both toxicological and nutritional interest possibly involved in disease etiology and progression, are modified by tofersen administration. We determined concentrations of selenium species by anion exchange chromatography hyphenated to inductively coupled plasma-dynamic reaction cell-mass spectrometry and overall selenium by using inductively coupled plasma sector-field mass spectrometry, at baseline and 6 months after active tofersen treatment in ten Italian ALS patients carrying the SOD1 gene mutation. Concentrations of total selenium and many selenium species substantially increased after the intervention, particularly of inorganic (tetravalent and hexavalent) selenium and of the organic species selenomethionine and a compound co-eluting with the selenocystine standard. Overall, these findings suggest that tofersen treatment markedly alters selenium status and probably the redox status within the central nervous system, possibly due to a direct effect on neurons and/or the blood-brain barrier. Further studies are required to investigate the biological and clinical relevance of these findings and how they might relate to the pharmacological effects of the drug and to disease progression.

2024 - Climate change-related factors and west nile virus spread in italy: a systematic review [Abstract in Atti di Convegno]
Granata, Michele; Tommasi, Luigi; Verzelloni, Pietro; Lorenzon, Antonio; Paduano, Stefania; Malavolti, Marcella; Bargellini, Annalisa; Filippini, Tommaso; Righi, Elena; Vinceti, Marco
abstract

West Nile Virus (WNV) is a vector-transmitted pathogen affecting both humans and animals, whose presence has recently risen in Europe and particularly in Italy, concurrently with climate changes that favoured the diffusion of mosquitoes. Our review aims to assess such relation with environmental and meteorological factors focusing on the WNV spread in the Italian territory. Following PRISMA guidelines, we performed a literature search in online databases up to May 31, 2023 on four different databases: PubMed, Web of Science, Embase, Scopus. We used keywords and MeSH terms related to WNV and its vectors (C. pipiens and modestus). Following the PECOS criteria, we included observational studies examining vector dynamics and the WNV infection epidemiology in the Italian population and the possible association with environmental factors. The protocol registration on PROSPERO is in process. Out of the 341 articles retrieved, 222 remained after duplicates exclusion and 44 papers were selected after screening of title and abstract by two blinded reviewers. After full-text screening, 31 studies (published between 2011 and 2023) were included. Climatic factors such as temperature, daylight hours and humidity seem to be strongly associated with the spread of WNV and its vectors, while rainfall showed less influence. Among environmental factors, soil characteristics and population dynamics (of both vector and host) were found to be the most predictive. By contrast, distance from specific areas (e.g. urban or protected areas) seems to have no influence. These findings suggest that some climatic and environmental factors linked with climate change strongly affect the presence of WNV and its vectors. This issue can be considered a warning bell about the potential future increase in cases related to climate change, but offers helpful resources for predicting its spread and implement tailored public health interventions.

2024 - Correction: Comment on “Relation of fruit juice with adiposity and diabetes depends on how fruit juice is defined: a re-analysis of the EFSA draft scientific opinion on the tolerable upper intake level for dietary sugars” by Chen et al. 2023 (European Journal of Clinical Nutrition, (2023), 77, 12, (1176-1177), 10.1038/s41430-023-01337-0) [Articolo su rivista]
Valtuena Martinez, S.; Turck, D.; Craciun, I.; Vinceti, M.
abstract

Correction to: European Journal of Clinical Nutrition , published online 15 September 2023 The following disclaimer was added in the article backmatter: “The authors Silvia VALTUEÑA MARTINEZ and Ionut CRACIUN are employed with the European Food Safety Authority (EFSA) in NIF Unit that provides scientific and administrative support to the EFSA NDA Panel in the area of nutrition. However, the present article is published under the sole responsibility of the authors and may not be considered as an EFSA scientific output. The positions and opinions presented in this article are those of the authors alone and do not necessarily represent any official position of EFSA. To know about the views or scientific outputs of EFSA, please consult its website under.” The original article has been corrected.

2024 - Dairy Intake and Risk of Cognitive Decline and Dementia: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies [Articolo su rivista]
Villoz, F.; Filippini, T.; Ortega, N.; Kopp-Heim, D.; Voortman, T.; Blum, M. R.; Del Giovane, C.; Vinceti, M.; Rodondi, N.; Chocano-Bedoya, P. O.
abstract

Dairy intake may influence cognition through several molecular pathways. However, epidemiologic studies yield inconsistent results, and no dose-response meta-analysis has been conducted yet. Therefore, we performed a systematic review with a dose-response meta-analysis about the association between dairy intake and cognitive decline or incidence of dementia. We investigated prospective studies with a follow-up ≥6 mo on cognitive decline or dementia incidence in adults without known chronic conditions through a systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar from inception to 11 July 2023. We evaluated the dose-response association using a random-effects model. We identified 15 eligible cohort studies with >300,000 participants and a median follow-up of 11.4 y. We observed a negative nonlinear association between cognitive decline/dementia incidence and dairy intake as assessed through the quantity of consumption, with the nadir at ∼150 g/d (risk ratio: 0.88; 95% confidence interval: 0.78, 0.99). Conversely, we found an almost linear negative association when we considered the frequency of consumption (risk ratio for linear trend: 0.84; 95% confidence interval: 0.77, 0.92 for 1 time/d increase of dairy products). Stratified analysis by dairy products showed different shapes of the association with linear inverse relationship for milk intake, whereas possibly nonlinear for cheese. The inverse association was limited to Asian populations characterized by generally lower intake of dairy products, compared with the null association reported by European studies. In conclusion, our study suggests a nonlinear inverse association between dairy intake and cognitive decline or dementia, also depending on dairy types and population characteristics, although the heterogeneity was still high in overall and several subgroup analyses. Additional studies should be performed on this topic, including a wider range of intake and types of dairy products, to confirm a potential preventing role of dairy intake on cognitive decline and identify ideal intake doses. This review was registered at PROSPERO as CRD42020192395.

2024 - Early fluoride intake and Molar Incisor Hypomineralisation (MIH) defects: A systematic review and dose-response meta-analysis [Articolo su rivista]
Veneri, F.; Filippini, T.; Cecchini, M.; Vinceti, M.; Consolo, U.; Generali, L.
abstract

Background: Excessive intake of fluoride has been implicated in the complex multifactorial etiology of hypomineralisation (MIH) defects. Objective: To study the possible effect of early exposure to fluoride on the risk of molar incisor hypomineralisation, also through a dose-response approach. Methods: Observational and clinical studies investigating the relation between fluoride exposure from any source or evaluating exposure biomarkers and MIH defects. PubMed MEDLINE, Embase and Web of Science databases were con-sulted up to December 1, 2023, using terms related to “fluoride”, “enamel defects” and “demarcated opacities”. We performed a meta-analysis comparing the highest versus lowest fluoride exposure using a random-effects model, and we quantitively assessed this relation using piece-wise linear meta-regression. Results: Thirteen studies were included in the meta-analysis, 12 of which were eligible for the dose-response analysis, all regarding exposure from fluoride in drinking water. Three of them specifically addressed MIH, while the remaining concerned “demarcated opacities”, yet with features attributable to MIH. Comparing the highest versus lowest water fluoride exposure categories, virtually no evidence of a fluoride effect was identified, with an overall odds ratio of 0.93 [95% confidence interval 0.60; 1.45]. The dose-response meta-regression showed a decreasing risk for MIH defects exposure up to 1 mg/L, whereas an increase in risk emerged at higher exposure levels. Conclusions: This meta-analysis suggests that early systemic exposure to fluoride may affect the occurrence of MIH defects differently depending on fluoride concentration. However, these results need to be evaluated with caution due to potential methodological limitations of the studies included. (www.actabiomedica.it).

2024 - Extension of use of isomalto‐oligosaccharide as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Null, Null; Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; De , ; Henauw, Stefaan; Hirsch‐ernst, Karen Ildico; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Aguilera‐gómez, Margarita; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser‐berthold, Monika; Poulsen, Morten; Prieto Maradona, Miguel; Schlatter, Josef Rudolf; Siskos, Alexandros; van Loveren, Henk; Albert, Océane; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the extension of use of isomalto-oligosaccharide (IMO) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of glucose oligomers with degrees of polymerisation of 3-9, along with various amounts of mono- and disaccharides. The NF comes in both syrup and powder form. The applicant intends to extend the current uses of the NF as an ingredient in several foods, and use the NF in food supplements aimed at the general population older than 10 years of age. The information provided on the manufacturing process, composition and specifications of the NF is sufficient and does not raise safety concerns. Along with literature data, the applicant carried out a tolerability study in adult volunteers with the NF at doses up to 120 g/day. The Panel concludes that this study provides reassurance that the NF is tolerable at doses of 120 g/day. Conservative intake estimates resulting from the use of the NF as an ingredient according to the currently authorised uses and new proposed uses result in a highest intake estimate in adolescents of 112 g/day at the 95th percentile, and reach 142 g/day in adolescents when the use as a food supplement is included. The Panel notes this amount is higher than the dose of 120 g/day for which tolerability has been demonstrated. However, considering the source, compositional characterisation, production process and nature of the NF, as well as the available nutritional and toxicological data on the NF, the Panel considers that the NF does not present safety concerns under the proposed conditions of use.

2024 - Greenness and diabetes: a systematic review and meta-analysis of observational studies [Abstract in Atti di Convegno]
De Pasquale, L; Iamandii, I; Mullalli, A; Righi, E; Vinceti, M; Filippini, T
abstract

Since diabetes represents a serious Public Health problem and access to green spaces seems to influence some of its risk behaviors, we performed a systematic review to evaluate the association between greenness exposure and diabetes mellitus type 2 (TDM2), prediabetes and gestational diabetes. Following the PRISMA guidelines, we conducted an online literature search in PubMed, Embase and Web of Science databases by using terms related to «green space», «diabetes mellitus», «gestational diabetes» and «prediabetes». The identified studies were imported into the Rayyan web app where we performed a triple-blind screening of title, abstract and full-text, including only original studies with observational design that assessed the relation between exposure to greenness and diabetes incidence/mortality reporting effect measures (relative risk, hazard ration and odds ratio) with 95% confidence intervals (CI). Lastly, we performed a metaanalysis using both a restricted maximum likehood random effects model, comparing the highest versus lowest greenness categories or continuous increase of greenness, and a onestage dose-response using a 3-knots restricted cubic spline model with fixed percentiles (10th, 50th and 90th). We identified 212 potentially eligible articles, 34 of which were eventually included in the quantitative analyses. In the preliminary forest-plot analyses almost all studies reported a decreased TDM2 risk, regardless of the heterogeneity in the satellite-based methodologies to assess greenness. Furthermore, the dose-response curve showed a progressive reduction of the RR of TDM2 incidence, especially for exposure above 0.5 NDVI (risk ratio=0.93; 95% CI: 0.15, 5.67). We observed a growing interest concerning the topic in recent years, and, considering the increasing disease burden, the identification of a protective role of greenness could help implement community preventive measures.

2024 - Maternal residential exposure to solvents from industrial sources during pregnancy and childhood cancer risk in California [Articolo su rivista]
Chen, Y.; Van Deventer, D.; Nianogo, R.; Vinceti, M.; Kang, W.; Cockburn, M.; Federman, N.; Heck, J. E.
abstract

Background: Maternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer. Methods: The present study included 15,744 cancer cases (aged 0–19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998–2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned “ever/never” and “high/low exposed/unexposed” exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy. Results: 1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the “ever exposed” group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74). Conclusions: Overall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

2024 - Ozone Treatment for the Management of Caries in Primary Dentition: A Systematic Review of Clinical Studies [Articolo su rivista]
Veneri, F.; Filippini, T.; Consolo, U.; Vinceti, M.; Generali, L.
abstract

Dental caries in children is a frequent and debilitating condition, whose management is often challenging. The aim of this systematic review was to investigate the effectiveness of ozone applications for the treatment of caries in primary dentition. According to PRISMA guidelines, a systematic literature search was performed up to 6 January 2024. Clinical studies using ozone to treat caries of deciduous teeth were considered for inclusion. Out of the 215 records retrieved, seven studies were eventually included in the review, all of which used gaseous ozone. Four studies were judged at high risk of bias, two at low risk, and one of some concerns. The great heterogeneity of designs, outcomes, and protocols made it impossible to conduct a meta-analysis. Despite some limitations, the evidence yielded by the included studies suggests that ozone application, regardless of the protocol applied, is comparable to other interventions in terms of clinical outcomes and anti-bacterial activity, with no reported adverse effects and good patient acceptance. Therefore, ozone application may be a non-invasive approach to treat caries in primary dentition, especially in very young and poorly cooperative patients. Further standardized and rigorous studies are, however, needed to identify the best clinical protocols for this specific field.

2024 - Proposing new procedures for the management and prevention of foodborne diseases: An Italian experience [Articolo su rivista]
Di Federico, S.; Maione, D.; Cilloni, S.; Raschi, E.; Montanari, N.; Di Ruocco, S.; Rizzi, S.; Lionetti, F. P.; Bisaccia, E.; Poeta, A.; De Vita, D.; Bedeschi, E.; Vinceti, M.; Filippini, T.
abstract

Background and aim: Foodborne diseases are a public health issue with more than 4,000 outbreaks in 2021 in European Union countries and United Kingdom and their management is important for prevention and controls of outbreaks. Recently, new technological tools and strategies, including whole genome sequencing (WGS), have become available to allow the highest level of discrimination in the investigation of foodborne outbreak. In this study, we presented the updated procedure for assessment of foodborne disease in a community of a Northern-Italy region, Emilia-Romagna. Methods: In the Reggio Emilia National Health Service Local Unit (AUSL-RE), foodborne disease monitoring and control are managed by the following health services: public health and hygiene (SIP); hygiene of foodstuffs and nutrition (SIAN) and veterinary public health (SSPV) composing the developed MTA group (‘Gruppo Malattie Trasmesse da Alimenti’). Among the new tools being implemented, there is a shared computerized folder and new related managements procedures available to MTA members only, allocating information regarding any material useful to the MTA group. Results: The main new features of the new procedure are: information sharing in all phases of the management of the infectious episode, integration of the three services through the creation of the MTA group and updated criteria for procedure activation, and finally a dedicated training programme. Conclusions: Timely investigation, management and control of MTA outbreaks is essential for both health and economic reasons. The new features and procedures implemented in this Italian community may allow to identify rapidly the causes of a case or outbreak and better counteract their spread. (www.actabiomedica.it).

2024 - Residential exposure to magnetic fields from transformer stations and risk of childhood leukemia [Articolo su rivista]
Malavolti, M.; Malagoli, C.; Wise, L. A.; Poli, M.; Notari, B.; Taddei, I.; Fabbi, S.; Teggi, S.; Balboni, E.; Pancaldi, A.; Palazzi, G.; Vinceti, M.; Filippini, T.
abstract

Background: Several studies have documented an increased risk of leukemia among children exposed to magnetic fields from high-voltage power lines, with some evidence of dose-response relation. However, findings in some studies have been inconsistent, and data on the effects of different sources of exposure are lacking. In this study, we evaluated the relation of childhood leukemia risk to exposure to magnetic fields from transformer stations. Methods: We conducted a population-based case-control study in a pediatric population of two Northern Italian provinces of Modena and Reggio Emilia. We included 182 registry-identified childhood leukemia cases diagnosed during 1998-2019 and 726 population controls matched on sex, year of birth, and province of residence. We assessed exposure by calculating distance from childhood residence to the nearest transformer station within a geographical information system, computing disease odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, adjusting for potential confounders. We evaluated exposure using two buffers (15 m and 25 m radius) and assessed two case groups: leukemia (all subtypes) and acute lymphoblastic leukemia (ALL). Results: Residing within 15 m of a transformer station (vs. ≥15 m) was not appreciably associated with risk of leukemia (all subtypes) or ALL. We found similar results using a less stringent exposure buffer (25 m). Among children aged ≥5 years, the adjusted ORs were 1.3 (95% CI 0.1-12.8) for leukemia and 1.3 (95% CI 0.1-12.4) for ALL using the 15 m buffer, while they were 1.7 (95% CI 0.4-7.0) for leukemia and 0.6 (95% CI 0.1-4.8) for ALL using the 25 m buffer. Conclusions: While we found no overall association between residential proximity to transformer stations and childhood leukemia, there was some evidence for elevated risk of childhood leukemia among children aged ≥5 years. Precision was limited by the low numbers of exposed children.

2024 - Safety of HelixComplex snail mucus (HSM) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Null, Null; Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; De , ; Henauw, Stefaan; Hirsch‐ernst, Karen Ildico; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Aguilera‐gómez, Margarita; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser‐berthold, Monika; Peláez, Carmen; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; Siskos, Alexandros; van Loveren, Henk; Magani, Maura; Muñoz, Alejandra; Rossi, Annamaria; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on HelixComplex Snail Mucus (HSM) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of snail mucus collected from Helix aspersa maxima and is proposed to be used by adults as a food supplement. The data provided by the applicant about the composition and stability of the NF together with the report of the subchronic toxicity study were overall considered unsatisfactory. The Panel noted inconsistencies in the reporting of the certificates of analysis and of the data on the subchronic toxicity provided by the applicant. Owing to these deficiencies, the Panel cannot establish a safe intake level of the NF. The Panel concludes that the safety of the NF has not been established.

2024 - Safety of ashitaba sap as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Null, Null; Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; De , ; Henauw, Stefaan; Hirsch‐ernst, Karen Ildico; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Aguilera‐gómez, Margarita; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Prieto Maradona, Miguel; Neuhäuser‐berthold, Monika; Poulsen, Morten; Schlatter, Josef Rudolf; Siskos, Alexandros; van Loveren, Henk; Glymenaki, Maria; Kouloura, Eirini; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on ashitaba sap as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Ashitaba sap is collected from harvested stems of Angelica keiskei plants. The principal constituents of the sap with regard to the safety assessment are chalcones (1%-2.25%) and furanocoumarins (< 0.01%). The applicant proposed to use the NF in food supplements at a maximum dose of 780 mg per day. The target population is adults excluding pregnant and lactating women. Taking into consideration the composition of the NF and the proposed uses, the composition of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day oral toxicity study performed with the product as intended to be placed on the market (30% ashitaba sap powder and 70% cyclodextrins), the Panel establishes a safe dose of 0.5 mg/kg body weight (bw) per day for the product as it is intended to be placed on the market. For the target population, i.e. adults, this safe dose corresponds to 35 mg per day of the product as it is intended to be placed on the market and 137 mg per day of the NF, which is lower than the use level proposed by the applicant. The Panel concludes that the NF is safe for the target population at intake levels up to 137 mg per day.

2024 - Safety of isomaltulose syrup (dried) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Null, Null; Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; De , ; Henauw, Stefaan; Hirsch‐ernst, Karen Ildico; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Aguilera‐gómez, Margarita; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser‐berthold, Monika; Poulsen, Morten; Prieto Maradona, Miguel; Schlatter, Josef Rudolf; Siskos, Alexandros; van Loveren, Henk; Ferreira da Costa, Lucien; Albert, Océane; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on isomaltulose syrup (dried) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of a mixture of mono- and disaccharides in powder form, mainly composed of isomaltulose (>= 75%) and trehalulose (< 13%). The applicant intends to use the NF as a replacement for sucrose already on the market. The information provided on the manufacturing process, composition and specifications of the NF is sufficient and does not raise safety concerns. No absorption, distribution, metabolism and excretion (ADME) or toxicological data were provided for the NF. Instead, the safety of the NF was assessed based on literature data available on isomaltulose and mixtures of isomaltulose and trehalulose. In addition, considering the nature, compositional characterisation and production process of the NF, the Panel considered that such data were sufficient to conclude that the NF is as safe as sucrose.

2024 - Safety of magnesium l‐threonate as a novel food pursuant to regulation (EU) 2015/2283 and bioavailability of magnesium from this source in the context of Directive 2002/46/EC [Articolo su rivista]
Null, Null; Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; De , ; Henauw, Stefaan; Hirsch‐ernst, Karen Ildico; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Aguilera‐gómez, Margarita; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser‐berthold, Monika; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; Siskos, Alexandros; van Loveren, Henk; Gelbmann, Wolfgang; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of magnesium l-threonate as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and to address the bioavailability of magnesium from this source in the context of Directive 2002/46/EC. The NF, produced by chemical synthesis, is intended to be used as new source for magnesium in food supplements at a maximum intake level of 3000 mg per day by adults, except for pregnant and lactating women. This dose corresponds to similar to 2730 mg l-threonate and 250 mg magnesium, which also corresponds to the UL for supplemental magnesium from readily dissociable magnesium salts. Based on results obtained from a dissociation study, two rat studies and one human trial, the Panel considers that magnesium is bioavailable from the NF. The NF may contain up to 1% oxalic acid. The Panel considers that an additional exposure to oxalic acid, that is up to 30 mg daily from the NF, is not to be of safety concern. The Panel concludes that the NF is not nutritionally disadvantageous. In 2008, the EFSA ANS Panel concluded that a human intake of l-threonate of 2700 mg per day is safe. This intake is similar to the maximum intake of l-threonate from the NF under the maximum proposed uses, and the NDA Panel concurs with the ANS Panel that this intake is safe. The Panel considers that there are no concerns regarding the genotoxicity of the NF. The Panel concludes that the NF, Mg l-threonate, is safe under the proposed conditions of use. The Panel concludes that the NF is a source from which magnesium is bioavailable.

2024 - Selenium: A global contaminant of significant concern to environment and human health [Capitolo/Saggio]
Vinceti, Marco; Filippini, Tommaso; Biswas, Ashis; Michalke, Bernhard; Dhillon, Karaj S.; Naidu, Ravi
abstract

Selenium (Se) is one of the most interesting and controversial elements found in the environment. It has long attracted interest due to its strong toxicity and potential carcinogenicity, while more recently it garnered interest as an essential nutrient, as a cofactor of selenoproteins, and due to the claim of a beneficial effect against cancer and other chronic diseases, which was recently found to be unwarranted. Selenium is ubiquitous in the environment, being present particularly in rocks, soils, combustion sources, such as smoking and industrial emissions, and water bodies, and therefore living organisms can be overly exposed to it. Selenium is found in several valence states and organic and inorganic compounds, and exposure is generally done by determining overall Se, its species and the selenoproteins in environmental and biological samples. Examples are serum and plasma, urine, hair and nails, and cerebrospinal fluid Se and Se species concentrations. The environmental effects and health outcomes attributable to both Se deficiency and excess, in animals and humans, have been the subject of a large number of studies, and attracted strong interest in environmental sciences and environmental health, also fueling considerable debate. While little evidence of adverse effects of Se deficiency has been detected so far, except for a cardiomyopathy described in some parts of China, a number of serious effects have been reported or suggested by human and animal studies, particularly those carried out in seleniferous areas and by those with experimental design, such as randomized controlled trials. Legislation and recommendations to control Se exposure and avoid the risk of overexposure widely differ throughout the world, and most of them need to be updated taking into account the most recent epidemiological and toxicological evidence. This is particularly due to the toxic effects on human health of even unexpectedly small doses of Se and some selenoproteins, such as type 2 diabetes, dermatological alterations, liver toxicity, endocrine alterations, and neurological disease. Due to the potential contamination of the environment, particularly soil, food, and water with excessive amounts of Se, effective remediation approaches and technologies are being devised and need to be implemented.

2024 - The key role of public health in renovating Italian biomedical doctoral programs [Articolo su rivista]
Palandri, Lucia; Urbano, Teresa; Pezzuoli, Carla; Miselli, Francesca; Caraffi, Riccardo; Filippini, Tommaso; Bargellini, Annalisa; Righi, Elena; Mazzi, Davide; Vigezzi, Giacomo Pietro; Odone, Anna; Marmiroli, Sandra; Boriani, Giuseppe; Vinceti, Marco
abstract

Background: A key renovation of doctoral programs is currently ongoing in Italy. Public health and its competencies may play a pivotal role in high-level training to scientific research, including interdisciplinary and methodological abilities. Methods: As a case study, we used the ongoing renovation of the Clinical and Experimental Medicine doctoral program at the University of Modena and Reggio Emilia. We focused on how the program is designed to meet national requirements as well as students' needs, thus improving educational standards for scientific research in the biomedical field, and on the specific contribution of public health and epidemiology in such an effort. Results: The renovation process of doctoral programs in Italy, with specific reference to the biomedical field, focuses on epidemiologic-statistical methodology, ethics, language and communication skills, and open science from an interdisciplinary and international perspective. In the specific context of the doctoral program assessed in the study and from a broader perspective, public health appears to play a key role, taking advantage of most recent methodological advancements, and contributing to the renovation of the learning process and its systematic quality monitoring. Conclusions: From a comparative assessment of this case study and Italian legislation, the key role of public health has emerged in the renovation process of doctoral programs in the biomedical field.

2023 - A potential role for zinc to enhance treatment for COVID-19? [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Fairweather-Tait, Susan
abstract

2023 - Alcohol Intake and Blood Pressure Levels: A Dose-Response Meta-Analysis of Nonexperimental Cohort Studies [Articolo su rivista]
Di Federico, Silvia; Filippini, Tommaso; Whelton, Paul K; Cecchini, Marta; Iamandii, Inga; Boriani, Giuseppe; Vinceti, Marco
abstract

Background: Alcohol consumption may increase blood pressure but the details of the relationship are incomplete, particularly for the association at low levels of alcohol consumption, and no meta-analyses are available for nonexperimental cohort studies. Methods: We performed a systematic search of longitudinal studies in healthy adults that reported on the association between alcohol intake and blood pressure. Our end points were the mean differences over time of systolic (SBP) and diastolic blood pressure (DBP), plotted according to baseline alcohol intake, by using a dose-response 1-stage meta-analytic methodology. Results: Seven studies, with 19 548 participants and a median follow-up of 5.3 years (range, 4-12 years), were included in the analysis. We observed a substantially linear positive association between baseline alcohol intake and changes over time in SBP and DBP, with no suggestion of an exposure-effect threshold. Overall, average SBP was 1.25 and 4.90 mm Hg higher for 12 or 48 grams of daily alcohol consumption, compared with no consumption. The corresponding differences for DBP were 1.14 and 3.10 mm Hg. Subgroup analyses by sex showed an almost linear association between baseline alcohol intake and SBP changes in both men and women, and for DBP in men while in women we identified an inverted U-shaped association. Alcohol consumption was positively associated with blood pressure changes in both Asians and North Americans, apart from DBP in the latter group. Conclusions: Our results suggest the association between alcohol consumption and SBP is direct and linear with no evidence of a threshold for the association, while for DBP the association is modified by sex and geographic location.

2023 - Alcohol intake and risk of hypertension: a systematic review and dose-response meta-analysis of cohort studies [Abstract in Rivista]
Cecchini, M.; Di Federico, S.; Iamandii, I.; Filippini, T.; Vinceti, M.
abstract

2023 - Appethyl® and reduction of body weight: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Fiolet, T.; Siani, A.
abstract

Following an application from Greenleaf Medical AB, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Sweden, the EFSA Panel on Nutrition, Novel Foods and Food allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Appethyl® and reduction of body weight. Appethyl® is an aqueous extract from spinach leaves standardised by the manufacturing process and its lipase/colipase inhibition capacity in vitro. The Panel considers that the food is sufficiently characterised. A reduction in body weight is a beneficial physiological effect for overweight/obese individuals. The applicant identified a total of three human intervention studies that investigated the effects of Appethyl® on body weight as being pertinent to the claim. In weighing the evidence, the Panel took into account that Appethyl® (5 g/day for 12 weeks) had no effect on body weight as compared to placebo under minimal dietary counselling and moderate physical activity, and that no beneficial physiological effects are to be expected for the target population of overweight/obese individuals from the weight loss that could be attributed to the intervention with Appethyl® under predefined energy restriction and moderate physical activity. The Panel also considered that the effect of Appethyl® (5 g/day for 24 weeks) on body weight maintenance after initial weight loss shown in one study has not been replicated in different settings, which questions the external validity of the results, and that no evidence was provided for a plausible mechanism by which daily consumption of Appethyl® could exert a sustained effect on body weight in humans. The Panel concludes that a cause-and-effect relationship has not been established between the consumption of Appethyl® and a reduction of body weight under the conditions of use proposed by the applicant.

2023 - Artificial light at night and night-shift work: Emerging threats for human health [Articolo su rivista]
Urbano, Teresa; Vinceti, Marco; Filippini, Tommaso
abstract

2023 - Association between metals and metalloids with cognitive status in Mild Cognitive Impairment subjects [Abstract in Rivista]
Urbano, T; Filippini, T; Carbone, C; Chiari, A; Marti, A; Zamboni, G; Michalke, B; Vinceti, M
abstract

2023 - Availability of open data related to COVID-19 epidemic in Italy [Articolo su rivista]
Di Federico, S; Filippini, T; Marchesi, C; Vinceti, M
abstract

Since the beginning of the COVID-19 outbreak in Italy, health authorities have released epidemiologic data about this disease. These data were the most important sources of information which were periodically updated and analyzed by researchers to predict the spread of the epidemic. However, comprehensive and timely data on the evolution of COVID-19 have not always been made available to researchers and physicians.

2023 - Cadmium and risk of cardiovascular disease and stroke: a systematic review and dose-response meta-analysis [Abstract in Rivista]
Verzelloni, Pietro; Urbano, Teresa; Vinceti, Marco; Filippini, Tommaso
abstract

2023 - Cadmium exposure and hypertension: a systematic review and a dose-response meta-analysis [Abstract in Rivista]
Giuliano, V.; Vinceti, M.; Filippini, T.
abstract

Background and Objective: Cadmium (Cd) is a silvery white, malleable metal present in trace amounts in the Earths crust, air and water. Its name derives from that of the city of Cadmo, near Thebes, where it was extracted in antiquity. This heavy metal reacts easily with zinc and to a lesser extent with lead forming various compounds. The main routes of exposure for humans are diet and inhalation. Breathing low levels of Cd for many years (e.g. smokers) or consuming food and water contaminated at levels normally present in the environment (chronic exposure) can cause its accumulation in the body and lead to various pathological conditions, including hypertension. Our aim is to quantify the increase in blood pressure following chronic Cd exposure. Methods: The protocol of the review has been submitted in PROSPERO. The literature search has been carried out on 3 different databases: PubMed, Web of Science and Embase. We used as mesh-terms: “hypertension”, “cadmium” and “blood pressure”. We defined the following inclusion criteria according to PICOS statement: P = healthy adult population, I = exposure to cadmium, C = subjects not exposed to cadmium, O = variation of arterial blood pressure in relation to the cadmium dose to which one is exposed, S = observational studies (cohort, cross-sectional or case-control). We also plan to perform a dose-response meta-analysis whenever possible. Results: We found 678 articles, of which 95 duplicates. After removing these duplicates, we are scanning the abstract and full-text of the remaining 583 papers. Conclusions: The study is currently ongoing and its results will be presented at the Congress.

2023 - Cardiac Surgery in Jehovah's Witnesses Patients and Association With Peri-Operative Outcomes: A Systematic Review and Meta-Analysis [Articolo su rivista]
Vitolo, M.; Mei, D. A.; Cimato, P.; Bonini, N.; Imberti, J. F.; Cataldo, P.; Menozzi, M.; Filippini, T.; Vinceti, M.; Boriani, G.
abstract

Background: Strategies for blood conservation, coupled with a careful preoperative assessment, may be applied to Jehovah's Witnesses (JW) patients who are candidates for cardiac surgery interventions. There is a need to assess clinical outcomes and safety of bloodless surgery in JW patients undergoing cardiac surgery. Methods: We performed a systematic review and meta-analysis of studies comparing JW patients with controls undergoing cardiac surgery. The primary endpoint was short-term mortality (in-hospital or 30-day mortality). Peri-procedural myocardial infarction, re-exploration for bleeding, pre-and postoperative Hb levels and cardiopulmonary bypass (CPB) time were also analyzed. Results: A total of 10 studies including 2,302 patients were included. The pooled analysis showed no substantial differences in terms of short-term mortality among the two groups (OR 1.13, 95% CI 0.74-1.73, I2=0%). There were no differences in peri-operative outcomes among JW patients and controls (OR 0.97, 95% CI 0.39-2.41, I2=18% for myocardial infarction; OR 0.80, 95% CI 0.51-1.25, I2=0% for re-exploration for bleeding). JW patients had a higher level of preoperative Hb (Standardized Mean Difference [SMD] 0.32, 95% CI 0.06-0.57) and a trend toward a higher level of postoperative Hb (SMD 0.44, 95% CI -0.01-0.90). A slightly lower CPB time emerged in JWs compared with controls (SMD -0.11, 95% CI -0.30-0.07). Conclusions: JW patients undergoing cardiac surgery, with avoidance of blood transfusions, did not have substantially different peri-operative outcomes compared with controls, with specific reference to mortality, myocardial infarction, and re-exploration for bleeding. Our results support the safety and feasibility of bloodless cardiac surgery, applying patient blood management strategies.

2023 - Choline and contribution to normal liver function of the foetus and exclusively breastfed infants: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Fiolet, T.; Siani, A.
abstract

Following an application from Procter & Gamble BV pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to choline and contribution to normal liver function of the foetus and exclusively breastfed infant. The scope of the application was proposed to fall under a health claim referring to children's development and health. The Panel considers that choline is sufficiently characterised. The claimed effect proposed by the applicant is contribution ‘to normal foetal and infant development, especially liver’. The proposed target population is ‘unborn fetuses and breastfed infants’. Choline is involved in the structure of cell membranes, cell signalling, metabolism and transport of lipids and cholesterol and neurotransmitter synthesis. Although choline can be synthesised de novo by the human body, depletion-repletion studies in humans show that low choline intake leads to liver dysfunction and muscle damage, which are reverted by the administration of dietary choline. For these functions, de novo synthesis of choline by the human body is insufficient and choline must be obtained from dietary sources. No human studies have addressed the effect of low maternal dietary choline intake on liver function in the fetus or exclusively breastfed infants. However, the Panel considers that the biological role of choline in normal liver function and dietary choline being essential for the function applies to all ages, including fetus and infants. The Panel concludes that a cause and effect relationship has been established between the intake of choline by pregnant and lactating women and contribution to normal liver function of the fetus and exclusively breastfed infants.

2023 - Comment on “Relation of fruit juice with adiposity and diabetes depends on how fruit juice is defined: a re-analysis of the EFSA draft scientific opinion on the tolerable upper intake level for dietary sugars” by Chen et al. 2023 [Articolo su rivista]
Valtuena Martinez, S.; Turck, D.; Craciun, I.; Vinceti, M.
abstract

2023 - Does fluoride exposure affect thyroid function? A systematic review and dose-response meta-analysis [Articolo su rivista]
Iamandii, Inga; De Pasquale, Lisa; Giannone, Maria Edvige; Veneri, Federica; Generali, Luigi; Consolo, Ugo; Birnbaum, Linda S; Castenmiller, Jacqueline; Halldorsson, Thorhallur I; Filippini, Tommaso; Vinceti, Marco
abstract

Introduction: Fluoride exposure may have various adverse health effects, including affecting thyroid function and disease risk, but the pattern of such relation is still uncertain. Methods: We systematically searched human studies assessing the relation between fluoride exposure and thyroid function and disease. We compared the highest versus the lowest fluoride category across these studies, and we performed a one-stage dose-response meta-analysis for aggregated data to explore the shape of the association. Results: Most retrieved studies (27 of which with a cross-sectional design) were conducted in Asia and in children, assessing fluoride exposure through its concentrations in drinking water, urine, serum, or dietary intake. Twenty-four studies reported data on thyroid function by measuring thyroid-related hormones in blood (mainly thyroid-stimulating-hormone - TSH), 9 reported data on thyroid disease, and 4 on thyroid volume. By comparing the highest versus the lowest fluoride categories, overall mean TSH difference was 1.05 μIU/mL. Dose-response curve showed no change in TSH concentrations in the lowest water fluoride exposure range, while the hormone levels started to linearly increase around 2.5 mg/L, also dependending on the risk of bias of the included studies. The association between biomarkers of fluoride exposure and TSH was also positive, with little evidence of a threshold. Evidence for an association between fluoride exposure and blood concentrations of thyroid hormones was less evident, though there was an indication of inverse association with triiodothyronine. For thyroid disease, the few available studies suggested a positive association with goiter and with hypothyroidism in both children and adults. Conclusions: Overall, exposure to high-fluoride drinking water appears to non-linearly affect thyroid function and increase TSH release in children, starting above a threshold of exposure, and to increase the risk of some thyroid diseases.

2023 - Effect of tauroursodeoxycholic acid on survival and safety in amyotrophic lateral sclerosis: a retrospective population-based cohort study [Articolo su rivista]
Zucchi, E.; Musazzi, U. M.; Fedele, G.; Martinelli, I.; Gianferrari, G.; Simonini, C.; Fini, N.; Ghezzi, A.; Caputo, M.; Sette, E.; Vacchiano, V.; Zinno, L.; Anceschi, P.; Canali, E.; Vinceti, M.; Ferro, S.; Mandrioli, J.; Ferri, L.; Gessani, A.; Liguori, R.; Cortelli, P.; Michelucci, R.; Salvi, F.; Bartolomei, I.; Borghi, A. M.; Zini, A.; Rinaldi, R.; Tugnoli, V.; Pugliatti, M.; Codeluppi, L.; Valzania, F.; Stragliati, F.; Nuredini, A.; Romano, S.; D'Orsi, A.; Parrino, L.; Medici, D.; Pilurzi, G.; Terlizzi, E.; Guidetti, D.; De Pasqua, S.; Santangelo, M.; De Massis, P.; Gizzi, M.; Casmiro, M.; Querzani, P.; Morresi, S.; Vitiello, M.; Longoni, M.; Patuelli, A.; Malagu, S.; Bianchi, F.; Dossi, M. C.; Ganino, C.
abstract

Background: Oral tauroursodeoxycholic acid (TUDCA) is a commercial drug currently tested in patients with amyotrophic lateral sclerosis (ALS) both singly and combined with sodium phenylbutyrate. This retrospective study aimed to investigate, in a real-world setting, whether TUDCA had an impact on the overall survival of patients with ALS who were treated with this drug compared to those patients who received standard care only. Methods: This propensity score–matched study was conducted in the Emilia Romagna Region (Italy), which has had an ALS regional registry since 2009. Out of 627 patients with ALS diagnosed from January 1st, 2015 to June 30th, 2021 and recorded in the registry with available information on death/tracheostomy, 86 patients took TUDCA and were matched in a 1:2 ratio with patients who received only usual care according to age at onset, sex, phenotype, diagnostic latency, ALS Functional Rating Scale-Revised (ALSFRS-R) at first visit, disease progression rate at first visit, and BMI at diagnosis. The primary outcome was survival difference (time from onset of symptoms to tracheostomy/death) between TUDCA exposed and unexposed patients. Findings: A total of 86 patients treated with TUDCA were matched to 172 patients who did not receive treatment. TUDCA-exposed patients were stratified based on dosage (less than or equal to 1000 mg/day or greater) and duration (less than or equal to 12 months or longer) of treatment. The median overall survival was 49.6 months (95% CI 41.7–93.5) among those treated with TUDCA and 36.2 months (95% CI 32.7–41.6) in the control group, with a reduced risk of death observed in patients exposed to a higher dosage (defined as ≥ 1000 mg/day) of TUDCA (HR 0.56; 95% CI 0.38–0.83; p = 0.0042) compared to both the control group and those with lower TUDCA dosages (defined as < 1000 mg/day). TUDCA was generally well-tolerated, except for a minority of patients (n = 7, 8.1%) who discontinued treatment due to side effects, primarily gastrointestinal and mild in severity; only 2 adverse events required hospital access but resolved without sequelae. Interpretation: In this population-based exploratory study, patients with ALS who were treated with TUDCA may have prolonged survival compared to patients receiving standard care only. Additional prospective randomized studies are needed to confirm the efficacy and safety of this drug. Funding: Emilia-Romagna Region.

2023 - Effects of selenium supplementation on blood lipids: a systematic review and a dose-response meta-analysis [Abstract in Rivista]
Fiore, G.; Vinceti, M.; Filippini, T.
abstract

Background and Objective: Selenium is a trace element with both nutritional and toxicological properties, depending on the dose and the chemical species. Several studies have shown an association between selenium exposure and cardiovascular risk, focusing on lipid profile and blood pressure. In particular, there is an indication that selenium overexposure may raise the risk of dyslipidemia, but uncertainties still apply to such evidence. The aim of our study is to assess the relation between selenium exposure and the effects on lipid profile in experimental human studies. Material and Methods: The protocol registration in PROSPERO has been submitted for publication. We conducted a preliminary literature search in the following databases: PubMed, Web of Science, Embase and Cochrane Library with no language restrictions. We used MeSH terms and keywords related to “selenium”, “lipid profile”, “LDL”, “VLDL”, “HDL”, “cholesterol”, and “randomized clinical trials”. We defined the following inclusion criteria according the PICOS statement: adult population, exposure to selenium through supplementation as specific difference between intervention and control groups and evaluation of internal exposure using blood biomarker (e.g. serum/plasma levels), assessment of lipid profile as outcome, randomized clinical controlled trials as study design. Results: In the preliminary search, we found 865 records. After duplicate removal, 622 articles were screened by title and abstract. At this stage, we discarded 565 articles, and we reviewed the full-texts of the remaining 56 records to confirm eligibility. Five articles were additionally found through citation chasing techniques and added to the review. We excluded 29 articles due to missing data about outcome of interest. In total, 27 studies met the inclusion criteria and were could be included. Conclusions: The study is currently ongoing and results will be presented during the Congress.

2023 - Exposure to alcohol and risk of dementia: a systematic review and dose-response meta-analysis [Abstract in Rivista]
Rossetti, A.; Mazzoleni, E.; Filippini, T.; Vinceti, M.
abstract

Background: The relation between alcohol intake and cognitive function risk has been established, especially for high levels of exposure. Conversely, the effects at low-moderate levels is still debated and the aim of this study is to characterize the dose-response relation between different degree of alcohol intake and cognitive decline and dementia. Methods: We carried out a comprehensive literature search in PubMed and Embase online databases for cohort and case-control studies investigating the association between alcohol intake on cognitive function. For study identification and selection, we will use the Rayyan online open-source program. Whenever possible, we will conduct a dose-response meta-analysis using the new one stage cubic spline mixed-effects model in order to evaluate the nonlinear relation of such association. According to inclusion criteria, we selected studies on human population with no major comorbidities (e.g. CVD, diabetes, immunological deficits and cancer) and without a diagnosis of dementia and MCI at baseline. Further exclusion criteria were binge drinking and alcoholism, in addition to articles in which no exposure dose was reported. Results: Out of total 3676 articles, we excluded 951 duplicates and after title and abstract screening, we further excluded 2496 records to be subjected to a more accurate analysis. After full-text evaluation, of the 266 resulting articles, we identified 20 eligible studies, with alcohol intake ranging from 0 to 50.4 g alcohol/day and 0 to 4.8 drinks/day. Conclusions: The study is currently ongoing; data extraction and prediction of the database for the dose-response meta- analysis will be presented at the Congress.

2023 - Factors predicting disease progression in C9ORF72 ALS patients [Articolo su rivista]
Mandrioli, Jessica; Zucchi, Elisabetta; Martinelli, Ilaria; Van der Most, Laura; Gianferrari, Giulia; Moglia, Cristina; Manera, Umberto; Solero, Luca; Vasta, Rosario; Canosa, Antonio; Grassano, Maurizio; Brunetti, Maura; Mazzini, Letizia; De Marchi, Fabiola; Simonini, Cecilia; Fini, Nicola; Tupler, Rossella; Vinceti, Marco; Chiò, Adriano; Calvo, Andrea
abstract

Objective To unveil clinical features, comorbidities, disease progression and prognostic factors in a population-based cohort of ALS patients carrying C9ORF72 expansion (C9 + ALS). Methods This is a retrospective observational study on ALS patients residing in Emilia Romagna and Piedmont-Valle D'Aosta regions whose data are available through population based registers. We analysed patients who underwent genetic testing, focusing on C9 + ALS subgroup. Results Among 2204 genotyped patients of the two registers, 150 were C9 + ALS. In comparison with patients without mutation, a higher proportion of family history (12.85 vs 68%, p < 0.001) and frontotemporal dementia (3.93% vs 10.67%, p < 0.001) was detected in C9 + ALS. C9 + ALS presented a faster disease progression as measured by monthly decline in ALS Functional Rating Scale-Revised (1.86 +/- 3.30 vs 1.45 +/- 2.35, p < 0.01) and in forced vital capacity (5.90 +/- 5.24 vs 2.97 +/- 3.47, p < 0.01), a shorter diagnostic delay (8.93 +/- 6.74 vs 12.68 +/- 12.86 months, p < 0.01) and earlier onset (58.91 +/- 9.02 vs 65.04 +/- 11.55 years, p < 0.01). Consistently, they reached death or tracheostomy earlier than other patients (31 vs 37 months, HR = 1.52, 95% C.I. 1.27-1.82, p < 0.001). With respect to other genotyped patients, C9 + ALS patients did not present a significantly higher prevalence of concomitant diseases. Independent prognostic factors of survival of C9 + ALS included sex, age, progression rate, presence of frontotemporal dementia and thyroid disorders, with the latter being associated with prolonged ALS survival (43 vs 29 months, HR = 0.42, 95% C.I. 0.24-0.74, p = 0.003). Conclusion Even in the context of a more aggressive disease, C9 + ALS had a longer survival in presence of thyroid disorders. This finding may suggest protective pathogenic pathways in C9 + ALS to be explored, looking for therapeutic strategies to slow disease course.

2023 - Fluoride Exposure and ADHD: A Systematic Review of Epidemiological Studies [Articolo su rivista]
Fiore, Gianluca; Veneri, Federica; Di Lorenzo, Rosaria; Generali, Luigi; Vinceti, Marco; Filippini, Tommaso
abstract

Background and objectives: Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder characterized by two dimensions: inattentiveness and hyperactivity/impulsivity. ADHD may be the result of complex interactions between genetic, biological and environmental factors possibly including fluoride exposure. Materials and methods: A literature search was performed on 31 March 2023 in the following databases: PubMed, Embase and Web of Science. We defined the following inclusion criteria according to the PECOS statement: a healthy child and adolescent population (P), fluoride exposure of any type (E), comparison with low or null exposure (C), ADHD spectrum disorder (O), and ecological, cross-sectional, case-control and cohort studies (S). Results: We found eight eligible records corresponding to seven different studies investigating the effect of fluoride exposure on children and adolescents. One study had a cohort design and one a case-control one, while five were cross-sectional. Only three studies applied validated questionnaires for the purpose of ADHD diagnosis. As regards exposure assessment, levels of fluoride in urine and tap water were, respectively used in three and two studies, while two used both. Three studies reported a positive association with ADHD risk, all assessing exposure through fluoride levels. By using urinary fluoride, conversely, a positive correlation with inattention, internalizing symptoms, cognitive and psychosomatic problems was found in three studies, but no relation was found in the other one. Conclusions: The present review suggests that early exposure to fluoride may have neurotoxic effects on neurodevelopment affecting behavioral, cognitive and psychosomatic symptoms related to ADHD diagnosis. However, due to the heterogeneity of the studies included, current evidence does not allow to conclusively confirm that fluoride exposure is specifically linked to ADHD development.

2023 - Fluoride Exposure and Skeletal Fluorosis: a Systematic Review and Dose-response Meta-analysis [Articolo su rivista]
Veneri, F.; Iamandii, I.; Vinceti, M.; Birnbaum, L. S.; Generali, L.; Consolo, U.; Filippini, T.
abstract

Purpose of Review: We performed a systematic review and meta-analysis on the relation between fluoride exposure and skeletal fluorosis (SF) using a novel statistical methodology for dose-response modeling. Recent Findings: Skeletal fluorosis, a major health issue that is endemic in some regions, affects millions of people worldwide. However, data regarding the dose-response relation between fluoride exposure and SF are limited and outdated. Summary: We included twenty-three studies in the meta-analysis. When comparing the highest versus the lowest fluoride category, the summary risk ratio (RR) for SF prevalence was 2.05 (95% CI 1.60; 2.64), with a value of 2.73 (95% CI 1.92; 3.90) for drinking water and 1.40 (95% CI 0.90; 2.17) for urinary fluoride. The RR by the risk of bias (RoB) was 2.37 (95% CI 1.56; 3.58) and 1.78 (95% CI 1.34; 2.36) for moderate and high RoB studies, respectively. The dose-response curve based on a one-stage cubic spline regression model showed an almost linear positive relation between exposure and SF occurrence starting from relatively low concentrations up to 5 mg/L and 2.5 mg/L, respectively, for water and urinary fluoride, with no substantial increase above this threshold. The RR for developing moderate-severe forms increases at 5.00 mg/L and 2.5 mg/L of water and urinary fluoride, respectively. Better-quality studies are needed to confirm these results, but greater attention should be given to water fluoride levels to prevent SF, in addition to the other potential adverse effects of fluoride exposure.

2023 - Fluoride exposure and cognitive neurodevelopment: Systematic review and dose-response meta-analysis [Articolo su rivista]
Veneri, Federica; Vinceti, Marco; Generali, Luigi; Giannone, Maria Edvige; Mazzoleni, Elena; Birnbaum, Linda S; Consolo, Ugo; Filippini, Tommaso
abstract

: Many uncertainties still surround the possible harmful effect of fluoride exposure on cognitive neurodevelopment in children. The aim of this systematic review and meta-analysis was to characterize this relation through a dose-response approach, by comparing the intelligence quotient (IQ) scores in the highest versus the lowest fluoride exposure category with a random-effects model, within a one-stage dose-response meta-analysis based on a cubic spline random-effects model. Out of 1996 potentially relevant literature records, 33 studies were eligible for this review, 30 of which were also suitable for meta-analysis. The summary mean difference of IQ score, comparing highest versus lowest fluoride categories and considering all types of exposure, was -4.68 (95% confidence interval-CI -6.45; -2.92), with a value of -5.60 (95% CI -7.76; -3.44) for drinking water fluoride and -3.84 (95% CI -7.93; 0.24) for urinary fluoride. Dose-response analysis showed a substantially linear IQ decrease for increasing water fluoride above 1 mg/L, with -3.05 (95% CI -4.06; -2.04) IQ points per 1 mg/L up to 2 mg/L, becoming steeper above such level. A weaker and substantially linear decrease of -2.15 (95% CI -4.48; 0.18) IQ points with increasing urinary fluoride emerged above 0.28 mg/L (approximately reflecting a water fluoride content of 0.7 mg/L). The inverse association between fluoride exposure and IQ was particularly strong in the studies at high risk of bias, while no adverse effect emerged in the only study judged at low risk of bias. Overall, most studies suggested an adverse effect of fluoride exposure on children's IQ, starting at low levels of exposure. However, a major role of residual confounding could not be ruled out, thus indicating the need of additional prospective studies at low risk of bias to conclusively assess the relation between fluoride exposure and cognitive neurodevelopment.

2023 - GRADE guidance 38: updated guidance for rating up certainty of evidence due to a dose-response gradient [Articolo su rivista]
Murad, M Hassan; Verbeek, Jos; Schwingshackl, Lukas; Filippini, Tommaso; Vinceti, Marco; Akl, Elie A; Morgan, Rebecca L; Mustafa, Reem A; Zeraatkar, Dena; Senerth, Emily; Street, Renee; Lin, Lifeng; Falck-Ytter, Yngve; Guyatt, Gordon; Schünemann, Holger J
abstract

Introduction: This updated guidance from the Grading of Recommendations Assessment, Development, and Evaluation addresses rating up certainty of evidence due to a dose-response gradient (DRG) observed in synthesis of intervention and exposure studies. Study design and setting: This guidance was developed using iterative discussions and consensus in multiple meetings and was presented to attendees of the Grading of Recommendations Assessment, Development, and Evaluation Working Group meeting for feedback in November 2022 and for final approval in May 2023. Results: The guidance consists of two steps. The first is to determine whether the DRG is credible. We describe five items for assessing credibility: a) is DRG identified using a proper analytical approach; b) is confounding the cause of the DRG; c) is there serious concern about ecological bias; d) is the DRG consistent across studies; and e) is there indirect evidence supporting the DRG. The first two of these items are the most critical. If the DRG was judged to be credible, then the second step is to apply the DRG domain and consider rating up, but only by one level due to the concern about residual confounding. Conclusion: Systematic review authors should only rate up certainty in evidence when a DRG is deemed credible.

2023 - Healthy dietary patterns and cognitive status in Mild Cognitive Impairment subjects [Abstract in Rivista]
Urbano, T; Filippini, T; Carbone, C; Malavolti, M; Marti, A; Agnoli, C; Sieri, S; Chiari, A; Zamboni, G; Vinceti, M
abstract

2023 - Human serum albumin-bound selenium (Se-HSA) in serum and its correlation with other selenium species [Articolo su rivista]
Filippini, Tommaso; Urbano, Teresa; Grill, Peter; Malagoli, Carlotta; Ferrari, Angela; Marchesi, Cristina; Natalini, Nicoletta; Michalke, Bernhard; Vinceti, Marco
abstract

Introduction: Selenium (Se) is a trace element with different toxicological and nutritional properties according to its chemical forms. Among the wide range of selenium species, human serum albumin-bound selenium (Se-HSA) has still uncertain composition in terms of organic or inorganic selenium species. This study aimed at investigating the relation between Se-HSA levels with total selenium and the specific organic and inorganic selenium species. Methods: We determined levels of total selenium and selenium species in serum of participants enrolled in two populations of the Emilia-Romagna region, in Northern Italy. Anion exchange chromatography coupled with inductively coupled plasma dynamic reaction cell mass spectrometry was used as quantification method. Correlations between Se-HSA and the other selenium compounds were analyzed using linear regression and restricted cubic spline regression models, adjusted for potential confounders. Results: The first cohort comprised 50 participants (men/women: 26/24) with median (interquartile range, IQR) age 50 (55-62) years, while the second was composed of 104 participants (M/W: 50/54), median (IQR) age 48 (44-53) years. Median (IQR) levels of total selenium were 118.5 (109-136) µg/L and 116.5 (106-128) µg/L, respectively, while Se-HSA was 25.5 µg/L (16.2-51.5) and 1.1 (0.03-3.1) µg/L, respectively. In both populations, Se-HSA was positively associated with inorganic selenium species. Conversely, Se-HSA was inversely associated with organic selenium, especially with selenoprotein P-bound-Se (Se-SELENOP) and less strongly with selenomethionine-bound-Se (Se-Met), while the relation was null or even positive with other organic species. Evaluation of non-linear trends showed a substantially positive association with inorganic selenium, particularly selenite, until a concentration of 30 µg/L, above which a plateau was reached. The association with Se-SELENOP was inverse and strong until 100 µg/L, while it was almost null at higher levels. Conclusions: Our findings seem to indicate that Se-HSA incorporates more selenium when circulating levels of inorganic compounds are higher, thus supporting its mainly inorganic nature, particularly at high circulating levels of selenite.

2023 - Influence of dietary patterns on urinary excretion of cadmium in an Italian population: A cross-sectional study [Articolo su rivista]
Urbano, Teresa; Verzelloni, Pietro; Malavolti, Marcella; Sucato, Sabrina; Polledri, Elisa; Agnoli, Claudia; Sieri, Sabina; Natalini, Nicoletta; Marchesi, Cristina; Fustinoni, Silvia; Vinceti, Marco; Filippini, Tommaso
abstract

Introduction: Cadmium is a toxic heavy metal with detrimental effects on human health. Apart from smoking and occupational factors, diet is the main source of cadmium. However, the relation between adherence to so-called "healthy" dietary patterns and cadmium exposure has not been investigated in detail. In this study, we aimed at assessing such association in a Northern Italian population. Methods: Using a cross-sectional study design, we investigated a population of non-smokers aged 30-60 years in the period 2017-2019. Each subject completed a validated food frequency questionnaire (FFQ) in order to estimate adherence to four dietary patterns, namely the Dietary Approach to Stopping Hypertension-DASH diet, Greek Mediterranean Index-GMI, the Italian Mediterranean Index-IMI, and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. We collected a fasting morning urinary sample to measure urinary levels of cadmium and cotinine. The association between increasing adherence to dietary patterns and cadmium exposure was evaluated using a cubic spline regression non-linear model and adjusting for relevant confounders (age, sex, body mass index, urinary cotinine levels, intake of fiber, and alcohol). Results: We recruited 137 participants (males/females: 62/75) with median (interquartile range-IQR) age of 47 (IQR: 43-53) years. Median scores for the investigated dietary patterns were 24 (IQR: 21-28), 4 (IQR: 3-6), 4 (IQR: 3-5), and 7.5 (IQR: 6.5-8.5) for DASH, GMI, IMI and MIND diets, respectively. The median urinary cadmium level was 0.21 μg/L (IQR: 0.11-0.34 μg/L). Spline regression analysis showed an inverse linear association between increasing adherence to the DASH and MIND diets and urinary cadmium levels, reaching a plateau at high adherence scores, approximately > 25 and > 9 for DASH and MIND diets, respectively. An increase of cadmium exposure with increasing MIND score also emerged. Conversely, the association was almost null for IMI, and slightly positive for GMI. Conclusions: The present findings suggest that increasing adherence to the DASH and MIND diets are associated with decreased cadmium levels only at moderate level. Overall, these results indicate that public health strategies, including the decrease of cadmium contamination in healthy foods should be implemented.

2023 - Insight into Elderly ALS Patients in the Emilia Romagna Region: Epidemiological and Clinical Features of Late-Onset ALS in a Prospective, Population-Based Study [Articolo su rivista]
Gianferrari, Giulia; Martinelli, Ilaria; Simonini, Cecilia; Zucchi, Elisabetta; Fini, Nicola; Caputo, Maria; Ghezzi, Andrea; Gessani, Annalisa; Canali, Elena; Casmiro, Mario; De Massis, Patrizia; Curro' Dossi, Marco; De Pasqua, Silvia; Liguori, Rocco; Longoni, Marco; Medici, Doriana; Morresi, Simonetta; Patuelli, Alberto; Pugliatti, Maura; Santangelo, Mario; Sette, Elisabetta; Stragliati, Filippo; Terlizzi, Emilio; Vacchiano, Veria; Zinno, Lucia; Ferro, Salvatore; Amedei, Amedeo; Filippini, Tommaso; Vinceti, Marco; Errals Group, Null; Mandrioli, Jessica
abstract

: Few studies have focused on elderly (>80 years) amyotrophic lateral sclerosis (ALS) patients, who represent a fragile subgroup generally not included in clinical trials and often neglected because they are more difficult to diagnose and manage. We analyzed the clinical and genetic features of very late-onset ALS patients through a prospective, population-based study in the Emilia Romagna Region of Italy. From 2009 to 2019, 222 (13.76%) out of 1613 patients in incident cases were over 80 years old at diagnosis, with a female predominance (F:M = 1.18). Elderly ALS patients represented 12.02% of patients before 2015 and 15.91% from 2015 onwards (p = 0.024). This group presented with bulbar onset in 38.29% of cases and had worse clinical conditions at diagnosis compared to younger patients, with a lower average BMI (23.12 vs. 24.57 Kg/m2), a higher progression rate (1.43 vs. 0.95 points/month), and a shorter length of survival (a median of 20.77 vs. 36 months). For this subgroup, genetic analyses have seldom been carried out (25% vs. 39.11%) and are generally negative. Finally, elderly patients underwent less frequent nutritional- and respiratory-supporting procedures, and multidisciplinary teams were less involved at follow-up, except for specialist palliative care. The genotypic and phenotypic features of elderly ALS patients could help identify the different environmental and genetic risk factors that determine the age at which disease onset occurs. Since multidisciplinary management can improve a patient's prognosis, it should be more extensively applied to this fragile group of patients.

2023 - Interplay of Metallome and Metabolome in Amyotrophic Lateral Sclerosis: A Study on Cerebrospinal Fluid of Patients Carrying Disease-Related Gene Mutations [Articolo su rivista]
Solovyev, N.; Lucio, M.; Mandrioli, J.; Forcisi, S.; Kanawati, B.; Uhl, J.; Vinceti, M.; Schmitt-Kopplin, P.; Michalke, B.
abstract

2023 - It's (not) rocket science! a quick guide to a successful scientific communication in public health [Abstract in Rivista]
Palandri, Lucia; Filippini, Tommaso; Ferrari, Eleonora; Lugli, Camilla; Odone, Anna; Grignolio, Andrea; Righi, Elena; Vinceti, Marco
abstract

A Brief Outline Of The Overall Workshop: Our workshop is intended to act as an overview of effective Public Health communication. We will examine various contexts, beneficiaries, and actors in Preventive Medicine and Public Health communication, stressing the importance of effective knowledge transfer in this field. * First sub-session “HOW TO: COMMUNICATE DATA TO HEALTH PROFESSIONALS” (20 min): * How to: Data Visualization - Lucia Palandri, MD, DrPH, PhDc * How to: Digital Communication - Prof. Tommaso Filippini, MD, DrPH, PhD - [HALF-TIME - 10 min]: DO’S AND DON’TS: INFOGRAPHICS FOR HEALTH PROFESSIONALS VS GENERAL PUBLIC - Eleonora Ferrari, MD; Camilla Lugli, MD * Second sub-session “COMMUNICATE HEALTH TO PEOPLE: SUCCESSFUL EXAMPLES” (20 min): * Leo and Giulia - Prof. Anna Odone, MD, MSc, MPH, PhD * Vaccine Pills on TV - Prof. Andrea Grignolio, MA, PhD * Q&A session (10 min) Moderator: Prof. Elena Righi, PhD Specific Aims/Objectives And Component Parts As Public Health professionals and residents, COVID-19 pandemic had a significant impact on our work, shedding light on a major issue: communication. As a matter of fact, in the last few years, scientific communication has undoubtedly been a challenge in two ways. On one hand, communication has been difficult even among professionals due to the significant volume of data constantly gathered and analyzed during the pandemic. On the other hand, we faced some difficulty with the necessity to constantly interface with the population in an infodemic setting. Both challenges should be considered as important priorities in public health: the lessons learnt from the pandemic (and beyond) should routinely and inextricably guide us in carrying out our roles as PH specialists. Hence, our necessity to delve into this topic and share what we have learnt with coworkers. To this end, we chose to organize our workshop into two sections. A first skill-building sub-session will be dedicated to the communication of scientific information and data among health professionals and “insiders”. In the second sub-session we would like to present a couple of examples of successful general public scientific communication campaigns. We will merge the two sub-session with a practical guide about do’s and don’ts in scientific posters and general public infographic creation. The Key Questions That The Workshop Will Address - How to present scientific findings and relevant data to scientists and health professionals? How to make data more comprehensible? - How to deliver a clear message and maintain public trust in science through successful campaigns?”

2023 - Mercuric chloride (HgCl2) [Capitolo/Saggio]
Urbano, Teresa; Malavolti, Marcella; Vinceti, Marco; Filippini, Tommaso
abstract

2023 - Nutritional safety and suitability of a specific protein hydrolysate derived from a whey protein concentrate and used in an infant formula and follow-on formula manufactured from hydrolysed protein by FrieslandCampina Nederland B.V [Articolo su rivista]
Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Castle, L.; Fewtrell, M.; Przyrembel, H.; Dumas, C.; Titz, A.; Turck, D.
abstract

The European Commission asked EFSA to deliver an opinion on the nutritional safety and suitability of a specific protein hydrolysate. It is derived from a whey protein concentrate and used in an infant and follow-on formula manufactured by FrieslandCampina Nederland B.V., which submitted a dossier to the European Commission to request an amendment of Regulation (EU) 2016/127 with respect to the protein sources that may be used in the manufacture of infant and/or follow-on formula. The protein hydrolysate under evaluation is sufficiently characterised with respect to the fraction of the hydrolysed protein. In the pertinent intervention study provided, an infant formula manufactured from the protein hydrolysate with a protein content of 2.4 g/100 kcal and consumed as the sole source of nutrition by infants for 3 months led to a growth equivalent to a formula manufactured from intact cow's milk protein with a protein content of 2.1 g/100 kcal. Data on gastrointestinal tolerance of the formula did not raise any concerns. No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. Given that it is consumed with complementary foods and the protein source is nutritionally safe and suitable in an infant formula that is the sole source of nutrition of infants, the Panel considers that the protein hydrolysate is also a nutritionally safe and suitable protein source for use in follow-on formula. The Panel concludes that the protein hydrolysate under evaluation is a nutritionally safe and suitable protein source for use in infant and follow-on formula, as long as the formula in which it is used contains a minimum of 2.4 g/100 kcal protein and complies with the compositional criteria of Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA.

2023 - Outdoor artificial light at night and risk of early-onset dementia: A case-control study in the Modena population, Northern Italy [Articolo su rivista]
Mazzoleni, E.; Vinceti, M.; Costanzini, S.; Garuti, C.; Adani, G.; Vinceti, G.; Zamboni, G.; Tondelli, M.; Galli, C.; Salemme, S.; Teggi, S.; Chiari, A.; Filippini, T.
abstract

Background Dementia is a neurological syndrome characterized by severe cognitive impairment with functional impact on everyday life. It can be classified as young onset dementia (EOD) in case of symptom onset before 65, and late onset dementia (LOD). The purpose of this study is to assess the risk of dementia due to light pollution, and specifically outdoor artificial light at night (LAN). Methods Using a case-control design, we enrolled dementia patients newly-diagnosed in the province of Modena in the period 2017–2019 and a referent population from their caregivers. We geo-referenced the address of residence on the date of recruitment, provided it was stable for the previous five years. We assessed LAN exposure through 2015 nighttime luminance satellite images from the Visible Infrared Imaging Radiometer Suite (VIIRS). Using a logistic regression model adjusted for age, sex, and education, we calculated the risk of dementia associated with increasing LAN exposure, namely using <10 nW/cm2/sr as reference and considering ≥10-<40 nW/cm2/sr intermediate and ≥40 nW/cm2/sr high exposure, respectively We also implemented non-linear assessment using a spline regression model. Results We recruited 58 EOD cases, 34 LOD cases and 54 controls. Average LAN exposure levels overlapped for EOD cases and controls, while LOD cases showed higher levels. Compared with the lowest exposure, the risk of EOD associated with LAN was higher in the intermediate exposure (OR = 1.36, 95% CI 0.54–3.39), but not in the high exposure category (OR = 1.04, 95% CI 0.32–3.34). In contrast, the risk of LOD was positively associated with LAN exposure, with ORs of 2.58 (95% CI 0.26–25.97) and 3.50 (95% CI 0.32–38.87) in the intermediate and high exposure categories, respectively. The spline regression analysis showed substantial lack of association between LAN and EOD, while almost linear although highly imprecise association emerged for LOD. Conclusions Although the precision of the estimates was affected by the limited sample size and the study design did not allow us to exclude the presence of residual confounding, these results suggest a possible role of LAN in the etiology of dementia, particularly of its late-onset form.

2023 - Particulate matter exposure and dementia risk: a prospective cohort study in Northern Italy [Abstract in Atti di Convegno]
Urbano, T.; Malagoli, C.; Vinceti, M.; Filippini, T.
abstract

2023 - Particulate matter exposure from motorized traffic and risk of conversion from mild cognitive impairment to dementia: An Italian prospective cohort study [Articolo su rivista]
Urbano, Teresa; Chiari, Annalisa; Malagoli, Carlotta; Cherubini, Andrea; Bedin, Roberta; Costanzini, Sofia; Teggi, Sergio; Maffeis, Giuseppe; Vinceti, Marco; Filippini, Tommaso
abstract

Background: Based on epidemiologic and laboratory studies, exposure to air pollutants has been linked to many adverse health effects including a higher risk of dementia. In this study, we aimed to evaluate the effect of long-term exposure to outdoor air pollution on risk of conversion to dementia in a cohort of subjects with mild cognitive impairment (MCI). Methods: We recruited 53 Italian subjects newly-diagnosed with MCI. Within a geographical information system, we assessed recent outdoor air pollutant exposure, by modeling air levels of particulate matter with equivalent aerodynamic diameter ≤10 μm (PM10) from motorized traffic at participants' residence. We investigated the relation of PM10 concentrations to subsequent conversion from MCI to any type of dementia. Using a Cox-proportional hazards model combined with a restricted cubic spline model, we computed the hazard ratio (HR) of dementia with its 95% confidence interval (CI) according to increasing PM10 exposure, adjusting for sex, age, and educational attainment. Results: During a median follow up of 47.3 months, 34 participants developed dementia, in 26 cases diagnosed as Alzheimer's dementia. In non-linear restricted spline regression analysis, mean and maximum annual PM10 levels positively correlated with cerebrospinal fluid total and phosphorylated tau proteins concentrations, while they were inversely associated with β-amyloid. Concerning the risk of dementia, we found a positive association starting from above 10 μg/m3 for mean PM10 levels and above 35 μg/m3 for maximum PM10 levels. Specific estimates for Alzheimer's dementia were substantially similar. Adding other potential confounders to the multivariable model or removing early cases of dementia onset during the follow-up had little effect on the estimates. Conclusions: Our findings suggest that exposure to outdoor air pollutants, PM10 in particular, may non-linearly increase conversion from MCI to dementia above a certain ambient air concentration.

2023 - Predictors for progression in amyotrophic lateral sclerosis associated to SOD1 mutation: insight from two population-based registries [Articolo su rivista]
Martinelli, Ilaria; Ghezzi, Andrea; Zucchi, Elisabetta; Gianferrari, Giulia; Ferri, Laura; Moglia, Cristina; Manera, Umberto; Solero, Luca; Vasta, Rosario; Canosa, Antonio; Grassano, Maurizio; Brunetti, Maura; Mazzini, Letizia; De Marchi, Fabiola; Simonini, Cecilia; Fini, Nicola; Vinceti, Marco; Pinti, Marcello; Chiò, Adriano; Calvo, Andrea; Mandrioli, Jessica
abstract

BackgroundUncovering distinct features and trajectories of amyotrophic lateral sclerosis (ALS) associated with SOD1 mutations (SOD1-ALS) can provide valuable insights for patient' counseling and stratification for trials, and interventions timing. Our study aims to pinpoint distinct clinical characteristics of SOD1-ALS by delving into genotype-phenotype correlations and factors that potentially impact disease progression.MethodsThis is a retrospective observational study of a SOD1-ALS cohort from two Italian registers situated in the regions of Emilia-Romagna, Piedmont and Valle d'Aosta.ResultsOut of 2204 genotyped ALS patients, 2.5% carried SOD1 mutations, with a M:F ratio of 0.83. SOD1-ALS patients were younger, and more frequently reported a family history of ALS and/or FTD. SOD1-ALS had a longer survival compared to patients without ALS-associated gene mutations. However, here was considerable variability in survival across distinct SOD1 mutations, with an average survival of less than a year for the L39V, G42S, G73S, D91N mutations. Among SOD1-ALS, multivariate analysis showed that, alongside established clinical prognostic factors such as advanced age at onset and high progression rate at diagnosis, mutations located in exon 2 or within highly conserved gene positions predicted worse survival. Conversely, among comorbidities, cancer history was independently associated with longer survival.InterpretationWithin the context of an overall slower disease, SOD1-ALS exhibits some degree of heterogeneity linked to the considerable genetic diversity arising from the multitude of potential mutations sites and specific clinical prognostic factors, including cancer history. Revealing the factors that modulate the phenotypic heterogeneity of SOD1-ALS could prove advantageous in improving the efficacy of upcoming therapeutic approaches.

2023 - Re-evaluation of behenic acid from mustard seeds to be used in the manufacturing of certain emulsifiers pursuant to Article 21(2) of Regulation (EU) No 1169/2011 – for permanent exemption from labelling [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Marchelli, R.; Van Loveren, H.; Valtuena Martinez, S.; de Henauw, S.
abstract

Following a request from the European Commission, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to review a scientific assessment related to a notification from DuPont Nutrition Biosciences Aps on behenic acid from mustard seeds to be used in the manufacturing of certain emulsifiers pursuant to Article 21(2) of Regulation (EU) No 1169/2011 – for permanent exemption from labelling. The EC requested EFSA to consider comments raised by the German authorities in relation to: (a) the maximum amount of mustard protein that could be consumed from the emulsifiers manufactured from behenic acid (E470a, E471 and E477) on a single occasion and (b) the minimal observed eliciting dose (MOED) triggering allergic reactions in mustard-allergic individuals. The maximum amount of mustard protein content in behenic acid was re-assessed in view of new analytical data provided by the applicant. Intake estimates by the EFSA ANS Panel for E471 (adults) were used as a proxy for the combined intake (E470a, E471 and E477). Food challenge data and systematic reviews thereof deriving population minimal observed eliciting dose distributions for mustard protein were used to calculate the MOED and estimate the risk. The margin of exposure between the MOED (0.26 mg mustard protein) and the maximum amount of mustard protein that could be consumed from the emulsifiers on a single occasion (0.00895475 mg) is 29. It is predicted that between 0.1% and 1% of the mustard allergic population would react with mild objective symptoms to that dose. Overall, the assessment is conservative, particularly in relation to the exposure. Based on the information and data available, the NDA Panel concludes that it is extremely unlikely (≤ 1% probability) that oral consumption of emulsifiers to be manufactured using behenic acid from mustard seeds (i.e. E470a, E471 and E477) will trigger an allergic reaction in mustard-allergic individuals under the proposed conditions of use.

2023 - Residential exposure to magnetic fields from high-voltage power lines and risk of childhood leukemia [Articolo su rivista]
Malagoli, C.; Malavolti, M.; Wise, L. A.; Balboni, E.; Fabbi, S.; Teggi, S.; Palazzi, G.; Cellini, M.; Poli, M.; Zanichelli, P.; Notari, B.; Cherubini, A.; Vinceti, M.; Filippini, T.
abstract

Background: Several studies have suggested an excess risk of leukemia among children living close to high-voltage power lines and exposed to magnetic fields. However, not all studies have yielded consistent results, and many studies may have been susceptible to confounding and exposure misclassification. Methods: We conducted a case-control study to investigate the risk of leukemia associated with magnetic field exposure from high-voltage power lines. Eligible participants were children aged 0–15 years residing in the Northern Italian provinces of Modena and Reggio Emilia. We included all 182 registry-identified childhood leukemia cases diagnosed in 1998–2019, and 726 age-, sex- and province-matched population controls. We assessed exposure by calculating distance from house to nearest power line and magnetic field intensity modelling at the subjects’ residence. We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders (distance from nearest petrol station and fuel supply within the 1000 m-buffer, traffic-related particulate and benzene concentrations, presence of indoor transformers, percentage of urban area and arable crops). Results: In multivariable analyses, the OR comparing children living <100 m from high-voltage power-lines with children living ≥400 m from power-lines was 2.0 (95% CI 0.8–5.0). Results did not differ substantially by age at disease diagnosis, disease subtype, or when exposure was based on modeled magnetic field intensity, though estimates were imprecise. Spline regression analysis showed an excess risk for both overall leukemia and acute lymphoblastic leukemia among children with residential distances <100 m from power lines, with a monotonic inverse association below this cutpoint. Conclusions: In this Italian population, close proximity to high-voltage power lines was associated with an excess risk of childhood leukemia.

2023 - Residential exposure to magnetic fields from high-voltage power lines and risk of childhood leukemia in an Italian population [Abstract in Rivista]
Malavolti, M.; Malagoli, C.; Filippini, T.; Poli, M.; Cellini, M.; Palazzi, G.; Vinceti, M.
abstract

Background: An excess risk of leukemia in children living close to high-voltage power-lines and therefore exposed to extremely low frequency magnetic fields has been suggested, though not all studies yielded consistent results, and a possible role of confounding and exposure misclassification could not be entirely ruled out. Methods: We investigated the risk of childhood leukemia associated with magnetic fields exposure from 132+ kV power lines within a population-based case-control study in two Northern Italy provinces, Modena and Reggio Emilia. We included all the 182 registry-based childhood leukemia cases diagnosed from 1998 to 2019, and 726 age, sex and province of residence-matched controls. We assessed exposure by calculating distance from house to nearest power line in a geographical information system database and by modeling magnetic fields at the subjects’ residence. We run analyses in the overall population, restricted to acute lymphoblastic leukemia (ALL) cases, and stratified by age (<5 and ≥5 years). Results: Compared to those living ≥ 400 m from high-voltage power-lines, children living <50 m and 50-<100 m from power lines showed a disease odds ratio (OR) of 3.0 (95% CI 0.7–13.3) and 1.6 (95% CI 0.5–5.1), respectively. The excess risk close to the power lines was higher for the ALL subtype (OR 3.0, 95% CI 0.7–13.3) and among children diagnosed after 5 years (4.1, 95% CI 0.8–20.6). Results did not substantially differ when exposure was based on modeled magnetic fields, though risk ratio estimates became more statistically unstable. Conclusions: We found a statistically imprecise excess risk for childhood leukemia associated with close proximity to high-voltage power lines, which appeared to be stronger for the youngest children.

2023 - Residential proximity to petrol stations and risk of childhood leukemia [Articolo su rivista]
Malavolti, Marcella; Malagoli, Carlotta; Filippini, Tommaso; Wise, Lauren A; Bellelli, Alessio; Palazzi, Giovanni; Cellini, Monica; Costanzini, Sofia; Teggi, Sergio; Vinceti, Marco
abstract

Petrol stations emit benzene and other contaminants that have been associated with an increased risk of childhood leukemia. We carried out a population-based case-control study in two provinces in Northern Italy. We enrolled 182 cases of childhood leukemia diagnosed during 1998-2019 and 726 age- and sex-matched population controls. We geocoded the addresses of child residences and 790 petrol stations located in the study area. We estimated leukemia risk according to distance from petrol stations within a 1000 m buffer and amount of supplied fuel within a buffer of 250 m from the child's residence. We used conditional logistic regression models to approximate risk ratios (RRs) and 95% confidence intervals (CIs) for associations of interest, adjusted for potential confounders. We also modeled non-linear associations using restricted cubic splines. In secondary analyses, we restricted to acute lymphoblastic leukemia (ALL) cases and stratifed by age (<5 and >= 5 years). Compared with children who lived >= 1000 m from a petrol station, the RR was 2.2 (95% CI 0.5-9.4) for children living<50 m from nearest petrol station. Associations were stronger for the ALL subtype (RR=2.9, 95% CI 0.6-13.4) and among older children (age >= 5 years: RR=4.4, 95% CI 0.6-34.1; age<5 years: RR=1.6, 95% CI 0.1-19.4). Risk of leukemia was also greater (RR=1.6, 95% CI 0.7-3.3) among the most exposed participants when assigning exposure categories based on petrol stations located within 250 m of the child's residence and total amount of gasoline delivered by the stations. Overall, residence within close proximity to a petrol station, especially one with more intense refueling activity, was associated with an increased risk of childhood leukemia, though associations were imprecise.

2023 - Role of vegetarian and plant-based diet in the prevention of mild cognitive impairment and dementia [Abstract in Rivista]
Barbolini, G.; Vinceti, M.; Filippini, T.
abstract

Background and Objective: The increasing number of people with Mild Cognitive Impairment (MCI) and dementia represents a relevant public health problem. For this reason, there is interest in the assessment of factors affecting disease risk, in order to implement effective prevention strategies and promote a healthy lifestyle. In particular, diet as a determinant of cognitive impairment and dementia represents an important field of research, and many studies focused on the effects of plant-based, vegetarian or vegan diets on cognitive functions and dementia risk. The aim of this systematic review is to assess whether a plant-based or a ‘strict’ vegetarian diet is protective or detrimental towards cognitive functions. Methods: The protocol of this systematic review and meta-analysis has been submitted to PROSPERO. The literature search has been conducted on 4 different databases: PubMed, Web of Science, Embase and Cochrane library. We used MeSH terms and keywords related to “plant-based diet”, “vegetarian diet”, “Mild Cognitive Impairment”, “dementia” and “memory impairment”. We found 2 additional articles through citation chasing techniques. We defined the following inclusion criteria according to the PICOS statement: adult population, adherence to plant-based, vegetarian or vegan diets, assessment of cognitive functions through dementia risk or cognitive decline at increasing adherence to different dietary patterns, and both observational studies (cohort, cross-sectional or case-control) and randomized clinical controlled trials. We will also perform a dose-response meta-analysis whenever possible. Results: In the preliminary literature search, we found a total of 1537 articles (including 2 studies added through citations), 255 of which were duplicates. After duplicate removal, the abstract and the full-text of 1282 articles were screened, leading to the exclusion of 1263 of them. Nineteen studies met our inclusion criteria and could be included in the systematic review. Conclusions: The study is currently ongoing and its results will be presented at the Congress.

2023 - Safety of 2′-fucosyllactose (2’-FL) produced by a derivative strain (Escherichia coli SGR5) of E. coli W (ATCC 9637) as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Pelaez, C.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 2′-fucosyllactose (2’-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 2’-FL, but it also contains d-lactose, l-fucose, fucosylgalactose, difucosyllactose, d-glucose and d-galactose, and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli SGR5) of E. coli W (ATCC 9637). The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant applies for the same use and use levels as already authorised for 2’-FL and included in the Union list of NFs, with the general population as target population. The Panel noted that the available intake estimate is not recent (2015) and based on a different database (2008–2010 UK data) than that used by EFSA. For this reason, the Panel decided to perform a new intake estimate according to the current EFSA approach. The Panel notes that the highest P95 daily intake of the NF from the use as food ingredient is higher than the estimated natural highest mean daily intake in breastfed infants and marginally higher in young children. The applicant also proposes to extend the use of 2’-FL in food supplements (FS) for infants at the use level of 1.2 g/day. The resulting estimated intake in infants from the proposed use in FS is within the natural intake of 2’-FL in breastfed infants. FS are not intended to be used if other foods with added 2’-FL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2023 - Safety of 3-fucosyllactose (3-FL) produced by a derivative strain of Escherichia coli K-12 DH1 as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3-fucosyllactose (3-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3-FL, but it also contains d-lactose, l-fucose, 3-fucosyllactulose and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli K-12 DH1 MDO MAP1834) of E. coli K-12 DH1 (DSM 4235). The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for special medical purposes and food supplements (FS). The target population is the general population. The anticipated daily intake of 3-FL from both proposed and combined (authorised and proposed) uses at their respective maximum use levels in all population categories does not exceed the highest intake level of 3-FL from human milk in infants on a body weight basis. The intake of 3-FL in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to 3-FL is also considered of no safety concern. FS are not intended to be used if other foods with added 3-FL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2023 - Safety of 3′-sialyllactose (3′-SL) sodium salt produced by a derivative strain (Escherichia coli NEO3) of E. coli W (ATCC 9637) as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Pelaez, C.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3′-sialyllactose (3′-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3′-SL (sodium salt), but it also contains sialic acid, d-glucose, d-lactose, 3′-sialyllactulose and 6′-sialyllactose sodium salts and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli NEO3) of E. coli W (ATCC 9637). The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for special medical purposes and food supplements (FS). The target population is the general population. The applicant applies for the same uses and use levels as already assessed for 3′-SL sodium salt produced by a genetically modified strain of E. coli K-12 DH1, with the exception for the use in FS, which is proposed to be higher (from 0.5 to 1.0 g/day) in individuals from 3 years of age. Since the NF as a food ingredient would be consumed at the same extent as the already assessed 3′-SL sodium salt, no new estimates of the intakes have been carried out. The Panel notes that the maximum daily intake of 3′-SL from the proposed use of the NF in FS for individuals from 3 years of age (1.0 g/day) is lower than the estimated highest mean daily intake of 3′-SL in breastfed infants. FS are not intended to be used if other sources of 3′-SL are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2023 - Safety of 6′-sialyllactose (6′-SL) sodium salt produced by a derivative strain (Escherichia coli NEO6) of E. coli W (ATCC 9637) as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 6′-sialyllactose (6′-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 6′-SL (sodium salt), but it also contains sialic acid, d-glucose, d-lactose, 6′-sialyllactulose sodium salt, 3′-sialyllactose (3′-SL) sodium salt and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli NEO6) of E. coli W (ATCC 9637). The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for special medical purposes and food supplements (FS). The target population is the general population. The applicant applies for the same uses and use levels already assessed for 6′-SL sodium salt produced by fermentation by a genetically modified strain of E. coli K-12 DH1. Therefore, since the NF would be consumed at the same extent as the already assessed 6′-SL sodium salt, no new estimates of the intake have been carried out. Similarly, FS are not intended to be used if other foods with added 6′-SL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2023 - Safety of a change in specifications of the novel food oleoresin from Haematococcus pluvialis containing astaxanthin pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of a change of specifications of the novel food (NF) oleoresin from Haematococcus pluvialis containing astaxanthin (ATX) pursuant to Regulation (EU) 2015/2283. The NF is already authorised as ingredient for the use in food supplements as defined in Directive 2002/46EC in accordance to Regulation (EU) 2017/2470. The NF concerns an oleoresin which contains ~ 10% ATX, obtained by supercritical CO2 extraction of the homogenised and dried biomass of cultivated H. pluvialis. This NF has been assessed by the Panel in 2014. With the present dossier, the applicant proposed to lower the minimum specification limits for protein and ATX monoesters for the NF, and to increase the maximum specification limit for the relative amount of ATX diesters in total ATX. An increase of the maximum specification limit for the 9-cis isomer is also applied for. Although the data are limited regarding bioavailability and distribution in humans of these three naturally occurring ATX isomers, the available in vitro and in vivo data suggest that the 13-cis rather than the 9-cis ATX is selectively absorbed, i.e. has a higher bioavailability and/or possibly emerges from isomerisation of all-trans ATX. The Panel notes that the toxicity of the individual ATX isomers has not been studied individually. However, the ADI of 0.2 mg/kg, which was established for synthetic ATX and ATX from H. pluvialis, applies also for ATX in the oleoresin from H. pluvialis with the proposed changes of specifications. The Panel concludes that the NF, oleoresin from H. pluvialis containing ATX, is safe with the proposed specification limits.

2023 - Safety of an ethanolic extract of the dried biomass of the microalga Phaeodactylum tricornutum as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Siskos, A.; Schlatter, J. R.; van Loveren, H.; Munoz Gonzalez, A.; Rossi, A.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on an ethanolic extract of the dried biomass of the microalga Phaeodactylum tricornutum as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is an ethanolic extract of the dried biomass of the microalga P. tricornutum diluted in a medium-chain triglyceride oil carrier, with standardised fucoxanthin and tocopherol content. The main component of the NF is fat (78% on average), followed by crude protein (10% on average). The Panel is of the view that a consistent and safe production process has not been demonstrated. Additionally, the Panel considers that the information provided on the composition of the NF is not complete and may raise safety concerns. The applicant proposed to use the NF as a food supplement at the use level of 437 mg/day, with the target population being adults, excluding pregnant and breastfeeding women. There is no history of use of the NF or of its source, i.e. P. tricornutum. The Panel notes that the source of the NF, P. tricornutum, was not granted the qualified presumption of safety (QPS) status by the EFSA Panel on Biological Hazards (BIOHAZ), due to the lack of a safe history of use in the food chain and on its potential for production of bioactive compounds with toxic effects. There were no concerns regarding genotoxicity of the NF. In the 90-day study provided, a number of adverse effects were observed, some of them seen already at the lowest dose tested (750 mg/kg body weight (bw) day), which was identified by the Panel as the lowest-observed-adverse-effect-level (LOAEL). The potential phototoxicity of pheophorbide A and pyropheophorbide A in the NF was not addressed in this study. Although noting the uncertainties identified by the Panel regarding the analytical determination of these substances in the NF and the limitations in the publicly available toxicity data, a low margin of exposure (MoE) was calculated for these substances at the proposed use levels. The Panel concludes that the safety of the NF under the proposed uses and use levels has not been established.

2023 - Safety of an extension of use of Yarrowia lipolytica yeast biomass as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use of Yarrowia (Y.) lipolytica yeast biomass as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The extension of use pertains to the use of the NF as a food ingredient in a number of food categories, in foods for special medical purposes and in foods for total diet replacement for weight control. In 2018, Y. lipolytica was attributed the qualified presumption of safety (QPS) status for production purposes, including food and feed products based on biomass. The Panel considers that the data provided sufficient information with respect to the stability of the NF, also when used as a food ingredient. The concentrations of the analysed processing contaminants do not raise safety concerns. The Panel also considers that consumption of the NF is not nutritionally disadvantageous under the proposed conditions of use. The Panel concludes that the NF, Y. lipolytica yeast biomass, is safe under the proposed conditions of use.

2023 - Safety of apple fruit cell culture biomass as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an apple fruit cell culture biomass as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and intended as an ingredient for food supplements in adults. The cells have been sourced from the callus grown on a piece of apple placed on a solid medium under sterile conditions. The de-differentiated apple cells are then cultivated in liquid medium. The medium contains sucrose, vitamins, minerals, trace elements and the two synthetic plant hormone analogues, benzylaminopurine (< 0.1 mg/kg) and 2,4-dichlorophenoxyacetic acid (< 0.25 mg/kg). These plant hormones are regulated under the EU pesticide legislation and their residue levels in the NF are in compliance with the EU maximum residue levels. The main components of the NF are carbohydrates (including sugars and non-digestible carbohydrates), ash, proteins and smaller amounts of fatty acids and organic acids. Except for the amount of total fat and the organic acids (succinic and l-malic acid), the quantities of the compositional parameters of the NF and apple have little in common. The Panel considers that a provided subchronic toxicity study was not needed to establish the safety of this NF, when taking into account the source of the NF, i.e. apples, the production process, the low intended use level and the composition of the NF, despite the noted differences to apple. The Panel considers that the NF contains proteins, which were not detected in apple and which may be allergenic. The Panel concludes that the NF, an apple fruit cell culture biomass, is safe under the proposed conditions of use.

2023 - Safety of lacto-N-fucopentaose I/2’-fucosyllactose (LNFP-I/2’-FL) mixture as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Pelaez, C.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on lacto-N-fucopentaose I (LNFP-I)/2′-fucosyllactose (2’-FL) mixture as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharides (HiMO) LNFP-I and 2’-FL, but it also contains d-lactose, lacto-N-tetraose, difucosyllactose, 3-fucosyllactose, LNFP-I fructose isomer, 2′-fucosyl-d-lactulose, l-fucose and 2′-fucosyl-d-lactitol, and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli K-12 DH1 MDO MP2173b) of E. coli K-12 DH1 (DSM 4235). The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant formula (IF) and follow-on formula, foods for infants and toddlers, foods for special medical purposes and food supplements (FS). The target population is the general population. The anticipated daily intake of LNFP-I from use in IF is similar to the estimated natural mean highest daily intake in breastfed infants. Overall, the anticipated daily intake of LNFP-I from the NF as a food ingredient at the maximum proposed use levels is unlikely to exceed the intake level of breastfed infants on a body weight basis. The intake in breastfed infants on a body weight basis is expected to be safe also for other population groups. The anticipated 2’-FL intake is generally rather low. The use of the NF in FS is not intended if other foods with added NF components or human milk (for infants and young children) are consumed on the same day. The Panel concludes that the NF, a mixture of LNFP-I and 2’-FL, is safe under the proposed conditions of use.

2023 - Safety of monosodium salt of l-5-methyltetrahydrofolic acid as a novel food pursuant to Regulation (EU) 2015/2283 and the bioavailability of folate from this source in the context of Directive 2002/46/EC, Regulation (EU) No 609/2013 and Regulation (EC) No 1925/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Matijevic, L.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on monosodium salt of l-5-methyltetrahydrofolic acid (5-MTHF) as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and to address the bioavailability of folate from this source in the context of Directive 2002/46/EC, Regulation (EU) No 609/2013 and Regulation (EC) No 1925/2006. The NF is produced by chemical synthesis and consists of at least 95% (w/w) of 5-MTHF and 4%–5% (w/w) of sodium. It is proposed to be used as a partial or complete substitute to folic acid and other sources of added folate in a number of food categories. The production process, composition, specifications and stability of the NF do not raise safety concerns. When used as an ingredient in different food matrices, proper processing/storage conditions need to be considered to preserve the stability of the NF. Regarding bioavailability, the Panel considers that the NF readily dissociates into Na and l-methylfolate ions, which subsequently are absorbed and enter the circulation. Thus, the bioavailability of 5-MTHF from the NF is comparable to that of other currently authorised salts of 5-MTHF. The Panel considers that the consumption of the NF is not nutritionally disadvantageous as long as the combined intake of the NF and the other supplemental forms of folate under their authorised conditions of use is below the ULs established for the different age groups of the general population. The Panel concludes that the NF is safe under the proposed conditions of use. The Panel also concludes that the NF is a source from which folate is bioavailable.

2023 - Safety of oil from Schizochytrium limacinum (strain TKD-1) for use in infant and follow-on formula as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. (TKD-1) oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single-cell microalga. The strain TKD-1, used by the applicant (ATK Biotech Co. Ltd.), belongs to the species Schizochytrium limacinum. The NF is a mixture of triglycerides in which docosahexaenoic acid (DHA) represents 53%–61% of fatty acids. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use levels proposed by the applicant were derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20–50 mg/100 kcal. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’. Data provided by the applicant demonstrated the absence of viable cells in the NF. No toxicological studies were performed with the NF. However, based on the available toxicological data on oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process, the composition of the NF and the absence of marine biotoxins and viable cells in the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

2023 - Safety of oil from Schizochytrium sp. (strain CABIO-A-2) for use in infant and follow-on formula as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. (strain CABIO-A-2) oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. S. sp. is a single-cell microalga. The NF is a mixture of triglycerides in which docosahexaenoic acid (DHA) represents 38%–44% of fatty acids. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use levels proposed by the applicant were derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20–50 mg/100 kcal. The evidence provided demonstrated that the strain S. sp. CABIO-A-2 is phylogenetically closely related to the strain S. sp. ATCC 20888. The assessment of some already authorised S. sp. oils in the Union list were also based on similarities with the strain ATCC 20888. The applicant provided a 90-day repeated dose toxicity study in rats with the NF. No adverse effects were observed up to the highest dose tested, i.e. 10.2 g/kg body weight (bw) per day. Taking into account the toxicity studies performed with the NF and with DHA-oils derived from strains belonging to the genus Schizochytrium, its phylogenetical profile, the production process, the composition of the NF and the absence of marine biotoxins and viable cells in the NF, the Panel considers that there are no concerns with regard to the toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

2023 - Safety of paramylon as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on paramylon as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Paramylon is a linear, unbranched beta-1,3-ᴅ-glucan polymer that is isolated from the single-cell microalga Euglena gracilis. The NF consists of at least 95% beta-glucan and minor amounts of protein, fat, ash and moisture. The applicant proposed to use the NF in food supplements, as a food ingredient added to a number of food categories and in foods for total diet replacement for weight control. In 2019, E. gracilis was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’, which includes food products based on microbial biomass of the microalga. Based on the information provided, E. gracilis is not expected to survive the manufacturing process. The submitted toxicity studies did not raise safety concerns. No adverse effects were observed in the subchronic toxicity studies, up to the highest dose tested, i.e. 5,000 mg NF/kg body weight per day. In view of the QPS status of the source of the NF, supported by the manufacturing process, compositional data and lack of toxicity observed in the toxicity studies, the Panel has no safety concerns and concludes that the NF, i.e. paramylon, is safe under the proposed uses and use levels.

2023 - Safety of partially hydrolysed protein from spent barley (Hordeum vulgare) and rice (Oryza sativa) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Aguilera-Gomez, M.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Siskos, A.; Schlatter, J. R.; van Loveren, H.; Zakidou, P.; Mendes, V.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on partially hydrolysed protein from spent barley (Hordeum vulgare) and rice (Oryza sativa) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is produced by enzymatically treating the pasteurised spent barley and rice residues of the mash step of beer production. Several mechanical treatment steps of the partial hydrolysate are employed to obtain the final product. The NF consists mainly of partially-hydrolysed proteins from spent barley and rice and it is in powdered form. The Panel notes that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf life of 15 months. The NF is proposed to be used as an ingredient in various foods such as dairy products, bakery products, pasta, fruit and vegetable spreads, snacks, and single meal replacements for weight reduction. The target population is the general population. Considering protein quality aspects, the Panel concludes that the NF is not a suitable protein source for the nutrition of infants. The Panel notes that, considering the composition of the NF, the proposed conditions of use and that the NF will not be the sole source of dietary protein, the consumption of the NF is not nutritionally disadvantageous. Taking into account the production process, the extensive compositional characterisation of the NF and the history of use of the source the Panel considers that no toxicological studies are required on the NF. Moreover, the Panel considers that the NF has the potential capacity to sensitise individuals and to induce allergic reactions in individuals allergic to barley and rice. With the exception of possible allergenicity, the Panel concludes that the NF is safe under the proposed uses and use levels.

2023 - Safety of the extension of use of 2′-fucosyllactose (2′-FL) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Pelaez, C.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of the extension of use of 2′-fucosyllactose (2′-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is already authorised as ingredient in several food categories, including infant formula (IF) and follow-on formula (FOF). The applicant proposed to increase the maximum use levels of the NF in IF and FOF. EFSA estimated the anticipated daily intake of the NF from the proposed extension of use, including the already authorised conditions of use in other food categories. Additionally, a new intake estimate limited to the already authorised conditions of use of the NF was carried out following EFSA's current approach. The estimated daily intake of the NF from high consumption of IF alone at the proposed maximum use level in infants < 16 weeks of age is similar to the estimated natural highest mean daily intake of 2′-FL from human milk in breastfed infants. The estimated highest P95 daily intakes of the NF from the proposed extension of use in IF and FOF (including the authorised uses in other food categories) and from the already authorised conditions of use, are comparable and both higher than the estimated natural highest mean daily intake of 2′-FL from human milk in infants and to a lesser extent in young children. The Panel considers that the proposed extension of use of the NF in IF and FOF only marginally affects the highest P95 daily intake estimate from the authorised conditions of use, and therefore does not affect the safety of the NF. The Panel concludes that the NF, 2′-FL, is safe under the proposed conditions of use.

2023 - Safety of the extension of use of partially defatted chia seed (Salvia hispanica L.) powder with a high fibre content as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Gerazova-Efremova, K.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of the extension of use of partially defatted chia seed (Salvia hispanica L.) powder with a high fibre content as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is already authorised and included in the Union list of NFs and is produced according to the same production process. This application is limited to an assessment of the extension of use of the NF as a food ingredient in several food categories with a high moisture content that are subject to thermal processing. The target population for the extension of use is the general population. The information provided on the formation of process contaminants (acrylamide, furan and methylfurans) in a selected food category with added NF (bread) subjected to heat treatment is sufficient for this assessment and does not raise safety concerns. Noting that no safety concerns were identified from the information available on the production process, composition, specifications and proposed uses of the NF, the Panel considers that intake estimates for the NF are not needed for this assessment. The Panel concludes that the NF, partially defatted chia seeds powder with a high fibre content, is safe under the proposed conditions of use.

2023 - Safety of water lentil protein concentrate from a mixture of Lemna gibba and Lemna minor as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Kouloura, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on water lentil protein concentrate from a mixture of Lemna gibba and Lemna minor as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Water lentil protein concentrate is produced from two water lentil species (L. gibba and L. minor) by separation of the protein fraction of the plant material from fibres, followed by pasteurisation and spray drying. The NF consists mainly of protein, fibre, fat and ash. The applicant proposed to use the NF as a food ingredient in a variety of food categories and as a food supplement. The target population is the general population when used as a food ingredient and exclusively adults when used as a food supplement. The Panel considers that taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. The Panel considers that the risk of the NF triggering allergic reactions is low. The Panel concludes that the NF, water lentil protein concentrate from a mixture of L. gibba and L. minor, is safe under the proposed conditions of use.

2023 - Safety of whole seeds of oilseed rape (Brassica napus L emend. Metzg.) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Fernandez Dumont, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on whole seeds of oilseed rape as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of seeds of oilseed rape, in particular double low white flowering varieties of Brassica napus (oilseed rape Brassica napus L. emend. Metzg). The NF's oilseed rape is produced following drying, cleaning and storage procedures traditionally used for oilseed rape in oil production. The NF is proposed to be used as an ingredient in ‘Bread and rolls with special ingredients added’ and ‘Gluten free bread’. The target population is the general population. The highest daily intake of the NF was estimated for young children as 92.6 mg/kg body weight (bw) per day. The Panel notes that intakes of the NF can result in considerably increased levels of glucosinolates consumption as compared to intakes of glucosinolates from background diets. The Panel asked the applicant for additional studies to support the safety of the NF, but these were not provided. The Panel concludes that the safety of whole seeds of oilseed rape under the proposed conditions of use has not been established.

2023 - Safety of yellow/orange tomato extract as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Gerazova-Efremova, K.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on yellow/orange tomato extract used as a novel food (NF) pursuant to Regulation (EU) 2283/2015. The NF which is the subject of the application is a carotenoid-rich extract from the yellow/orange tomato containing predominantly phytoene and phytofluene, as well as a lesser amount of beta-carotene, zeta-carotene and lycopene. The NF is produced from the tomato pulp using supercritical CO2 extraction. The applicant proposes the use of the NF in cereal bars, functional drinks and as a food supplement in individuals above 15 years of age. For the use of the NF in cereal bars and functional drinks, the Panel considers, the target population is the general population. According to EFSA's latest exposure assessment for lycopene as a food additive (EFSA ANS Panel, 2017), the highest P95 intakes for children (< 10 and 10–17 years) and adults when combined to the use of lycopene as a food colour from natural occurrence would exceed the established acceptable daily intake (ADI) for lycopene (0.5 mg/kg body weight (bw) day). The estimated intakes of the NF would lead to an exceedance of the ADI when considering natural occurrence and exposure to lycopene when used as a food additive. Due to the absence of safety data regarding phytoene and phytofluene intake from the NF, and the contribution of the NF to the estimated high daily intakes of lycopene, the Panel considers that it cannot be established whether or not the consumption of the NF is nutritionally disadvantageous. The Panel concludes that the safety of the NF has not been established under the proposed conditions of use.

2023 - Scientific opinion on the tolerable upper intake level for folate [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Crous-Bou, M.; Molloy, A.; Ciccolallo, L.; De, Sesmaisons ; Lecarré, A.; Fabiani, L.; Horvath, Z.; Karavasiloglou, N.; Naska, A.
abstract

2023 - Scientific opinion on the tolerable upper intake level for manganese [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bornhorst, J.; Cubadda, F.; Dopter, A.; Fitzgerald, R.; de SesmaisonsLecarre, A.; das NevesFerreira, P.; Fabiani, L.; Horvath, Z.; Matijevic, L.; Naska, A.
abstract

Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for manganese. Systematic reviews of the literature of human and animal data were conducted to assess evidence regarding excess manganese intake (including authorised manganese salts) and the priority adverse health effect, i.e. manganese-induced neurotoxicity. Available human and animal studies support neurotoxicity as a critical effect, however, data are not sufficient and suitable to characterise a dose–response relationship and identify a reference point for manganese-induced neurotoxicity. In the absence of adequate data to establish an UL, estimated background dietary intakes (i.e. manganese intakes from natural dietary sources only) observed among high consumers (95th percentile) were used to provide an indication of the highest level of intake where there is reasonable confidence on the absence of adverse effects. A safe level of intake of 8 mg/day was established for adults ≥ 18 years (including pregnant and lactating women) and ranged between 2 and 7 mg/day for other population groups. The application of the safe level of intake is more limited than an UL because the intake level at which the risk of adverse effects starts to increase is not defined.

2023 - Scientific opinion on the tolerable upper intake level for selenium [Articolo su rivista]
Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; de Henauw, Stefaan; Hirsch-Ernst, Karen-Ildico; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Peláez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Aggett, Peter; Crous Bou, Marta; Cubadda, Francesco; Ciccolallo, Laura; de Sesmaisons Lecarré, Agnès; Fabiani, Lucia; Titz, Ariane; Naska, Androniki
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for selenium. Systematic reviews of the literature were conducted to identify evidence regarding excess selenium intake and clinical effects and potential biomarkers of effect, risk of chronic diseases and impaired neuropsychological development in humans. Alopecia, as an early observable feature and a well-established adverse effect of excess selenium exposure, is selected as the critical endpoint on which to base a UL for selenium. A lowest-observed-adverse-effect-level (LOAEL) of 330 mu g/day is identified from a large randomised controlled trial in humans (the Selenium and Vitamin E Cancer Prevention Trial (SELECT)), to which an uncertainty factor of 1.3 is applied. A UL of 255 mu g/day is established for adult men and women (including pregnant and lactating women). ULs for children are derived from the UL for adults using allometric scaling (body weight(0.75)). Based on available intake data, adult consumers are unlikely to exceed the UL, except for regular users of food supplements containing high daily doses of selenium or regular consumers of Brazil nuts. No risk has been reported with the current levels of selenium intake in European countries from food (excluding food supplements) in toddlers and children, and selenium intake arising from the natural content of foods does not raise reasons for concern. Selenium-containing supplements in toddlers and children should be used with caution, based on individual needs.

2023 - Scientific opinion on the tolerable upper intake level for vitamin B6 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Fairweather-Tait, S.; Vrolijk, M.; Fabiani, L.; Titz, A.; Naska, A.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for vitamin B6. Systematic reviews of the literature were conducted by a contractor. The relationship between excess vitamin B6 intakes and the development of peripheral neuropathy is well established and is the critical effect on which the UL is based. A lowest-observed-effect-level (LOAEL) could not be established based on human data. A reference point (RP) of 50 mg/day is identified by the Panel from a case–control study, supported by data from case reports and vigilance data. An uncertainty factor (UF) of 4 is applied to the RP to account for the inverse relationship between dose and time to onset of symptoms and the limited data available. The latter covers uncertainties as to the level of intake that would represent a LOAEL. This leads to a UL of 12.5 mg/day. From a subchronic study in Beagle dogs, a LOAEL of 50 mg/kg body weight (bw) per day can be identified. Using an UF of 300, and a default bw of 70 kg, a UL of 11.7 mg/day can be calculated. From the midpoint of the range of these two ULs and rounding down, a UL of 12 mg/day is established by the Panel for vitamin B6 for adults (including pregnant and lactating women). ULs for infants and children are derived from the UL for adults using allometric scaling: 2.2–2.5 mg/day (4–11 months), 3.2–4.5 mg/day (1–6 years), 6.1–10.7 mg/day (7–17 years). Based on available intake data, EU populations are unlikely to exceed ULs, except for regular users of food supplements containing high doses of vitamin B6.

2023 - Scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Lanham-New, S.; Passeri, G.; Craciun, I.; Fabiani, L.; De Sousa, R. F.; Martino, L.; Martinez, S. V.; Naska, A.
abstract

Following two requests from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for vitamin D and to propose a conversion factor (CF) for calcidiol monohydrate into vitamin D3 for labelling purposes. Vitamin D refers to ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), and calcidiol monohydrate. Systematic reviews of the literature were conducted to assess the relative bioavailability of calcidiol monohydrate versus vitamin D3 on serum 25(OH)D concentrations, and for priority adverse health effects of excess vitamin D intake, namely persistent hypercalcaemia/hypercalciuria and endpoints related to musculoskeletal health (i.e. falls, bone fractures, bone mass/density and indices thereof). Based on the available evidence, the Panel proposes a CF for calcidiol monohydrates of 2.5 for labelling purposes. Persistent hypercalciuria, which may be an earlier sign of excess vitamin D than persistent hypercalcaemia, is selected as the critical endpoint on which to base the UL for vitamin D. A lowest-observed-adverse-effect-level (LOAEL) of 250 μg/day is identified from two randomised controlled trials in humans, to which an uncertainty factor of 2.5 is applied to account for the absence of a no-observed-adverse-effect-level (NOAEL). A UL of 100 μg vitamin D equivalents (VDE)/day is established for adults (including pregnant and lactating women) and for adolescents aged 11–17 years, as there is no reason to believe that adolescents in the phase of rapid bone formation and growth have a lower tolerance for vitamin D compared to adults. For children aged 1–10 years, a UL of 50 μg VDE/day is established by considering their smaller body size. Based on available intake data, European populations are unlikely to exceed the UL, except for regular users of food supplements containing high doses of vitamin D.

2023 - Selenium and immune function: a systematic review and meta-analysis of experimental human studies [Articolo su rivista]
Filippini, Tommaso; Fairweather-Tait, Susan; Vinceti, Marco
abstract

Background Selenium is an essential trace element with both beneficial and detrimental effects on health depending on dose and chemical form. Currently, there is debate about recommendations for selenium supplementation as a public health measure to improve immune function and reduce infectious disease susceptibility. Objectives We performed a systematic review and meta-analysis of experimental studies assessing the effect of selenium supplementation on immunity-related outcomes in healthy people. Methods We undertook a search of published and unpublished studies in literature databases PubMed/MEDLINE, Embase and Clinicaltrials.gov up to October 17, 2022, and performed a meta-analysis comparing the effects on immunity-related outcomes between supplemented versus control arms. Whenever possible we assessed the nonlinear relation using a dose-response approach. Results Nine trials were included, five in North America, and four in Europe, with duration between 8-48 weeks and supplementation of both inorganic and organic selenium forms. Selenium supplementation did not substantially affect immunoglobulin or white blood cell levels, and the dose-response meta-analysis indicated that an increase in plasma selenium concentrations above 100 μg/L did not further increase IgA levels nor T-cells. An inverted U-shaped relation emerged for Natural killer (NK) cell count, with lower number of these cells both below and above 120 μg/L. The only beneficial effect of selenium supplementation was increased activity for NKlysis, but the available data did not permit dose-response analysis. Cytokine levels were substantially unaffected by selenium supplementation. Conclusions Although some of the data suggested beneficial effects of selenium supplementation on immune function, the overall picture appears to be inconsistent and heterogenous due to differences in trial duration and interventions, plus evidence of null and even detrimental effects. Overall, the evidence that we extracted from the literature in this systematic review does not support the need to supplement selenium beyond the recommended dietary intake to obtain beneficial effects on immune function. Keywords seleniumimmune functioninfectious diseaseexperimental studiessystematic reviewdose-response meta-analysis

2023 - Selenium exposure and oxidative stress and genotoxicity risk in a healthy Italian population: a cross sectional study [Abstract in Rivista]
Urbano, Teresa; Filippini, Tommaso; Malavolti, Marcella; Michalke, Bernhard; Fustinoni, Silvia; Vinceti, Marco
abstract

2023 - Selenium exposure and urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine: Major effects of chemical species and sex [Articolo su rivista]
Urbano, Teresa; Filippini, Tommaso; Wise, Lauren A; Sucato, Sabrina; Polledri, Elisa; Malavolti, Marcella; Fustinoni, Silvia; Michalke, Bernhard; Vinceti, Marco
abstract

: Selenium is an element present in trace amounts and different chemical forms. It may exert both beneficial and adverse effects on cellular redox status and on the generation of reactive oxygen species. 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG) is an oxidized derivative of deoxyguanosine, and a sensitive biomarker of oxidative stress and genotoxicity. The present study assessed the extent to which selenium status was associated with urinary 8-oxodG concentrations in a Northern Italian population. We recruited healthy, non-smoking blood donors living in the Reggio Emilia province during 2017-2019. We measured urinary 8-oxodG concentrations and used restricted cubic spline regression analyses to investigate the association between selenium status (estimated using food frequency questionnaires, urinary concentrations, and serum concentrations of selenium and selenium species) and 8-oxodG/g creatinine. Among 137 participants aged 30-60 years, median urinary selenium and 8-oxodG concentrations were 22.02 μg/L and 3.21 μg/g creatinine, respectively. Serum samples and selenium speciation analyses were available for 104 participants. Median total serum selenium levels and dietary intake were 116.5 μg/L and 78.7 μg/day, respectively. In spline regression analysis, there was little association between dietary, serum, or urinary selenium with 8-oxodG concentrations. In sex-specific analyses, urinary selenium showed a positive association with the endpoint among males. For single selenium species, we observed positive associations with urinary 8-oxodG for serum organic selenium species, and negative associations for inorganic selenium forms. In the most adjusted analysis, urinary 8-oxodG concentrations showed a strong positive association with selenomethione-bound selenium (Se-Met) and a negative association with inorganic tetravalent selenium, selenite. In sex-specific analyses, these associations were considerably stronger in males than in females. Overall, study findings indicate that selenium species exhibited very different patterns of associations with the biomarker of oxidative stress, and that these associations also depended on sex. Background exposure to Se-Met appears to be strongly and positively associated with oxidative stress.

2023 - Selenoprotein P concentrations and risk of progression from mild cognitive impairment to dementia [Articolo su rivista]
Vinceti, Marco; Urbano, Teresa; Chiari, Annalisa; Filippini, Tommaso; Wise, Lauren A; Tondelli, Manuela; Michalke, Bernhard; Shimizu, Misaki; Saito, Yoshiro
abstract

: There is a growing literature investigating the effects of selenium on the central nervous system and cognitive function. However, little is known about the role of selenoprotein P, the main selenium transporter, which can also have adverse biological effects. We conducted a prospective cohort study of individuals aged 42-81 years who received a clinical diagnosis of mild cognitive impairment. Using sandwich ELISA methods, we measured full-length selenoprotein P concentrations in serum and cerebrospinal fluid to assess the relation with dementia incidence during a median follow-up of 47.3 months. We used Cox proportional hazards regression and restricted cubic splines to model such relation. Of the 54 participants, 35 developed dementia during follow-up (including 26 cases of Alzheimer's dementia). Selenoprotein P concentrations in serum and cerebrospinal fluid were highly correlated, and in spline regression analyses they each showed a positive non-linear association with dementia risk, particularly after excluding dementia cases diagnosed within 24 months of follow-up. We also observed differences in association according to the dementia subtypes considered. Risk ratios of dementia peaked at 2-6 at the highest levels of selenoprotein P, when compared to its median level, also depending on matrix, analytical methodology and dementia subtype. Findings of this study, the first to assess selenoprotein P levels in the central nervous system in vivo and the first to use a prospective study design to evaluate associations with dementia, suggest that higher circulating concentrations of selenoprotein P, both in serum and cerebrospinal fluid, predict progression of MCI to dementia. However, further confirmation of these findings is required, given the limited statistical precision of the associations and the potential for residual confounding.

2023 - Serum selenium concentrations and adherence to the MIND diet in a Northern Italian population: a cross sectional study [Abstract in Rivista]
Filippini, Tommaso; Urbano, Teresa; Malavolti, Marcella; Grioni, Sara; Agnoli, Claudia; Sieri, Sabina; Michalke, Bernhard; Vinceti, Marco
abstract

2023 - Social disparities and unhealthy lifestyles increase risk of dementia, particularly at a young age [Articolo su rivista]
Filippini, Tommaso; Vinceti, Marco
abstract

2023 - Sulfur content in foods consumed in an Italian population and impact of diet quality on sulfur intake [Articolo su rivista]
Passafiume, A.; Rossetti, A.; Vescovi, L.; Malavolti, M.; Baraldi, C.; Rovesti, S.; Vinceti, M.; Filippini, T.
abstract

Sulfur is an essential nutrient but data about its intake are scarce. We aimed to measure sulfur content in food samples and assess its habitual intake in relation to adherence to healthy dietary patterns in 719 Italian adults. Using a food frequency questionnaire, we estimated overall sulfur intake, and its relation with adherence to healthy dietary patterns. The highest sulfur content was found in preserved/canned fish (3.0 g/kg), seafood (2.8 g/kg), white meat (2.8 g/kg) and dairy products, particularly aged cheeses (2.1 g/kg) and lowest in fresh fruit (87 mg/kg), oils and fats (157 mg/kg), and beverages (141 mg/kg), with the exception of onion and garlic (1.3 g/kg). The mean sulfur intake in the study population was 1.1 g/day, slightly higher in men than women. The foods contributing most to sulfur intake were meat (29%) and cereals (19%), with also substantial contribution (>10%) from beverages and dairy products. Adherence to dietary patterns had little influence on sulfur intake, except for adherence to MIND diet positively and linearly associated with sulfur intake. Our study provides an updated overview of sulfur content in foods composing the Italian diet, as well as of sulfur intake in an Italian community of Northern Italy.

2023 - Tea and coffee consumption and risk of dementia: a systematic review and dose-response meta-analysis [Abstract in Rivista]
Mazzoleni, E.; Rossetti, A.; Filippini, T.; Vinceti, M.
abstract

Background and Objective: Dementia is a chronic progressive disease characterized by multifactorial aetiology. Among the factors of greatest interest for prevention is lifestyle, including dietary habits. In particular, tea and coffee are still a matter of debate, being associated both with protective and detrimental effects. The aim of our study is to assess the relation between tea and coffee intake and risk of developing dementia through a dose-response meta-analysis based on cohort studies. Methods: We performed a literature search in PubMed and EMBASE databases up to 28 November 2022. Inclusion criteria were: population without chronic diseases or previous dementia diagnosis, cohort study design, assessment of tea or coffee intake by increasing categories of exposure, assessment of incident dementia risk. Exclusion criteria were: type of study (non-cohort), type of publication (letters, commentaries and systematic reviews), missing information about exposure level for tea and coffee in each category. For statistical analysis, we used cubic splines through a non-linear random-effects regression model (drmeta routine in Stata/SE 17.0). Results: We identified 9 articles published between 2009-2021, 1 assessing tea consumption, 6 coffee and 2 both. As the amount of tea consumed increases, risk of dementia decreases progressively. Conversely, we found a U-shaped association between coffee intake and dementia risk: as the number of cups of coffee consumed increases, the risk of dementia decreases progressively up to two cups of coffee (approx. 300 mL) per day, whereas as the daily amount increases, there is a reversal up to five cups (approx. 750 mL) per day. Conclusions: Moderate coffee intake appears to have a protective effect, while intake in higher amounts seems to increase the risk of dementia. Concerning tea, the relation is almost linear in a protective way.

2023 - The dark side of light at night: assessing breast cancer risk with a dose-response meta-analysis [Abstract in Rivista]
Urbano, T; Vinceti, M; Wise, L A; Filippini, T
abstract

2023 - The influence of meteorological factors on COVID-19 spread in Italy during the first and second wave [Articolo su rivista]
Balboni, Erica; Filippini, Tommaso; Rothman, Kenneth J; Costanzini, Sofia; Bellino, Stefania; Pezzotti, Patrizio; Brusaferro, Silvio; Ferrari, Fabrizio; Orsini, Nicola; Teggi, Sergio; Vinceti, Marco
abstract

: The relation between meteorological factors and COVID-19 spread remains uncertain, particularly with regard to the role of temperature, relative humidity and solar ultraviolet (UV) radiation. To assess this relation, we investigated disease spread within Italy during 2020. The pandemic had a large and early impact in Italy, and during 2020 the effects of vaccination and viral variants had not yet complicated the dynamics. We used non-linear, spline-based Poisson regression of modeled temperature, UV and relative humidity, adjusting for mobility patterns and additional confounders, to estimate daily rates of COVID-19 new cases, hospital and intensive care unit admissions, and deaths during the two waves of the pandemic in Italy during 2020. We found little association between relative humidity and COVID-19 endpoints in both waves, whereas UV radiation above 40 kJ/m2 showed a weak inverse association with hospital and ICU admissions in the first wave, and a stronger relation with all COVID-19 endpoints in the second wave. Temperature above 283 K (10 °C/50 °F) showed a strong non-linear negative relation with COVID-19 endpoints, with inconsistent relations below this cutpoint in the two waves. Given the biological plausibility of a relation between temperature and COVID-19, these data add support to the proposition that temperature above 283 K, and possibly high levels of solar UV radiation, reduced COVID-19 spread.

2023 - The shape of water - preliminary data from a cluster of patients infected by Mycobacterium saskatchewanense in Haemodialysis setting in Emilia-Romagna, Northern Italy [Abstract in Rivista]
Ferrari, Eleonora; Vecchi, Elena; Mattei, Giovanna; Belloli, Gian; Diegoli, Giuseppe; Monte, Paola; Santoro, Antonio; Palma, Alessandra; Amadori, Nicola; Falcone, Patrizia; Patuelli, Melania; Palandri, Lucia; Vinceti, Marco; Righi, Elena
abstract

Background and Objective: Nontuberculous mycobacteria (NTM) are common environmental contaminants and, as opportunistic pathogens, they can colonize/infect immunocompromised patients. Our work Aims to report the main features of a cluster of haemodialysis patients infected by Mycobacterium saskatchewanense, and to describe the infection prevention and control (IPC) strategies implemented accordingly. Methods: We conducted a descriptive analysis of data coming from the infectious diseases data stream of the Emilia-Romagna Region. Spectrometric and DNA-sequencing analyses in ultrafiltered liquid were done in the regional reference laboratory, while blood cultures were performed in the local hospital laboratory. Results: Between 04/01/2022 and 18/07/2022, a cluster of 6 patients (3 males and 3 females, median age 63.5 years) with positive blood culture for Mycobacterium saskatchewanense was reported in two HUB hospitals of the Region Emilia-Romagna, Northern Italy. All patients underwent online haemodiafiltration before the symptom’s onset; water samples from the dialysis machines’ ultrafilters also tested positive. The key clinical features reported were varied, including weight loss, asthenia, gastrointestinal symptoms, cough, night sweats, recurrent fever of unknown origin. In addition, common Findings were cytopenia, increased blood levels of systemic inflammation markers, splenomegaly, osteo-medullary granulomas, and pulmonary pathologic imaging. Conclusions: The application of the best IPC strategies (clinical and environmental surveillance, switch to traditional haemodialysis and heat disinfection...) is currently supervised by a regional interdisciplinary team, and preliminary data indicate positive outcomes. As a precaution, considering the extreme fragility of haemodialysis patients, a constant epidemiological monitoring based on clinical and diagnostic criteria is still in place, and regular environmental sampling is being performed.

2023 - Unique cerebrospinal fluid peptides: potential amyotrophic lateral sclerosis biomarkers and etiological factors [Articolo su rivista]
Wormser, Uri; Sintov, Amnon; Vinceti, Marco; Mandrioli, Jessica; Brodsky, Berta; Proscura, Elena; Finkelstein, Yoram
abstract

2022 - A Systematic Review and Dose-response Meta-analysis on Fluoride Exposure and Neurodevelopmental Toxicity in Children [Abstract in Atti di Convegno]
Veneri, Federica; Giannone, Maria Edvige; Mazzoleni, Elena; Filippini, Tommaso; Consolo, Ugo; Generali, Luigi; Vinceti, Marco
abstract

Background The possible harmful effect of fluoride exposure on neurodevelopment in children is widely discussed, however, the magnitude of this relation is still controversial. The aim of this systematic review and meta-analysis was to characterize this relation through a dose-response approach. Methods/Approach We performed an online literature search in PubMed, Web of Science and Embase up to September 10, 2022. From each eligible study we extracted the effect size as a mean difference (MD) of intelligence quotient (IQ) scores and its 95% confidence intervals (CI). We performed a meta-analysis comparing the highest versus lowest fluoride exposure using a random-effects model, stratifying for type of exposure (fluoride in drinking water or urinary fluoride). Finally, we quantitively assessed such relation by performing a one-stage dose-response meta-analysis based on a cubic spline random-effects model. Results Out of 1955 potentially relevant records retrieved through a systematic literature search, we identified 34 eligible studies for review; 32 were also included for meta-analysis. The analysis comparing the highest-versus-lowest exposure showed decreased IQ scores for both water and urinary fluoride with MD of -6.62 (95% CI -8.61, -4.63) and -3.58 (95% CI -7.28, 0.12), respectively. The dose-response analysis showed a decrease in IQ score from 1 mg/L, considerably steeper above 2.5 mg/L for water fluoride. The dose-response curve for urinary fluoride showed a weaker but constant decrease in IQ scores with increasing fluoride levels. Conclusions Overall, a substantial consistency in the effect direction emerged, with adverse effects of different magnitude on children’s intelligence, arising from rather low fluoride exposure previously considered safe from a public health perspective. However, potential methodological limitations, such as heterogeneity in outcome measures and lack of consideration of possible confounders in some of the studies, may have affected these findings.

2022 - A deep learning approach for Spatio-Temporal forecasting of new cases and new hospital admissions of COVID-19 spread in Reggio Emilia, Northern Italy [Articolo su rivista]
Sciannameo, Veronica; Goffi, Alessia; Maffeis, Giuseppe; Gianfreda, Roberta; Jahier Pagliari, Daniele; Filippini, Tommaso; Mancuso, Pamela; Giorgi Rossi, Paolo; Dal Zovo, Leonardo Alberto; Corbari, Angela; Vinceti, Marco; Berchialla, Paola
abstract

Since February 2020, the COVID-19 epidemic has rapidly spread throughout Italy. Some studies showed an association of environmental factors, such as PM10, PM2.5, NO2, temperature, relative humidity, wind speed, solar radiation and mobility with the spread of the epidemic. In this work, we aimed to predict via Deep Learning the real-time transmission of SARS-CoV-2 in the province of Reggio Emilia, Northern Italy, in a grid with a small resolution (12 km × 12 km), including satellite information.

2022 - Artificial light at night and risk of mental disorders: A systematic review [Articolo su rivista]
Tancredi, Stefano; Urbano, Teresa; Vinceti, Marco; Filippini, Tommaso
abstract

Background: Emerging evidence suggests a possible association between artificial light at night (LAN) exposure and physiological and behavioral changes, with implications on mood and mental health. Due to the increased amount of individuals' LAN exposure, concerns have been raised regarding harmful impact of LAN on mental health at the population level. Aim: To perform a systematic review of observational studies to investigate if light-at-night, assessed both indoor and outdoor, may be associated with an increased risk of mental diseases in humans. Methods: We reviewed the epidemiological evidence on the association between LAN exposure, assessed either via satellite photometry or via measurements of bedroom brightness, and mental disorders. We systematically searched the MEDLINE, Embase and Web of Science databases up to April 1, 2022. Studies were included if they assessed the link between indoor or outdoor artificial light at night and one or more mental disorders in human populations. Results: Nine eligible studies were included in this review: six studies had a cross-sectional design, two had a longitudinal design with a median follow-up of 24 months, and one was a case-cohort study. Overall, we found moderate evidence of a positive association between LAN exposure and depressive symptoms and to a lesser extent other mental disorders, though the number of studies was limited and potential residual confounding such as socioeconomic factors, noise, or pollution may have influenced the results. Conclusions: Although more robust evidence is needed, the epidemiological evidence produced so far seems to support an association between LAN and depressive disorders. Keywords: Depression; Environmental risk factors; Light-at-night; Mental disorders; Systematic review.

2022 - Association between dietary patterns and urinary cadmium levels in an Italian population [Abstract in Atti di Convegno]
Filippini, T.; Urbano, T.; Malavolti, M.; Fustinoni, S.; Vinceti, M.
abstract

2022 - Association between selenium species and hippocampal volume in subjects with mild cognitive impairment [Abstract in Atti di Convegno]
Vinceti, Marco; Balboni, Erica; Filippini, Tommaso; Wise, Lauren A.; Nocetti, Luca; Eichmüller, Marcel; Tondelli, Manuela; Vinceti, Giulia; Zamboni, Giovanna; Chiari, Annalisa; Michalke, Bernhard
abstract

Background Selenium is a trace element with nutritional and toxicological properties. Its influence on human health is thought to depend on exposure dose and chemical form. The effects of selenium exposure on medical conditions that involve the central nervous system have been insufficiently studied. In a cohort of individuals with mild cognitive impairment, we have previously documented a positive relation between cerebrospinal fluid (CSF) levels of inorganic hexavalent selenium (selenate) and risk of dementia. Methods/Approach We assessed the relation between CSF levels of selenium species and volume of the hippocampus among the 33 cohort members aged 43-82 years who had undergone magnetic resonance imaging at baseline (2008-2014) using both linear and spline regression analyses. We also performed a surface-based analysis using SPHARM-PDM to evaluate differences in shape of the hippocampus in addition to its volume in relation to CSF levels of selenium species. Results We found an inverse association between selenate and total hippocampal volume (β regression coefficient in multivariable linear regression analysis -3.05, 95% confidence interval -5.74 to -0.37), which was similar for the right and left hippocampus and emerged mainly at the highest exposure levels. We found little association between the other selenium forms and hippocampal volume. In the surface-based analysis, the left hippocampus showed considerably more pronounced shape differences in the ventro-medial region of the head. Conclusions This is the first study to analyze selenium species in relation to hippocampal volume and structure, suggesting that a selenium form with high toxicological potential may adversely affect a key structure involved in dementia onset and progression as the hippocampus, possibly the left one in particular. However, we cannot entirely rule out the influence of reverse causation or unmeasured confounding on these results.

2022 - Association between serum selenium species and 8-oxo-7,8-dihydro-2’deoxyguanosine levels: an Italian cross-sectional study [Abstract in Atti di Convegno]
Urbano, T.; Filippini, T.; Michalke, B.; Fustinoni, S.; Vinceti, M.
abstract

Introduction: Selenium (Se) is a metalloid present in trace amounts in the organism, with toxicological and nutritional properties depending on the dose and the species considered. Both organic and inorganic selenium species are involved in oxidoreduction reaction regulation and pathways. 8-oxo-7,8-dihydro-2’deoxyguanosine (8-oxodG) is a derivative of deoxyguanosine, used as biomarker of oxidative stress in urine. In this study, we aimed to assess total serum selenium levels along with its species in a population in Northern Italy and to evaluate the associations between selenium exposure with 8-oxodG levels. Material and methods: The present study consisted in a cross-sectional survey carried out in blood donors aged 30-60 years enrolled in the Transfusion Medicine Center ‘Casa del Dono’ of the AUSL-IRCCS of Reggio Emilia, Northern Italy, in the period April 2017-April 2019. Of 148 eligible subjects, 137 were eventually enrolled. They were all non-smokers, and not affected by any disease or clinical condition. Each participant gave urinary and blood samples in order to quantify selenium levels in these matrices; urinary samples were used to quantify cotinine and 8-oxodG levels, while speciation analysis was performed in serum samples. We performed spline regression analyses to assess the possible nonlinear associations of the different biomarkers of selenium exposure with 8-oxodG levels using a multivariable model adjusted for potential confounders. Results: Our population had a mean age of 47.4 years. Mean (standard deviation) level of serum selenium was 117.4±19.1 mcg/L, respectively. Association of serum selenium level with 8-oxodG levels adjusted for urinary creatinine was almost null. For what concerns selenium species, selenoprotein P-bound-Se showed a slightly inverted U-shaped association with 8-oxodG levels with a positive association until 90 mcg/L and negative above that amount. Selenomethionine-bound-Se, glutathione peroxidase-bound-Se, and selenocysteine-bound-Se were positively associate with 8-oxodG, though for the latter two the association was very imprecise. A negative association emerged for thioredoxin reductase-bound-Se. Total inorganic selenium along with the two inorganic species, i.e., selenite and selenate, were negatively and linearly associated with 8-oxodG levels. For Se-bound to human serum albumin-bound-Se the association was almost null. Conclusion: Our results suggest that even though total selenium exposure seems not associated with 8-oxodG, selected selenium species may largely differ in their association with this oxidative stress biomarker, thus strengthening the importance of selenium speciation analysis for the evaluation of selenium health effects.

2022 - Associations of human serum albumin-bound selenium (Se-HSA) with other selenium species in two cohorts of Northern Italy [Abstract in Atti di Convegno]
Urbano, T.; Michalke, B.; Filippini, T.; Vinceti, M.
abstract

2022 - Associations of urinary and dietary cadmium with urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine and blood biochemical parameters [Articolo su rivista]
Urbano, Teresa; Filippini, Tommaso; Wise, Lauren A.; Lasagni, Daniela; De Luca, Tiziana; Sucato, Sabrina; Polledri, Elisa; Malavolti, Marcella; Rigon, Chiara; Santachiara, Annalisa; Pertinhez, Thelma A.; Baricchi, Roberto; Fustinoni, Silvia; Vinceti, Marco
abstract

Cadmium is a heavy metal with established adverse effects on human health, namely on bone, liver and kidney function and the cardiovascular system. We assessed cadmium exposure and its correlation with biomarkers of toxicity. We recruited 137 non-smoking blood donors without a history of chronic disease or cancer who resided in the Northern Italy province of Reggio Emilia (mean age 47 years, range 30–60 years) in the 2017–2019 period. We used a semi-quantitative food frequency questionnaire to estimate dietary cadmium intake and urine samples to assess concentrations of urinary cadmium and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG). Median urinary cadmium and 8-oxodG concentrations were 0.21 μg/L (interquartile range (IQR): 0.11–0.34 μg/L) and 3.21 μg/g creatinine (IQR: 2.21–4.80 μg/g creatinine), respectively, while median dietary cadmium intake was 6.16 μg/day (IQR: 5.22–7.93 μg/day). We used multivariable linear and spline regression models to estimate mean differences exposure concentrations. Dietary and urinary cadmium were positively correlated, and both were positively and linearly correlated with 8-oxodG. We found a positive association of urinary cadmium with blood alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein (LDL)-cholesterol and thyroid-stimulating hormone (TSH) concentrations. We also observed a positive association with triglycerides, in both linear (beta regression coefficient = 77.03, 95% confidence interval 32.27–121.78) and non-linear spline regression analyses. Despite the positive correlation between dietary and urinary cadmium estimates, dietary cadmium intake showed inconsistent results with the study endpoints and generally weaker associations, suggesting a decreased capacity to reflect actual cadmium exposure. Overall, these findings suggest that even low levels of cadmium exposure may adversely alter hematological and biochemical variables and induce oxidative stress.

2022 - Associazione tra livelli di cadmio e 8‑oxo‑7,8‑diidro‑2’‑deossiguanosina in una popolazione italiana [Articolo su rivista]
Urbano, Teresa; Filippini, Tommaso; Malavolti, Marcella; Fustinoni, Silvia; Vinceti, Marco
abstract

2022 - Associazione tra livelli di cadmio e parametri ematologici e biochimici in una popolazione del Nord Italia [Abstract in Atti di Convegno]
Urbano, Teresa; Filippini, Tommaso; Lasagni, Daniela; De Luca, Tiziana; Sucato, Sabrina; Polledri, Elisa; Malavolti, Marcella; Santachiara, Annalisa; Pertinhez Thelma, A.; Baricchi, Roberto; Fustinoni, Silvia; Vinceti, Marco
abstract

2022 - Atrial Fibrillation and the Risk of Early‐Onset Dementia: A Systematic Review and Meta‐Analysis [Articolo su rivista]
Giannone, Maria Edvige; Filippini, Tommaso; Whelton, Paul K.; Chiari, Annalisa; Vitolo, Marco; Boriani, Giuseppe; Vinceti, Marco
abstract

BACKGROUNDRecent studies have identified an increased risk of dementia in patients with atrial fibrillation (AF). However, both AF and dementia usually manifest late in life. Few studies have investigated this association in adults with early‐onset dementia. The aim of this study was to investigate the relationship between AF and early‐onset dementia. METHODS AND RESULTSWe searched the PubMed/MEDLINE, Embase, and Scopus databases through April 15, 2022, for studies reporting on the association between AF and dementia in adults aged <70 years, without language restrictions. Two reviewers independently performed the study selection, assessed the risk of bias, and extracted the study data. We performed a meta‐analysis of early‐onset dementia risk according to occurrence of AF using a random‐effects model. We retrieved and screened 1006 potentially eligible studies. We examined the full text of 33 studies and selected the 6 studies that met our inclusion criteria. The pooled analysis of their results showed an increased risk of developing dementia in individuals with AF, with a summary relative risk of 1.50 (95% CI, 1.00–2.26) in patients aged <70 years, and 1.06 (95% CI, 0.55–2.06) in those aged <65 years. CONCLUSIONSIn this systematic review and meta‐analysis, AF was a risk factor for dementia in adults aged <70 years, with an indication of a slight and statistically imprecise excess risk already at ages <65 years. Further research is needed to assess which characteristics of the arrhythmia and which mechanisms play a role in this relationship.

2022 - Blood and cerebrospinal fluid selenoprotein P levels and risk of progression from mild cognitive impairment to dementia [Abstract in Atti di Convegno]
Vinceti, M.; Urbano, T.; Chiari, A.; Filippini, T.; Wise, L.; Tondelli, M.; Michalke, B.; Shimizu, M.; Saito, Y.
abstract

2022 - Conversion of calcium-l-methylfolate and (6S)-5-methyltetrahydrofolic acid glucosamine salt into dietary folate equivalents [Articolo su rivista]
Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Peláez, Carmen; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Abrahantes, José Cortiñas; Dumas, Céline; Ercolano, Valeria; Titz, Ariane; Pentieva, Kristina
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the conversion of calcium-l-methylfolate and (6S)-5-methyltetrahydrofolic acid glucosamine salt (collectively called 5-MTHF hereafter) into dietary folate equivalents (DFE). Following a systematic review, the conclusions of the opinion are based on one intervention study in adults for intakes < 400 μg/day and three intervention studies in adults for intakes ≥ 400 μg/day. At intakes below 400 μg/day, folic acid (FA) is assumed to be linearly related to responses of biomarkers of intake and status and is an appropriate comparator for deriving a DFE conversion factor for 5-MTHF. It is proposed to use the same factor as for folic acid for conversion of 5-MTHF into DFE for intakes < 400 μg/day. As such intake levels are unlikely to be exceeded through fortified food consumption, the conversion factor of 1.7 relative to natural food folate (NF) could be applied to 5-MTHF added to foods and to food supplements providing < 400 μg/day. At 400 μg/day, 5-MTHF was found to be more bioavailable than folic acid and a conversion factor of 2 is proposed for this intake level and for higher intakes. The derived DFE equations are DFE = NF + 1.7 × FA + 1.7 × 5-MTHF for fortified foods and food supplements providing intakes < 400 μg/day; and DFE = NF + 1.7 × FA + 2.0 × 5-MTHF for food supplements providing intakes ≥ 400 μg/day. Although this assessment applies to calcium-L-methylfolate and 5-MTHF glucosamine salt, it is considered that the influence of the cation on bioavailability is likely to be within the margin of error of the proposed DFE equations. Therefore, the proposed equations can also be applied to 5-MTHF associated with other cations.

2022 - Dietary Acrylamide Exposure and Risk of Site-Specific Cancer: A Systematic Review and Dose-Response Meta-Analysis of Epidemiological Studies [Articolo su rivista]
Filippini, Tommaso; Halldorsson, Thorhallur I; Capitão, Carolina; Martins, Raquel; Giannakou, Konstantinos; Hogervorst, Janneke; Vinceti, Marco; Åkesson, Agneta; Leander, Karin; Katsonouri, Andromachi; Santos, Osvaldo; Virgolino, Ana; Laguzzi, Federica
abstract

: Diet is a main source of acrylamide exposure to humans. Existing observational data on the relationship between dietary exposure to acrylamide and risk of cancer are inconsistent. We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the association between dietary acrylamide exposure and several site-specific cancer. A systematic literature search was conducted in PubMed, Scopus, and Web of Science databases until March 7, 2022. Studies were eligible if they were carried out in non-occupationally exposed adults, assessed dietary acrylamide exposure (μg/day) and reported risk estimates of cancer incidence (all but gynecological cancers). Using a random-effects model, we performed a meta-analysis of site-specific cancer risk comparing the highest vs. lowest category of dietary acrylamide exposure. We also carried out a one-stage dose-response meta-analysis assessing the shape of the association. Out of 1,994 papers screened, 31 were eligible (total of 16 studies), which included 1,151,189 participants in total, out of whom 48,175 developed cancer during the median follow-up period of 14.9 years (range 7.3-33.9). The mean estimated dose of dietary acrylamide across studies was 23 μg/day. Pooled analysis showed no association between the highest vs. lowest dietary acrylamide exposure and each site-specific cancer investigated, with no evidence of thresholds in the dose-response meta-analysis. There were also no associations between dietary acrylamide exposure and the risk of cancers when stratifying by smoking status, except for increased risk of lung cancer in smokers. In conclusion, high dietary acrylamide exposure was not associated with an increased risk of site-specific non-gynecological cancer.

2022 - Dietary Patterns and Blood Biochemical and Metabolic Parameters in an Italian Population: A Cross-Sectional Study [Articolo su rivista]
Cecchini, Marta; Urbano, Teresa; Lasagni, Daniela; De Luca, Tiziana; Malavolti, Marcella; Baraldi, Claudia; Grioni, Sara; Agnoli, Claudia; Sieri, Sabina; Santachiara, Annalisa; Pertinhez, Thelma A.; Fustinoni, Silvia; Baricchi, Roberto; Vinceti, Marco; Filippini, Tommaso
abstract

Diet has long been identified as a major determinant of cardiovascular and other chronic diseases. In this study, we assess the relation between adherence to different dietary patterns and biochemical and metabolic parameters as well as the 10-year risk of major cardiovascular diseases (CVDs) in a community of blood donors in Northern Italy. We assess their adherence to four dietary patterns, namely, the Dietary Approach to Stop Hypertension (DASH) diet, the Mediterranean diet through the Greek and Italian Mediterranean Indices (GMI and IMI) and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, using a validated semi-quantitative food frequency questionnaire (FFQ). We then assess their association with blood parameters and the 10-year risk of major CVD using a spline regression model. We found an inverse association between the DASH and MIND diets and total and LDL cholesterol, and triglyceride and HDL cholesterol values for the Mediterranean diets (IMI and GMI). Additionally, according to our sex-stratified analyses, men who have greater adherence to dietary patterns have a decreased risk of major CVD for all patterns. The results suggest that greater adherence to dietary patterns positively influences blood biochemical and metabolic parameters, thus reducing the risk of developing cardiovascular disease and delaying the use of drug treatments

2022 - Dietary intake of potentially toxic elements and children's chemical exposure [Articolo su rivista]
Urbano, T.; Zagnoli, F.; Malavolti, M.; Halldorsson, T. I.; Vinceti, M.; Filippini, T.
abstract

Environmental pollution is a major global public health problem, which has been extensively associated with several adverse health outcomes in both developed and undeveloped countries. In this review, we aimed at summarizing the most recent epidemiological evidence on the association between environmental pollutants intake and possible adverse health effects in children. What emerged is that several contaminants negatively affect children's health. In particular, exposure to heavy metals, plastic-derived chemicals, pesticides, and per- and polyfluoroalkyl substances have been associated with developmental disorders, cancers, allergies, and obesity in children.

2022 - Environmental and lifestyle risk factors for early-onset dementia: a systematic review [Articolo su rivista]
Bosi, Matteo; Malavolti, Marcella; Garuti, Caterina; Tondelli, Manuela; Marchesi, Cristina; Vinceti, Marco; Filippini, Tommaso
abstract

The term early-onset dementia (EOD) encompasses several forms of neurodegenerative diseases characterized by symptom onset before 65 years and leading to severe impact on subjects already in working activities, as well as on their family and caregivers. Despite the increasing incidence, the etiology is still unknown, with possible association of environmental factors, although the evidence is still scarce. In this review, we aimed to assess how several environmental and lifestyle factors may be associated with the onset of this disease.

2022 - Epidemiological, Clinical and Genetic Features of ALS in the Last Decade: A Prospective Population-Based Study in the Emilia Romagna Region of Italy [Articolo su rivista]
Gianferrari, G.; Martinelli, I.; Zucchi, E.; Simonini, C.; Fini, N.; Vinceti, M.; Ferro, S.; Gessani, A.; Canali, E.; Valzania, F.; Sette, E.; Pugliatti, M.; Tugnoli, V.; Zinno, L.; Stano, S.; Santangelo, M.; De Pasqua, S.; Terlizzi, E.; Guidetti, D.; Medici, D.; Salvi, F.; Liguori, R.; Vacchiano, V.; Casmiro, M.; Querzani, P.; Dossi, M. C.; Patuelli, A.; Morresi, S.; Longoni, M.; De Massis, P.; Rinaldi, R.; Borghi, A.; Amedei, A.; Mandrioli, J.
abstract

Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype–phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS. The age-and sex-adjusted incidence rate was 3.13/100,000 population (M/F ratio: 1.21). The mean age at onset was 67.01 years; women, bulbar and respiratory phenotypes were associated with an older age, while C9orf72-mutated patients were generally younger. After peaking at 70–75 years, incidence rates, among women only, showed a bimodal distribution with a second slight increase after reaching 90 years of age. Familial cases comprised 12%, of which one quarter could be attributed to an ALS-related mutation. More than 70% of C9orf72-expanded patients had a family history of ALS/fronto-temporal dementia (FTD); 22.58% of patients with FTD at diagnosis had C9orf72 expansion (OR 6.34, p = 0.004). In addition to a high ALS incidence suggesting exhaustiveness of case ascertainment, this study highlights interesting phenotype–genotype correlations in the ALS population of ERR.

2022 - Exposure to overhead high-voltage power lines and childhood leukemia risk: an Italian population-based case-control study [Abstract in Atti di Convegno]
Malagoli, Carlotta; Malavolti, Marcella; Fabbi, Sara; Zanichelli, Paolo; Notari, Barbara; Poli, Maurizio; Palazzi, Giovanni; Cellini, Monica; Filippini, Tommaso; Teggi, Sergio; Vinceti, Marco
abstract

Background Previous epidemiologic findings suggest a positive association between magnetic field exposure induced by high voltage power lines and childhood leukemia (CL). Contrasting results are still reported, possibly biased by exposure misclassification, relying on different assessment methods across studies, and by unmeasured confounders. Methods/Approach We further studied this relation in the Modena and Reggio Emilia provinces (Northern Italy), and through a modelling exposure assessment we identified the corridors along high voltage power lines with magnetic field intensity in the 0.1-0.4 µT ranges. Then we identified 182 cases of newly-diagnosed CL within these provinces from 1998 to 2019. We sampled four age-, sex-, province of residence- and calendar year- matched controls for each case. We computed the odds ratio (OR) and its 95% confidence interval (CI) of CL in a conditional logistic regression analysis according to distance between home address at the time of diagnosis of the case and the nearest high voltage power line and also to residential magnetic field modeled intensity. Results OR of CL was 0.9 (95% CI 0.5-1.6), 0.9 (95% CI 0.4-2.0), 1.5 (95% CI 0.5-4.7) and 4.0 (95% CI 1.0-16.0) for children living respectively 200-400 m, 100-200 m, 50-100 m, and less than 50 m from the nearest high voltage power line compared to those residing further than 400 m. OR of CL associated with residence in the area with exposure >0.1 µT was 8.0 (95% CI 0.7-88.2). Conclusions Though the number of exposed children in this study was too low to allow firm conclusions, yielding in such cases high but very imprecise estimates, our results seem more suggestive of an excess risk of leukemia among children living close to electric power lines or exposed to higher magnetic fields intensity.

2022 - GRADE Guidance article 35: Update on rating imprecision for assessing contextualized certainty of evidence and making decisions [Articolo su rivista]
Schünemann, Holger J; Neumann, Ignacio; Hultcrantz, Monica; Brignardello-Petersen, Romina; Zeng, Linan; Murad, M Hassan; Izcovich, Ariel; Morgano, Gian Paolo; Baldeh, Tejan; Santesso, Nancy; Cuello, Carlos Garcia; Mbuagbaw, Lawrence; Guyatt, Gordon; Wiercioch, Wojtek; Piggott, Thomas; De Beer, Hans; Vinceti, Marco; Mathioudakis, Alexander G; Mayer, Martin G; Mustafa, Reem; Filippini, Tommaso; Iorio, Alfonso; Nieuwlaat, Robby; Marcucci, Maura; Coello, Pablo Alonso; Bonovas, Stefanos; Piovani, Daniele; Tomlinson, George; Akl, Elie A
abstract

GRADE guidance to rate the certainty domain of imprecision is presently not fully operationalized for rating down by two levels and when different or uncertainty in baseline risks are considered. In addition, there are scenarios in which lowering the certainty of evidence by three levels for imprecision is more appropriate than lowering it by two levels. In this article, we conceptualize and operationalize rating down for imprecision by one, two and three levels for imprecision using the contextualized GRADE approaches.

2022 - Guidance for establishing and applying tolerable upper intake levels for vitamins and essential minerals: Draft for internal testing [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aggett, P.; Crous Bou, M.; Cubadda, F.; de Sesmaisons Lecarre, A.; Martino, L.; Naska, A.
abstract

Vitamins and essential minerals are micronutrients that are essential for the normal functioning of the human body. However, they may lead to adverse health effects if consumed in excess. The concept of a tolerable upper intake level (UL) is a science-based reference value, which was introduced to support policy-makers and other relevant actors in managing the risks of excess nutrient intake. EFSA’s principles for establishing ULs for vitamins and minerals were originally developed by the Scientific Committee on Food in 2000. Since then, experience has been gained and the scientific field developed. This guidance from the EFSA Panel on Nutrition, Novel Foods and Food Allergens provides an updated framework to support EFSA’s UL assessments. It covers aspects related to the planning of the risk assessment (problem formulation and definition of methods) and its implementation (evidence retrieval, appraisal, synthesis, integration, uncertainty analysis). As in the previous framework, the general principles developed for the risk assessment of chemicals in food are applied (hazard identification, hazard characterisation, intake assessment, risk characterisation). Peculiar to nutrients are their biochemical and physiological roles and the specific and selective mechanisms that maintain the systemic homoeostasis and body burden of the nutrient. These must be considered when conducting a risk assessment of nutrients. This document constitutes a draft guidance that will be applied in EFSA’s assessments during a 1-year pilot phase and be revised and complemented as necessary. Before finalisation of the guidance, a public consultation will be launched.

2022 - Healing Time of Skin Ulcers in Homecare Residents in the Province of Reggio Emilia, Northern Italy [Articolo su rivista]
Iamandii, Inga; Kouassi, Abram Beatrice; Simonazzi, Davide; Marchesi, Cristina; Vinceti, Marco; Filippini, Tommaso
abstract

The growing phenomenon of skin ulcers represents an important health problem; therefore, we conducted a pilot study to evaluate the ulcer healing time among adult subjects followed by the Home Nursing Service of the AUSL-IRCCS of Reggio Emilia, Northern Italy, and diagnosed with at least one skin ulcer during the period of January-August 2020. We recruited 138 subjects (45.5% men) with a mean age of 86.1 years. The subjects presented with 232 ulcers, of which 76.7% were pressure ulcers (60.1% were stage II), 18.1% were vascular ulcers, and 4.7% were diabetic foot ulcers. Ulcer management required only one weekly access for the majority of subjects, with a recovery frequency of 53.6% at the end of the observation period. The median ulcer healing time was 3.6 months and was shorter in women (2.6 months) than men (5.1 months), with an increasing trend according to the number of ulcers and the severity of pressure ulcers for vascular and diabetic foot ulcers. In conclusion, this is the first study carried out in an Italian population describing the distribution and characteristics of homecare residents with skin ulcers and highlighting the factors influencing the healing time and as consequence the duration of nursing care.

2022 - Is Greenness Associated with Dementia? A Systematic Review and Dose–Response Meta-analysis [Articolo su rivista]
Zagnoli, Federico; Filippini, Tommaso; Jimenez, Marcia P.; Wise, Lauren A.; Hatch, Elizabeth E.; Vinceti, Marco
abstract

Purpose of review: We assessed the relation between environmental greenness and risk of dementia and cognitive impairment, based on a systematic review and meta-analysis up to March 30, 2022, characterizing whenever possible the shape of the association using dose-response meta-analysis. Recent findings: Twelve studies were included in this review, either using normalized difference vegetation index (NDVI) or land use/cover (LU/LC) methodology to assess greenness. Comparing the highest versus lowest exposure categories of greenness assessed using the NDVI (6 studies) or LU/LC (6 studies), we found no association with dementia. Dose-response meta-analysis of the association between greenness measured by LU/LC and dementia, based on only 3 studies, indicated a U-shaped association, but estimates were imprecise. Our systematic review and meta-analysis provided some evidence of a slight inverse association between greenness and dementia at intermediate exposure levels, but not at high levels. Potential methodological limitations, such as exposure misclassification and unmeasured confounding, may have affected the results.

2022 - Light at night exposure and risk of depression and other mental disorders: a systematic review [Abstract in Atti di Convegno]
Tancredi, Stefano; Urbano, Teresa; Vinceti, Marco; Filippini, Tommaso
abstract

Background In modern society, individuals are increasingly exposed to artificial light at night (LAN) i.e., different sources of light altering the natural day-night cycle. Emerging evidence suggests a possible association between LAN exposure and physiological and behavioral changes, with implications on mood and mental health at the population level. We performed a systematic review of observational studies to investigate if LAN exposure, may be associated with an increased risk of mental diseases in humans. Methods/Approach We reviewed the epidemiological evidence about the association between LAN exposure as assessed either via satellite photometry (outdoor LAN) or via measurements of bedroom brightness (indoor LAN), and risk of mental disorders. We systematically searched the PubMed, Embase and Web of Science databases up to September 1, 2022. Studies were included if they assessed the link between exposure to indoor or outdoor LAN and one or more mental disorders. Results Ten eligible studies were included in this review: six studies had a cross-sectional design, two had a longitudinal design with a median follow-up of 24 months, and one was a case-cohort study. Studies were published between 2002 and 2022. Eight studies were conducted in adult populations, one in adolescents, and one in children. Mental disorders investigated include anxiety and mood disorders, depression, bipolar disorder, autism and mild cognitive impairment. Overall, we found moderate evidence of a positive association between LAN exposure and depressive symptoms and to a lesser extent other mental disorders, though the number of studies was limited and potential residual confounding such as socioeconomic factors, noise, or air pollution may have influenced the results. Conclusions Although more robust evidence is needed, the epidemiological evidence produced so far seems to support an association between LAN and risk of depressive disorders.

2022 - Light at night exposure and risk of depression and other mental disorders: a systematic review [Abstract in Rivista]
Tancredi, Stefano; Urbano, Teresa; Vinceti, Marco; Filippini, Tommaso
abstract

BACKGROUND AND AIM: In modern society, individuals are increasingly exposed to artificial light at night (LAN) i.e., different sources of light altering the natural day-night cycle. Emerging evidence suggests a possible association between LAN exposure and physiological and behavioral changes, with implications on mood and mental health at the population level. We performed a systematic review of observational studies to investigate if LAN exposure, may be associated with an increased risk of mental diseases in humans. METHODS: We reviewed the epidemiological evidence about the association between LAN exposure as assessed either via satellite photometry (outdoor LAN) or via measurements of bedroom brightness (indoor LAN), and risk of mental disorders. We systematically searched the PubMed, Embase and Web of Science databases up to April 1, 2022. Studies were included if they assessed the link between exposure to indoor or outdoor LAN and one or more mental disorders. RESULTS: Nine eligible studies were included in this review: six studies had a cross-sectional design, two had a longitudinal design with a median follow-up of 24 months, and one was a case-cohort study. Studies were published between 2002 and 2022. Seven studies were conducted in adult populations, one in adolescents, and one in children. Mental disorders investigated include anxiety and mood disorders, depression, bipolar disorder and autism. Overall, we found moderate evidence of a positive association between LAN exposure and depressive symptoms and to a lesser extent other mental disorders, though the number of studies was limited and potential residual confounding such as socioeconomic factors, noise, or air pollution may have influenced the results. CONCLUSIONS: Although more robust evidence is needed, the epidemiological evidence produced so far seems to support an association between LAN and risk of depressive disorders. KEYWORDS: mental disorders; light at night; depression; systematic review, environmental risk factors

2022 - Maternal acrylamide exposure during pregnancy and fetal growth: A systematic review and dose-response meta-analysis of epidemiological studies [Articolo su rivista]
Hogervorst, Janneke; Virgolino, Ana; Halldorsson, Thorhallur I; Vinceti, Marco; Åkesson, Agneta; Leander, Karin; Nawrot, Tim; Filippini, Tommaso; Laguzzi, Federica
abstract

Background: Acrylamide is a food contaminant linked to developmental toxicity in animals and possibly in humans. Objectives: We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the relationship between maternal acrylamide exposure during pregnancy and the risk of being small for gestational age (SGA) and birth weight, birth head circumference and birth length. Methods: We performed the literature search in PubMed, Scopus, and Web of Science, until June 6th, 2022. Studies carried out in mother-newborn pairs, assessing maternal acrylamide exposure during pregnancy, either via dietary assessments or biomarkers i.e., hemoglobin adducts of acrylamide (AA-Hb) and glycidamide (GA-Hb), and evaluating birth outcomes were included. We employed a random-effects model to assess the pooled effect estimates and their 95% confidence intervals (CI) for the association between acrylamide exposure and birth outcomes. Risk of Bias for Nutrition Observational Studies tool was used for bias assessment. Results: Out of 169 records identified, five original studies were eligible, including 53,870 mother-newborn pairs in total. Means were 21.9 μg/day for estimated dietary acrylamide exposure (3 studies), and 18.4 and 14.9 pmol/g for AA-Hb and GA-Hb, respectively (2 studies). Higher risk of SGA and lower birth weight and head circumference were observed in the highest quartile of AA-Hb [odds ratio (OR): 1.20 (95% CI: 1.08; 1.33); mean difference (MD): -131 g (95% CI: -204; -58) and -0.31 cm (95% CI: -0.58; -0.04), respectively], and GA-Hb [OR: 1.36 (95% CI: 1.13; 1.64), MD: -161 g (95% CI: -271; -52); and MD: -0.38 cm (95% CI: -0.66; -0.10), respectively], whereas a lower birth length was observed only in the highest quartile of GA-Hb (MD: -0.85 cm (95% CI: -1.38; -0.33). Results from the dose-response meta-analysis between increasing maternal acrylamide exposure during pregnancy and birth weight showed no clear evidence of a deviation from linearity. Conclusions: Overall, our findings strengthen the evidence of an adverse effect of maternal acrylamide exposure during pregnancy on fetal growth. These results encourage to increase preventive actions towards lowering acrylamide exposure in the population.

2022 - Mitigating Indoor Risk of Airborne Infections: the MIRAI project [Abstract in Atti di Convegno]
Filippini, Tommaso; Vinceti, Marco; Ghermandi, Grazia; Bigi, Alessandro
abstract

2022 - Nutritional safety and suitability of a specific protein hydrolysate derived from whey protein concentrate and used in an infant and follow-on formula manufactured from hydrolysed protein by HIPP-Werk Georg Hipp OHG (dossier submitted by meyer.science GmbH) [Articolo su rivista]
Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Katrine Knutsen, H.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Castle, L.; Fewtrell, M.; Przyrembel, H.; Dumas, C.; Titz, A.; Turck, D.
abstract

The European Commission asked EFSA to deliver an opinion on the nutritional safety and suitability of a specific protein hydrolysate. It is derived from whey protein concentrate and used in infant and follow-on formula by HIPP-Werk Georg Hipp OHG. The dossier that was submitted to the European Commission aimed at requesting an amendment of Regulation (EU) 2016/127 with respect to the protein sources that may be used in infant and/or follow-on formula. This opinion does not cover the assessment of the safety of the food enzymes used in the manufacture of the protein hydrolysate. The protein hydrolysate under evaluation is sufficiently characterised with respect to the fraction of the hydrolysed protein. In the pertinent intervention study provided, an infant formula manufactured from the protein hydrolysate with a protein content of 1.9 g/100 kcal and consumed as the sole source of nutrition by infants for 3 months led to growth equivalent to a formula manufactured from intact cow’s milk protein with the same protein content. No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. However, given that it is consumed with complementary foods and the protein source is considered nutritionally safe and suitable in an infant formula that is the sole source of nutrition of infants, the Panel considers that the protein hydrolysate is also a nutritionally safe and suitable protein source for use in follow-on formula. The Panel concludes that the protein hydrolysate under evaluation is a nutritionally safe and suitable protein source for use in infant and follow-on formula, as long as the formula in which it is used contains a minimum of 1.9 g/100 kcal protein and complies with the compositional criteria of Commission Delegated Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA.

2022 - Prediagnostic Levels of Copper and Zinc and Breast Cancer Risk in the ORDET Cohort [Articolo su rivista]
Pala, V.; Agnoli, C.; Cavalleri, A.; Rinaldi, S.; Orlandi, R.; Segrado, F.; Venturelli, E.; Vinceti, M.; Krogh, V.; Sieri, S.
abstract

Background: Case–control studies show that copper (Cu) is high and zinc (Zn) low in blood and urine of women with breast cancer compared with controls. Methods: To assess whether prediagnostic Cu and Zn are associated with breast cancer risk, OR of breast cancer according to Cu, Zn, and Cu/Zn ratio in plasma and urine was estimated in a nested case–control study within the ORDET cohort, using conditional logistic regression adjusted for multiple variables: First 496 breast cancer cases and matched controls, diagnosed ≥2 years after recruitment (to eliminate reverse causation) were analyzed. Then all eligible cases/controls were analyzed with stratification into years from recruitment to diagnosis. Results: For women diagnosed ≥2 years, compared with lowest tertiles, breast cancer risk was higher in the highest tertile of plasma Cu/Zn ratio (OR, 1.75; 95% CI, 1.21–2.54) and the highest tertile of both plasma and urine Cu/Zn ratio (OR, 2.37; 95% CI, 1.32–4.25). Risk did not vary with ER/PR/HER2 status. For women diagnosed <2 years, high Cu/Zn ratio was strongly associated with breast cancer risk. Conclusions: Our prospective findings suggest that increased Cu/Zn ratio in plasma and urine may be both an early marker of, and a risk factor for, breast cancer development. Further studies are justified to confirm or otherwise our results and to investigate mechanisms. Impact: Our finding that prediagnostic Cu/Zn ratio is a strong risk factor for breast cancer development deserves further investigation and, if confirmed, might open the way to interventions to reduce breast cancer risk in women with disrupted Cu/Zn homeostasis.

2022 - Relation between adherence to dietary patterns and serum selenium species levels in a healthy Italian cohort [Abstract in Atti di Convegno]
Urbano, T.; Filippini, T.; Malavolti, M.; Michalke, B.; Vinceti, M.
abstract

2022 - Relation between adherence to dietary patterns and urinary selenium levels in an Italian cohort [Abstract in Atti di Convegno]
Malavolti, M.; Urbano, T.; Filippini, T.; Fustinoni, S.; Vinceti, M.
abstract

2022 - Residence in proximity of petrol stations and childhood leukemia risk [Abstract in Atti di Convegno]
Malavolti, Marcella; Malagoli, Carlotta; Costanzini, Sofia; Palazzi, Giovanni; Cellini, Monica; Filippini, Tommaso; Teggi, Sergio; Vinceti, Marco
abstract

Background Air pollutant concentrations close to petrol stations tend to increase, especially for benzene and other carcinogenic contaminants, depending on meteorological factors, features of nearby buildings and station activity. For this reason, it is suggested that petrol stations increase the risk of cancer, in particular, childhood leukemia. Methods/Approach We carried-out a population-based case-control study in two Northern Italy provinces, Modena and Reggio Emilia. We included 182 cases of childhood leukemia diagnosed in the period 1998-2019, and 726 age and sex-matched controls. We geocoded child residence and the 790 petrol stations located in the study area, of which we retrieved the annual refueling activity. Exposure was assessed based on both residential distance from the nearest petrol station and on the activity of all plants located up to 1000 m from the home. Risk ratio of leukemia was estimated by computing disease odds ratio (OR) through conditional logistic regression models adjusted for potential confounders. Results We found an increased risk for childhood leukemia associated to residence in close proximity to petrol stations. Compared to those who live ≥ 1000m, OR was 2.30 (95% CI 0.53-9.97) for children living <50 m from nearest petrol station in bivariate analysis and 2.16 (95% CI 0.49-9.42) in multivariable analysis. The excess risk was higher when considering acute lymphoblastic leukemia (ALL) subtype (OR=2.83, 95% CI 0.61-13.21), and in children diagnosed after 5 years of age (OR=4.68, 95% CI 0.61-35.95) compared with < 5 years (OR=1.63, 95% CI 0.14-18.84). Conclusions Our study found an increased childhood leukemia risk for residence in close proximity (<50 meters) to a petrol station. Such excess risk was higher for the ALL subtype and for children diagnosed after 5 years.

2022 - Safety of 2′-fucosyllactose (2’-FL) produced by a derivative strain (APC199) of Corynebacterium glutamicum ATCC 13032 as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

: Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 2'-fucosyllactose (2'-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 2'-FL, but it also contains d-lactose, l-fucose, 3-fucosyllactose, difucosyllactose, d-glucose and d-galactose. The NF is produced by fermentation with a genetically modified strain (APC199) of Corynebacterium glutamicum ATCC 13032. 2'-FL, when chemically synthesised or produced by fermentation with derivative strains of Escherichia coli K-12 DH1 or E. coli BL21 (DE3), is already authorised and included in the EU list of NFs. This application refers to a change in the production process and specifications, while target population, conditions of use and consequently, the anticipated intake remain unchanged. The information provided on the identity, production process, composition and specifications of the NF does not raise safety concerns. The intake of other carbohydrate-type compounds structurally related to 2'-FL is also considered of no safety concern. In line with other milk oligosaccharides that are natural components of human milk, the safety assessment of this NF is mainly based on the comparison between the intake of breastfed infants and the estimated intake as NF. Given that the NF would be consumed at the same extent as the already authorised 2'-FL, the Panel considers that the consumption of the NF at the proposed uses and use levels does not raise safety concerns. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of 3-fucosyllactose (3-FL) produced by a derivative strain of Escherichia coli BL21 (DE3) as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3-fucosyllactose (3-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3-FL, but it also contains d-lactose, l-fucose, d-glucose and d-galactose, and a small fraction of other related saccharides. The NF is produced by fermentation with a genetically modified strain of Escherichia coli BL21 (DE3). The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for infants and young children, food for special medical purposes and food supplements. The target population is the general population. The anticipated daily intake of 3-FL from both proposed and combined (authorised and proposed) uses at their respective maximum use levels in all population categories does not exceed the highest intake level of 3-FL from human milk in infants on a body weight basis. The intake of 3-FL in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to 3-FL is also considered of no safety concern. Food supplements are not intended to be used if other foods with added 3-FL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of 3’-sialyllactose (3’-SL) sodium salt produced by derivative strains of Escherichia coli BL21 (DE3) as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3’-sialyllactose (3’-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3’-SL, but it also contains d-lactose, 3’-sialyllactulose, sialic acid, N-acetyl-d-glucosamine and a small fraction of other related oligosaccharides. The NF is produced by fermentation with two genetically modified strains of Escherichia coli BL21 (DE3), the production strain and the optional degradation strain. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for infants and young children, food for special medical purposes and food supplements. The target population is the general population. The anticipated daily intake of 3’-SL from both proposed and combined (authorised and proposed) uses at their respective maximum use levels in all population categories does not exceed the highest intake level of 3’-SL from human milk in infants on a body weight basis. The intake of 3’-SL in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to 3’-SL is also considered of no safety concern. Food supplements are not intended to be used if other foods with added 3’-SL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of 6′-sialyllactose (6’-SL) sodium salt produced by derivative strains of Escherichia coli BL21 (DE3) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 6′-sialyllactose (6’-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 6’-SL, but it also contains d-lactose, 6′-sialyllactulose, sialic acid, N-acetyl-d-glucosamine and a small fraction of other related oligosaccharides. The NF is produced by fermentation with two genetically modified strains of Escherichia coli BL21 (DE3), the production strain and the optional degradation strain. The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for special medical purposes and food supplements. The target population is the general population. In some scenarios at the maximum use levels, the estimated intakes per kg body weight were higher than the high average natural intake of 6’-SL from human milk. However, given the intrinsic nature of human milk oligosaccharides (HMOs), the wide range of intakes from human milk, and considering that infants are naturally exposed to similar amounts of these substances, the Panel considers that the consumption of the NF at the proposed conditions of use does not raise safety concerns. The intake of 6’-SL in breastfed infants on a body weight basis is also expected to be safe for other population groups. The intake of other carbohydrate-type compounds structurally related to 6’-SL is also considered of no safety concern. Food supplements are not intended to be used if other foods with added 6’-SL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of Beta-lactoglobulin as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Fernandez Dumont, A.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on beta-lactoglobulin (BLG) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF (≥ 90% w/w dry matter protein) consists of BLG as primary component (≥ 90% of total protein), which is equivalent to BLG present in bovine milk and whey protein isolate (WPI). The NF is produced from bovine whey by crystallisation under acidic or neutral conditions. The NF is proposed to be used as a food ingredient in isotonic and sport drinks, whey powder and milk-based drinks and similar products, and in food for special medical purposes as defined in Regulation (EU) No 609/2013. The target population is the general population. The highest daily intake of the NF was estimated for children of 3 to < 10 years of age as 667 mg/kg body weight (bw) per day. The NF presents proximate composition and content of essential amino acids similar to those in WPI. The Panel notes that the highest mean and highest 95th percentile daily protein intakes from the NF are below the protein population reference intakes for all population groups. Although a tolerable upper intake level has not been derived for protein, the protein intake from the NF may nevertheless further contribute to an already high dietary protein intake in Europe. The exposure to the reported minerals does not raise concerns. The Panel considers that the consumption of the NF is not nutritionally disadvantageous. No genotoxic concerns were identified from the standard in vitro test battery. No adverse effects were observed in the subchronic toxicity study, up to the highest dose tested, i.e. 1,000 mg NF/kg bw per day. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of Lemna minor and Lemna gibba whole plant material as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Kouloura, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on Lemna minor and Lemna gibba whole plant material as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Lemna minor and Lemna gibba are aquatic plants commonly named water lentils. The NF is produced by cultivation of Lemna minor and Lemna gibba plants, washing with water and heat treatment. The main constituents of the NF are water, protein and fibre. The Panel notes that the concentration of trace elements and contaminants in the NF is highly dependent on the conditions of cultivation of the plant and the fertiliser composition. The NF is intended to be used as a vegetable, similar to other leafy vegetables. The target population is the general population. The Panel considers that, with the exception of concerns related to the manganese intake, taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The Panel considers that the risk that the consumption of the NF may trigger allergic reactions in humans is low. The Panel concludes that the NF, in consideration of its proposed uses and the concentration of manganese as compared to the normally present concentration of manganese in other leafy vegetables, may be of safety concern, therefore, the safety of the NF cannot currently be established.

2022 - Safety of an aqueous ethanolic extract of Labisia pumila as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Albert, O.; Matijevic, L.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on aqueous extract of Labisia pumila as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a standardised hydroalcoholic extract from a dried whole plant (including roots) of L. pumila, mixed with maltodextrin (as a drying aid), and proposed by the applicant to be used as a food supplement in amounts up to 750 mg/day. The target population is the general adult population, except pregnant and lactating women. The major constituents of this NF are carbohydrates (up to 85.5%), with a smaller amount of proteins (up to 6.5%), gallic acid (up to 3.7%) and fats (up to 1.6%). The Panel considers that taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. The provided genotoxicity studies do not raise concerns about the genotoxicity of the NF. Based on the available toxicological data, the Panel considers an intake of up to 5 mg/kg body weight per day as safe. For the target population, this level corresponds to 350 mg/day, which is lower than the use level proposed by the applicant. The Panel concludes that the NF is safe for the target population up to 350 mg/day.

2022 - Safety of an extension of use of Yarrowia lipolytica yeast biomass as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use for Yarrowia lipolytica yeast biomass as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The extension of use pertains to the use of the NF as a food ingredient in single meal replacement products for weight reduction for adults at a maximum amount of 6 g NF per day, which is the same amount of NF as already authorised in food supplements for this population group. According to the applicant, food supplements with Yarrowia lipolytica biomass (as already authorised) should not be consumed concomitantly with the meal replacement products in order not to exceed the 6 g NF per day. The Panel considers that the consumption of the NF is not nutritionally disadvantageous under the proposed conditions of use. The Panel concludes that the NF, Yarrowia lipolytica yeast biomass, is safe under the proposed conditions of use.

2022 - Safety of bovine milk osteopontin as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on bovine milk osteopontin (bmOPN) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF concerns OPN derived from bovine whey. The NF is intended to be used at a maximum use level of 151 mg/L, in infant formula (IF), follow-on formula (FoF) and ready-to-eat dairy-based meals for children up to 35 months of age. As compared to the concentrations naturally present in cow’s milk and concentrations found in IF on the market reported in the literature, the proposed use level of the NF represents an about 10-fold higher concentration of bmOPN. The intended use levels of the NF would provide bmOPN at a concentration within the range of human milk (hm) OPN. In a 6-month study, 14, 72 and 140 mg bmOPN/L in reconstituted (as consumed) IF were given to 279 infants in order to study possible effects on frequency and severity of adverse events, and growth, formula intake and stool consistency. Despite that a number of inconsistencies and limitations were noted in the study report, the Panel considers that the results obtained from this study do not raise safety concerns. Considering the source of the NF, that neither the toxicological studies nor the provided infant study do raise safety concerns, and the low bmOPN plasma levels in infants resulting from the consumption of the NF, the Panel considers that the margin of exposure (i.e. 36) between the NOAEL of the subchronic toxicity study (1,200 mg/kg bw per day) and the highest P95 estimate for infants (33.4 mg/kg bw per day) is sufficient. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of cellobiose as a novel food pursuant to regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Albert, O.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on cellobiose as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of two glucose monomers linked by a β-(1–4) glucosidic bond. The applicant intends to add the NF to a variety of foods, and to food supplements aimed at the general population 3 years and older. The information provided on the manufacturing process, composition and specifications of the NF is sufficient and does not raise safety concerns. The applicant provided a subchronic toxicological study which did not raise safety concerns. The applicant provided a human dose-escalation study from which the Panel concludes that the consumption of 20 g per day of cellobiose (equivalent to 290 mg/kg body weight (bw) per day in a 70-kg adult) does not raise concern regarding gastrointestinal tolerability. The maximum anticipated daily intake of cellobiose from the proposed uses is below 290 mg/kg bw per day in the target population. Considering the nature, source, compositional characterisation, and production process of the NF, as well as the toxicological data provided, the Panel considers that the NF does not raise safety concerns under the proposed conditions of use.

2022 - Safety of dried coffee husk (cascara) from Coffea arabica L. as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubbada, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J.; van Loveren, H.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on dried coffee husk (cascara) from Coffea arabica L. as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF comprises the skin (exocarp), pulp (mesocarp), mucilage (pectin), parchment (endocarp) and a portion of the silver skin of the coffee fruit, and consists mainly of digestible carbohydrates, dietary fibre and water. The Panel considers that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf-life. The NF as such will not be consumed, instead, beverages produced with the infusion of the NF in water will be available to consumers. Considering an 100% extraction of caffeine from the NF to the beverage, the specification limit set for caffeine and the proposed use levels, the maximum concentration of caffeine in infusions produced using the NF could be up to 600 mg/L of drink, a concentration comparable to those in coffee beverages. The Panel notes that consumption of beverages produced using the NF will add significantly to the total dietary intake of caffeine of the general population. The consumption of beverages containing caffeine is not recommended for children, pregnant or breast-feeding women if the caffeine content exceeds 150 mg/L. Taking into account the nature of the NF, the history of use of the NF as food and the proposed uses and use levels, the Panel considers that no toxicological studies are required on the NF. The risk of allergic reactions to the NF is considered low. The Panel concludes that the NF, dried husk of the fruit of Coffea arabica L., is safe under the proposed conditions of use.

2022 - Safety of freeze-dried mycelia of Antrodia camphorata as a novel food pursuant to regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on freeze-dried mycelia of Antrodia camphorata as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is produced by solid-state cultivation from tissue cultures derived from the fungus Antrodia camphorata. The applicant intends to market the NF in food supplements at a maximum dose of 990 mg per day. The target population is the general population. The NF mainly consists of carbohydrates, proteins and fats, and it contains numerous constituents, such as β-glucans, antroquinonol and triterpenoids. Taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day repeated dose toxicity study and a prenatal developmental toxicity study performed with the NF, the Panel derives a safe level of 16.5 mg/kg body weight per day. The Panel concludes that the NF, freeze-dried mycelia of Antrodia camphorata, is safe at the proposed use level for individuals aged 14 years and above.

2022 - Safety of frozen and freeze-dried formulations of the lesser mealworm (Alphitobius diaperinus larva) as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on frozen and dried formulations from whole lesser mealworm (Alphitobius diaperinus larva) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The term lesser mealworm refers to the larval form of the insect species Alphitobius diaperinus. The NF comprises the frozen and freeze-dried formulations of the lesser mealworm as whole or in the form of a paste or powder. Apart from water in the frozen formulations (whole, paste), the main components of the NF are crude protein and fat, besides smaller amounts of digestible carbohydrates and fibre (chitin). The Panel notes that the levels of contaminants in the NF depend on the concentration of such substances in the insect feed. The Panel notes furthermore that the true protein levels in the NF are overestimated when using the nitrogen-to-protein conversion factor of 6.25, due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF formulations added as an ingredient to various food products such as cereal bars, pasta, meat imitates and bakery products. The target population is the general population. Additionally, the applicant proposed to use the NF as a food supplement in adults. The Panel notes that, considering that the NF will not be the sole source of dietary protein, and the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The submitted subchronic 90-day toxicity study with the NF as testing material did not raise safety concerns. The Panel considers that the consumption of the NF may induce primary sensitisation and allergic reactions to lesser mealworm proteins and may cause allergic reactions in subjects with allergy to crustaceans and dust mites. Additionally, allergens from the feed may end up in the NF. Allergenicity aside, the Panel concludes that the NF is safe under the proposed uses and use levels.

2022 - Safety of hydrothermally treated kernels from edible Jatropha curcas L. (Chuta) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on hydrothermally treated kernels from edible Jatropha curcas (Chuta) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Although Jatropha curcas is generally considered a toxic plant due to the presence of phorbol esters (PEs), edible varieties exist in Central America. The applicant has developed a breeding programme for an edible cultivar and proposes the kernels from this cultivar as an NF as whole kernels or fragments thereof to be used as a snack or as a food ingredient. Procedures are in place to avoid commingling with non-edible kernels, with the last steps being the analytical control of PEs concentrations in all produced batches. The Panel considers that the production process of the NF is sufficiently described and that the information provided on the composition of the NF is sufficient for its characterisation. Components of the NF were tested for genotoxicity applying the standard in vitro test battery and no genotoxic concerns have been identified. In a conservative scenario for exposure to PEs from the NF, it was assumed that all kernels contain PEs at the level of detection of the analytical method. When comparing the estimated maximum exposure to PEs with a reference point from a subchronic study in pigs, a margin of exposure ≥ 900 is obtained, which is considered sufficiently large. The presence of anti-nutritional factors does not pose safety concerns as they are within the ranges found in vegetables. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of iron milk proteinate as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of iron from this source in the context of Directive 2002/46/EC [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on iron milk proteinate as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and to address the bioavailability of iron from this source in the context of Directive 2002/46/EC. The NF is a complex of iron, casein and phosphate, which is produced from iron salts (i.e. ferric chloride or ferric sulfate), sodium caseinate and potassium orthophosphate. The NF is proposed by the applicant to be used as a source of iron, of which the NF contains 2–4%. The applicant intends to market the NF as an ingredient in a number of food categories; in food supplements, in total diet replacement for weight control and in foods for special medical purposes. The Panel considers that, taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. The studies provided for ADME and bioavailability indicate that iron from the NF is bioavailable. Overall, the evidence indicates that upon ingestion the NF undergoes digestion into small peptides to yield iron-bound caseinophosphopeptides that are normal constituents of the human diet, and that the iron from the NF does not bypass the homeostatic control of iron as a nutrient. The Panel concludes that the NF, iron milk proteinate, is safe under the proposed conditions of use. The Panel also concludes that the NF is a source from which iron is bioavailable.

2022 - Safety of lacto-N-tetraose (LNT) produced by derivative strains of Escherichia coli BL21 (DE3) as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on lacto-N-tetraose (LNT) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a powdered mixture mainly composed of the human-identical milk oligosaccharide (HiMO) LNT, but it also contains d-lactose, lacto-N-triose II and para-lacto-N-hexaose, and a small fraction of other related saccharides. The NF is produced by fermentation with two genetically modified strains of Escherichia coli BL21 (DE3), the production strain and the optional degradation strain. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant and follow-on formula, food for infants and young children, food for special medical purposes and food supplements. The target population is the general population. The anticipated daily intake of LNT from the NF at the maximum proposed use levels does not exceed the intake level of naturally occurring LNT in breastfed infants on a body weight basis. The intake of LNT in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to LNT is also considered of no safety concern. Food supplements are not intended to be used if other foods with added LNT or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of oil from Schizochytrium sp. (strain ATCC 20889) for use in infant and follow-on formula as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF which is the subject of the application is an oil rich in docosahexaenoic acid (DHA) that is produced by the microalgae Schizochytrium sp. (strain ATCC-20889). The applicant proposed to add the NF in infant formulae (IF) and follow-on formulae (FOF) at use levels in accordance with Regulation (EU) No 609/2013. The evidence provided by the applicant does not demonstrate to which species the strain Schizochytrium sp. ATCC 20889 belongs. As the source organism of the NF is not characterised at species level, no assessment for inclusion in the Qualified Presumption of Safety (QPS) list can be performed by EFSA. Marine biotoxins (including cyanotoxins) in the NF were below their limits of quantification. However, since it is unknown to which species the strain Schizochytrium sp. ATCC 20889 belongs, the concern that this strain has the potential to produce other toxins remains. No toxicological studies with the NF were provided by the applicant. Toxicological studies are available with DHA-rich algal oils produced from other strains of Schizochytrium sp. However, the Panel considers that those toxicological studies cannot be used to establish the safety of the oil produced by the strain which is under assessment in this application (Schizochytrium sp. ATCC 20889). Therefore, based on the information provided by the applicant, the Panel concludes that the safety of the NF has not been established.

2022 - Safety of partially defatted house cricket (Acheta domesticus) powder as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Azzollini, D.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on defatted house cricket (Acheta domesticus) powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is proposed as dry powder. The main components of the NF are protein, fat and fibre (chitin). The Panel notes that the concentration of contaminants in the NF depends on the occurrence levels of these substances in the insect feed. The Panel further notes that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf life. The NF has a high protein content, although the true protein levels are overestimated when using the nitrogen-to-protein conversion factor of 6.25 due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF as food ingredient in a number of food products. The target population proposed by the applicant is the general population. The Panel notes that, considering the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The Panel notes that no genotoxicity and no subchronic toxicity studies with the NF were provided by the applicant. Considering that no safety concerns arise from the history of use of the source of the NF (A. domesticus), and the limited difference between the whole insect and the partially defatted NF, the Panel identified no other safety concerns than allergenicity. The Panel considers that the consumption of the NF might trigger primary sensitisation to A. domesticus proteins and may cause allergic reactions in subjects allergic to crustaceans, mites and molluscs. Additionally, allergens from the feed may end up in the NF. That aside, the Panel concludes that the NF is safe under the proposed uses and use levels.

2022 - Safety of pea and rice protein fermented by Shiitake (Lentinula edodes) mycelia as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on pea and rice protein fermented by Shiitake mushroom (Lentinula edodes) mycelia as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a mixture of fermented pea and rice protein concentrates (65% and 35%, respectively). The NF is proposed to be used as a food ingredient in specific food categories. The target population is the general population. The major constituent of this NF is protein (≥ 75% dry weight), which is well digestible and provides sufficient amounts of essential amino acids. Although a tolerable upper intake level (UL) has not been derived for protein, the protein intake from the NF may nevertheless further contribute to an already high dietary protein intake in Europe. The Panel notes that the cumulative exposure to the nutrients and contaminants analysed does not raise concern. The reported values for the levels of antinutritional factors in the NF are comparable to those in other foodstuffs. The Panel considers that taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. No toxicological studies with the NF were provided by the applicant; however, the Panel considers that no toxicological studies are required for this NF. The NF has the potential capacity to sensitise individuals or to induce allergic reactions in individuals allergic to pea, rice and Shiitake mushroom. However, this risk is expected not to be higher than that resulting from the normal consumption of pea, rice or the fruiting body of the Shiitake mushroom. The Panel considers that the NF is safe at the proposed conditions of use.

2022 - Safety of selenium exposure and limitations of selenoprotein maximization: Molecular and epidemiologic perspectives [Articolo su rivista]
Vinceti, M.; Filippini, T.; Jablonska, E.; Saito, Y.; Wise, L. A.
abstract

Recent evidence from laboratory and epidemiologic studies has shed a different light on selenium health effects and its recommended range of environmental exposure, compared with earlier research. Specifically, epidemiologic studies in Western populations have shown adverse effects of selenium exposure at low levels, sometimes below or slightly above selenium intakes needed to maximize selenoprotein expression and activity. In addition, three recent lines of evidence in molecular and biochemical studies suggest some potential drawbacks associated with selenoprotein maximization: 1) the possibility that selenoprotein upregulation is a compensatory response to oxidative challenge, induced by selenium itself or other oxidants; 2) the capacity of selenoproteins to trigger tumor growth in some circumstances; and 3) the deleterious metabolic effects of selenoproteins and particularly of selenoprotein P. The last observation provides a toxicological basis to explain why in humans selenium intake levels as low as 60 μg/day, still in the range of selenium exposure upregulating selenoprotein expression, might start to increase risk of type 2 diabetes. Overall, these new pieces of evidence from the literature call into question the purported benefit of selenoprotein maximization, and indicate the need to reassess selenium dietary reference values and upper intake level. This reassessment should clarify which range of selenoprotein upregulation follows restoration of adequate selenium availability and which range is driven by a compensatory response to selenium toxicity and oxidative stress.

2022 - Safety of the extension of use of 2’-fucosyllactose (2’-FL) and lacto-N-neotetraose (LNnT) as novel foods in food supplements for infants pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of the extensions of use of the authorised novel foods (NFs) 2’-fucosyllactose (2’-FL) and lacto-N-neotetraose (LNnT) in food supplements (FS) for infants pursuant to Regulation (EU) 2015/2283. The NFs are produced by fermentation with genetically modified strains of Escherichia coli K-12 and already included in the EU list of NFs. The applicant stated that no changes in the production process or the identity of the NFs occurred. The applicant proposes an extension of use of the NF containing 2’-FL in FS intended for infants (< 1 year), at a maximum use level of 1.2 g/day. The applicant also proposes an extension of use of LNnT in FS intended for infants, at a maximum use level of 0.6 g/day. The intake of 2’-FL per kg body weight from the proposed maximum use levels in FS for infants is lower than the lowest estimated mean intake of naturally occurring 2’-FL from human milk. Similarly, the intake of LNnT per kg body weight is lower than the highest estimated mean intake of naturally occurring 2’-FL from human milk. Furthermore, the Panel notes that the proposed uses of 2’-FL in FS for infants are lower than the estimated intake from the already authorised uses of the NF for the same population group. The Panel also notes that the proposed uses of LNnT in FS for infants are similar to the estimated intake from the already authorised uses of the NF for the same population group. The Panel concludes that the use of the NFs containing 2’-FL or LNnT in FS for infants is safe under the proposed conditions of use.

2022 - Safety of the extension of use of 2’-fucosyllactose/difucosyllactose (2’-FL/DFL) mixture and lacto-N-tetraose (LNT) as novel foods in food supplements for infants pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; Loveren, H. V.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of the extensions of use of the authorised novel foods (NFs) 2’-fucosyllactose/difucosyllactose (2’-FL/DFL) mixture and lacto-N-tetraose (LNT) in food supplements (FS) for infants pursuant to Regulation (EU) 2015/2283. The NFs are produced by fermentation with genetically modified strains of Escherichia coli K-12 DH1 and already included in the EU list of NF. The applicant stated that no changes in the production process or the identity of the NFs occurred. The applicant proposes an extension of use of the NF containing 2’-FL/DFL mixture in FS intended for infants (< 1 year), at a maximum use level of 1.6 g/day for infants ≤ 6 months and up to 1.2 g/day for infants > 6 months. The applicant also proposes an extension of use of LNT in FS intended for infants (< 1 year), at a maximum use level of 0.8 g/day for infants ≤ 6 months and up to 0.6 g/day for infants > 6 months. The intake per kg body weight of 2’-FL/DFL and LNT from the proposed maximum use levels of the respective NFs in FS for infants does not exceed the lowest estimated mean intake of naturally occurring 2’-FL/DFL and it is similar to the highest estimated mean intake of LNT by breastfed infants. In addition, the Panel notes that the proposed uses of the NFs in FS for infants result in lower maximum daily intakes than those from the already authorised uses of the NFs for the same population group. The Panel concludes that the uses of the NFs containing either 2’-FL/DFL or LNT in FS for infants are safe under the proposed conditions of use.

2022 - Safety of the extension of use of galacto-oligosaccharides (GOS) as a novel food in food for special medical purposes pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the extension of use of galacto-oligosaccharides (GOS) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF (β-GOS) is produced from milk lactose using a β-galactosidase derived from Bifidobacterium bifidum and it is proposed to be used in food for special medical purposes (FSMP). The target population is the general population from 4 years of age onwards. GOS produced according to the same production process are already authorised and included in the EU Union list of novel foods. The applicant stated that the maximum daily intake from the use in FSMP is 8.25 g GOS. GOS are already authorised for use in food supplements up to a daily dose of 16.2 g. FSMP containing GOS are not intended to be used if food supplements containing GOS are consumed on the same day. The information provided on the proposed use levels and anticipated intake does not raise safety concerns. The Panel concludes that the proposed extension of use of GOS in FSMP is safe under the proposed conditions of use.

2022 - Safety of vitamin D2 mushroom powder as a Novel food pursuant to Regulation (EU) 2015/2283 (NF 2019/1471) [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Gerazova-Efremova, K.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on vitamin D2 mushroom powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is produced from Agaricus bisporus mushroom that has been exposed to ultraviolet (UV) irradiation to induce the conversion of provitamin D2 (ergosterol) to vitamin D2 (ergocalciferol). The NF contains levels of vitamin D in the form of vitamin D2 in the range of 125–375 µg/g. The information provided on the production process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF as an ingredient in a variety of foods and beverages in amounts that result in either 1.125 or 2.25 µg vitamin D2 per 100 g or 100 mL of the food as consumed. The applicant also intends to add the NF in food supplements, for infants from 7 to 11 months at a maximum of 10 µg vitamin D2/day and of 15 µg vitamin D2/day for individuals aged 1 year or older, as well as in foods for special medical purposes (FSMPs) and total and meal diet replacement for weight control. For the adult population, the maximum intended use level in FSMPs is 15 µg vitamin D2/day and 5 µg vitamin D2/meal in total and meal diet replacement for weight control. The Panel concludes that the NF is safe under the proposed conditions of use. The Panel notes uncertainty regarding the calculated combined exposures to vitamin D for the general population, given the fact that the range of foods fortified with vitamin D has increased over the years, as well as the marketing of high-dose vitamin D supplements.

2022 - Safety of zinc l-carnosine as a Novel food pursuant to Regulation (EU) 2015/2283 and the bioavailability of zinc from this source in the context of Directive 2002/46/EC on food supplements [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on zinc l-carnosine as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and as a source of zinc for use in food supplements. The NF is produced by chemical synthesis and is proposed to be used in food supplements as a source of zinc. The target population proposed by the applicant is individuals above the age of 12, excluding pregnant and lactating women. The NF which is the subject of the application is a chelate-complex, formed between Zn2+ and l-carnosine and is present as a mixture of a monomer and a dimer. The material is a powder with particulate nature and is insoluble in water at neutral pH. No relevant data using an existing zinc source as comparator have been made available by the applicant and the actual bioavailability of the zinc provided by the NF at the proposed use levels remains uncharacterised. Owing to the lack of a correct characterisation of the fraction of small particles, including nanoparticles of the NF, the Panel is not in the position to evaluate specification limits for the size of the constituent particles in the NF. Owing to the lack of information on the size distribution and the physico-chemical properties of the particles constituting the NF, the Panel is not in the position to confirm whether the ADME studies and the toxicological studies provided by the applicant are appropriate to assess the safety of the NF. The Panel concludes that the NF is absorbed and provides zinc, but as it is in an insufficiently characterised particulate form, its safety has not been established and the bioavailability has not been determined.

2022 - Safety of β-hydroxybutyrate salts as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Albert, O.; Goumperis, T.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on β-hydroxybutyrate (BHB) salts as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of sodium, magnesium and calcium BHB salts, and is proposed to be used by adults as a food ingredient in a number of food categories and as food supplement. The data provided by the applicant about the identity, the production process and the compositional data of the NF over the course of the risk assessment period were overall considered unsatisfactory. The Panel noted inconsistencies in the reporting of the test item used in the subchronic toxicity study and human studies provided by the applicant. Owing to these deficiencies, the Panel cannot establish a safe intake level of the NF. The Panel concludes that the safety of the NF has not been established.

2022 - Scientific advice related to nutrient profiling for the development of harmonised mandatory front-of-pack nutrition labelling and the setting of nutrient profiles for restricting nutrition and health claims on foods [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver scientific advice related to nutrient profiling for the development of harmonised mandatory front-of-pack nutrition labelling and the setting of nutrient profiles for restricting nutrition and health claims on foods. This Opinion is based on systematic reviews and meta-analyses of human studies on nutritionally adequate diets, data from the Global Burden of Disease framework, clinical practice guidelines, previous EFSA opinions and the priorities set by EU Member States in the context of their Food-Based Dietary Guidelines and associated nutrient/food intake recommendations. Relevant publications were retrieved through comprehensive searches in PubMed. The nutrients included in the assessment are those likely to be consumed in excess or in inadequate amounts in a majority of European countries. Food groups with important roles in European diets have been considered. The Panel concludes that dietary intakes of saturated fatty acids (SFA), sodium and added/free sugars are above, and intakes of dietary fibre and potassium below, current dietary recommendations in a majority of European populations. As excess intakes of SFAs, sodium and added/free sugars and inadequate intakes of dietary fibre and potassium are associated with adverse health effects, they could be included in nutrient profiling models. Energy could be included because a reduction in energy intake is of public health importance for European populations. In food group/category-based nutrient profiling models, total fat could replace energy in most food groups owing to its high-energy density, while the energy density of food groups with low or no fat content may be well accounted for by the inclusion of (added/free) sugars. Some nutrients may be included in nutrient profiling models for reasons other than their public health importance, e.g. as a proxy for other nutrients of public health importance, or to allow for a better discrimination of foods within the same food category.

2022 - Selenium Species in Cerebrospinal Fluid and Hippocampal Volume among Individuals with Mild Cognitive Impairment [Articolo su rivista]
Vinceti, Marco; Balboni, Erica; Filippini, Tommaso; Wise, Lauren A; Nocetti, Luca; Eichmüller, Marcel; Zamboni, Giovanna; Chiari, Annalisa; Michalke, Bernhard
abstract

2022 - Selenium and its association with oxidative stress and genotoxicity risk in a healthy Italian population: a cross sectional study [Abstract in Atti di Convegno]
Urbano, Teresa; Filippini, Tommaso; Malavolti, Marcella; Fustinoni, Silvia; Michalke, Bernhard; Vinceti, Marco
abstract

Background Selenium is present in trace amounts and different chemical forms in living organisms, which may beneficially and adversely affect cellular redox status. 8-oxo-7,8-dihydro-2’deoxyguanosine (8-oxodG) is an oxidized derivative of deoxyguanosine and a sensitive biomarker of oxidative stress and genotoxicity in biological systems. In this study, we aimed to determine if selenium exposure in a population in Northern Italy may be associated with 8-oxodG levels in urine and if sex and other factors may influence such association. Methods/Approach We recruited 137 substantially healthy and non-smoking blood donors from the Reggio Emilia province at the Transfusion Medicine Unit of the Reggio Emilia Hospital. Their median age was 48.2 years, and the recruitment occurred 2017-19. We assessed selenium in urine and serum, and urinary 8-oxodG levels. We also speciated selenium in serum. We used cubic spline regression analyses to investigate the association between selenium matrices and urinary content of 8-oxodG/g creatinine. Results Median urinary selenium and 8-oxodG levels were 22.02 µg/L and 3.21 µg/g creatinine, respectively. Median total serum concentrations were 116.50 µg/L in the 104 individuals for which a serum sample was available. We found that urinary selenium positively correlated with 8-oxodG levels in men, while in women an inverted U-shaped association emerged. Total organic selenium and selenoprotein P levels were positively associated with 8-oxodG until 100 µg/L and then the association became slightly inverse in both sexes. In males, glutathione peroxidase-bound selenium, selenomethionine and human serum albumin-bound selenium were positively correlated with 8-oxodG, while negative associations emerged for inorganic selenium species. In females, positive associations, though slightly positive, emerged for organic species. Conclusions Our study highlights the different role played by selenium compounds, suggesting that organic selenium - but not its inorganic species - may exert genotoxic effects, and that sex considerably influences the risk of oxidative stress and genotoxicity associated with selenium exposure.

2022 - Selenium status and immunity [Articolo su rivista]
Fairweather-Tait, S. J.; Filippini, T.; Vinceti, M.
abstract

Selenium is found at the active centre of twenty-five selenoproteins which have a variety of roles, including the well-characterised function of antioxidant defense, but it also is claimed to be involved in the immune system. However, due to limited and conflicting data for different parameters of immune function, intakes of selenium that have an influence on immune function are uncertain. This review covers the relationship between selenium and immune function in man, focusing on the highest level of evidence, namely that generated by randomized controlled trials (RCTs), in which the effect of selective administration of selenium, in foods or a supplement, on immune function was assessed. A total of nine RCTs were identified from a systematic search of the literature, and some of these trials reported effects on T and NK cells, which were dependent on the dose and form of selenium administered, but little effect of selenium on humoral immunity. There is clearly a need to undertake dose-response analysis of cellular immunity data in order to derive quantitative relationships between selenium intake and measures of immune function. Overall, limited effects on immunity emerged from experimental studies in humans, though additional investigation on the potential influence of selenium status on cellular immunity appears to be warranted.

2022 - Selenocompounds and neurological disease [Abstract in Atti di Convegno]
Vinceti, M.; Ferrante, M; Filippini, T.; Urbano, T.
abstract

2022 - Selenoprotein P Concentrations in the Cerebrospinal Fluid and Serum of Individuals Affected by Amyotrophic Lateral Sclerosis, Mild Cognitive Impairment and Alzheimer’s Dementia [Articolo su rivista]
Urbano, Teresa; Vinceti, Marco; Mandrioli, Jessica; Chiari, Annalisa; Filippini, Tommaso; Bedin, Roberta; Tondelli, Manuela; Simonini, Cecilia; Zamboni, Giovanna; Shimizu, Misaki; Saito, Yoshiro
abstract

Selenoprotein P, a selenium-transporter protein, has been hypothesized to play a role in the etiology of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's dementia (AD). However, data in humans are scarce and largely confined to autoptic samples. In this case-control study, we determined selenoprotein P concentrations in both the cerebrospinal fluid (CSF) and the serum of 50 individuals diagnosed with ALS, 30 with AD, 54 with mild cognitive impairment (MCI) and of 30 controls, using sandwich enzyme-linked immunosorbent assay (ELISA) methods. We found a positive and generally linear association between CSF and serum selenoprotein P concentrations in all groups. CSF selenoprotein P and biomarkers of neurodegeneration were positively associated in AD, while for MCI, we found an inverted-U-shaped relation. CSF selenoprotein P concentrations were higher in AD and MCI than in ALS and controls, while in serum, the highest concentrations were found in MCI and ALS. Logistic and cubic spline regression analyses showed an inverse association between CSF selenoprotein P levels and ALS risk, and a positive association for AD risk, while an inverted-U-shaped relation with MCI risk emerged. Conversely, serum selenoprotein P concentrations were positively associated with risk of all conditions but only in their lower range. Overall, these findings indicate some abnormalities of selenoprotein P concentrations in both the central nervous system and blood associated with ALS and neurocognitive disorders, though in different directions. These alterations may reflect either phenomena of etiologic relevance or disease-induced alterations of nutritional and metabolic status.

2022 - Seroprevalence Survey of Anti-SARS-CoV-2 Antibodies in a Population of Emilia-Romagna Region, Northern Italy [Articolo su rivista]
Paduano, Stefania; Galante, Pasquale; Berselli, Nausicaa; Ugolotti, Luca; Modenese, Alberto; Poggi, Alessandro; Malavolti, Marcella; Turchi, Sara; Marchesi, Isabella; Vivoli, Roberto; Perlini, Paola; Bellucci, Rossana; Gobba, Fabriziomaria; Vinceti, Marco; Filippini, Tommaso; Bargellini, Annalisa
abstract

taly was the first Western European country to be severely hit by the COVID-19 pandemic. Variations in seroprevalence rates were reported according to geographical and temporal differences of previous surveys, as well as depending on demographic and occupational factors. In this cross-sectional study, we evaluated the prevalence of anti-SARS-CoV-2 antibodies in a population of the Emilia-Romagna region in Northern Italy after the first wave in the period from 26 September 2020–26 March 2021. We included 5128 subjects who voluntarily underwent serological tests to determine anti-SARS-CoV-2 antibody positivity, including both self-referred individuals (24.2%) and workers adhering to company screening programs (76.8%). Overall, seroprevalence was 11.3%, higher in self-referred (13.8%) than employed-referred (10.5%) individuals. A slightly higher seroprevalence emerged in women compared to men (12.3% and 10.7%), as well as in the extreme age categories (18.6% for 60–69 years, 18.0% for ≥70 years, and 17.1% for <20 years compared to 7.6% for 20–39 years). Healthcare professionals showed the highest prevalence of seropositivity (22.9%), followed by workers in direct contact with customers, such as the communication, finance, and tourism sectors (15.7%). Overall subgroups seroprevalence increased compared to the first wave data but the trends agreed between the first and subsequent waves, except for an increase in the younger age group and in the sector in direct contact with customers. Among the occupational categories, our study confirms that healthcare workers and workers in the sports sector were at high risk of exposure to SARS-CoV-2.

2022 - Sodium Intake and Risk of Hypertension: A Systematic Review and Dose-Response Meta-analysis of Observational Cohort Studies [Articolo su rivista]
Filippini, Tommaso; Malavolti, Marcella; Whelton, Paul K; Vinceti, Marco
abstract

Purpose of the review: To assess the relationship between sodium intake and hypertension risk in cohort studies, based on a systematic review up to January 21, 2022, that also employed a dose-response meta-analysis. Recent findings: Dose-response analysis of available cohort studies (n = 11), using a dietary intake or urinary sodium excretion of 2 g/day as the reference category, showed an excess risk starting at 3 g/day. However, we found a linear relationship across the entire range of sodium exposure in an analysis restricted to studies that used 24 h urinary sodium excretion information and had a low risk of bias. This review confirms prior findings based on experimental studies and identified an almost linear relationship between sodium intake/excretion and hypertension risk in cohort studies, reinforcing the validity of recommendations to prevent cardiovascular disease through the reduction of sodium intake in both normotensive and hypertensive adults.

2022 - Sodium intake and cardiovascular diseases: a systematic review and dose–response meta‑analysis [Abstract in Atti di Convegno]
Malavolti, M; Filippini, T; Urbano, T; Vinceti, M.
abstract

2022 - Statement on safety of cannabidiol as a novel food: data gaps and uncertainties [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; Trezza, V.; van Loveren, H.; Albert, O.; Dumas, C.; Germini, A.; Gelbmann, W.; Kass, G.; Kouloura, E.; Noriega Fernandez, E.; Rossi, A.; Knutsen, H. K.
abstract

The European Commission has determined that cannabidiol (CBD) can be considered as a novel food (NF), and currently, 19 applications are under assessment at EFSA. While assessing these, it has become clear that there are knowledge gaps that need to be addressed before a conclusion on the safety of CBD can be reached. Consequently, EFSA has issued this statement, summarising the state of knowledge on the safety of CBD consumption and highlighting areas where more data are needed. Literature searches for both animal and human studies have been conducted to identify safety concerns. Many human studies have been carried out with Epidyolex®, a CBD drug authorised to treat refractory epilepsies. In the context of medical conditions, adverse effects are tolerated if the benefit outweighs the adverse effect. This is, however, not acceptable when considering CBD as a NF. Furthermore, most of the human data referred to in the CBD applications investigated the efficacy of Epidyolex (or CBD) at therapeutic doses. No NOAEL could be identified from these studies. Given the complexity and importance of CBD receptors and pathways, interactions need to be taken into account when considering CBD as a NF. The effects on drug metabolism need to be clarified. Toxicokinetics in different matrices, the half-life and accumulation need to be examined. The effect of CBD on liver, gastrointestinal tract, endocrine system, nervous system and on psychological function needs to be clarified. Studies in animals show significant reproductive toxicity, and the extent to which this occurs in humans generally and in women of child-bearing age specifically needs to be assessed. Considering the significant uncertainties and data gaps, the Panel concludes that the safety of CBD as a NF cannot currently be established.

2022 - Substantial impact of mobility restrictions on reducing COVID-19 incidence in Italy in 2020 [Articolo su rivista]
Vinceti, Marco; Balboni, Erica; Rothman, Kenneth J; Teggi, Sergio; Bellino, Stefania; Pezzotti, Patrizio; Ferrari, Fabrizio; Orsini, Nicola; Filippini, Tommaso
abstract

Italy was the first country after China to be severely affected by the COVID-19 pandemic, in early 2020. The country responded swiftly to the outbreak with a nationwide two-step lockdown, the first one light, and the second one tight. By analysing 2020 national mobile phone movements, we assessed how lockdown compliance influenced its efficacy.

2022 - The questionnaire design process in the European Human Biomonitoring Initiative (HBM4EU) [Articolo su rivista]
Gonzalez-Alzaga, B.; Hernandez, A. F.; Kim Pack, L.; Iavicoli, I.; Tolonen, H.; Santonen, T.; Vinceti, M.; Filippini, T.; Moshammer, H.; Probst- Hensch, N.; Kolossa-Gehring, M.; Lacasana, M.
abstract

Background: Designing questionnaires is a key point of epidemiological studies assessing human exposure to chemicals. The lack of validated questionnaires can lead to the use of previously developed and sub-optimally adapted questionnaires, which may result in information biases that affect the study's validity. On this ground, a multidisciplinary group of researchers developed a series of tools to support data collection within the HBM4EU initiative. The objective of this paper is to share the process of developing HBM4EU questionnaires, as well as to provide researchers with harmonized procedures that could help them to design future questionnaires to assess environmental exposures. Methods: In the frame of the work package on survey design and fieldwork of the HBM4EU, researchers carried out procedures necessary for the development of quality questionnaires and related data collection tools. These procedures consisted of a systematic search to identify questionnaires used in previous human biomonitoring (HBM) studies, as well as the development of a checklist and evaluation sheet to assess the questionnaires identified. The results of these evaluations were taken into consideration for the development of the final questionnaires. Results: The main points covered by each of the sections included in HBM4EU questionnaires are described and discussed in detail. Additional tools developed for data collection in the HBM4EU (e.g. non-responder questionnaire, satisfaction questionnaire, matrix-specific questionnaire) are also addressed. Special attention is paid to the limitations faced and hurdles overcome during the process of questionnaire development. Conclusions: Designing questionnaires for use in HBM studies requires substantial effort by a multidisciplinary team to guarantee that the quality of the information collected meets the study's objectives. The process of questionnaire development described herein will contribute to improve the harmonization of HBM studies within the social and environmental context of the EU countries.

2022 - Tolerable upper intake level for dietary sugars [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Adan, R.; Emmett, P.; Galli, C.; Kersting, M.; Moynihan, P.; Tappy, L.; Ciccolallo, L.; de Sesmaisons-Lecarre, A.; Fabiani, L.; Horvath, Z.; Martino, L.; Munoz Guajardo, I.; Valtuena Martinez, S.; Vinceti, M.
abstract

Following a request from five European Nordic countries, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was tasked to provide scientific advice on a tolerable upper intake level (UL) or a safe level of intake for dietary (total/added/free) sugars based on available data on chronic metabolic diseases, pregnancy-related endpoints and dental caries. Specific sugar types (fructose) and sources of sugars were also addressed. The intake of dietary sugars is a well-established hazard in relation to dental caries in humans. Based on a systematic review of the literature, prospective cohort studies do not support a positive relationship between the intake of dietary sugars, in isocaloric exchange with other macronutrients, and any of the chronic metabolic diseases or pregnancy-related endpoints assessed. Based on randomised control trials on surrogate disease endpoints, there is evidence for a positive and causal relationship between the intake of added/free sugars and risk of some chronic metabolic diseases: The level of certainty is moderate for obesity and dyslipidaemia (> 50–75% probability), low for non-alcoholic fatty liver disease and type 2 diabetes (> 15–50% probability) and very low for hypertension (0–15% probability). Health effects of added vs. free sugars could not be compared. A level of sugars intake at which the risk of dental caries/chronic metabolic diseases is not increased could not be identified over the range of observed intakes, and thus, a UL or a safe level of intake could not be set. Based on available data and related uncertainties, the intake of added and free sugars should be as low as possible in the context of a nutritionally adequate diet. Decreasing the intake of added and free sugars would decrease the intake of total sugars to a similar extent. This opinion can assist EU Member States in setting national goals/recommendations.

2022 - Zinc and selenium supplementation in COVID-19 prevention and treatment: a systematic review of the experimental studies [Articolo su rivista]
Balboni, E.; Zagnoli, F.; Filippini, T.; Fairweather-Tait, S. J.; Vinceti, M.
abstract

Background and aim: The COVID-19 pandemic has severely affected the world's population in the last two years. Along with non-pharmacological public health interventions, major efforts have also been made to identify effective drugs or active substances for COVID-19 prevention and treatment. These include, among many others, the trace elements zinc and selenium, based on laboratory studies and some observational human studies. However, both of these study designs are not adequate to identify and approve treatments in human medicine, and experimental studies in the form of randomized controlled trials are needed to demonstrate the effectiveness and the safety of any interventions. Methods: We undertook a systematic review in which we searched for published and unpublished clinical trials using zinc or selenium supplementation to treat or prevent COVID-19 in the Pubmed, Scopus and ClinicalTrials databases up to 10 January 2022. Results: Amongst the published studies, we did not find any trial with selenium, whereas we retrieved four eligible randomized clinical trials using zinc supplementation, only one of which was double-blind. One of these trials looked at the effect of the intervention on the rate of new SARS-CoV-2 infections, and three at the COVID-19 clinical outcome in already infected individuals. The study populations of the four trials were very heterogeneous, ranging from uninfected individuals to those hospitalized for COVID-19. Only two studies investigated zinc alone in the intervention arm with no differences in the endpoints. The other two studies examined zinc in association with one or more drugs and supplements in the intervention arm, therefore making it impossible to disentangle any specific effects of the element. In addition, we identified 22 unpublished ongoing clinical trials, 19 on zinc, one on selenium and two on both elements. Conclusion: No trials investigated the effect of selenium supplementation on COVID-19, while the very few studies on the effects of zinc supplementation did not confirm efficacy. Therefore, preventive or therapeutic interventions against COVID-19 based on zinc or selenium supplementation are currently unjustified, although when the results of the on-going studies are published, this may change our conclusion.

2021 - A systematic review and dose-response meta-analysis of exposure to environmental selenium and the risk of type 2 diabetes in nonexperimental studies [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Wise, Lauren A; Rothman, Kenneth J
abstract

Accumulating evidence from both experimental and nonexperimental human studies in the last 15 years indicates that exposure to high levels of the trace element selenium increases the risk of type 2 diabetes. However, the relation of dose to effect is not well understood because randomized controlled trials used only one dose (200 mug/day) of selenium supplementation. While no new trial on this topic has been published since 2018, several nonexperimental studies have appeared. We therefore updated a previous meta-analysis to include recently published observational studies, and incorporated the recently developed one-stage random-effects model to display the dose-response relation between selenium and diabetes. We retrieved 34 potentially eligible nonexperimental studies on selenium and diabetes risk up to April 15, 2021. The bulk of the evidence indicates a direct relation between blood, dietary and urinary levels of selenium and risk of diabetes, but not with nail selenium, which is considered a less reliable biomarker. The association was nonlinear, with risk increasing above 80 mug/day of dietary selenium. Whole blood/plasma/serum selenium concentrations of 160 mug/L corresponded to a risk ratio of 1.96 (95% CI 1.27-3.03) compared with a concentration of 90 mug/L (approximately 60 mug of daily selenium intake). The cohort studies, which are less susceptible to reverse causation bias, indicated increased risk for both blood and urine selenium levels and dietary selenium intake, whereas no such pattern emerged from studies relying on nail selenium content. Overall, the nonexperimental studies agree with findings from randomized controlled trials, indicating that moderate to high levels of selenium exposure are associated with increased risk for type 2 diabetes.

2021 - Affron® and increase in positive mood: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Bresson, Jean-Louis; Siani, Alfonso
abstract

Following an application from Pharmactive Biotech Products, S.L. submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Spain, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to affron (R) and contributes to maintain a healthy mood. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is affron (R), an aqueous saffron extract with a content of the sum of crocins and safranal typically between 3.5% and 3.9%. The Panel notes that affron (R) is sufficiently characterised. The claimed effect proposed by the applicant is 'contributes to maintain a healthy mood'. The Panel notes that increase in positive mood is a beneficial physiological effect for individuals with low mood or anxiety. One human intervention study showed that consumption of affron (R) at a dose of 28 mg/day for 4 weeks improves mood in a population of adults with low mood. However, the results have not been replicated in other studies. The information supplied by the applicant did not provide evidence for a plausible mechanism by which affron (R) could exert the claimed effect. The Panel concludes that the evidence is insufficient to establish a cause and effect relationship between the consumption of affron (R) and increase in positive mood. (C) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2021 - An assessment of case-fatality and infection-fatality rates of first and second COVID-19 waves in italy [Articolo su rivista]
Filippini, T.; Zagnoli, F.; Bosi, M.; Giannone, M. E.; Marchesi, C.; Vinceti, M.
abstract

Background and aim: The exact COVID-19 severity is still not well defined and it is hotly debated due to a few methodological issues such as the uncertainties about the spread of the SARS-CoV-2 infection. Methods: We investigated COVID-19 case-fatality rate and infection-fatality rate in 2020 in Italy, a country severely affected by the pandemic, basing our assessment on publicly available data, and calculating such measures during the first and second waves. Results: We found that province-specific crude case-fatality rate in the first wave (February-July 2020) had a median value of 12.0%. Data about infection-fatality rate was more difficult to compute, due to large underestimation of SARS-CoV-2 infection during the first wave when asymptomatic individuals were very rarely tested. However, when using reference population-based seroprev-alence data for anti-SARS-CoV-2 antibodies collected in May-July 2020, we computed an infection-fatality rate of 2.2%. During the second wave (Sep-Dec 2020), when SARS-CoV-2 testing was greatly increased and extended to many asymptomatic individuals, we could only compute a ‘hybrid’ case/infection-fatality rate with a value of 2.2%, similar to the infection-fatality rate of the first wave. Conclusions: Overall, this study al-lowed to assess the COVID-19 case-and infection-fatality rates in Italy before of variant spread and vaccine availability, confirming their high values compared with other airborne infections like influenza. Our findings for Italy were similar to those characterizing other Western European countries.

2021 - Anti-SARS-CoV-2 antibodies frequency in non-Health Care Workers in a highly industrialized province of northern Italy [Relazione in Atti di Convegno]
Modenese, Alberto; Mazzoli, Tommaso; Berselli, Nausicaa; Ferrari, Davide; Bargellini, Annalisa; Borella, Paola; Filippini, Tommaso; Marchesi, Isabella; Paduano, Stefania; Vinceti, Marco; Gobba, Fabriziomaria
abstract

2021 - Artificial light at night and breast cancer risk: A systematic review and dose-response meta-analysis [Abstract in Rivista]
Urbano, Teresa; Vinceti, Marco; Wise, Lauren Anne; Filippini, Tommaso
abstract

BACKGROUND AND AIM: Artificial lightning has been suggested to be one of the environmental risk factor of breast cancer onset and progression, based on epidemiologic evidence and biological plausibility. Possible mechanisms include DNA damage, impairment of melatonin and estrogens secretion, inflammation, and metabolic function. METHODS: We performed a systematic review of the epidemiological studies examining the association between light-at-night (LAN) exposure and breast cancer risk and we modeled the shape of the relation using a dose-response meta-analysis. After performing an online literature search up to March 21, 2021, we retrieved 16 eligible publications, including eight cohort and eight case-control studies. RESULTS:In analyses comparing highest versus lowest LAN exposure, there was a positive association between LAN exposure and disease risk (risk ratio (RR)=1.10, 95% confidence interval (CI): 1.06-1.14), with relatively consistent associations observed in case-control studies (RR=1.14, 95% CI: 0.98-1.34) and cohort studies (RR=1.10, 95% CI: 1.06-1.14). In stratified analyses, RRs were similar for outdoor and indoor LAN exposure, while a stronger RR was observed among premenopausal women, women in the BMI category 20-25 kg/m2, and for estrogen-receptor positive breast cancer. The dose-response meta-analysis, implemented in studies investigating outdoor LAN only (for comparable exposure assessment), indicated a linear association with increasing risk up to 40 nW/cm2/sr after which a plateau was reached, especially among premenopausal women. CONCLUSIONS:Overall, this first review assessing the dose-response relation between LAN and breast cancer generally supports a positive association. KEYWORDS: Light pollution, Cancer and cancer precursors, Environmental epidemiology, Non-chemical stressors

2021 - Association between cadmium and genotoxicity and oxidative stress risk biomarkers in a population of Northern Italy [Abstract in Rivista]
Urbano, Teresa; Filippini, Tommaso; Lasagni, Daniela; De Luca, Tiziana; Sucato, Sabrina; Polledri, Elisa; Malavolti, Marcella; Baraldi, Claudia; Santachiara, Annalisa; Pertinhez, Thelma A.; Baricchi, Roberto; Fustinoni, Silvia; Vinceti, Marco
abstract

Cadmium is a toxic heavy metal exerting several adverse effects in humans, especially for kidney, bone, liver, and cardiovascular system. In particular, genotoxic effects may occur through several epigenetic mechanisms, but a direct genotoxicity has been suggested. 8-oxo-7,8-dihydro-2’deoxyguanosine (8-oxodG) is an oxidized derivative of deoxyguanosine, largely used as biomarker of oxidative stress in urine. In this study, we aimed to assess cadmium levels in a population in Northern Italy, in order to evaluate the correlation between cadmium exposure with different haematological and biochemical parameters, as well as the relationship with 8-oxodG levels. METHODS: We recruited healthy and non-smoking subjects living in the Reggio Emilia province in the period 2017-2019 at the Transfusion Medicine Unit of Santa Maria Nuova Hospital, AUSL-IRCCS of Reggio Emilia, Northern Italy. Urinary cadmium and 8-oxodG, and fasting blood haematological and biochemical parameters were assessed. RESULTS:We eventually recruited 140 participants (mean age 47.4 years). Mean urinary cadmium and 8-oxodG levels were 0.25 µg/L (range: 0.01–1.33 µg/L) and 3.68 µg/g creatinine respectively. All haematological and biochemical parameters were in the normal range. We found a positive association of cadmium concentrations with alanine aminotransferase, total cholesterol, triglyceride, and TSH levels, while a negative one was observed with glycaemia, HDL levels. In addition, we found a strong positive correlation between urinary cadmium and 8-oxodG. CONCLUSIONS:Our study suggests that cadmium exposure is associated with detrimental effects on some haematological and biochemical parameters even at very low levels, generally considered safe for the general population. The positive association between urinary cadmium levels and oxidative stress, as assessed through 8-oxodG levels, highlights the potential role of this heavy metal in causing direct genotoxic effects. We acknowledge the collaboration of Transfusion Medicine Unit-Reggio Emilia Hospital personnel, AVIS-Section of Reggio Emilia staff and volunteers, and all blood donors who participated to this study

2021 - Association between outdoor traffic air pollutants and spread of SARS-CoV-2 pandemic in Modena, Northern Italy [Abstract in Rivista]
Filippini, Tommaso; Bigi, Alessandro; Teggi, Sergio; Bargellini, Annalisa; Vinceti, Marco
abstract

BACKGROUND AND AIM: Italy was the first European country severely affected by the SARS-CoV-2 pandemic, especially during the first wave in the North of the country. In particular, Modena is a city of Emilia-Romagna which is a region entirely included in the Po valley, one of European areas characterized by the heaviest air pollution levels due also to its orography. Previous studies yielded at a regional level suggested that higher air pollutant levels may increase both SARS-CoV-2 infection and mortality. METHODS: In this study, we further investigated the association between air pollutant exposure and spread of the SARS-CoV-2 using data collected from Modena municipality in the period February 2020-April 2021. We used traffic pollutant levels collected from an urban air quality monitoring station in the period January 2020-January 2021, including particulate matter (PM10), nitrogen oxides (NO2 and NOx), benzene, and black carbon (BC). We used a random-effects linear regression model within panel data analysis over the study period and we computed beta correlation coefficients (beta) with 95% confidence interval-CI between mean daily pollutant concentrations and SARS-CoV-2 daily positive cases diagnosed in Modena. RESULTS:We found a positive correlation between all traffic pollutants and SARS-CoV-2 cases, namely for PM10 beta was 1.23 (95%CI 1.00-1.46), lower for NOx (beta=0.66, 95%CI 0.56-0.75), and higher for NO2 (beta=1.95, 95%CI 1.59-2.31), benzene (beta=41.41, 95%CI 36.23-46.59), and BC (beta=5.95, 95%CI 1.19-10.72). CONCLUSIONS:Notwithstanding the limitations of use of aggregated data and potential the residual confounding, these findings seem to support the hypothesis that high levels of air pollution may favor the spread of SARS-CoV-2 infection, or alternatively that they reflect a higher mobility and number of social contacts that favor the spread of the infection. KEYWORDS: Air pollution, Traffic-related, Infectious diseases, Environmental epidemiology, Exposure assessment

2021 - Association of urinary and dietary selenium and of serum selenium species with serum alanine aminotransferase in a healthy italian population [Articolo su rivista]
Urbano, T.; Filippini, T.; Lasagni, D.; De Luca, T.; Grill, P.; Sucato, S.; Polledri, E.; Noumbi, G. D.; Malavolti, M.; Santachiara, A.; Pertinhez, T. A.; Baricchi, R.; Fustinoni, S.; Michalke, B.; Vinceti, M.
abstract

The trace element selenium is of considerable interest due to its toxic and nutritional properties, which markedly differ according to the dose and the chemical form. It has been shown that excess selenium intake increases the risk of type 2 diabetes and, possibly, other metabolic diseases like hyperlipidemia and non-alcoholic fatty liver disease (NAFLD). For the latter, however, epidemiologic evidence is still limited. We carried out a cross-sectional study recruiting 137 healthy blood donors living in Northern Italy and assessed their exposure to selenium through different methods and measuring serum selenium species. We performed linear and spline regression analyses to assess the relation of selenium and its forms with serum alanine aminotransferase (ALT) levels, a marker of NAFLD. Urinary selenium levels were positively and somewhat linearly correlated with ALT (beta regression coefficient (β) 0.11). Conversely, the association of dietary selenium intake with ALT was positive up to 100 µg/day and null above that amount (β 0.03). Total serum selenium was inversely associated with ALT up to 120 µg/L, and slightly positive above that amount. Concerning the different serum selenium species, ALT positively correlated with two organic forms, selenocysteine (β 0.27) and glutathione peroxidase-bound selenium (β 0.09), showed a U-shaped relation with the inorganic tetravalent form, selenite, and an inverse association with human serum albumin-bound selenium (β −0.56). Our results suggest that overall exposure to selenium, and more specifically to some of its chemical forms, is positively associated with ALT, even at levels so far generally considered to be safe. Our findings add to the evidence suggesting that low-dose selenium overexposure is associated with NAFLD.

2021 - Associations between mortality from COVID-19 in two Italian regions and outdoor air pollution as assessed through tropospheric nitrogen dioxide [Articolo su rivista]
Filippini, T.; Rothman, K. J.; Cocchio, S.; Narne, E.; Mantoan, D.; Saia, M.; Goffi, A.; Ferrari, F.; Maffeis, G.; Orsini, N.; Baldo, V.; Vinceti, M.
abstract

After the appearance of COVID-19 in China last December 2019, Italy was the first European country to be severely affected by the outbreak. The first diagnosis in Italy was on February 20, 2020, followed by the establishment of a light and a tight lockdown on February 23 and on March 8, 2020, respectively. The virus spread rapidly, particularly in the North of the country in the ‘Padan Plain’ area, known as one of the most polluted regions in Europe. Air pollution has been recently hypothesized to enhance the clinical severity of SARS-CoV-2 infection, acting through adverse effects on immunity, induction of respiratory and other chronic disease, upregulation of viral receptor ACE-2, and possible pathogen transportation as a virus carrier. We investigated the association between air pollution and subsequent COVID-19 mortality rates within two Italian regions (Veneto and Emilia-Romagna). We estimated ground-level nitrogen dioxide through its tropospheric levels using data available from the Sentinel-5P satellites of the European Space Agency Copernicus Earth Observation Programme before the lockdown. We then examined COVID-19 mortality rates in relation to the nitrogen dioxide levels at three 14-day lag points after the lockdown, namely March 8, 22 and April 5, 2020. Using a multivariable negative binomial regression model, we found an association between nitrogen dioxide and COVID-19 mortality. Although ecological data provide only weak evidence, these findings indicate an association between air pollution levels and COVID-19 severity.

2021 - Associations between urinary and dietary selenium and blood metabolic parameters in a healthy northern italy population [Articolo su rivista]
Urbano, T.; Filippini, T.; Lasagni, D.; De Luca, T.; Sucato, S.; Polledri, E.; Bruzziches, F.; Malavolti, M.; Baraldi, C.; Santachiara, A.; Pertinhez, T. A.; Baricchi, R.; Fustinoni, S.; Vinceti, M.
abstract

Selenium is both an essential nutrient and a highly toxic element, depending on its dose and chemical forms. We aimed to quantify urinary selenium excretion and dietary selenium intake in 137 healthy non-smoking blood donors living in the northern Italian province of Reggio Emilia. We assessed selenium status by determining urinary selenium levels (mean 26.77 µg/L), and by estimating dietary selenium intake (mean 84.09 µg/day) using a validated semi-quantitative food frequency questionnaire. Fasting blood levels of glucose, lipids and thyroid-stimulating hormone were measured using automatized laboratory procedures. Dietary and urinary selenium were correlated (beta coefficient (β) = 0.19). Despite this, the association of the two indicators with health endpoints tended to diverge. Using linear regression analysis adjusted for age, sex, body mass index, cotinine levels and alcohol intake, we observed a positive association between urinary selenium and blood triglyceride (β = 0.14), LDL-cholesterol (β = 0.07) and glucose levels (β = 0.08), and an inverse one with HDL-cholesterol (β = −0.12). Concerning dietary selenium, a slightly positive association could be found with glycemic levels only (β = 0.02), while a negative one emerged for other endpoints. The two selenium indicators showed conflicting and statistically highly imprecise associations with circulating TSH levels. Our findings suggest that higher selenium exposure is adversely associated with blood glucose levels and lipid profile. This is the case even at selenium exposures not exceeding tolerable upper intake levels according to current guidelines.

2021 - Atrial fibrillation and other risk factors for early-onset dementia: an Italian case-control study [Abstract in Rivista]
Filippini, T; Adani, G; Garuti, C; Malavolti, M; Vinceti, G; Zamboni, G; Tondelli, M; Galli, C; Costa, M; Chiari, A; Vinceti, M
abstract

2021 - Back to basics in COVID-19: Antigens and antibodies—Completing the puzzle [Articolo su rivista]
Neagu, M.; Calina, D.; Docea, A. O.; Constantin, C.; Filippini, T.; Vinceti, M.; Drakoulis, N.; Poulas, K.; Nikolouzakis, T. K.; Spandidos, D. A.; Tsatsakis, A.
abstract

The outbreak of the coronavirus disease 2019 (COVID-19) has gathered 1 year of scientific/clinical information. This informational asset should be thoroughly and wisely used in the coming year colliding in a global task force to control this infection. Epidemiology of this infection shows that the available estimates of SARS-CoV-2 infection prevalence largely depended on the availability of molecular testing and the extent of tested population. Within molecular diagnosis, the viability and infectiousness of the virus in the tested samples should be further investigated. Moreover, SARS-CoV-2 has a genetic normal evolution that is a dynamic process. The immune system participates to the counterattack of the viral infection by pathogen elimination, cellular homoeostasis, tissue repair and generation of memory cells that would be reactivated upon a second encounter with the same virus. In all these stages, we still have knowledge to be gathered regarding antibody persistence, protective effects and immunological memory. Moreover, information regarding the intense pro-inflammatory action in severe cases still lacks and this is important in stratifying patients for difficult to treat cases. Without being exhaustive, the review will cover these important issues to be acknowledged to further advance in the battle against the current pandemia.

2021 - Beta-glucans from oats and/or barley in a ready-to-eat cereal manufactured via pressure cooking and reduction of blood-glucose rise after consumption: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Bresson, Jean-Louis; Siani, Alfonso
abstract

Following an application from Nestle S.A. submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to beta-glucans from oats and/or barley in a ready-to-eat cereal manufactured via pressure cooking and reduction of blood glucose rise after consumption. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed is `beta- glucans from oats and/or barley incorporated into ready-to-eat breakfast cereals manufactured via pressure cooking'. The applicant proposed that at least 1.3 g of beta-glucans/ 25 g of available carbohydrates in ready-to-eat breakfast cereals manufactured via pressure cooking should be consumed. Beta-glucans from oats, barley or any combination thereof incorporated into readyto-eat cereals manufactured by pressure cooking, are sufficiently characterised. The claimed effect proposed is `reduction of the blood glucose rise after the meal'. The reduction of post-prandial glycaemic responses (as long as post-prandial insulinaemic responses are not disproportionally increased) may be a beneficial physiological effect. One human intervention study showed an effect of beta-glucans from oats and/or barley, incorporated into breakfast cereals manufactured via pressure cooking at a level of at least 1.2 g/25 g available carbohydrates, on decreasing post-prandial glycaemic responses without disproportionally increasing insulinaemic responses. Dose-response relationships were not tested, and no evidence has been provided that beta-glucans incorporated into cereals processed using pressure cooking would exert a higher effect on post-prandial glucose responses than beta-glucans added to other carbohydrate containing foods. Whereas the effect of beta- glucans in reducing post-prandial blood glucose responses is well established, the evidence provided is insufficient to establish such an effect at doses of 1.3 g beta- glucans per 25 g of available carbohydrate incorporated into ready-to-eat breakfast cereals manufactured via pressure cooking (i.e. either batch cooking or extrusion). (c) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2021 - Blood Pressure Effects of Sodium Reduction: Dose-Response Meta-Analysis of Experimental Studies [Articolo su rivista]
Filippini, Tommaso; Malavolti, Marcella; Whelton, Paul K; Naska, Androniki; Orsini, Nicola; Vinceti, Marco
abstract

2021 - Cadmium exposure and risk of diabetes and prediabetes: A systematic review and dose-response meta-analysis [Articolo su rivista]
Filippini, Tommaso; Wise, Lauren A; Vinceti, Marco
abstract

Background: Cadmium exposure has been associated with increased diabetes risk in several studies, though there is still considerable debate about the magnitude and shape of the association. Objective: To perform a systematic review and meta-analysis of observational studies investigating the relation between cadmium exposure and risk of type 2 diabetes and prediabetes, and to summarize data on the magnitude and shape of the association. Data source: After conducting an online literature search through October 1, 2021, we identified 42 eligible studies investigating the association between cadmium exposure and risk of diabetes and prediabetes. Study eligibility criteria: We included studies that assessed cadmium exposure through biomarker levels; examined type 2 diabetes or prediabetes among outcomes; and reported effect estimates for cadmium exposure for meta-analysis only. Study appraisal and synthesis methods: Studies were evaluated using ROBINS-E risk of bias tool. We quantitively assessed the relation between exposure and study outcomes using one-stage dose-response meta-analysis with a random effects meta-analytical model. Results: In the meta-analysis, comparing highest-versus-lowest cadmium exposure levels, summary relative risks (RRs) for type 2 diabetes were 1.24 (95% confidence interval 0.96-1.59), 1.21 (1.00-1.45), and 1.47 (1.01-2.13) for blood, urinary, and toenail matrices, respectively. Similarly, there was an increased risk of prediabetes for cadmium concentrations in both urine (RR = 1.41, 95% CI: 1.15-1.73) and blood (RR = 1.38, 95% CI: 1.16-1.63). In the dose-response meta-analysis, we observed a consistent linear positive association between cadmium exposure and diabetes risk, with RRs of 1.25 (0.90-1.72) at 2.0 µg/g of creatinine. Conversely for blood cadmium, diabetes risk appeared to increase only above 1 µg/L. Prediabetes risk increased up to approximately 2 µg/g creatinine above which it reached a plateau with RR of 1.42 (1.12-1.76) at 2 µg/g creatinine. Limitations and conclusions: This analysis provides moderate-certainty evidence for a positive association between cadmium exposure (measured in multiple matrices) and risk of both diabetes and prediabetes.

2021 - Cadmium exposure and risk of prediabetes and diabetes: A systematic review and dose-response meta-analysis [Abstract in Rivista]
Filippini, Tommaso; Wise, Lauren Anne; Vinceti, Marco
abstract

BACKGROUND AND AIM: Elevated cadmium exposure has been associated with altered glucose metabolism, albeit the shape of such relation is still debated. We aimed at investigating the shape of the relation between cadmium exposure and type 2 diabetes and prediabetes. METHODS: We performed a systematic review with meta-analysis on the relation between biomarkers of cadmium exposure and disease risk. After performing an online literature search through March 15, 2021, we identified 34 eligible studies with cohort, cross-sectional and case-control design. RESULTS:In the meta-analysis comparing highest-versus-lowest cadmium exposure, there was an increased type 2 diabetes risk, with summary risk ratios (RRs) of 1.30 (95% confidence interval (CI): 1.00-1.69), 1.22 (95% CI 1.00-1.50), and 1.47 (95% CI 1.01-2.13) for blood, urine, and toenail cadmium concentrations, respectively. Similarly, we found a higher prediabetes risk in subjects with higher both urine and blood cadmium concentrations with RRs of 1.41 (95% CI 1.15-1.73) and 1.38 (95% CI 1.16-1.63), respectively. In the dose-response meta-analysis, compared with no exposure, prediabetes risk increased up to approximately 2 µg Cd/g creatinine, above which it reached a plateau with RR of 1.40 (95% CI 1.12-1.76) at 2 µg Cd/g creatinine. We also detected a substantial linear positive association between diabetes risk and urinary cadmium, with RR of 1.30 (95% CI 0.92-1.84) at 2.0 µg Cd/g creatinine. Diabetes risk also appeared to increase with higher blood cadmium concentrations but only above 1 µg/L, with RR of 3.25 (95% CI 1.13-9.37) at 2 µg/L. Despite limited data, there was little indication of differences in association by study design (cohort vs. case-control or cross-sectional), method of cadmium assessment, or sex (male vs. female). CONCLUSIONS:Overall, there was consistent evidence for a positive association between cadmium exposure and both prediabetes and diabetes risk. KEYWORDS: Heavy metals, Cardiovascular diseases, Endocrine disrupting chemicals, Environmental epidemiology, Toxicology

2021 - Characteristics and risk factors of isolated and quarantined children and adolescents during the first wave of SARS-CoV-2 pandemic: A cross-sectional study in Modena, Northern Italy [Articolo su rivista]
Paduano, S.; Facchini, M. C.; Greco, A.; Borsari, L.; Mingrone, V. M.; Tancredi, S.; Fioretti, E.; Creola, G.; Iacuzio, L.; Casaletti, G.; Vinceti, M.; Bargellini, A.; Filippini, T.
abstract

Background and aim: In early 2020, SARS-CoV-2 was declared a pandemic by the WHO and Italy was one of the first and most severely affected country in Europe. Despite the global interest about COVID-19 pandemic, several aspects of this infection are still unclear, especially in pediatric population. This study aims to investigate the characteristics of the isolated or quarantined children and adolescents followed by the Public Health Department of the Italian province of Modena during the first wave of COVID-19. Methods: The study population included all non-adult subjects aged 0-18 years who underwent isolation or quarantine during the first wave of SARS-CoV-2 pandemic from February 24 to June 18, 2020 in Modena province, Northern Italy. Results: In Modena province, 1230 children and adolescents were isolated in case of SARS-CoV-2 infection (6.3%), or quarantined due to close contact with confirmed cases (88.7%) or travelling from a high-risk area (5.0%). Among 349 individuals who underwent swab testing, 294 (84.2%) reported close contact with an infected cohabiting relative and 158 (45.3%) were symptomatic. Among all tested subjects, 78 (22.4%) resulted positive, with a higher proportion of symptomatic subjects compared with the SARS-CoV-2-negative (78.2% vs. 35.8%). Fever was mostly present in SARS-CoV-2-positive children (48.7% vs. 12.6%). Both anosmia (58.3% vs. 41.7%) and dysgeusia (54.5% vs. 45.5%) had only slightly higher frequency in SARS-CoV-2-positive. Conclusions: These findings allow to expand the knowledge regarding characteristics of non-adult subjects isolated or quarantined during the first wave of SARS-CoV-2 pandemic. (www.actabiomedica.it).

2021 - Dietary acrylamide and risk of specific subtypes of cancer: a dose response meta-analysis of epidemiological studies [Abstract in Rivista]
Filippini, Tommaso; Halldorsson, Thorhallur I.; Capitão, Carolina; Martins, Raquel; Vinceti, Marco; Santos, Osvaldo; Virgolino, Ana; Laguzzi, Federica
abstract

BACKGROUND AND AIM: Acrylamide is a probable carcinogen in humans. The main source of exposure to acrylamide in the general population is through diet. We performed a systematic literature review and dose-response meta-analysis of epidemiological studies evaluating the associations between dietary intake and specific subtypes of cancers. METHODS: A systematic literature search following PRISMA guidelines was conducted using Pubmed, Scopus and Web of Science until October 2020. Eligible studies included adults,assessment of dietary acrylamide (μg/day), risk estimates for increasing exposure to acrylamide, and cancer incidence. Quality of papers was assessed using the NIH’s Quality Assessment Tools for Observational Cohort and Case-Control Studies. We employed random-effects models comparing the highest versus the lowest intake of acrylamide and using the one-stage approach for dose-response meta-analysis. RESULTS:Out of 835 studies screened 28 studies were eligible for this meta-analysis. A total of 1 109 365 (mean age 60 years, range 45-70 years) participants were included, of which 61957 developed cancer. The mean follow-up period was 15.1 years (range 7.3-33.9). Mean estimated dose of acrylamide intake across studies was 22.6 µg/day. Pooled HR showed that high intake of acrylamide (35 µg/day) vs low intake (10 µg/day) was associated with increased risk of hematological malignances (summary HR: 1.4 95%CI:1.03-1.23). Dose-response meta-analysis showed evidence of linear association. No clear associations were noted between high intake of acrylamide (vs low) and esophageal, stomach, pancreatic, lung, renal, bladder-urothelial, and prostate cancers. Similar results were observed in the smoking stratification analysis CONCLUSIONS:From this dose-response meta-analysis of epidemiological studies investigating the association between dietary intake of acrylamide and specific subtypes of cancer, high intake of acrylamide was noted to be associated with increased risk of hematological malignancies. Further studies based on human biomonitoring data are needed to clarify the relationship of dietary acrylamide and cancers in humans. KEYWORDS: acrylamide, dietary exposure, neoplasms, epidemiological studies, Systematic Review

2021 - Dietary selenium intake and risk of hospitalization for type 2 diabetes in the Moli-sani study cohort [Articolo su rivista]
Vinceti, M.; Bonaccio, M.; Filippini, T.; Costanzo, S.; Wise, L. A.; Di Castelnuovo, A.; Ruggiero, E.; Persichillo, M.; Cerletti, C.; Donati, M. B.; de Gaetano, G.; Iacoviello, L.
abstract

Background and aims: Experimental and non-experimental human studies have consistently shown a positive association between exposure to the trace element selenium, which occurs primarily through diet, and risk of type 2 diabetes mellitus. Plausible biological mechanisms include adverse effects of selenium and selenium-containing proteins on glucose metabolism. However, the levels of exposure above which risk increases are uncertain. Methods and results: We examined the association between selenium intake and first hospitalization for type 2 diabetes during a median follow-up period of 8.2 years among 21,335 diabetes-free participants in the Moli-sani cohort, Italy. Selenium intake was ascertained at baseline using a food frequency questionnaire, showing a median value of 59 μg/day. During follow-up, we identified 135 incident cases of hospitalization for diabetes, based on population-based hospital discharge data. We used a Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization for diabetes, adjusting for potential confounders. HRs (95% CIs) were 1.01 (0.60–1.70), 1.13 (0.66–1.96) and 1.75 (0.99–3.10) comparing the second, third, and fourth sex-specific quartiles with the first quartile, respectively. Risk was 64% greater in the fourth quartile as compared with the previous three. Spline regression analysis also indicated a steeper increase in risk occurring among men compared with women. Conclusions: In a large population of Italian adults free of type 2 diabetes at cohort entry, high dietary selenium intake was associated with increased risk of hospitalization for diabetes.

2021 - Disentangling the association of hydroxychloroquine treatment with mortality in covid-19 hospitalized patients through hierarchical clustering [Articolo su rivista]
Di Castelnuovo, A.; Gialluisi, A.; Antinori, A.; Berselli, N.; Blandi, L.; Bonaccio, M.; Bruno, R.; Cauda, R.; Costanzo, S.; Guaraldi, G.; Menicanti, L.; Mennuni, M.; My, I.; Parruti, G.; Patti, G.; Perlini, S.; Santilli, F.; Signorelli, C.; Stefanini, G.; Vergori, A.; Ageno, W.; Agodi, A.; Agostoni, P.; Aiello, L.; Moghazi, S. A.; Arboretti, R.; Aucella, F.; Barbieri, G.; Barchitta, M.; Bonfanti, P.; Cacciatore, F.; Caiano, L.; Cannata, F.; Carrozzi, L.; Cascio, A.; Castiglione, G.; Cicullo, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Colombo, C.; Crisetti, A.; Crosta, F.; Danzi, G. B.; D'Ardes, D.; de Gaetano Donati, K.; Di Gennaro, F.; Di Tano, G.; D'Offizi, G.; Fusco, F. M.; Gaudiosi, C.; Gentile, I.; Gianfagna, F.; Giuliano, G.; Graziani, E.; Guarnieri, G.; Langella, V.; Larizza, G.; Leone, A.; Maccagni, G.; Magni, F.; Maitan, S.; Mancarella, S.; Manuele, R.; Mapelli, M.; Maragna, R.; Marcucci, R.; Maresca, G.; Marongiu, S.; Marotta, C.; Marra, L.; Mastroianni, F.; Mengozzi, A.; Meschiari, M.; Milic, J.; Minutolo, F.; Mussinelli, R.; Mussini, C.; Musso, M.; Odone, A.; Olivieri, M.; Palimodde, A.; Pasi, E.; Pesavento, R.; Petri, F.; Pivato, C. A.; Poletti, V.; Ravaglia, C.; Righetti, G.; Rognoni, A.; Rossato, M.; Rossi, I.; Rossi, M.; Sabena, A.; Salinaro, F.; Sangiovanni, V.; Sanrocco, C.; Moriello, N. S.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Spinicci, M.; Tamburrini, E.; Torti, C.; Trecarichi, E. M.; Vettor, R.; Vianello, A.; Vinceti, M.; Virdis, A.; de Caterina, R.; Iacoviello, L.
abstract

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR [CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

2021 - Dismissing the use of P-values and statistical significance testing in scientific research: new methodological perspectives in toxicology and risk assessment [Capitolo/Saggio]
Berselli, Nausicaa; Filippini, Tommaso; Adani, Giorgia; Vinceti, Marco
abstract

2021 - Efficacy of an infant formula manufactured from a specific protein hydrolysate derived from whey protein isolate and concentrate produced by Société des Produits Nestlé S.A. in reducing the risk of developing atopic dermatitis [Articolo su rivista]
Castenmiller, Jacqueline; Hirsch-Ernst, Karen-Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Turck, Dominique; Vinceti, Marco; Marchelli, Rosangela; van Loveren, Henk; Dumas, Céline; Titz, Ariane; de Henauw, Stefaan
abstract

The European Commission asked EFSA to evaluate the efficacy of an infant formula, containing a specific protein hydrolysate derived from whey protein isolate and concentrate and manufactured by Société des Produits Nestlé S.A., in reducing the risk of developing atopic dermatitis in infants with a family history of allergy. This was following the submission of a dossier by Société des Produits Nestlé S.A. to the European Commission, in the context of Regulation (EU) 2016/127. The protein hydrolysate from which the infant formula is produced is included in Annex I and II of Commission delegated Regulation (EU) 2016/127 as suitable protein source for the manufacture of infant and follow-on formulae. This opinion does not cover the assessment of the nutritional safety and suitability of the infant formula or the safety of the food enzymes used in the manufacture of the protein hydrolysate. The Panel considers that, in relation to the effect that is claimed, the infant formula under evaluation is not sufficiently characterised with respect to the molecular weight distribution of peptides. From the human intervention studies submitted, no conclusions could be drawn on the efficacy of the infant formula in reducing the risk of developing atopic dermatitis. The Panel concludes that a cause-and-effect relationship has not been established between the consumption of the infant formula under evaluation and the reduction in the risk of developing atopic dermatitis in infants with a family history of allergy.

2021 - Epidemiology of early onset dementia and its clinical presentations in the province of Modena, Italy [Articolo su rivista]
Chiari, A.; Vinceti, G.; Adani, G.; Tondelli, M.; Galli, C.; Fiondella, L.; Costa, M.; Molinari, M. A.; Filippini, T.; Zamboni, G.; Vinceti, M.
abstract

Introduction: Patients with early onset dementia (EOD), defined as dementia with symptom onset at age <65, frequently present with atypical syndromes. However, the epidemiology of different EOD presentations, including variants of Alzheimer's disease (AD) and frontotemporal dementia (FTD), has never been investigated all together in a population-based study. Epidemiologic data of all-cause EOD are also scarce. Methods: We investigated EOD epidemiology by identifying patients with EOD seen in the extended network of dementia services of the Modena province, Northern Italy (≈700,000 inhabitants) from 2006 to 2019. Results: In the population age 30 to 64, incidence was 13.2 per 100,000/year, based on 160 new cases from January 2016 to June 2019, and prevalence 74.3 per 100,000 on June 30, 2019. The most frequent phenotypes were the amnestic variant of AD and behavioral variant of FTD. Discussion: EOD affects a significant number of people. Amnestic AD is the most frequent clinical presentation in this understudied segment of the dementia population.

2021 - Extension of use of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Albert, O.; de Sesmaisons Lecarre, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use of the novel food (NF) nicotinamide riboside chloride (NRC) pursuant to Regulation (EU) 2015/2283. The assessment addresses the use of NRC in ‘meal replacement products’ and ‘nutritional drink mixes’ at levels up to 300 mg/day for the general population, and in food for special medical purposes (FSMP) and total diet replacement for weight control (TDRWC) (as per Regulation (EU) No 609/2013) at levels up to 500 mg/day in adults. Benchmark dose modelling was carried out on data from the 90-day oral toxicity studies in rats relevant to the safety assessment. Considering the lack of tolerable upper intake level (UL) for nicotinamide in infants and the narrow margin of exposure between the estimated intake in infants and the lower confidence bound of the benchmark doses (BMDL05) estimated by the models, the Panel concludes that the safety of the NF has not been established for use in ‘meal replacement products’ and ‘nutritional drink mixes’ under the proposed conditions of use. For FSMP and TDRWC, the proposed maximum use level corresponds to an intake of 210 mg nicotinamide per day, which is below the current UL for nicotinamide of 900 mg/day for adults. The Panel considers that the NF is as safe as pure nicotinamide for use in FSMP and TDRWC. The Panel, however, notes experimental data which indicate several pathways by which intakes of nicotinamide (or its precursors), at levels that are substantially higher than the physiological requirement, might cause adverse effects. The Panel considers that further investigations are required and that a re-evaluation of the UL for nicotinamide may be warranted.

2021 - Frequency of anti-sars-cov-2 antibodies in various occupational sectors in an industrialized area of northern italy from may to october 2020 [Articolo su rivista]
Modenese, A.; Mazzoli, T.; Berselli, N.; Ferrari, D.; Bargellini, A.; Borella, P.; Filippini, T.; Marchesi, I.; Paduano, S.; Vinceti, M.; Gobba, F.
abstract

The results of a voluntary screening campaign for the presence of anti-SARS-CoV-2 serum antibodies are presented, performed on workers in the highly industrialized province of Modena in northern Italy in the period 18 May–5 October 2020. The employment activities of the subjects that tested positive for anti-SARS-CoV-2 IgM and/or IgG antibodies were determined and classified using the International Standard Industrial Classification of All Economic Activities (ISIC). The distribution across different sectors was compared to the proportion of workers employed in the same sectors in the province of Modena as a whole. Workers with anti-SARS-CoV-2 serum antibodies were mainly employed in manufacturing (60%), trade (12%), transportation (9%), scientific and technical activities (5%), and arts, entertainment and recreation activities (4.5%). Within the manufacturing sector, a cluster of workers with positive serological tests was observed in the meat processing sector, confirming recent data showing a possible increased risk of SARS-CoV-2 infection in these workers.

2021 - Frutalose®, a mixture of fructans obtained from enzymatic hydrolysis of chicory inulin, and normal defecation: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Vinceti, Marco
abstract

Following an application from Sensus B.V. (Royal Cosun), submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Frutalose® and maintenance of normal defecation. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The Panel considers that Frutalose®, a mixture of fructans obtained from enzymatic hydrolysis of chicory inulin, is sufficiently characterised. The claimed effect proposed by the applicant is ‘contributes to regular bowel function by increasing stool frequency’. The proposed target population is ‘the general healthy adult population’. Maintenance of normal defecation is a beneficial physiological effect provided that it does not result in diarrhoea. One human intervention study showed an effect of Frutalose® on the maintenance of normal defecation by increasing stool frequency and improving stool consistency (softer stools) when consumed daily at a dose of 15 g for 8 weeks. The results have not been replicated in other studies. There is a plausible mechanism by which Frutalose® could exert the claimed effect. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of Frutalose® and maintenance of normal defecation under the proposed conditions of use.

2021 - Green kiwifruit (lat. Actinidia deliciosa var. Hayward) and maintenance of normal defecation: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Bresson, Jean-Louis; Siani, Alfonso
abstract

Following an application from Zespri International Limited, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to green kiwifruit (lat. Actinidia deliciosa var. Hayward) and maintenance of normal defecation. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is green kiwifruit. The Panel considers that green kiwifruit (Actinidia deliciosa var. Hayward) is sufficiently characterised. The claimed effect proposed by the applicant is 'maintenance of normal defecation'. Maintenance of normal defecation is a beneficial physiological effect provided that it does not result in diarrhoea. All human intervention studies submitted had different limitations and could not be used on their own for the scientific substantiation of the claim. However, the results of six pertinent human intervention studies are consistent with respect to an effect of consuming daily between two and four green kiwifruits var. Hayward on an increase in stool frequency. Two out of four studies in which a validated instrument was used to assess stool consistency showed an effect also on stool consistency. There is evidence for a plausible mechanism by which kiwifruit could exert an effect on normal defecation. The consumption of kiwifruit in the studies did not result in diarrhoea. A cause and effect relationship has been established between the consumption of green kiwifruit (Actinidia deliciosa var. Hayward) and maintenance of normal defecation. The following wordings reflect the scientific evidence: 'consumption of kiwifruit contributes to the maintenance of normal defecation'. In order to obtain the claimed effect, two large green kiwifruits (i.e. around 200 g of kiwi flesh) should be consumed.

2021 - Greenness, cognitive impairment and dementia: a systematic review and meta-analysis [Abstract in Rivista]
Zagnoli, Federico; Giannone, Maria Edvige; Filippini, Tommaso; Vinceti, Marco
abstract

BACKGROUND AND AIM: Many recent studies identified the benefits of green space exposure for the improvment of human health, especially mental health. The involved patways could be increased physical activity, improved sleep quality, reduced stress and also increased social interaction. The relation between greenness and cognitive decline, however, is still uncertain. METHODS: We searched epidemiological studies related to green space exposure and cognitive impairment and dementia in two electronic databases (PubMed and EMBASE) using terms related to residential greenness, including Normalized Difference Vegetation Index-NDVI, land cover, land use, green index, greenness, green space, urban park, urban green and recreational park, along with cognitive impairment, decline and dementia. A meta-analysis comparing the highest versus the lowest greenness exposure and risk of cognitive decline was performed using a random-effects model. RESULTS:Out of 64 studies retrieved from the online search 11 studies were eligible for the review. The majority of included reports used satellied-derived NDVI, while the remaining studies used land cover maps to determine the greenness-related exposure areas. Cognitive impairment or dementia risk are calculated using different exposure types (greenness within a buffer, the areal radius, or greenness of census block) at subject residential address. Overall, summary risk ratio-RR showed no effect of greenness on cognitive decline (RR 0.99, 95% confidence interval-CI 0.91-1.07), whereas a slight indication of a beneficial effect of NDVI emerged (RR 0.96, 95%CI 0.90-1.03). Two studies that reported correlation coefficents only did not suggest an association between cognitive impairment and dementia measurement. CONCLUSIONS:Overall, our study yielded limited evidence of a protective effect of greenness on cognitive decline. The rapid evolution of greenness definition over time and the limitations in exposure assessment, however, suggest the need to further investigate this issue in order to draw more reliable conclusions. KEYWORDS: Green space, Neurodegenerative outcomes, Environmental epidemiology

2021 - Guidance on the preparation and submission of an application for authorisation of a novel food in the context of Regulation (EU) 2015/22831 (Revision 1)2 [Articolo su rivista]
Nutrition, ; Allergies, A.; Turck, D.; Bresson, J. -L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K. I.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Neuhauser-Berthold, M.; Nowicka, G.; Pentieva, K.; Sanz, Y.; Siani, A.; Sjodin, A.; Stern, M.; Tome, D.; Vinceti, M.; Willatts, P.; Engel, K. -H.; Marchelli, R.; Poting, A.; Poulsen, M.; Salminen, S.; Schlatter, J.; Arcella, D.; Gelbmann, W.; de Sesmaisons-Lecarre, A.; Verhagen, H.; van Loveren, H.
abstract

(Table presented.). Following the adoption of Regulation (EU) 2015/2283 on novel foods, the European Commission requested EFSA develop scientific and technical guidance for the preparation and submission of applications for authorisation of novel foods. This guidance presents a common format for the organisation of the information to be presented by the applicant when preparing a well-structured application to demonstrate the safety of the novel food. It outlines the data needed for the safety assessments of novel foods. Requirements relate to the description of the novel food, production process, compositional data, specification, proposed uses and use levels, and anticipated intake of the novel food. Further sections on the history of use of the novel food and/or its source, absorption, distribution, metabolism, excretion, nutritional information, toxicological information and allergenicity should be considered by the applicant by default. If not covered in the application, this should be justified. The applicant should integrate the data presented in the different sections to provide their overall considerations on how the information supports the safety of the novel food under the proposed conditions of use. Where potential health hazards have been identified, they should be discussed in relation to the anticipated intakes of the novel food and the proposed target populations. On the basis of the information provided, EFSA will assess the safety of the novel food under the proposed conditions of use. This guidance was originally adopted in 2016.It has beenrevised to informapplicants of the new provisions introduced by Regulation (EC) No 178/2002, as amended by Regulation (EU) 2019/1381 on the transparency and sustainability of the EU risk assessment in the food chain.This revised guidance applies to all dossiers submitted as of 27 March 2021. The 2016 version of this guidance remains applicable to applications submitted before 27 March 2021.

2021 - Guidance on the preparation and submission of the notification and application for authorisation of traditional foods from third countries in the context of Regulation (EU) 2015/2283 (Revision 1)1 [Articolo su rivista]
Turck, D.; Bresson, J. -L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K. I.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Neuhauser-Berthold, M.; Nowicka, G.; Pentieva, K.; Sanz, Y.; Siani, A.; Sjodin, A.; Stern, M.; Tome, D.; Vinceti, M.; Willatts, P.; Engel, K. -H.; Marchelli, R.; Poting, A.; Poulsen, M.; Schlatter, J.; Gelbmann, W.; de Sesmaisons-Lecarre, A.; Verhagen, H.; van Loveren, H.
abstract

(Table presented.). Following the adoption of Regulation (EU) 2015/2283 on Novel Foods, the European Commission requested EFSA to develop a scientific and technical guidance for the preparation and submission of notifications for traditional foods from third countries. This guidance presents a common format for the organisation of the information to be presented by applicant for the preparation of a well-structured dossier. The safety of a traditional food should be substantiated by reliable data on its composition, its experience of continued use and its proposed conditions of use. Its normal consumption should not be nutritionally disadvantageous. This guidance is also intended to support applicants in providing the type and quality of information EU Member States and EFSA need for the assessments of traditional foods from third countries. The applicant should integrate the information on the composition and the experience of continued use and provide a concise overall consideration on how this substantiates the history of safe use of the traditional food and how this relates to the proposed conditions of use for the EU. Where potential health hazards have been identified on the basis of the composition and/or data from the experience of continued use, they should be discussed. On the basis of the information provided, EFSA will assess the safety related to the consumption of the traditional food under the proposed conditions of use. This guidance was originally adopted by the NDA Panel in 2016. It has been revised in 2020 to inform applicants of the new provisions introduced by Regulation (EC) No 178/2002, as amended by Regulation (EU) 2019/1381 on the transparency and sustainability of the EU risk assessment in the food chain.It is applicable to allnotifications and applications submitted as of 27 March 2021. The 2016 version remains applicable to notifications and applications submitted before 27 March 2021.

2021 - Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study [Articolo su rivista]
Di Castelnuovo, A.; Costanzo, S.; Antinori, A.; Berselli, N.; Blandi, L.; Bonaccio, M.; Cauda, R.; Guaraldi, G.; Menicanti, L.; Mennuni, M.; Parruti, G.; Patti, G.; Santilli, F.; Signorelli, C.; Vergori, A.; Abete, P.; Ageno, W.; Agodi, A.; Agostoni, P.; Aiello, L.; Al Moghazi, S.; Arboretti, R.; Astuto, M.; Aucella, F.; Barbieri, G.; Bartoloni, A.; Bonfanti, P.; Cacciatore, F.; Caiano, L.; Carrozzi, L.; Cascio, A.; Ciccullo, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Colombo, C.; Crosta, F.; Danzi, G. B.; D'Ardes, D.; De Gaetano Donati, K.; Di Gennaro, F.; Di Tano, G.; D'Offizi, G.; Fantoni, M.; Fusco, F. M.; Gentile, I.; Gianfagna, F.; Grandone, E.; Graziani, E.; Grisafi, L.; Guarnieri, G.; Larizza, G.; Leone, A.; Maccagni, G.; Madaro, F.; Maitan, S.; Mancarella, S.; Mapelli, M.; Maragna, R.; Marcucci, R.; Maresca, G.; Marongiu, S.; Marotta, C.; Marra, L.; Mastroianni, F.; Mazzitelli, M.; Mengozzi, A.; Menichetti, F.; Meschiari, M.; Milic, J.; Minutolo, F.; Molena, B.; Montineri, A.; Mussini, C.; Musso, M.; Niola, D.; Odone, A.; Olivieri, M.; Palimodde, A.; Parisi, R.; Pasi, E.; Pesavento, R.; Petri, F.; Pinchera, B.; Poletti, V.; Ravaglia, C.; Rognoni, A.; Rossato, M.; Rossi, M.; Sangiovanni, V.; Sanrocco, C.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Taddei, E.; Torti, C.; Vettor, R.; Vianello, A.; Vinceti, M.; Virano, A.; Vocciante, L.; De Caterina, R.; Iacoviello, L.
abstract

Introduction A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. Aim We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. Methods In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. Results Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. Conclusion In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

2021 - Impact of the environment on the health: From theory to practice [Articolo su rivista]
Carducci, A. L.; Agodi, A.; Ancona, C.; Angelini, P.; Bagordo, F.; Barbone, F.; Birbaum, L.; Carreri, V.; Casuccio, A.; Conti, A.; Conversano, M.; De Donno, A.; De Giglio, O.; Desiante, F.; Di Pietro, A.; Dogliotti, E.; Donato, F.; Fara, G. M.; Fiore, M.; Forastiere, F.; Giammanco, G.; Izzotti, A.; Montagna, M. T.; Oliveri Conti, G.; Petronio, M. G.; Sciacca, S.; Signorelli, C.; Testai, E.; Verani, M.; Vinceti, M.; Vitale, F.; Ferrante, M.; Adani, G.; Berghella, L.; Calia, C.; Calzolari, R.; Canale, A.; Castiglione, D.; Copat, C.; Cristaldi, A.; Cuffari, G.; Coronel Vargas, G.; De Vita, E.; De Nard, F.; Federigi, I.; Filippini, T.; Grasso, A.; Leonardi, N.; Letzgus, M.; Lo Bianco, G.; Mazzucco, W.; Nicolosi, I.; Orlandi, P.; Paladino, G.; Pizzo, S.; Pousis, C.; Raffo, M.; Rivolta, S.; Scarpitta, F.; Trani, G.; Triggiano, F.; Tumbarello, A.; Vecchio, V.; Zuccarello, P.; Vassallo, M.
abstract

The Erice 56 Charter titled “Impact of the environment on the health: from theory to practice” was unanimously approved at the end of the 56th course of the “International School of Epidemiology and Preventive Medicine G. D'Alessandro” held from 3rd to November 7, 2019 in Erice – Sicily (Italy) and promoted by the Study Group of “Environment and Health” of the Italian Society of Hygiene, Preventive Medicine and Public Health. The course, that included lectures, open discussions and guided working groups, was aimed to provide a general training on epidemiological and toxicological aspects of the environmental health impact, to be used by public health professionals for risk assessment, without forgetting the risk communications. At the end of the course 12 key points were agreed among teachers and students: they underlined the need of specific training and research, in the perspective of “One Health” and “Global Health”, also facing emerging scientific and methodological issues and focusing on communication towards stakeholders. This Discussion highlight the need to improve knowledge of Health and Environment topic in all sectors of health and environmental prevention and management.

2021 - Is artificial light-at-night associated with increased breast cancer risk? A systematic review and dose-response meta-analysis [Abstract in Rivista]
Urbano, Teresa; Vinceti, Marco; Filippini, Tommaso
abstract

2021 - Is dairy intake associated with less cognitive decline? A systematic review and meta-analysis of longitudinal studies [Abstract in Rivista]
Villoz, Fanny; Filippini, Tommaso; Blum, Manuel; DEL GIOVANE, Cinzia; Vinceti, Marco; Rodondi, Nicolas; Chocano-Bedoya, Patricia
abstract

Introduction: With aging population, prevention of cognitive de- cline is a major concern in primary care. Nutrition is a modifiable factor that could have a clinical impact in this prevention. In par- ticular, the effects of the dairy intake on cognition are still contro- versial. We conducted a systematic review and meta-analysis on association between the dairy intake and cognitive decline or inci- dence of dementia with dose-response analysis. Methods: We included longitudinal studies with community-dwell- ing adults ≥ 18 years unselected on the basis of chronic conditions. Our primary outcomes were the decline of cognitive function as de- fined in studies and incidence of dementia at end of follow-up. We identified relevant literature through a systematic search of Em- base, Medline Ovid, Cochrane, Web of Science and Google Scholar from inception to end of July 2020. Two investigators conducted abstract and full-text screenings, data extractions, and risk-of-bias assessments using the Academy of Nutrition and Dietetics Quality Criteria Checklist (QCC). We performed a meta-analysis using a random-effects model. Results: We included 11 prospective studies with 46,896 partici- pants. We rated all studies at low risk of bias. Mean follow-up time was 11.7 years. Seven studies assessed cognitive decline through decrease in scores of various neuropsychological tests including MMSE (Mini-Mental State Examination). Three studies assessed dementia incidence using either MMSE threshold or DSM-IIIR/ DSM-IV criteria. Comparing highest vs. lowest dairy intake, we found no association between dairy and cognitive decline. (Sum- mary risk ratio-sRR=0.97; 95%CI 0.82, 1.16; 7 studies) although with large statistical heterogeneity (I2=76.75%). The dose-response anal- yses using g/day with 4 studies showed U-shaped curve, with low- est risk at approximately 120-130 g/day. We found an inverse asso- ciation between the dairy intake and dementia incidence (sRR=0.61; 95%CI 0.44, 0.86; I2 =43.65%; 3 studies)

2021 - Isomaltulose and normal energy-yielding metabolism: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from BENEO GmbH submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to isomaltulose and normal energy-yielding metabolism. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is isomaltulose. The Panel considers that isomaltulose is sufficiently characterised. The claimed effect proposed by the applicant is ‘normal energy-yielding metabolism’. The Panel considers that contribution to normal energy-yielding metabolism is a beneficial physiological effect. A number of human studies applying indirect calorimetry measurements or stable isotope methodologies have shown the postprandial metabolic utilisation of isomaltulose as energy source. However, all energy-containing macronutrients (i.e. carbohydrates, proteins, and lipids) supply the body with energy and this property is not specific to isomaltulose. The Panel concludes that a cause and effect relationship has been established between the intake of isomaltulose and contribution to energy-yielding metabolism. The following wording reflects the scientific evidence: ‘isomaltulose contributes to normal energy-yielding metabolism’. Since the contribution to energy-yielding metabolism is not specific to isomaltulose but applies to all energy containing macronutrients (i.e. carbohydrates, proteins, and lipids) that supply the body with metabolisable energy and any amount would contribute to the claimed effect, the Panel cannot set conditions of use for this claim. The applicant proposes that isomaltulose should replace other sugars in foods and/or beverages. The target population is the general population.

2021 - La pandemia Covid-19 a Modena nel 2020: quadro epidemiologico ed efficacia degli interventi di sanità pubblica. [Monografia/Trattato scientifico]
Vinceti, Marco; Filippini, Tommaso
abstract

2021 - Light at night and risk of breast cancer: a systematic review and dose–response meta-analysis [Articolo su rivista]
Urbano, Teresa; Vinceti, Marco; Wise, Lauren A.; Filippini, Tommaso
abstract

Breast cancer is the most common malignancy in women and the second leading cause of cancer death overall. Besides genetic, reproductive, and hormonal factors involved in disease onset and progression, greater attention has focused recently on the etiologic role of environmental factors, including exposure to artificial lighting such as light-at-night (LAN). We investigated the extent to which LAN, including outdoor and indoor exposure, affects breast cancer risk. We performed a systematic review of epidemiological evidence on the association between LAN exposure and breast cancer risk, using a dose-response meta-analysis to examine the shape of the relation. We retrieved 17 eligible studies through September 13, 2021, including ten cohort and seven case-control studies. In the analysis comparing highest versus lowest LAN exposure, we found a positive association between exposure and disease risk (risk ratio [RR] 1.11, 95% confidence interval-CI 1.07-1.15), with comparable associations in case-control studies (RR 1.14, 95% CI 0.98-1.34) and cohort studies (RR 1.10, 95% CI 1.06-1.15). In stratified analyses, risk was similar for outdoor and indoor LAN exposure, while slightly stronger risks were observed for premenopausal women (premenopausal: RR 1.16, 95% CI 1.04-1.28; postmenopausal: 1.07, 95% CI 1.02-1.13) and for women with estrogen receptor (ER) positive breast cancer (ER + : RR 1.09, 95% CI 1.02-1.17; ER-: RR 1.07, 95% CI 0.92-1.23). The dose-response meta-analysis, performed only in studies investigating outdoor LAN using comparable exposure assessment, showed a linear relation up to 40 nW/cm2/sr after which the curve flattened, especially among premenopausal women. This first assessment of the dose-response relation between LAN and breast cancer supports a positive association in selected subgroups, particularly in premenopausal women.

2021 - Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study [Articolo su rivista]
Di Castelnuovo, Augusto; Costanzo, Simona; Antinori, Andrea; Berselli, Nausicaa; Blandi, Lorenzo; Bonaccio, Marialaura; Bruno, Raffaele; Cauda, Roberto; Gialluisi, Alessandro; Guaraldi, Giovanni; Menicanti, Lorenzo; Mennuni, Marco; My, Ilaria; Parruti, Agostino; Patti, Giuseppe; Perlini, Stefano; Santilli, Francesca; Signorelli, Carlo; Stefanini, Giulio G; Vergori, Alessandra; Ageno, Walter; Aiello, Luca; Agostoni, Piergiuseppe; Al Moghazi, Samir; Arboretti, Rosa; Aucella, Filippo; Barbieri, Greta; Barchitta, Martina; Bartoloni, Alessandro; Bologna, Carolina; Bonfanti, Paolo; Caiano, Lucia; Carrozzi, Laura; Cascio, Antonio; Castiglione, Giacomo; Chiarito, Mauro; Ciccullo, Arturo; Cingolani, Antonella; Cipollone, Francesco; Colomba, Claudia; Colombo, Crizia; Crosta, Francesco; Dalena, Giovanni; Dal Pra, Chiara; Danzi, Gian Battista; D'Ardes, Damiano; de Gaetano Donati, Katleen; Di Gennaro, Francesco; Di Tano, Giuseppe; D'Offizi, Gianpiero; Filippini, Tommaso; Maria Fusco, Francesco; Gaudiosi, Carlo; Gentile, Ivan; Gini, Giancarlo; Grandone, Elvira; Guarnieri, Gabriella; Lamanna, Gennaro L F; Larizza, Giovanni; Leone, Armando; Lio, Veronica; Losito, Angela Raffaella; Maccagni, Gloria; Maitan, Stefano; Mancarella, Sandro; Manuele, Rosa; Mapelli, Massimo; Maragna, Riccardo; Marra, Lorenzo; Maresca, Giulio; Marotta, Claudia; Mastroianni, Franco; Mazzitelli, Maria; Mengozzi, Alessandro; Menichetti, Francesco; Milic, Jovana; Minutolo, Filippo; Molena, Beatrice; Mussinelli, R; Mussini, Cristina; Musso, Maria; Odone, Anna; Olivieri, Marco; Pasi, Emanuela; Perroni, Annalisa; Petri, Francesco; Pinchera, Biagio; Pivato, Carlo A; Poletti, Venerino; Ravaglia, Claudia; Rossato, Marco; Rossi, Marianna; Sabena, Anna; Salinaro, Francesco; Sangiovanni, Vincenzo; Sanrocco, Carlo; Scorzolini, Laura; Sgariglia, Raffaella; Simeone, Paola Giustina; Spinicci, Michele; Trecarichi, Enrico Maria; Veronesi, Giovanni; Vettor, Roberto; Vianello, Andrea; Vinceti, Marco; Visconti, Elena; Vocciante, Laura; De Caterina, Raffaele; Iacoviello, Licia
abstract

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

2021 - MegaNatural®-BP grape seed extract and maintenance of normal blood pressure: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Vinceti, Marco
abstract

Following an application from Praline i Čokolada j.d.o.o. submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Croatia, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to MegaNatural®-BP grape seed extract and maintenance of normal blood pressure. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. MegaNatural®-BP, a grape seed extract standardised for total phenolics, gallic acid and the catechin and epicatechin content, is sufficiently characterised. The proposed claimed effect, maintenance of normal blood pressure (BP), is a beneficial physiological effect. Among the two human intervention studies provided from which conclusions could be drawn, one showed an effect of MegaNatural®-BP (300 mg/day) on BP in adults with normal and high normal BP when consumed daily for 6 weeks, whereas the second study did not show an effect of MegaNatural®-BP at the same daily dose consumed for 8 weeks in adults with normal and high normal blood pressure or stage 1 hypertension. The evidence provided did not establish a plausible mechanism by which the food could exert the claimed effect in vivo in humans. The evidence provided is insufficient to establish a cause and effect relationship between the consumption of MegaNatural®-BP and maintenance of normal blood pressure.

2021 - Modeling Early Phases of COVID-19 Pandemic in Northern Italy and Its Implication for Outbreak Diffusion [Articolo su rivista]
Gandolfi, Daniela; Pagnoni, Giuseppe; Filippini, Tommaso; Goffi, Alessia; Vinceti, Marco; D'Angelo, Egidio; Mapelli, Jonathan
abstract

The COVID-19 pandemic has sparked an intense debate about the hidden factors underlying the dynamics of the outbreak. Several computational models have been proposed to inform effective social and healthcare strategies. Crucially, the predictive validity of these models often depends upon incorporating behavioral and social responses to infection. Among these tools, the analytic framework known as “dynamic causal modeling” (DCM) has been applied to the COVID-19 pandemic, shedding new light on the factors underlying the dynamics of the outbreak. We have applied DCM to data from northern Italian regions, the first areas in Europe to contend with the outbreak, and analyzed the predictive validity of the model and also its suitability in highlighting the hidden factors governing the pandemic diffusion. By taking into account data from the beginning of the pandemic, the model could faithfully predict the dynamics of outbreak diffusion varying from region to region. The DCM appears to be a reliable tool to investigate the mechanisms governing the spread of the SARS-CoV-2 to identify the containment and control strategies that could efficiently be used to counteract further waves of infection.

2021 - Organic foods and contribution to the protection of body cells and molecules (lipids and DNA) from oxidative damage: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Cyprus, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to organic foods and contribution to the protection of body cells and molecules (lipids and DNA) from oxidative damage. The scope of the application was proposed to fall under a health claim referring to children's development and health. The food proposed by the applicant as the subject of the health claim is ‘organic foods’. The applicant claimed that organic foods are characterised by their lower level of pesticides residues compared with foods not labelled as organic. The Panel notes, however, that in the application and the human studies submitted the nutritional composition and the pesticide concentration in ‘organic food’ are not reported. The Panel considers that organic foods which are the subject of the health claim, and the foods that they are intended to replace are not sufficiently characterised. Therefore, the Panel concludes that a cause and effect relationship cannot be established between the consumption of organic foods and contribution to the protection of body cells and molecules (lipids and DNA) from oxidative damage.

2021 - Pro-environmental behaviors: Determinants and obstacles among italian university students [Articolo su rivista]
Carducci, A.; Fiore, M.; Azara, A.; Bonaccorsi, G.; Bortoletto, M.; Caggiano, G.; Calamusa, A.; De Donno, A.; De Giglio, O.; Dettori, M.; Di Giovanni, P.; Di Pietro, A.; Facciola, A.; Federigi, I.; Grappasonni, I.; Izzotti, A.; Libralato, G.; Lorini, C.; Montagna, M. T.; Nicolosi, L. K.; Paladino, G.; Palomba, G.; Petrelli, F.; Schiliro, T.; Scuri, S.; Serio, F.; Tesauro, M.; Verani, M.; Vinceti, M.; Violi, F.; Ferrante, M.
abstract

The awareness of citizens concerning the health risks caused by environmental pollution is growing, but studies on determinants of pro-environmental behaviors have rarely examined health-related aspects. In this study, we investigated these determinants using data from a large survey among Italian university students (15 Universities: 4778 filled questionnaires). Besides the health-related aspects, represented by environmental health risk perception and functional health literacy, we considered social and demographic characteristics (gender, area of residence, sources of information, trust in institutional and non-institutional subjects, and students’ capacity of positive actions, indicated as internal locus of control). The attitudes towards pro-environmental behaviors were positive for more than 70% of students and positively related with health risk perception, internal locus of control, and health literacy. The correspondence between the positive attitudes towards pro-environmental behaviors and the real adoption of such behaviors was approximately 20% for most behaviors, except for the separate collection of waste (60%). Such a discrepancy can be attributable to external obstacles (i.e., lack of time, costs, lack of support). The health-related aspects were linked to the pro-environmental attitudes, but to a lesser extent to pro-environmental behaviors, owing to the complexity of their determinants. However, they should be taken in account in planning education interventions.

2021 - Residential exposure to electromagnetic fields and risk of amyotrophic lateral sclerosis: a dose-response meta-analysis [Articolo su rivista]
Filippini, Tommaso; Hatch, Elizabeth E; Vinceti, Marco
abstract

Amyotrophic lateral sclerosis (ALS) is neurodegenerative disease characterized by a fatal prognosis and still unknown etiology. Some environmental risk factors have been suggested, including exposure to magnetic fields. Studies have suggested positive associations in occupationally-exposed populations, but the link with residential exposure is still debated as is the shape of such relation. Due to recent availability of advanced biostatistical tools for dose-response meta-analysis, we carried out a systematic review in order to assess the dose-response association between ALS and residential exposure to magnetic fields. We performed an online literature searching through April 30, 2021. Studies were included if they assessed residential exposure to electromagnetic fields, based either on distance from overhead power lines or on magnetic field modelling techniques, and if they reported risk estimates for ALS. We identified six eligible studies, four using distance-based and one modelling-based exposure assessment, and one both methods. Both distance-based and particularly modelling-based exposure estimates appeared to be associated with a decreased ALS risk in the highest exposure category, although estimates were very imprecise (summary RRs 0.87, 95% CI 0.63-1.20, and 0.27, 95% CI 0.05-1.36). Dose-response meta-analysis also showed little association between distance from power lines and ALS, with no evidence of any threshold. Overall, we found scant evidence of a positive association between residential magnetic fields exposure and ALS, although the available data were too limited to conduct a dose-response analysis for the modelled magnetic field estimates or to perform stratified analyses.

2021 - Response by Filippini et al to Letter Regarding Article, "Blood Pressure Effects of Sodium Reduction: Dose-Response Meta-Analysis of Experimental Studies" [Articolo su rivista]
Filippini, Tommaso; Malavolti, Marcella; Whelton, Paul K; Naska, Androniki; Orsini, Nicola; Vinceti, Marco
abstract

2021 - Risk of Amyotrophic Lateral Sclerosis and Exposure to Particulate Matter from Vehicular Traffic: A Case-Control Study [Articolo su rivista]
Filippini, Tommaso; Mandrioli, Jessica; Malagoli, Carlotta; Costanzini, Sofia; Cherubini, Andrea; Maffeis, Giuseppe; Vinceti, Marco
abstract

(1) Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with still unknown etiology. Some occupational and environmental risk factors have been suggested, including long-term air pollutant exposure. We carried out a pilot case-control study in order to evaluate ALS risk due to particulate matter with a diameter of ≤10 µm (PM10) as a proxy of vehicular traffic exposure. (2) Methods: We recruited ALS patients and controls referred to the Modena Neurology ALS Care Center between 1994 and 2015. Using a geographical information system, we modeled PM10 concentrations due to traffic emissions at the geocoded residence address at the date of case diagnosis. We computed the odds ratio (OR) and 95% confidence interval (CI) of ALS according to increasing PM10 exposure, using an unconditional logistic regression model adjusted for age and sex. (3) Results: For the 132 study participants (52 cases and 80 controls), the average of annual median and maximum PM10 concentrations were 5.2 and 38.6 µg/m3, respectively. Using fixed cutpoints at 5, 10, and 20 of the annual median PM10 levels, and compared with exposure <5 µg/m3, we found no excess ALS risk at 5-10 µg/m3 (OR 0.87, 95% CI 0.39-1.96), 10-20 µg/m3 (0.94, 95% CI 0.24-3.70), and ≥20 µg/m3 (0.87, 95% CI 0.05-15.01). Based on maximum PM10 concentrations, we found a statistically unstable excess ALS risk for subjects exposed at 10-20 µg/m3 (OR 4.27, 95% CI 0.69-26.51) compared with those exposed <10 µg/m3. However, risk decreased at 20-50 µg/m3 (OR 1.49, 95% CI 0.39-5.75) and ≥50 µg/m3 (1.16, 95% CI 0.28-4.82). ALS risk in increasing tertiles of exposure showed a similar null association, while comparison between the highest and the three lowest quartiles lumped together showed little evidence for an excess risk at PM10 concentrations (OR 1.13, 95% CI 0.50-2.55). After restricting the analysis to subjects with stable residence, we found substantially similar results. (4) Conclusions: In this pilot study, we found limited evidence of an increased ALS risk due to long-term exposure at high PM10 concentration, though the high statistical imprecision of the risk estimates, due to the small sample size, particularly in some exposure categories, limited our capacity to detect small increases in risk, and further larger studies are needed to assess this relation.

2021 - SARS-CoV-2 infection incidence during the first and second COVID-19 waves in Italy [Articolo su rivista]
Vinceti, M.; Filippini, T.; Rothman, K. J.; Di Federico, S.; Orsini, N.
abstract

We assessed the relation between COVID-19 waves in Italy, which was severely affected during the pandemic. We evaluated the hypothesis that a larger impact from the first wave (February-May 2020) predicts a smaller peak during the second wave (September-October 2020), in the absence of local changes in public health interventions and area-specific differences in time trends of environmental parameters. Based on publicly available data on province-specific SARS-CoV-2 infections and both crude and multivariable cubic spline regression models, we found that for provinces with the lowest incidence rates in the first wave, the incidence in the second wave increased roughly in proportion with the incidence in the first wave until an incidence of about 500-600 cases/100,000 in the first wave. Above that value, provinces with higher incidences in the first wave experienced lower incidences in the second wave. It appears that a comparatively high cumulative incidence of infection, even if far below theoretical thresholds required for herd immunity, may provide noticeable protection during the second wave. We speculate that, if real, the mechanism for this pattern could be depletion of most susceptible individuals and of superspreaders in the first wave. A population learning effect regarding cautious behavior could have also contributed. Since no area-specific variation of the national policy against the SARS-CoV-2 outbreak was allowed until early November 2020, neither individual behaviors nor established or purported environmental risk factors of COVID-19, such as air pollution and meteorological factors, are likely to have confounded the inverse trends we observed in infection incidence over time.

2021 - Safety of 3-FL (3-Fucosyllactose) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser-Berthold, Monika; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; van Loveren, Henk; Colombo, Paolo; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3-fucosyllactose (3-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3-FL but also contains D-lactose and its monomers, L-fucose and a small fraction of other related saccharides. The NF is produced by fermentation with a genetically modified strain of Escherichia coli K-12. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and toddlers, foods for special medical purposes and food supplements. The target population is the general population, except for food supplements for which the target population is individuals above 1 year of age. The anticipated daily intake of 3-FL from the NF at the maximum proposed use levels is unlikely to exceed the intake level of breastfed infants on a body weight basis. The intake of 3-FL in breastfed infants on a body weight basis is expected to be safe also for other population groups. In infants below 1 year of age, a possible exceedance of a natural intake was observed, but the degree of this exceedance is not considered of safety concern in view of the wide range of 3-FL concentrations in human milk. Food supplements are not intended to be used if other foods with the added NF (as well as human milk for young children) are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2021 - Safety of Cetylated Fatty Acids as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on an application for cetylated fatty acids as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF concerns primarily a mixture of cetylated myristic acid and cetylated oleic acid synthesised from cetyl alcohol, myristic acid and oleic acid, and to a lesser degree, other cetylated fatty acids and other compounds from olive oil. The NF is intended for use in food supplements for the general adult population. The highest dose tested in a subchronic toxicity study in rats, i.e. 4,500 mg/kg per day, was considered to be the no-observed-adverse effect level. By applying the default uncertainty factor of 200 as suggested by the EFSA Scientific Committee (2012), and considering a default body weight of 70 kg for the adult target population, this would result in an intake of 1.6 g per day, which is lower than the maximum intake proposed by the applicant (i.e. 2.1 g per day). The Panel concludes that the NF, cetylated fatty acids, is safe at an intake of 1.6 g per day for the intended target population, i.e. adults.

2021 - Safety of Eurycoma longifolia (Tongkat Ali) root extract as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Marchelli, R.; Neuhaeuser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Matijevic, L.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on Eurycoma longifolia (Tongkat Ali) root extract as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is standardised water extract prepared from the dried ground root chips of Tongkat Ali (Eurycoma longifolia Jack) and proposed by the applicant to be used as food supplement in amounts up to 200 mg/day. The target population is the adult population, except pregnant and lactating women. The characteristic components of the NF are glycosaponins (40–65%) and eurycomanone (0.8–1.5%). It can also contain canthin-6-one alkaloids and isoscopoletin (coumarin). The NF has been present in various international markets since 2009. The Panel notes positive results from the submitted in vitro chromosome aberration test, which indicates clastogenic properties of the NF. In the requested follow-up in vivo mammalian alkaline comet assay, the NF induced positive results at the highest dose tested (2,000 mg/kg body weight (bw)) at the tissues of the first site of contact (stomach and duodenum). Histopathological evaluation of the tested tissues indicated that the positive results of the comet assay were rather due to genotoxicity than cytotoxicity. Taken together, the Panel concludes that the NF has the potential to induce DNA damage, which is of concern, particularly locally for tissues that represent first sites of contact. The Panel concludes that the safety of NF has not been established under any condition of use.

2021 - Safety of Vitamin D2 mushroom powder (Agaricus bisporus) as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on vitamin D2 mushroom powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is an ingredient produced from Agaricus bisporus mushroom powder that has been exposed to ultraviolet (UV) irradiation to induce the conversion of provitamin D2 (ergosterol) to vitamin D2 (ergocalciferol). The NF contains concentrations of vitamin D provided by vitamin D2 in the ranges of 580–595 μg/g. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods and beverages, including food for special medical purposes and food supplements. The target population is the general population except for food supplements and Foods for Special Medical Purposes (FSMPs), for which the target population is individuals above 1 year of age. The Panel concludes that the NF, used as an ingredient, is safe for the general population at the proposed condition of use in foods and beverages and that the NF used as a food supplement, is safe for individuals above 1 year.

2021 - Safety of Wolffia globosa powder as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Kouloura, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on Wolffia globosa powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Wolffia globosa is an aquatic plant, one out of the 38 species of the water lentil family which is composed by five genera (i.e. Spirodela, Landoltia, Lemna, Wolffiella and Wolffia). The NF is produced by cultivation of Wolffia globosa plants under controlled conditions, washing with hot water and drying. The main constituents of the NF are protein, fibre and fat. The Panel notes that the concentration of trace elements and contaminants in the NF is highly dependent on the conditions of cultivation of the plant and the fertiliser composition. The NF is intended to be used as food ingredient in a variety of food categories and as food supplement. The target population is the general population except for food supplements which are intended to be consumed exclusively by adults. The Panel considers that with the exception of concerns related to the manganese intake, taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The subchronic toxicity study provided with the NF revealed a number of significant findings and the Panel considers the middle dose (6.5 g/kg body weight (bw) per day) as the no observed adverse effect level (NOAEL). Based on the protein concentration, the Panel considers that the consumption of the NF may trigger allergic reactions. The Panel concluded that an increase in manganese intake from the NF used as food ingredient or food supplements is of safety concern and the safety of the NF cannot be established.

2021 - Safety of a change in the conditions of use of galacto-oligosaccharides as a novel food ingredient in food supplements pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the change in the conditions of use of galacto-oligosaccharides (GOS) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of GOS, consisting of different galactosyl residues (two to nine) linked to a terminal glucose by a β-glycosidic bond but also contains lactose and its monomers (galactose and glucose). The NF is a syrup containing ≥ 55% GOS (w/w dry matter) and is produced enzymatically by two β-galactosidases. GOS produced by β-galactosidases according to the same production process is already authorised and included in the EU Union list of novel foods. This application is limited to an assessment of the proposed increase of the use level as food supplement. The proposed change in the conditions of use increases the maximum level in food supplements from 0.333 kg GOS/kg food supplement (33.3%) to 0.450 kg GOS/kg food supplement (45.0%). Since it is recommended that individuals consume no more than 3 servings of 12 g/day, the maximum recommended daily intake would be no more than 16.2 g GOS. No new food uses or other increases to the already approved use levels are being proposed. The information provided on the proposed use levels and anticipated intake do not raise safety concerns. The Panel concludes that the proposed increase in the maximum level of galacto-oligosaccharides as a NF in food supplements is safe under the proposed changes in conditions of use.

2021 - Safety of calcidiol monohydrate produced by chemical synthesis as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Peláez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhauser-Berthold, Monika; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; van Loveren, Henk; Dumas, Céline; Roldán-Torres, Ruth; Steinkellner, Hans; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of calcidiol monohydrate as a novel food (NF) pursuant to Regulation (EU) 2015/2283, including its bioavailability as a metabolite of vitamin D3 when added for nutritional purposes to food supplements. The NF is produced chemically. It is proposed in food supplements up to 10 lg/day for individuals > 11 years of age, including pregnant and lactating women and up to 5 lg/day in 3- to 10-year-old children. The production process, composition, specifications and stability of the NF do not raise safety concerns. Animal and human data indicate efficient absorption. The NF contains a fraction of nanoparticles, which are fat soluble and unlikely to reach systemic distribution. There are no concerns regarding genotoxicity. Human adult studies do not raise safety concerns. Combined intake estimates of calcidiol from the NF and calcidiol and vitamin D from the diet were below the tolerable upper intake level (UL) for vitamin D for subjects above 11 years of age. The achieved mean serum 25(OH)D concentration in adults supplemented with 10 lg NF per day remained below 200 nmol/L. The Panel concludes that the NF is safe under the proposed conditions of use and use levels for individuals > 11 years old, including pregnant and lactating women. The applicant did not provide data on the bioavailability and safety of the NF in children. The combined intake estimation in children (3-10 years) is close to the UL for vitamin D. Therefore, the Panel could not conclude on the safety of consumption of the NF in children (3-10 years) at the proposed daily intake. The NF is a bioavailable source of the biologically active metabolite of vitamin D, i.e. 1,25-dihydroxyvitamin D. (C) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2021 - Safety of calcium fructoborate as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Peláez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhauser-Berthold, Monika; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; van Loveren, Henk; Rossi, Annamaria; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on calcium fructoborate as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF, produced by chemical synthesis, contains a maximum of 2.9% of boron and on average 4.7% calcium and 84.2% fructose. It is intended to be marketed as food supplements targeting the general adult population, excluding pregnant and lactating women, at a maximum level of 220 mg/day (maximum boron intake of 6.4 mg per day). The combined intake of boron from the background diet and the NF is in the range of 9.6-9.9 mg/day (corresponding to up to 0.14 mg/kg body weight (bw) per day given a default bw of 70 kg). This is in the range of the acceptable daily intake (ADI) of 0.16 mg/kg bw per day. Under conditions mimicking the gastrointestinal (GI) environment, the NF is fully hydrolysed and the Panel considered boron toxicity relevant for the safety assessment. The Panel considers that there is no concern with respect to genotoxicity of the NF. The effect induced by the NF in a 13-week rat study is consistent with toxicological findings induced by treatment with boron compounds in animal studies. Epididymides-to-brain weight ratio was identified as the most relevant endpoint and the reference point derived was the lowest model averaged BMDL10 value of 529 mg/kg bw per day. This corresponds to 14.8 mg/kg bw per day of boron, which is higher than the critical no observed adverse effect level (NOAEL) (9.6 mg boron/kg bw per day) used for establishing the ADI of 0.16 mg/kg bw per day for boron. The Panel therefore applied the present ADI for boron in the assessment of the NF. The Panel concludes that the NF, calcium fructoborate, is safe under the proposed uses and use levels.

2021 - Safety of dried fruits of Synsepalum dulcificum as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser-Berthold, Monika; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; van Loveren, Henk; Matijević, Leonard; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on dried fruits of Synsepalum dulcificum as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is pitted and dried (by lyophilisation) fruits of S. dulcificum. The NF contains the glycoprotein miraculin (≤ 2.5%) which causes sour and acidic foods to taste sweet. The fruits have a documented history of consumption in Africa and products thereof can be found in different markets worldwide. Information on the production process and the composition of the NF is sufficient and does not raise safety concerns. The applicant proposes to use the NF as or in food supplements for the adult population, excluding pregnant and lactating women, at a maximum daily amount of 0.9 g. Taking into account these conditions of use, the Panel considers that the consumption of the NF is not nutritionally disadvantageous. The provided genotoxicity studies do not raise concerns for genotoxicity of the NF. The Panel concludes that the only dose tested in a 90-day oral toxicity study of 2,000 mg/kg body weight (bw) per day was not associated with adverse effects. By applying an uncertainty factor of 200, the Panel concludes that the NF is safe at an intake level of 10 mg/kg bw per day, corresponding to a maximum daily intake of 0.7 g of the NF for the target population, rather than 0.9 g/day as proposed by the applicant.

2021 - Safety of dried yellow mealworm (Tenebrio molitor larva) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on dried yellow mealworm (Tenebrio molitor larva) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The term yellow mealworm refers to the larval form of the insect species Tenebrio molitor. The NF is the thermally dried yellow mealworm, either as whole dried insect or in the form of powder. The main components of the NF are protein, fat and fibre (chitin). The Panel notes that the levels of contaminants in the NF depend on the occurrence levels of these substances in the insect feed. The Panel notes that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf life. The NF has a high protein content, although the true protein levels in the NF are overestimated when using the nitrogen-to-protein conversion factor of 6.25, due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF as whole, dried insect in the form of snacks, and as a food ingredient in a number of food products. The target population proposed by the applicant is the general population. The Panel notes that considering the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The submitted toxicity studies from the literature did not raise safety concerns. The Panel considers that the consumption of the NF may induce primary sensitisation and allergic reactions to yellow mealworm proteins and may cause allergic reactions in subjects with allergy to crustaceans and dust mites. Additionally, allergens from the feed may end up in the NF. The Panel concludes that the NF is safe under the proposed uses and use levels.

2021 - Safety of extended uses of UV-treated baker's yeast as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser-Berthold, Monika; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; van Loveren, Henk; Gelbmann, Wolfgang; Knutsen, Helle Katrine
abstract

In 2014, the EFSA NDA Panel concluded that UV-treated baker's yeast containing up to 3.5 Mio IU of vitamin D/100 g, is safe under the proposed conditions of use for yeast-leavened breads, rolls and fine bakery wares, and food supplements. Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on an application for an extension of the use of UV-treated baker's yeast as a novel food (NF) pursuant to Regulation (EU) 2015/2283. In this extension of use, the applicant proposed a broad range of food categories to which the NF can be added. On the basis of the proposed uses and maximum use levels, the Panel estimated the potential exposure to vitamin D from the NF and the potential combined exposure to vitamin D including also exposure from the background diet and food supplements. The Panel notes that the upper level (UL) for one age group, i.e. children aged 4-10 years, is exceeded by 4%, when summing up the highest P95 estimate for the background diet (including food supplements) and the highest P95 estimate for vitamin D from the NF under the proposed uses and maximum use levels. The Panel notes, however, the highly conservative approach for estimating the potential intake of vitamin D from the NF, given that the applicant has proposed 34 FoodEx2 level 2 food categories. Thus, the Panel considers that the UL for children aged between 4 and 10 years is highly unlikely to be exceeded. The Panel concludes that the NF is safe under the proposed conditions of use.

2021 - Safety of frozen and dried formulations from migratory locust (Locusta migratoria) as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Azzollini, D.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Food and Food Allergens (NDA) was asked to deliver an opinion on the safety of frozen and dried formulations from migratory locust (Locusta migratoria) as a novel food pursuant to Regulation (EU) 2015/2283. The term migratory locust refers to the adult of the insect species Locusta migratoria. The NF is proposed in three formulations i) frozen without legs and wings; ii) dried without legs and wings; iii) ground with legs and wings. The main components of the NF are protein, fat and fibre (chitin) in the dried form of the NF, and water, protein, fat and fibre (chitin) in the frozen form of the NF. The Panel notes that the concentration of contaminants in the NF depends on the occurrence levels of these substances in the insect feed. The Panel notes that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf-life. The NF has a high protein content, although the true protein levels in the NF are overestimated when using the nitrogen-to-protein conversion factor of 6.25, due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF as frozen, dried and ground in the form of snack, and as a food ingredient in a number of food products. The target population proposed by the applicant is the general population. The Panel notes that considering the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The submitted history of use and toxicity studies from literature did not raise safety concerns. The Panel considers that the consumption of the NF might trigger primary sensitisation to L. migratoria proteins and may cause allergic reactions in subjects with allergy to crustaceans, mites and molluscs. Additionally, allergens from the feed may end up in the NF. The Panel concludes that the NF is safe under the proposed uses and use levels.

2021 - Safety of frozen and dried formulations from whole house crickets (Acheta domesticus) as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Goumperis, T.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Food and Food Allergens (NDA) was asked to deliver an opinion on the safety of frozen and dried formulations from house crickets (Acheta domesticus) as a novel food pursuant to Regulation (EU) 2015/2283. The NF is proposed in three formulations: (i) frozen, (ii) dried, (iii) ground. The main components of the NF are protein, fat and fibre (chitin) in the dried form of the NF, and water, protein, fat and fibre (chitin) in the frozen form of the NF. The Panel notes that the concentrations of contaminants in the NF depend on the occurrence levels of these substances in the insect feed. The Panel further notes that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf-life. The NF has a high-protein content, although the true protein levels in the NF are overestimated when using the nitrogen-to-protein conversion factor of 6.25, due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF in the form of a snack, and as a food ingredient in a number of food products. The target population proposed by the applicant is the general population. The Panel notes that, considering the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The Panel notes that no genotoxicity and no subchronic toxicity studies with the NF were provided by the applicant. Considering that no safety concerns arise from the history of use of A. domesticus or from the compositional data of the NF, the Panel identified no other safety concerns than allergenicity. The Panel considers that the consumption of the NF might trigger primary sensitisation to A. domesticus proteins and may cause allergic reactions in subjects allergic to crustaceans, mites and molluscs. Additionally, allergens from the feed may end up in the NF. The Panel concludes that the NF is safe under the proposed uses and use levels.

2021 - Safety of frozen and dried formulations from whole yellow mealworm (Tenebrio molitor larva) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on frozen and dried formulations from whole yellow mealworm (Tenebrio molitor larva) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The term yellow mealworm refers to the larval form of the insect species Tenebrio molitor. The NF comprises the frozen and freeze-dried formulations of the yellow mealworm, whole or in the form of powder. The frozen formulation consists mainly of water, crude protein and fat whereas the freeze-dried formulations of crude protein, fat, digestible carbohydrates and fibre (chitin). The Panel notes that the levels of contaminants in the NF depend on the occurrence levels of these substances in the insect feed. The Panel notes furthermore that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf-life. The dried formulations of the NF have a high protein content, although the true protein levels in the NF are overestimated when using the nitrogen-to-protein conversion factor of 6.25, due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF as whole frozen or whole dried insect, or in the form of powder, added as an ingredient to various food products such as cereal bars, pasta, meat imitates and bakery products. The target population is the general population. The Panel notes that, considering that the NF will not be the sole source of dietary protein, and the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The submitted toxicity studies from the literature did not raise safety concerns. The Panel considers that the consumption of the NF may induce primary sensitisation and allergic reactions to yellow mealworm proteins and may cause allergic reactions in subjects with allergy to crustaceans and dust mites. Additionally, allergens from the feed may end up in the NF. The Panel concludes that the NF is safe under the proposed uses and use levels.

2021 - Safety of iron hydroxide adipate tartrate as a novel food pursuant to Regulation (EU) 2015/2283 and as a source of iron in the context of Directive 2002/46/EC [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Ildico Hirsch-Ernst, K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Rudolf Schlatter, J.; van Loveren, H.; Germini, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on iron hydroxide adipate tartrate as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and as a source of iron in the context of Directive 2002/46/EC. The NF is intended to be used in food supplements up to a maximum dose of 100 mg per day, corresponding to a maximum daily intake of iron of 36 mg. The target population proposed by the applicant is the general population above 3 years of age. The NF which is the subject of the application is an engineered nanomaterial having primary particles, of almost spherical morphology, with a diameter typically smaller than 5 nm. The studies provided for absorption, distribution, metabolism and excretion (ADME) and bioavailability indicate that iron, once taken up into the epithelial cells of the gut, is subject to the same mechanisms of regulation and absorption as that of other forms of iron. Further studies provided in the context of the toxicological assessment indicate that the NF does not lead to iron bioaccumulation in tissues and organs at the doses tested. The Panel notes that the NF contains nickel at concentrations that may increase the risk of flare-up reactions in nickel-sensitised young individuals up to 10 years of age. In the 90-day toxicity study, findings related to haematology, clinical biochemistry and organ weights were observed and the Panel defined a no observed adverse effect level (NOAEL) of 231 mg/kg body weight (bw) per day, that is, the mid-dose used in the study. The Panel considers that the NF is a source from which iron is bioavailable and it is safe under the proposed conditions of use.

2021 - Safety of mung bean protein as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Fernandez, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on mung bean protein as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF, which is the subject of the application, is mung bean protein extracted from seeds of the plant Vigna radiata. The NF is proposed to be used as a food ingredient added to ‘protein products, excluding products covered in category 1.8’. The target population is the general population. The maximum estimated intake of the NF is 758 and 260 mg/kg body weight (bw) per day in children and adults, respectively. The major constituents of this NF are protein (~85%), fat (3–4%) and moisture (3–5.5%). The NF is rich in protein which is well digestible and provides sufficient amounts of most essential amino acids but only limited amounts of sulfur-containing amino acids. The Panel notes that the cumulative exposure to the minerals analysed does not raise concern. The reported values for the levels of antinutritional factors in the NF are comparable to those in other foodstuffs. The Panel considers that taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. No toxicological studies with the NFs were provided by the applicant; however, the Panel considers that no toxicological studies are required on this NF. This NF has the potential capacity to sensitise individuals and to induce allergic reactions in individuals allergic to soybean, peanuts, lupin and to birch pollen. The Panel considers that the NF, i.e. mung bean protein, is safe at the proposed conditions of use.

2021 - Safety of oil from Schizochytrium limacinum (strain FCC-3204) for use in food supplements as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single-cell microalga. The strain FCC-3204, used by the applicant (Fermentalg), belongs to the species Schizochytrium limacinum. The NF, an oil rich in docosahexaenoic acid (DHA), is obtained from microalgae after enzymatic lysis. The applicant proposed to increase the use level of the NF as a food supplement, from 250 mg DHA/day (currently authorised for the general population, excluding pregnant and lactating women) to 3 g DHA/day for adults, excluding pregnant and lactating women. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’. Data provided by the applicant demonstrated the absence of viable cells in the NF. No toxicological studies were performed with the NF. However, based on the available toxicological data on oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process, the composition of the NF and the absence of viable cells in the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel considers that the data provided by the applicant are not sufficient to conclude on the safety of the NF at the proposed uses (3 g DHA/day as a food supplement) in adults. However, in 2012, the Panel concluded that supplemental intakes of DHA alone up to about 1 g/day do not raise safety concerns for the general population. The Panel concludes that the NF is safe for the use in food supplements at the maximum intake level of 1 g DHA/day for the target population (adults, excluding pregnant and lactating women).

2021 - Safety of oil from Schizochytrium limacinum (strain FCC-3204) for use in infant and follow-on formula as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single-cell microalga. The strain FCC- 3204, used by the applicant (Fermentalg), belongs to the species Schizochytrium limacinum. The NF, an oil rich in docosahexaenoic acid (DHA), is obtained from microalgae after enzymatic lysis. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use level defined by the applicant was derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20–50 mg/100 kcal. The intake of DHA resulting from the use of the NF in IF and FOF is not expected to pose safety concerns. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’. Data provided by the applicant demonstrated the absence of viable cells in the NF. No toxicological studies were performed with the NF. However, based on the available toxicological data on oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process, the composition of the NF and the absence of viable cells in the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

2021 - Safety of pasteurised Akkermansia muciniphila as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on pasteurised Akkermansia muciniphila as a novel food (NF) pursuant to Regulation (EU) 2015/2283. A. muciniphila is a well-characterised non-toxin producing, avirulent microorganism that has been reported as part of normal gut microbiota. The NF, pasteurised A. muciniphila, is proposed by the applicant to be used as a food supplement at max. 5 × 1010 cells/day by adults excluding pregnant and lactating women, and in foods for special medical purposes. The Panel considers that the production process of the NF is sufficiently described and that the information provided on the composition of the NF is sufficient for its characterisation. Taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. Based on literature data, and by applying an uncertainty factor of 200 to the no observed adverse effect level (NOAEL) of a 90-day repeated dose oral toxicity study in rats, the Panel concludes that the consumption of 3.4 × 1010 cells/day is safe for the target population under the provision that the number of viable cells in the NF is < 10 colony forming units (CFU)/g (i.e. limit of detection).

2021 - Safety of tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Kouloura, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Tetrahydrocurcuminoids are derivatives of curcuminoids, produced chemically by hydrogenation of curcuminoids extracted from the rhizomes of C. longa L. The NF consists of more than 95% of tetrahydrocurcuminoids. The applicant proposed to use the NF in food supplements at a maximum dose of 300 mg/day for adults excluding pregnant and lactating women. Taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day oral toxicity study and a reproduction/developmental toxicity screening test performed with the NF, the Panel derives a safe level of 2 mg/kg body weight per day. For the target population this level corresponds to 140 mg/day, which is lower than the use level as proposed by the applicant. The Panel concludes that the NF, tetrahydrocurcuminoids from turmeric (C. longa L.), is safe for the target population at 140 mg/day.

2021 - Safety of the extension of use of galacto-oligosaccharides as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the extension of use of galacto-oligosaccharides (GOS) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a syrup containing ≥ 57% w/w GOS (w/w dry matter), consisting of different galactosyl residues linked to a terminal glucose by a β-glycosidic bond and also containing lactose and the constituent monomers of lactose (galactose and glucose). The NF is already authorised and included in the Union list of NFs and is produced according to the same production process. This application is limited to an assessment of the extension of use as a food ingredient in dairy confectionary, cheese and processed cheese, butter and spreads. There is a 10–30% increase in total GOS intake from the requested extension of use compared to the currently authorised uses at the highest 95th percentile. It is noted that the total intake at the highest mean (8.7–22.0 g/day) is below the adequate intake (AI) of 25 g/day for dietary fibre set to ensure a normal laxation in adults, while the highest 95th percentile (27.2–41.6 g/day) is higher than the AI. When the maximum use as a food supplement is added to the highest 95th percentile combined intake from all proposed and authorised food categories a total intake up to 58 g GOS/day is estimated. This highest intake level would exceed the AI for dietary fibre; however, no tolerable upper intake level for dietary fibre has been set and only transient gastrointestinal symptoms may be related to high intake of fibre. The Panel concludes that the NF, that is composed of ≥ 57% GOS dry matter, lactose and related saccharides, is safe under the proposed extension of use.

2021 - Safety of water extract of Cistanche tubulosa stems as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on water extract of Cistanche tubulosa stems as a novel food (NF) for its use in food supplements (FS) and foods for special medical purposes (FSMP). The target population is the general adult population excluding pregnant and lactating women. The applicant proposes a maximum daily intake of 2 g for FS and a maximum use level of 10% in FSMP. The characteristic components of the extract are phenylethanoid glycosides (at least 70% of the NF), in particular, echinacoside (25–45% of the NF). The NF has been authorised as a prescription drug in China in 2005 for the treatment of vascular dementia. The Panel notes that an integrated analysis of three studies covering 1,076 patients with vascular dementia treated with the proposed NF at a daily dose of 1,800 mg, reported that 12 adverse events (AEs) were classified to be ‘definitely’, ‘probably’ or ‘possibly related’ to the exposure to the NF. Two of these AE were classified as severe (cerebral haemorrhage and epilepsy). The Panel considers that the reported AEs raise safety concerns. The Panel also notes the limitations of the provided toxicological studies, in particular the non-compliance with the EFSA approach on the genotoxicity testing strategy and the non-compliance with good laboratory practice (GLP) and the respective OECD Guidance documents of the repeated dose toxicity studies. In view of the AEs in the human studies, the Panel considers that additional toxicological studies, following testing guidelines would not be able to overcome the concerns raised from the human studies. The Panel concludes that the safety of the NF has not been established.

2021 - Safety of water lentil powder from Lemnaceae as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Kouloura, E.; Steinkellner, H.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of water lentil powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Water lentils refer to aquatic plants belonging to the Araceae family and represented by five genera (Lemna, Wolffia, Wolffiella, Landoltia and Spirodela). The NF is thermally washed and dried water lentils, which are produced as a polyculture crop consisting of species from the Lemna genus (70–100%) and the Wolffia genus (0–30%). The main constituents of the NF are protein, fibre and fat. The Panel notes that the concentration of trace elements and contaminants in the NF is highly dependent on the conditions of cultivation of the plant and the fertiliser composition. The NF is expected to be stable and to comply with the specifications during the suggested shelf life. The NF is intended for human consumption as a food ingredient in herbs, spices and seasonings, sauces, soups and broths, protein products, dietary food for weight control and as a food supplement. The target population is the general population, except for food supplements which are exclusively intended for consumption by adults. The Panel considers that based on the composition of the NF and the proposed intended uses, the NF is not nutritionally disadvantageous, except for the concerns regarding intake of manganese from the NF. No adverse effect was observed in the submitted 90-day subchronic study, at the highest dose, 1,000 mg/kg body weight (bw) per day of NF. The Panel considers that, based on the protein concentration, the consumption of the NF may trigger allergic reactions. The Panel concluded that an increase in manganese intake from the NF used as food ingredient or food supplements is of safety concern and the safety of the NF cannot be established.

2021 - Scientific and technical guidance for the preparation and presentation of a dossier for evaluation of an infant and/or follow-on formula manufactured from protein hydrolysates (Revision 1) 1 [Articolo su rivista]
Turck, D.; Bresson, J. -L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K. I.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Neuhauser-Berthold, M.; Nowicka, G.; Pentieva, K.; Sanz, Y.; Sjodin, A.; Stern, M.; Tome, D.; Loveren, H. V.; Vinceti, M.; Willatts, P.; Fewtrell, M.; Przyrembel, H.; Titz, A.; Martinez, S. V.
abstract

(Table presented.). Following a request from the European Commission, EFSA was asked to provide scientific and technical guidance for the preparation and presentation of a dossierfor evaluation of an infant and/or follow-on formula manufactured from protein hydrolysates. This guidance document addresses the information and data to be submitted to EFSA on infant and follow-on formulae manufactured from protein hydrolysates with respect to the nutritional safety and suitability of the specific formula and/or the formula's efficacy in reducing the risk of developing allergy to milk proteins. The guidance will be further reviewed and updated with the experience gained from the evaluation of specificdossiers, and in the light of applicable Unionguidelines and legislation. The guidance was adopted by the Panel on Dietetic Products, Nutrition and Allergies on 5 April 2017.Upon request from the European Commission in 2020, it has been revised to inform food business operators of the new provisions in the pre-submission phase and in the procedure set out in the General Food Law, as amended by the Transparency Regulation. This revised guidance applies to all dossiers submitted as of 27 March 2021 and shall be consulted for the preparation of dossiers intended to be submitted from that date onwards. For dossiers submitted prior to 27 March 2021, the previous guidance, published in May 2017 remains applicable.

2021 - Scientific opinion on the relationship between intake of alpha-lipoic acid (thioctic acid) and the risk of insulin autoimmune syndrome [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; de Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Mangelsdorf, Inge; McArdle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cappellani, Daniele; Ijzerman, Richard; Van Loveren, Henk; Titz, Ariane; Maciuk, Alexandre
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the relationship between alpha-lipoic acid (ALA) and the risk of insulin autoimmune syndrome (IAS). The Panel was also asked to advise on the dose below which ALA added to foods is not expected to cause IAS. A review of all possible adverse effects associated with consumption of ALA was not requested. This mandate refers to the procedure under Article 8(2) of Regulation (EC) No 1925/2006 on addition of vitamins, minerals and certain other substances to foods. No pre-established rule exists for the evaluation of the safety of foods when classical toxicity tests cannot be used, e.g. for autoimmune diseases. Published scientific evidence was retrieved through comprehensive literature searches, particularly 49 case reports in which IAS developed following ALA consumption. In all cases, IAS resolved after a few weeks to months when ALA was discontinued. No publication linking the intake of ALA naturally occurring in foods to IAS was identified. The Panel concludes that the consumption of ALA added to foods, including food supplements, is likely to increase the risk of developing IAS in individuals with certain genetic polymorphisms, who cannot be readily identified without genetic testing. The plausible mechanism of such an effect has not yet been fully elucidated. The incidence of IAS in Europe is low and likely lower than in Japan where it has been estimated to be 0.017 per 100,000 inhabitants in 2017-2018. Considering the limited data available, the risk associated with the development of IAS following ALA consumption cannot be quantified precisely. An ALA dose below which IAS is not expected to occur is likely to vary between individuals and cannot be determined from the available data. (c) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2021 - Seroprevalence of anti-SARS-CoV-2 antibodies after the first COVID-19 wave: a cross-sectional study in the province of Modena, city of a Northern Italy region [Abstract in Rivista]
Berselli, N; Filippini, T; Paduano, S; Malavolti, M; Modenese, A; Gobba, F; Borella, P; Marchesi, I; Vivoli, R; Perlini, P; Bellucci, R; Bargellini, A; Vinceti, M
abstract

2021 - Seroprevalence of anti-SARS-CoV-2 antibodies in the Northern Italy population before the COVID-19 second wave [Articolo su rivista]
Berselli, Nausicaa; Filippini, Tommaso; Paduano, Stefania; Malavolti, Marcella; Modenese, Alberto; Gobba, Fabriziomaria; Borella, Paola; Marchesi, Isabella; Vivoli, Roberto; Perlini, Paola; Bellucci, Rossana; Bargellini, Annalisa; Vinceti, Marco
abstract

The COVID-19 pandemic is due to SARS-CoV-2 coronavirus infections. It swept across the world in the spring of 2020, and so far it has caused a huge number of hospitalizations and deaths. In the present study, the authors investigated serum anti-SARS-CoV-2 antibody prevalence in the period of June 1-September 25, 2020, in 7561 subjects in Modena, Northern Italy.

2021 - Sodium and potassium content of foods consumed in an italian population and the impact of adherence to a mediterranean diet on their intake [Articolo su rivista]
Malavolti, M.; Naska, A.; Fairweather-Tait, S. J.; Malagoli, C.; Vescovi, L.; Marchesi, C.; Vinceti, M.; Filippini, T.
abstract

High sodium and low potassium intakes are associated with increased levels of blood pressure and risk of cardiovascular diseases. Assessment of habitual dietary habits are helpful to evaluate their intake and adherence to healthy dietary recommendations. In this study, we determined sodium and potassium food-specific content and intake in a Northern Italy community, focusing on the role and contribution of adherence to Mediterranean diet patterns. We collected a total of 908 food samples and measured sodium and potassium content using inductively coupled plasma mass spectrometry. Using a validated semi-quantitative food frequency questionnaire, we assessed habitual dietary intake of 719 adult individuals of the Emilia-Romagna region. We then estimated sodium and potassium daily intake for each food based on their relative contribution to the overall diet, and their link to Mediterranean diet patterns. The estimated mean sodium intake was 2.15 g/day, while potassium mean intake was 3.37 g/day. The foods contributing most to sodium intake were cereals (33.2%), meat products (24.5%, especially processed meat), and dairy products (13.6%), and for potassium they were meat (17.1%, especially red and white meat), fresh fruits (15.7%), and vegetables (15.1%). Adherence to a Mediterranean diet had little influence on sodium intake, whereas potassium intake was greatly increased in subjects with higher scores, resulting in a lower sodium/potassium ratio. Although we may have underestimated dietary sodium intake by not including discretionary salt use and there may be some degree of exposure misclassification as a result of changes in food sodium content and dietary habits over time, our study provides an overview of the contribution of a wide range of foods to the sodium and potassium intake in a Northern Italy community and of the impact of a Mediterranean diet on intake. The mean sodium intake was above the dietary recommendations for adults of 1.5–2 g/day, whilst potassium intake was only slightly lower than the recommended 3.5 g/day. Our findings suggest that higher adherence to Mediterranean diet patterns has limited effect on restricting sodium intake, but may facilitate a higher potassium intake, thereby aiding the achievement of healthy dietary recommendations.

2021 - Statement on additional scientific evidence in relation to the essential composition of total diet replacement for weight control [Articolo su rivista]
Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Knutsen, H. K.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Titz, A.; Turck, D.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to revise the Opinion on the essential composition of total diet replacements for weight control (TDRs) regarding the minimum content of linoleic acid (LA) and alpha-linolenic acid (ALA) and the maximum content of magnesium (Mg). Through a comprehensive literature search, human studies were retrieved reporting on LA and ALA concentrations in adipose tissue (AT), on weight loss and gallstone formation following TDR consumption and on diarrhoea after supplemental Mg intake. The distribution of the amount of LA and ALA release from AT during weight loss when consuming TDRs was estimated using statistical simulations. Using the fifth percentile, the coverage of the adequate intake (AI) for both FA was estimated. For the risk of developing diarrhoea when consuming TDRs with an Mg content of 350 mg/day, four cross-over studies using 360–368 mg Mg/day were reviewed. The Panel concludes that (1) there is no need to add LA to TDRs, as the amount released from AT during weight loss when consuming TDRs is sufficient to cover the AI for LA; (2) a minimum of 0.8 g/day ALA is needed in TDRs in order to meet the AI for ALA; (3) the minimum fat content of TDRs of 20 g/day as derived in the Panel's previous opinion is proposed to be maintained until the availability of further evidence, given the considerable uncertainty as to the amount of fat required for reducing the risk of gallstone formation; and (4) the likelihood that Mg-induced diarrhoea occurs at a severity that may be considered of concern for overweight and obese individuals consuming TDRs is low when the total maximum Mg content in TDRs is 350 mg/day.

2021 - Studio di fattori di rischio/protettivi associati alla risposta anticorpale anti-SARS-CoV-2 in un campione di lavoratori della provincia di Modena e province limitrofe [Abstract in Rivista]
Paduano, S; Modenese, A; Filippini, T; Berselli, N; Marchesi, I; Vinceti, M; Borella, P; Gobba, F; Bargellini, A
abstract

2021 - Systematic Review and Meta-analysis on Association Between Air Pollutants and Hippocampal Volume from Magnetic Resonance Imaging in Adults [Abstract in Rivista]
Balboni, Erica; Filippini, Tommaso; Vinceti, Marco
abstract

BACKGROUND AND AIM: The neurotoxicity of air pollutants has been actively investigated in recent years, and there is increasing epidemiological evidence suggesting that air pollution can adversely affect the central nervous system. In neurodegenerative disease, one important diagnostic biomarker is volume reduction in a key brain structure, the hippocampus, as assessed with neuroimaging techniques. Few epidemiological articles investigated the association of hippocampal volume with air pollution, with inconsistent results. In this paper, we aimed to estimate such association through a systematic review and meta-analysis. METHODS: Scopus and PubMed literature databases were searched through 31 March 2021. Eligibility criteria were: 1) assessment of air pollutant levels; 2) assessment of hippocampal volume through structural magnetic resonance imaging; 3) reporting of correlation coefficients along with standard error. We performed a meta-analysis using a random-effects model. RESULTS:We retrieved four studies using linear regression models to evaluate the possible effect of air pollutants on hippocampal volume of adult populations. The investigated air pollutants were nitrogen dioxide (NO2) and particulate matter, with diameter ≤2.5µm (PM2.5) and ≤10μm (PM10). All studies used a similar methodology based on standard spatial coordinates of images, and considered intracranial volume as a covariate. We found that hippocampal volume was inversely associated with PM2.5 concentration (β regression coefficient -7.90, 95% confidence interval (CI) -14.60 to -1.20) and more slightly with PM10 concentrations (β -1.70, 95%CI -3.96 to 0.57), whereas no association with NO2 concentrations emerged (β -0.29, 95%CI -1.13 to 0.55). CONCLUSIONS:Our results suggest that PM2.5 and less clearly PM10 have an adverse effect on hippocampal volume, a phenomenon associated with cognitive decline and increased risk of neurodegenerative disease. These epidemiologic findings appear to be biologically plausible especially for PM2.5, also taking into account some studies carried out in animals. KEYWORDS: Neurotoxicity, Neuroimaging, Magnetic Resonance Imaging, Hippocampus, Meta-analysis, Nitrogen dioxide

2021 - The association between air pollutants and hippocampal volume from magnetic resonance imaging: A systematic review and meta-analysis [Articolo su rivista]
Balboni, Erica; Filippini, Tommaso; Crous-Bou, Marta; Guxens, Monica; Erickson, Lance D; Vinceti, Marco
abstract

Growing epidemiological evidence suggests that air pollution may increase the risk of cognitive decline and neurodegenerative disease. A hallmark of neurodegeneration and an important diagnostic biomarker is volume reduction of a key brain structure, the hippocampus. We aimed to investigate the possibility that outdoor air nitrogen dioxide (NO2) and particulate matter with diameter ≤2.5  μm (PM2.5) and ≤10 μm (PM10) adversely affect hippocampal volume, through a meta-analysis. We considered studies that assessed the relation between outdoor air pollution and hippocampal volume by structural magnetic resonance imaging in adults and children, searching in Pubmed and Scopus databases from inception through July 13, 2021. For inclusion, studies had to report the correlation coefficient along with its standard error or 95% confidence interval (CI) between air pollutant exposure and hippocampal volume, to use standard space for neuroimages, and to consider at least age, sex and intracranial volume as covariates or effect modifiers. We meta-analyzed the data with a random-effects model, considering separately adult and child populations. We retrieved four eligible studies in adults and two in children. In adults, the pooled summary β regression coefficients of the association of PM2.5, PM10 and NO2 with hippocampal volume showed respectively a stronger association (summary β -7.59, 95%CI -14.08 to -1.11), a weaker association (summary β -2.02, 95%CI -4.50 to 0.47), and no association (summary β -0.44, 95%CI -1.27 to 0.40). The two studies available for children, both carried out in preadolescents, did not show an association between PM2.5 and hippocampal volume. The inverse association between PM2.5 and hippocampal volume in adults appeared to be stronger at higher mean PM2.5 levels. Our results suggest that outdoor PM2.5 and less strongly PM10 could adversely affect hippocampal volume in adults, a phenomenon that may explain why air pollution has been related to memory loss, cognitive decline, and dementia.

2021 - The association between first and second wave COVID-19 mortality in Italy [Articolo su rivista]
Vinceti, M.; Filippini, T.; Rothman, K. J.; Di Federico, S.; Orsini, N.
abstract

Background: The relation between the magnitude of successive waves of the COVID-19 outbreak within the same communities could be useful in predicting the scope of new outbreaks. Methods: We investigated the extent to which COVID-19 mortality in Italy during the second wave was related to first wave mortality within the same provinces. We compared data on province-specific COVID-19 2020 mortality in two time periods, corresponding to the first wave (February 24–June 30, 2020) and to the second wave (September 1–December 31, 2020), using cubic spline regression. Results: For provinces with the lowest crude mortality rate in the first wave (February–June), i.e. < 22 cases/100,000/month, mortality in the second wave (September–December) was positively associated with mortality during the first wave. In provinces with mortality greater than 22/100,000/month during the first wave, higher mortality in the first wave was associated with a lower second wave mortality. Results were similar when the analysis was censored at October 2020, before the implementation of region-specific measures against the outbreak. Neither vaccination nor variant spread had any role during the study period. Conclusions: These findings indicate that provinces with the most severe initial COVID-19 outbreaks, as assessed through mortality data, faced milder second waves.

2020 - A new threat from an old enemy: Re-emergence of coronavirus (Review) [Articolo su rivista]
Docea, A. O.; Tsatsakis, A.; Albulescu, D.; Cristea, O.; Zlatian, O.; Vinceti, M.; Moschos, S. A.; Tsoukalas, D.; Goumenou, M.; Drakoulis, N.; Dumanov1, J. M.; Tutelyan, V. A.; Onischenko, G. G.; Aschner, M.; Spandidos, D. A.; Calina, D.
abstract

The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades.

2020 - Anxiofit-1 and reduction of subthreshold and mild anxiety: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from Anxiofit Ltd., submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Hungary, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Anxiofit-1 and reduction of subthreshold and mild anxiety. The food, Anxiofit-1, Echinacea angustifolia root extract, standardised for the content of echinacoside (at least 3%) and the profile of alkamides, which is the subject of the health claim, is sufficiently characterised. The Panel considers that reduction of subthreshold and mild anxiety is a beneficial physiological effect. Subthreshold and mild anxiety are risk factors for anxiety and depressive disorders. One human intervention study showed an effect of Anxiofit-1 (80 mg/day given for 7 days) on the state anxiety and not on the trait subscale in subjects with subthreshold or mild anxiety. These results are supported by two human intervention studies conducted with Anxiofit-1 at 40 mg/day for 7 days and 6 weeks, respectively, which, on their own, cannot be used for the substantiation of the claim either because of methodological limitations or because the results cannot be extrapolated to the target population for the claim. All the human intervention studies submitted have been conducted in a similar setting, the results of the study with Anxiofit-1 given at 80 mg/day have not been confirmed by other research groups. The information submitted by the applicant does not provide evidence for a plausible mechanism by which Anxiofit-1 could exert the claimed effect. The Panel concludes that the scientific evidence is insufficient to establish a cause and effect relationship between the consumption of Anxiofit-1 and reduction of subthreshold and mild anxiety.

2020 - Bifidobacterium animalis subsp. lactis Bi-07 contributes to increasing lactose digestion: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; s Bresson, J. -L.; Siani, A.
abstract

Following an application from DuPont Nutrition Biosciences ApS submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Ireland, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Bifidobacterium animalis subsp. lactis Bi-07 (Bi-07) and contribution to increasing lactose digestion. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is Bi-07. The Panel considers that Bi-07 is sufficiently characterised. The claimed effect proposed by the applicant is ‘improvement of lactose digestion’. The Panel considers that increasing lactose digestion is a beneficial physiological effect for individuals with lactose maldigestion provided that the symptoms of lactose maldigestion are improved. Two human intervention studies which investigated a single dose effect of Bi-07 on lactose digestion using the hydrogen breath test, as well as on gastrointestinal symptoms were submitted. These studies show that consumption of Bi-07 (1012 CFU) increases lactose digestion in individuals with lactose maldigestion and that Bi-07 exhibits lactase activity in vitro. However, these studies provide no evidence that increasing lactose digestion through the consumption of Bi-07 (1012 CFU) improves gastrointestinal symptoms of lactose maldigestion, which is considered a beneficial physiological effect. The Panel concludes that a cause and effect relationship has not been established between the consumption of Bifidobacterium animalis subsp. lactis Bi-07 and a beneficial physiological effect (i.e. the improvement of symptoms of lactose maldigestion) in individuals with lactose maldigestion.

2020 - COVID-19, an opportunity to reevaluate the correlation between long-term effects of anthropogenic pollutants on viral epidemic/pandemic events and prevalence [Articolo su rivista]
Tsatsakis, A.; Petrakis, D.; Nikolouzakis, T. K.; Docea, A. O.; Calina, D.; Vinceti, M.; Goumenou, M.; Kostoff, R. N.; Mamoulakis, C.; Aschner, M.; Hernandez, A. F.
abstract

Occupational, residential, dietary and environmental exposures to mixtures of synthetic anthropogenic chemicals after World War II have a strong relationship with the increase of chronic diseases, health cost and environmental pollution. The link between environment and immunity is particularly intriguing as it is known that chemicals and drugs can cause immunotoxicity (e.g., allergies and autoimmune diseases). In this review, we emphasize the relationship between long-term exposure to xenobiotic mixtures and immune deficiency inherent to chronic diseases and epidemics/pandemics. We also address the immunotoxicologic risk of vulnerable groups, taking into account biochemical and biophysical properties of SARS-CoV-2 and its immunopathological implications. We particularly underline the common mechanisms by which xenobiotics and SARS-CoV-2 act at the cellular and molecular level. We discuss how long-term exposure to thousand chemicals in mixtures, mostly fossil fuel derivatives, exposure toparticle matters, metals, ultraviolet (UV)–B radiation, ionizing radiation and lifestyle contribute to immunodeficiency observed in the contemporary pandemic, such as COVID-19, and thus threaten global public health, human prosperity and achievements, and global economy. Finally, we propose metrics which are needed to address the diverse health effects of anthropogenic COVID-19 crisis at present and those required to prevent similar future pandemics.

2020 - Cadmium exposure and risk of breast cancer: A dose-response meta-analysis of cohort studies [Articolo su rivista]
Filippini, T.; Torres, D.; Lopes, C.; Carvalho, C.; Moreira, P.; Naska, A.; Kasdagli, M. -I.; Malavolti, M.; Orsini, N.; Vinceti, M.
abstract

Background: Cadmium is a toxic heavy metal that has been implicated in breast cancer etiology, albeit with inconsistent results. Objective: To investigate the shape of the relation between cadmium exposure and breast cancer incidence and mortality in cohort studies. Data sources: Following a literature search through April 14, 2020, we carried out a systematic review and dose-response meta-analysis to investigate the shape of the relation between cadmium exposure (assessed either through diet or urine excretion) and disease incidence and mortality. Study eligibility criteria: For inclusion, a study had to report incidence or mortality for breast cancer according to baseline cadmium exposure category; be a prospective cohort, case-cohort or nested case-control study with a minimum one-year follow-up, and reporting effect estimates for all exposure categories. Study appraisal and synthesis methods: Studies were evaluated using the ROBINS-E risk of bias tool. The effects in humans were assessed quantitatively using one-stage dose-response meta-analysis in a random effects meta-analytical model. Results: We identified 10 studies eligible for inclusion in the dose-response meta-analysis, six based on cadmium dietary intake, and four on urinary excretion levels. We found a marginal and imprecise positive relation between dietary cadmium intake and breast cancer, and no association when urinary cadmium excretion was used for exposure assessment. Compared to no exposure, at 20 µg/day of cadmium intake the summary risk ratio was 1.12 (95% confidence interval 0.80–1.56), while at 2 µg/g creatinine of cadmium excretion the summary risk ratio was 0.89 (95% confidence interval 0.38–2.14). Analysis restricted to post-menopausal women showed no association between either dietary or urinary cadmium and subsequent breast cancer incidence and mortality. Limitations and conclusions: Overall, we found scant evidence of a positive association between cadmium and breast cancer. Available data were too limited to carry out stratified analyses according to age, smoking and hormone receptor status. Therefore, possible associations between cadmium exposure and breast cancer in selected subgroups cannot be entirely ruled out.

2020 - Calcium l-methylfolate as a source of folate added for nutritional purposes to infant and follow-on formula, baby food and processed cereal-based food [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Bernasconi, G.; Germini, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the extension of use of calcium l-methylfolate to be used as a source of folate added for nutritional purposes to infant and follow-on formula, baby food and processed cereal-based food pursuant to Regulation (EU) 609/2013. In 2004, EFSA assessed the use of calcium l-methylfolate as a source of folate in foods for particular nutritional uses, food supplements and foods intended for the general population. The new alternative synthetic step proposed to produce the nutrient source, using platinum as a catalyst, did not raise any safety concern and the production process was found to consistently yield a product in line with the proposed specifications. Based on the studies assessed in the previous evaluation, it was concluded that calcium l-methylfolate is non-genotoxic and that subchronic and embryotoxicity/teratogenicity studies in rats did not reveal any adverse effects up to the highest doses tested. The Panel considered that no additional toxicological studies are required on the nutrient source. The intervention study in healthy infants provided by the applicant did not indicate differences in growth and tolerance parameters in infants who consumed either an infant formula supplemented with calcium l-methylfolate or with folic acid, and did not raise concerns regarding safety or tolerability of the infant formula with the proposed nutrient source. The study also provided further supporting evidence for the bioavailability of calcium l-methylfolate. The Panel considers that calcium l-methylfolate is a source from which folate is bioavailable and concludes that calcium l-methylfolate is safe under the proposed uses and use levels for infants and young children.

2020 - Clinical and Lifestyle Factors and Risk of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study [Articolo su rivista]
Filippini, Tommaso; Fiore, Maria; Tesauro, Marina; Malagoli, Carlotta; Consonni, Michela; Violi, Federica; Arcolin, Elisa; Iacuzio, Laura; Oliveri Conti, Gea; Cristaldi, Antonio; Zuccarello, Pietro; Zucchi, Elisabetta; Mazzini, Letizia; Pisano, Fabrizio; Gagliardi, Ileana; Patti, Francesco; Mandrioli, Jessica; Ferrante, Margherita; Vinceti, Marco
abstract

Background: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease of the motor neurons. The etiology of ALS remains largely unknown, particularly with reference to the potential environmental determinants. Methods: We performed a population-based case-control study in four provinces from both Northern and Southern Italy in order to assess non-genetic ALS risk factors by collecting through tailored questionnaires information about clinical and lifestyle factors. We estimated ALS risk by calculating odds ratio (OR) with its 95% confidence interval (CI) using unconditional logistic regression models adjusted for sex, age and educational attainment. Results: We recruited 230 participants (95 cases and 135 controls). We found a possible positive association of ALS risk with trauma, particularly head trauma (OR = 2.61, 95% CI 1.19-5.72), electric shock (OR = 2.09, 95% CI 0.62-7.06), and some sports, although at a competitive level only. In addition, our results suggest an increased risk for subjects reporting use of private wells for drinking water (OR = 1.38, 95% CI 0.73-2.27) and for use of herbicides during gardening (OR = 1.95, 95% CI 0.88-2.27). Conversely, there was a suggestion of an inverse association with overall fish consumption (OR = 0.27, 95% CI 0.12-0.60), but with no dose-response relation. Consumption of some dietary supplements, namely those containing amino acids and, in the Southern Italy population, vitamins and minerals such as selenium, seemed associated with a statistically imprecise increased risk. Conclusions: Our results suggest a potential etiologic role a number of clinical and lifestyle factors with ALS risk. However, caution is needed due to some study limitations. These include the small sample size and the low number of exposed subjects, which affect statistical precision of risk estimates, the potential for exposure misclassification, and the uncertainties about mechanisms underpinning the possible association between these factors and disease risk.

2020 - Coffee C21 and protection of DNA from strand breaks: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Ildico Hirsch-Ernst, K.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from Tchibo GmbH submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Coffee C21 and protection of DNA from strand breaks. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is Coffee C21. The Panel considers that Coffee C21, a coffee standardised by its concentration of caffeoylquinic acids (CQA), trigonelline and N-methylpyridinium (NMP), is sufficiently characterised in relation to the claimed effect. The Panel considers that the claimed effect, protection of DNA from strand breaks, is a beneficial physiological effect. Out of the two human intervention studies from which conclusion could be drawn, one study provides some evidence that daily consumption of Coffee C21 (750 mL/day) for 4 weeks decreases DNA strand breaks in habitual coffee drinkers after coffee withdrawal over the previous four weeks. However, the results of this study were not replicated in another study conducted under similar conditions in the same study centre. No studies performed in a different setting, from which conclusions could be drawn, were available. No evidence has been provided for a mechanism by which coffee (including Coffee C21) would reduce DNA damage in human cells by reducing DNA strand breaks. The Panel concludes that a cause and effect relationship has not been established between the consumption of Coffee C21 and protection of DNA from strand breaks.

2020 - Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study [Articolo su rivista]
Di Castelnuovo, A.; Bonaccio, M.; Costanzo, S.; Gialluisi, A.; Antinori, A.; Berselli, Nausicaa; Blandi, L.; Bruno, R.; Cauda, R.; Guaraldi, Giovanni; My, I.; Menicanti, L.; Parruti, G.; Patti, G.; Perlini, S.; Santilli, F.; Signorelli, C.; Stefanini, G. G.; Vergori, A.; Abdeddaim, A.; Ageno, W.; Agodi, A.; Agostoni, P.; Aiello, L.; Al Moghazi, S.; Aucella, F.; Barbieri, G.; Bartoloni, A.; Bologna, C.; Bonfanti, P.; Brancati, S.; Cacciatore, F.; Caiano, L.; Cannata, F.; Carrozzi, L.; Cascio, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Crisetti, A.; Crosta, F.; Danzi, G. B.; D'Ardes, D.; de Gaetano Donati, K.; Di Gennaro, F.; Di Palma, G.; Di Tano, G.; Fantoni, M.; Filippini, Tommaso; Fioretto, P.; Fusco, F. M.; Gentile, I.; Grisafi, L.; Guarnieri, G.; Landi, F.; Larizza, G.; Leone, A.; Maccagni, G.; Maccarella, S.; Mapelli, M.; Maragna, R.; Marcucci, R.; Maresca, G.; Marotta, C.; Marra, L.; Mastroianni, F.; Mengozzi, A.; Menichetti, F.; Milic, Jovana; Murri, R.; Montineri, A.; Mussinelli, R.; Mussini, Cristina.; Musso, M.; Odone, A.; Olivieri, M.; Pasi, E.; Petri, F.; Pinchera, B.; Pivato, C. A.; Pizzi, R.; Poletti, V.; Raffaelli, F.; Ravaglia, C.; Righetti, G.; Rognoni, A.; Rossato, M.; Rossi, M.; Sabena, A.; Salinaro, F.; Sangiovanni, V.; Sanrocco, C.; Scarafino, A.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Spinoni, E.; Torti, C.; Trecarichi, E. M.; Vezzani, F.; Veronesi, G.; Vettor, R.; Vianello, A.; Vinceti, Marco; De Caterina, R.; Iacoviello, L.
abstract

Background and aims: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5–3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. Conclusions: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.

2020 - Comparison of Methodologies to Estimate Dietary Cadmium Intake in an Italian Population [Articolo su rivista]
Filippini, Tommaso; Upson, Kristen; Adani, Giorgia; Malagoli, Carlotta; Baraldi, Claudia; Michalke, Bernhard; Vinceti, Marco
abstract

Cadmium is a metal that is toxic to humans, and the major source of cadmium exposure in the non-smoking general population is diet. To identify major food sources and lower exposure from diet, an accurate estimate of dietary cadmium intake is needed. Hence, the objectives of this study are to develop a method to assess dietary cadmium intake using a biomarker measurement and to improve the estimation of dietary cadmium intake when using a food frequency questionnaire (FFQ). In a random sample of an Italian population, we collected dietary habits by FFQ and measured cadmium in foods and beverages. These data were used to compute the estimated weekly dietary intake (WDI) of cadmium (µg) by kilogram (kg) of body weight (bw) (WDIFFQ). We also measured fasting serum cadmium levels by inductively-coupled plasma mass spectrometry. We used these data to develop a model for the estimation of the biomarker-derived dietary cadmium intake (WDIbio). In the 51 subjects recruited, the median level of serum cadmium was 0.041 µg/L (interquartile range (IQR): 0.030-0.054). The median WDIFFQ and WDIbio were 1.34 µg/kg bw/week (IQR: 0.86-1.70) and 0.72 µg/kg bw/week (IQR: 0.55-1.11), respectively. The correlation between the two estimates was low-to-moderate (r = 0.291). In exploratory analyses, the correlation was slightly higher in women and participants ages <50 years, and markedly higher in participants with body mass index <25 kg/m2 and smokers. Our approach allows for the dietary contribution to be isolated from the overall cadmium exposure measured with a biomarker; the estimated dietary cadmium intake was roughly similar to that estimated using the FFQ, especially in select subgroups. Future refinements to the biomarker-derived dietary cadmium intake approach should take into consideration additional sources of cadmium exposure, as well as factors affecting its absorption and metabolism.

2020 - Deregulated PTEN/PI3K/AKT/mTOR signaling in prostate cancer: Still a potential druggable target? [Articolo su rivista]
Braglia, L.; Zavatti, M.; Vinceti, M.; Martelli, A. M.; Marmiroli, S.
abstract

Although the prognosis of patients with localized prostate cancer is good after surgery, with a favorable response to androgen deprivation therapy, about one third of them invariably relapse, and progress to castration-resistant prostate cancer. Overall, prostate cancer therapies remain scarcely effective, thus it is mandatory to devise alternative treatments enhancing the efficacy of surgical castration and hormone administration. Dysregulation of the phosphoinositide 3-kinase pathway has attracted growing attention in prostate cancer due to the highly frequent association of epigenetic and post-translational modifications as well as to genetic alterations of both phosphoinositide 3-kinase and PTEN to onset and/or progression of this malignancy, and to resistance to canonical androgen-deprivation therapy. Here we provide a summary of the biological functions of the major players of this cascade and their deregulation in prostate cancer, summarizing the results of preclinical and clinical studies with PI3K signaling inhibitors and the reasons of failure independent from genomic changes.

2020 - Dietary Estimated Intake of Trace Elements: Risk Assessment in an Italian Population [Articolo su rivista]
Filippini, T.; Tancredi, S.; Malagoli, C.; Malavolti, M.; Bargellini, A.; Vescovi, L.; Nicolini, F.; Vinceti, M.
abstract

Dietary intake to trace elements may represent the most relevant source of exposure for the general, non-occupationally population, but some of them have been rarely evaluated. We measured content of fifteen trace elements (antimony, barium, beryllium, boron, cobalt, lithium, molybdenum, nickel, silver, strontium, tellurium, thallium, titanium, uranium, and vanadium) in 908 food and beverage samples through inductively coupled plasma mass spectrometry. We estimated their dietary intake using a validated semi-quantitative food frequency questionnaire collected from a population of the Emilia-Romagna Region in Northern Italy. We compared our estimates with tolerable upper intake levels reported by international agencies and we assessed the non-carcinogenic risk through calculation of total hazard quotient for each trace element according to the US-EPA approach. Overall, estimates of their dietary intake were substantially similar to those reported from other countries, and they fell below the tolerable upper intake levels provided by international agencies. The total hazard quotient for each trace element was below 1. Our findings provide updated estimates of food levels and dietary intake of trace elements far frequently evaluated in a sample of Italian adult consumers. They also suggest that any non-carcinogenic risk associated with intake of investigated trace elements may be ruled out in our population.

2020 - Dietary Habits and Risk of Early-Onset Dementia in an Italian Case-Control Study [Articolo su rivista]
Filippini, Tommaso; Adani, Giorgia; Malavolti, Marcella; Garuti, Caterina; Cilloni, Silvia; Vinceti, Giulia; Zamboni, Giovanna; Tondelli, Manuela; Galli, Chiara; Costa, Manuela; Chiari, Annalisa; Vinceti, Marco
abstract

Risk of early-onset dementia (EOD) might be modified by environmental factors and lifestyles, including diet. The aim of this study is to evaluate the association between dietary habits and EOD risk. We recruited 54 newly-diagnosed EOD patients in Modena (Northern Italy) and 54 caregivers as controls. We investigated dietary habits through a food frequency questionnaire, assessing both food intake and adherence to dietary patterns, namely the Greek-Mediterranean, the Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. We modeled the relation between dietary factors and risk using the restricted cubic spline regression analysis. Cereal intake showed a U-shaped relation with EOD, with risk increasing above 350 g/day. A high intake (>400 g/day) of dairy products was also associated with excess risk. Although overall fish and seafood consumption showed no association with EOD risk, we found a U-shaped relation with preserved/tinned fish, and an inverse relation with other fish. Similarly, vegetables (especially leafy) showed a strong inverse association above 100 g/day, as did citrus and dry fruits. Overall, sweet consumption was not associated with EOD risk, while dry cake and ice-cream showed a positive relation and chocolate products an inverse one. For beverages, we found no relation with EOD risk apart from a U-shaped relation for coffee consumption. Concerning dietary patterns, EOD risk linearly decreased with the increasing adherence to the MIND pattern. On the other hand, an inverse association for the Greek-Mediterranean and DASH diets emerged only at very high adherence levels. To the best of our knowledge, this is the first study that explores the association between dietary factors and EOD risk, and suggests that adherence to the MIND dietary pattern may decrease such risk.

2020 - Dietary acrylamide intake and risk of cancer: a systematic review [Abstract in Atti di Convegno]
Capitão, Carolina; Martins, Raquel; Halldorsson, Thorhallur I.; Filippini, Tommaso; Vinceti, Marco; Santos, Osvaldo; Virgolino, Ana; Laguzzi, Federica
abstract

2020 - Dietary intake of acrylamide and risk of breast, endometrial and ovarian cancers: A systematic review and dose-response meta-analysis [Articolo su rivista]
Adani, Giorgia; Filippini, Tommaso; Wise, Lauren A; Halldorsson, Thorhallur I; Blaha, Ludek; Vinceti, Marco
abstract

Acrylamide is a probable human carcinogen. Aside from occupational exposures and smoking, diet is the main source of exposure in humans. We performed a systematic review of the association between estimated dietary intake of acrylamide and risk of female breast, endometrial, and ovarian cancers in non-experimental studies published through February 25, 2020, and conducted a dose-response meta-analysis. We identified 18 papers covering 10 different study populations: 16 cohort and 2 case-control studies. Acrylamide intake was associated with a slightly increased risk of ovarian cancer, particularly among never-smokers. For endometrial cancer, risk was highest at intermediate levels of exposure, whereas the association was more linear and positive among never-smokers. For breast cancer, we found evidence of a null or inverse relation between exposure and risk, particularly among never-smokers and post-menopausal women. In a subgroup analysis limited to premenopausal women, breast cancer risk increased linearly with acrylamide intake starting at 20 µg/day of intake. High acrylamide intake was associated with increased risks of ovarian and endometrial cancers in a relatively linear manner, especially among never-smokers. Conversely, little association was observed between acrylamide intake and breast cancer risk, with the exception of premenopausal women.

2020 - Draft for internal testing Scientific Committee guidance on appraising and integrating evidence from epidemiological studies for use in EFSA's scientific assessments [Articolo su rivista]
More, S.; Bambidis, V.; Benford, D.; Bragard, C.; Hernandez-Jerez, A.; Bennekou, S. H.; Koutsoumanis, K.; Machera, K.; Naegeli, H.; Nielsen, S. S.; Schlatter, J. R.; Schrenk, D.; Silano, V.; Turck, D.; Younes, M.; Fletcher, T.; Greiner, M.; Ntzani, E.; Pearce, N.; Vinceti, M.; Ciccolallo, L.; Georgiadis, M.; Gervelmeyer, A.; Halldorsson, T. I.
abstract

EFSA requested its Scientific Committee to prepare a guidance document on appraising and integrating evidence from epidemiological studies for use in EFSA's scientific assessments. The guidance document provides an introduction to epidemiological studies and illustrates the typical biases of the different epidemiological study designs. It describes key epidemiological concepts relevant for evidence appraisal. Regarding study reliability, measures of association, exposure assessment, statistical inferences, systematic error and effect modification are explained. Regarding study relevance, the guidance describes the concept of external validity. The principles of appraising epidemiological studies are illustrated, and an overview of Risk of Bias (RoB) tools is given. A decision tree is developed to assist in the selection of the appropriate Risk of Bias tool, depending on study question, population and design. The customisation of the study appraisal process is explained, detailing the use of RoB tools and assessing the risk of bias in the body of evidence. Several examples of appraising experimental and observational studies using a Risk of Bias tool are annexed to the document to illustrate the application of the approach. This document constitutes a draft that will be applied in EFSA's assessments during a 1-year pilot phase and be revised and complemented as necessary. Before finalisation of the document, a public consultation will be launched.

2020 - Environmental Risk Factors for Early-Onset Alzheimer's Dementia and Frontotemporal Dementia: A Case-Control Study in Northern Italy [Articolo su rivista]
Adani, G.; Filippini, T.; Garuti, C.; Malavolti, M.; Vinceti, G.; Zamboni, G.; Tondelli, M.; Galli, C.; Costa, M.; Vinceti, M.; Chiari, A.
abstract

Background: Early-onset dementia (EOD) is defined as dementia with symptom onset before 65 years. The role of environmental risk factors in the etiology of EOD is still undefined. We aimed at assessing the role of environmental risk factors in EOD etiology, taking into account its different clinical types. Methods: Using a case-control study, we recruited all EOD cases referred to Modena hospitals from 2016 to 2019, while the referent population was drawn from cases' caregivers. We investigated residential history, occupational and environmental exposures to chemicals and lifestyle behaviors through a self-administered questionnaire. We computed the odds ratios of EOD risk (overall and restricting to the Alzheimer's dementia (AD) or frontotemporal dementia (FTD) diagnoses) and the corresponding 95% confidence intervals using an unconditional logistic regression model. Results: Fifty-eight EOD patients (19 FTD and 32 AD) and 54 controls agreed to participate. Most of the investigated exposures, such as occupational exposure to aluminum, pesticides, dyes, paints or thinners, were associated with an increased odds ratio (OR) for FTD but not for AD. Long-term use of selenium-containing dietary supplements was associated with increased OR for EOD and, particularly, for FTD. For both EOD forms, smoking and playing football showed an increased odds ratio, while cycling was associated with increased risk only in FTD. Overall sports practice appeared to be a protective factor for both types. Conclusions: Our results suggest a role of environmental and behavioral risk factors such as some chemical exposures and professional sports in EOD etiology, in particular with reference to FTD. Overall sports practice may be associated with a reduced EOD risk.

2020 - Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study [Articolo su rivista]
Filippini, Tommaso; Tesauro, Marina; Fiore, Maria; Malagoli, Carlotta; Consonni, Michela; Violi, Federica; Iacuzio, Laura; Arcolin, Elisa; Oliveri Conti, Gea; Cristaldi, Antonio; Zuccarello, Pietro; Zucchi, Elisabetta; Mazzini, Letizia; Pisano, Fabrizio; Gagliardi, Ileana; Patti, Francesco; Mandrioli, Jessica; Ferrante, Margherita; Vinceti, Marco
abstract

Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with still unknown etiology. We aimed at investigating the association between environmental and occupational factors with ALS risk. Methods: We performed a population-based case-control study in four Italian provinces (Catania, Modena, Novara, and Reggio Emilia) by administration of tailored questionnaires to ALS cases (n = 95) and randomly selected population referents (n = 135). We estimated ALS risk by calculating the odds ratio (OR) with its 95% confidence interval (CI) using an unconditional logistic regression model. Results: We found a positive association with disease risk for history of occupation in the agricultural sector (OR = 2.09, 95% CI 0.79-7.54), especially for longer than 10 years (OR = 2.72, 95% 1.02-7.20). Overall occupational exposure to solvents also suggested a positive association, especially for thinners (OR = 2.27, 95% CI 1.14-4.54) and paint removers (OR = 2.01, 95% CI 0.90-4.48). Both occupational and environmental exposure to electromagnetic fields show a slightly increased risk with OR = 1.69 (95% CI 0.70-4.09) and 2.41 (95% CI 1.13-5.12), respectively. Occupational but not environmental exposure to pesticides (OR = 1.22, 95% CI 0.63-2.37), particularly fungicides, and exposure to metals (OR = 4.20, 95% CI 1.88-9.38), particularly lead, mercury, and selenium, showed an imprecise but positive association. Finally, there was an indication of increased risk for living in proximity to water bodies. Conclusions: Despite the caution that needs to be used due to some study limitations, such as the low number of exposed subjects and the possibility of recall bias, these results suggest the potential role of some environmental and occupational factors in ALS etiology.

2020 - Environmental and occupational risk factors for early onset dementia in an Italian community [Abstract in Rivista]
Adani, G.; Filippini, T.; Garuti, C.; Malavolti, M.; Vinceti, G.; Zamboni, G.; Tondelli, M.; Galli, C.; Costa, M.; Vinceti, M.; Chiari, A.
abstract

Background: Early onset dementia (EOD) is defined as dementia with symptoms onset before 65 years. Little is known about the etiological role of environmental and occupational risk factors. We aimed at assessing the role of these factors in disease etiology.Methods: Using a case-control design, we recruited all EOD cases resident in Modena province from October, 2016 to October, 2019, as well as a referent population drawn from patients’ care-givers. We investigated residential history of study participants, and their occupational and environmental exposures to pesticides, solvents and metals through a self-administered questionnaire. We computed the odds ratios (ORs) of disease risk, and the corresponding 95% confidence intervals (CIs), according to exposure to the investigated risk factors, using an unconditional logistic regression model adjusted for sex, age, and education. Results: Fifty-eight EOD cases and fifty-four controls agreed to participate. Among occupational factors, disease risk was associated with exposure to aluminum (OR 2.6, 95% CI 0.4-15.7), pesticides (OR 2.3, 95% CI 0.7-7.8) particularly from agricultural occupational exposure (OR 3.1, 95% CI 0.7-13.3) and dyes, paints or thinners (OR 1.7, 95% CI 0.6-5.0). Among lifestyles factors, smoking (OR 1.3, 95% CI 0.6-2.9) and playing football (OR 2.2, 95% CI 0.5-9.3) or cycling (OR 2.3, 95% CI 0.4-13.4) were associated with higher EOD risk, although overall sports practice appeared to be protective factor (OR 0.4, 95% CI 0.2-0.9). Risk was also positively associated with history of head trauma (OR 1.2, 95% CI 0.3-4.1) and particularly upper arm trauma (OR 2.2, 95% CI 0.7-7.5), but not overall trauma. No association emerged for exposure to electromagnetic fields. Conclusions:Despite the study limitations, our results appear to support a role of environmental risk factors in EOD etiology, particularly of some chemical exposures and professional sports, while overall sports practice may have a beneficial effect.

2020 - Exposure to a high selenium environment in Punjab, India: Biomarkers and health conditions [Articolo su rivista]
Chawla, R.; Filippini, T.; Loomba, R.; Cilloni, S.; Dhillon, K. S.; Vinceti, M.
abstract

Seleniferous areas have been identified and described in many parts of the world. Despite the interest in selenium as a trace element of considerable toxicologic and nutritional relevance, however, only a few studies have been carried out on human health effects of such high selenium environments. We collected blood, hair and nail samples from 680 adult volunteers (267 men and 413 women) living in seven villages located in the seleniferous area of Punjab, India. We measured selenium levels in these specimens. We also administered a questionnaire to collect information about diet and other lifestyle characteristics, to identify the sources of selenium exposure and to correlate it with a number of health conditions. Serum and hair selenium contents were highly correlated, while the association of these biomarkers with nail selenium content was weaker. Serum selenium showed limited association with consumption of locally produced foods, while pulses and vegetables, along with cereals and pulses, were associated to higher hair and nail selenium contents, respectively. Association of a number of adverse health endpoints with serum and hair selenium was stronger than for nail selenium contents. Such endpoints included higher prevalence of nausea and vomiting, bad breath, worm infestation, breathlessness exert and bad breath, chest pain, hair and nail abnormalities and loss, garlic odor, edema, spontaneous abortion, and overall selenosis. In contrast, we gathered no evidence of dermatitis or loss of appetite in residents most exposed to selenium. Overall, and despite some statistical imprecision in effect estimates, these results confirm the occurrence of adverse health effects in subjects exposed to high levels of environmental selenium. Nail selenium contents may be less adequate to reflect and monitor such overexposure, compared with blood and hair levels.

2020 - Exposure to a high selenium environment in Punjab, India: Effects on blood chemistry [Articolo su rivista]
Loomba, R.; Filippini, T.; Chawla, R.; Chaudhary, R.; Cilloni, S.; Datt, C.; Singh, S.; Dhillon, K. S.; Vinceti, M.
abstract

Many studies have shown that overexposure to environmental selenium may exert a wide pattern of adverse effects on human health, but much uncertainty still surrounds some of them as well as the exact amounts of exposure involved. In particular, very few studies have addressed the possible changes in blood chemistry following high selenium exposure. In a Northeastern part of Punjab, India, very high soil selenium content has been documented, with a value exceeding 2 mg/kg (up to 5) as compared with the <0.5 mg/kg selenium content characterizing the surrounding referent areas. In seven villages located in that seleniferous areas, we carried out a survey by recruiting volunteers and sampling blood, hair and nail specimens. We administered a questionnaire to the participants and analyzed the specimens for the selenium, along with a series of biochemical and haematological parameters in blood. We included 680 adult volunteers (267 men and 413 women), who showed median selenium levels of 171.30 µg/L in serum, 1.25 µg/g in hair, and 5.7 µg/g in nails. Overall, increasing selenium exposure tended to correlate with higher levels of total cholesterol, albumin, free triiodothyronine, deionidase activity, and with red cell and platelet counts. After stratifying the subjects according to category of selenium exposure, we observed a dose-response relation between serum selenium and risk of high total cholesterol, and between hair selenium and risk of high total and low-density lipoprotein cholesterol, high pancreatic lipase, altered thyroid-stimulating hormone and free triiodothyronine levels. Nail selenium exposure category positively correlated with risk of high alanine-aminotransferase, altered albumin levels, high pancreatic lipase and low levels of thyroid-stimulating hormone. Chronic selenium overexposure appears to adversely affect lipid profiles and pancreatic, liver, and thyroid function, with selenium biomarkers having different abilities to predict such effects.

2020 - Exposure to particulate matter and risk of amyotrophic lateral sclerosis: A case-control study in Northern Italy [Abstract in Rivista]
Filippini, T.; Mandrioli, J.; Malagoli, C.; Cherubini, A.; Maffeis, G.; Vinceti, M.
abstract

Background: Amyotrophic lateral sclerosis (ALS) is progressive neurodegenerative disease with still unknown etiology. Role of occupational and environmental risk factors has been investigated, including outdoor air pollutants, which have been recently associated to an excess disease risk. We carried out a case-control study in order to assess if environmental exposure to particulate matter ≤10 µm (PM10) may increase ALS risk. Methods: We recruited patients referred to the Modena Neurology Unit between 1994-2015 and controls from the Modena province population. Using a validated geographical information system-based dispersion model, we geocoded subjects’ addresses of residence at the time of diagnosis and we estimated outdoor air PM10 concentrations for each subjects. We computed odds ratio (OR) and 95% confidence interval (CI) of ALS according to increasing PM10 exposure, using an unconditional logistic regression model age- and sex-adjusted. Results: For the 132 study participants (52 cases/80 controls), mean of annual average and maximum PM10 concentrations were 5.2 and 38.6µg/m3, respectively. Using fixed cutpoints at 5, 10 and 20 of average annual PM10 concentrations, compared with subjects <5µg/m3, we did not find evidence for an excess ALS risk associated with PM10 exposure, since OR was 0.87 (95% CI 0.39-1.96), 0.94 (0.24-3.70), and 0.87 (0.05-15.01) at 5-10, 10-20 and ≥20µg/m3, respectively. Using maximum annual PM10 concentrations, we found an excess ALS risk for subjects exposed at 10-20µg/m3 (OR=4.27, 0.69-26.51) compared with exposure below 10µg/m3, although the risk tended to decrease at higher PM10 concentrations, with OR of 1.49 (0.39-5.75) at 20-50, and 1.16 (0.98-4.82) at ≥50µg/m3. Conclusions:Our findings do not suggest that PM10exposure is associated with ALS risk. However, some evidence of an increased risk associated with maximum annual exposure concentrations, although statistically imprecise, suggests the need of further investigations, also considering the high concentrations of particulate matter characterizing Northern Italy.

2020 - Exposure to particulate matter and risk of conversion from mild cognitive impairment to dementia: a cohort study in a Northern Italy population [Abstract in Rivista]
Vinceti, M.; Filippini, T.; Malagoli, C.; Cherubini, A.; Maffeis, G.; Chiari, A.
abstract

Background/Aim Exposure to air pollutants such as inhalable particulate matter has been linked to increased risk of chronic disease including neurodegenerative diseases, such as Alzheimer’s dementia. In this study, we aimed to evaluate the effect of long-term exposure to outdoor air pollution, and specifically to particulate matter ≤10 μm (PM10), on the risk of dementia in a cohort of subjects with mild cognitive impairment. MethodsWe recruited 53 subjects newly-diagnosed with mild cognitive impairment of non-vascular origin and residing in the Modena and Reggio Emilia provinces of Northern Italy. Using a Geographical Information System and a validated air pollution dispersion model, we assessed exposure to outdoor PM10 from motorized traffic at subjects’ residence. We investigated the relation of these concentrations to subsequent onset of dementia, using a Cox proportional hazards model. We computed hazard ratio (HR) and 95% confidence interval (CI) according to fixed categories of PM10 exposure, adjusting for sex, age, and educational attainment level. ResultsDuring a median follow-up of 42 months, 19 participants developed Alzheimer’s dementia, 3 frontotemporal dementia and 2 Lewy body dementia. Baseline PM10 exposure levels were 9.6 µg/m3 on average. Using PM10 levels below 5 µg/m3 as reference, we found a dose-response increase in any dementia risk with HR of 1.04 (95% CI 0.41-2.66) at 5-10 µg/m3, 1.32 (95% CI 0.36-4.92) at 10-20 µg/m3, and 1.38 (95% CI 0.14-13.13) above 20 µg/m3, respectively. Conclusions Our results suggest that exposure to particulate matter emitted by motorized vehicles increases the risk of conversion from mild cognitive impairment to dementia, though the low number of study participants suggests caution in the interpretation of these findings.

2020 - Green tea (Camellia sinensis) for the prevention of cancer [Articolo su rivista]
Filippini, T.; Malavolti, M.; Borrelli, F.; Izzo, A. A.; Fairweather-Tait, S. J.; Horneber, M.; Vinceti, M.
abstract

Background: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2009, Issue 3).Tea is one of the most commonly consumed beverages worldwide. Teas from the plant Camellia sinensis can be grouped into green, black and oolong tea, and drinking habits vary cross-culturally. C sinensis contains polyphenols, one subgroup being catechins. Catechins are powerful antioxidants, and laboratory studies have suggested that these compounds may inhibit cancer cell proliferation. Some experimental and nonexperimental epidemiological studies have suggested that green tea may have cancer-preventative effects. Objectives: To assess possible associations between green tea consumption and the risk of cancer incidence and mortality as primary outcomes, and safety data and quality of life as secondary outcomes. Search methods: We searched eligible studies up to January 2019 in CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and reference lists of previous reviews and included studies. Selection criteria: We included all epidemiological studies, experimental (i.e. randomised controlled trials (RCTs)) and nonexperimental (non-randomised studies, i.e. observational studies with both cohort and case-control design) that investigated the association of green tea consumption with cancer risk or quality of life, or both. Data collection and analysis: Two or more review authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We summarised the results according to diagnosis of cancer type. Main results: In this review update, we included in total 142 completed studies (11 experimental and 131 nonexperimental) and two ongoing studies. This is an additional 10 experimental and 85 nonexperimental studies from those included in the previous version of the review. Eleven experimental studies allocated a total of 1795 participants to either green tea extract or placebo, all demonstrating an overall high methodological quality based on 'Risk of bias' assessment. For incident prostate cancer, the summary risk ratio (RR) in the green tea-supplemented participants was 0.50 (95% confidence interval (CI) 0.18 to 1.36), based on three studies and involving 201 participants (low-certainty evidence). The summary RR for gynaecological cancer was 1.50 (95% CI 0.41 to 5.48; 2 studies, 1157 participants; low-certainty evidence). No evidence of effect of non-melanoma skin cancer emerged (summary RR 1.00, 95% CI 0.06 to 15.92; 1 study, 1075 participants; low-certainty evidence). In addition, adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions. Consumption of green tea extracts induced a slight improvement in quality of life, compared with placebo, based on three experimental studies. In nonexperimental studies, we included over 1,100,000 participants from 46 cohort studies and 85 case-control studies, which were on average of intermediate to high methodological quality based on Newcastle-Ottawa Scale 'Risk of bias' assessment. When comparing the highest intake of green tea with the lowest, we found a lower overall cancer incidence (summary RR 0.83, 95% CI 0.65 to 1.07), based on three studies, involving 52,479 participants (low-certainty evidence). Conversely, we found no association between green tea consumption and cancer-related mortality (summary RR 0.99, 95% CI 0.91 to 1.07), based on eight studies and 504,366 participants (low-certainty evidence). For most of the site-specific cancers we observed a decreased RR in the highest category of green tea consumption compared with the lowest one. After stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: oesophageal, prostate and urinary tract cancer, and leukaemia showed an increased RR in cohort studies and a d

2020 - Identification of cement in atmospheric particulate matter using the hybrid method of laser diffraction analysis and Raman spectroscopy [Articolo su rivista]
Kholodov, A.; Zakharenko, A.; Drozd, V.; Chernyshev, V.; Kirichenko, K.; Seryodkin, I.; Karabtsov, A.; Olesik, S.; Khvost, E.; Vakhnyuk, I.; Chaika, V.; Stratidakis, A.; Vinceti, M.; Sarigiannis, D.; Hayes, A. W.; Tsatsakis, A.; Golokhvast, K.
abstract

Environmental science; Atmospheric science; Ecology; Environmental chemistry; Environmental pollution; Atmospheric particulate matter, Laser diffraction analysis, PM10, Raman spectroscopy

2020 - Insights into the association of potassium intake with blood pressure: results of a dose-response meta-analysis of randomized controlled trials [Abstract in Atti di Convegno]
Filippini, T; Torres, D; Lopes, C; Carvalho, C; Moreira, P; Naska, A; Kasdagli, M-I; Malavolti, M; Orsini, N; Vinceti, M
abstract

Introduction: Observational studies provide evidence for an association between potassium intake and BP levels. However, uncertainties still exist about the size and the shape of this relation. Conversely, experimental studies have not been used to estimate dose-response curves, since standard methods can only be applied in trials including at least three exposure groups. Materials and Methods: We carried out a systematic review of the evidence concerning the effect of potassium supplementation on blood pressure in epidemiologic experimental studies. Following a PubMed search up to June 20, 2019, we included randomized controlled trials (RCTs) encompassing potassium supplementation as the only intervention for at least four weeks. We used a restricted cubic spline model and the ‘one-stage’ approach to perform a dose-response meta-analysis, a newly-developed statistical procedure which allows inclusion of studies with as few as two categories of exposure (Stat Methods Med Res. 2019;28:1579-1596). Finally, we repeated the analyses stratifying for hypertensive status and use of anti-hypertensive medication. Results: Overall, we included 33 studies carried out in adult population, with potassium supplementation ranging from 30 to 140 mmol/day. RCTs’ duration ranged from 4 up to 26 weeks. Most of the studies have a cross-over design (N=24), include hypertensive individuals (N=27) and subjects not under anti-hypertensive medication (N=27). Overall, an increase of 40, 80 and 120 mmol/day of potassium resulted in reductions of SBP by -5.64 (95% CI - 8.78, -2.50), -4.62 (-6.41, -2.84) and -2.54 mmHg (95% CI -5.14, +0.06), respectively. Higher potassium intakes also resulted in reduced DBP levels by -3.57 (95% CI -5.55, -1.59), -3.07 (95% CI -5.07, -1.08), and -1.92 mmHg (95% CI -5.65, 1.81). The effect of increasing potassium intake on BP was larger among hypertensives than normotensives, and among pharmacologically untreated hypertensives compared to their treated counterparts. Subgroup analyses according to study design (parallel vs. crossover) yielded similar results. Discussion: With the application of advanced dose-response modeling on RCT results, we found a U-shaped relation between potassium intake and blood pressure. A low to moderate increase in potassium intake resulted in a progressive reduction in blood pressure, which was reversed at higher levels of potassium supplementation. The effect was stronger among untreated hypertensives. Supported by grant GP-EFSA-AFSCO-2017-01 GA09 of the European Food Safety Authority - EFSA. The text reflects only the authors' view; and EFSA is not responsible for any use that may be made of the information it contains. Conflict of Interest: There is no conflict of interest

2020 - Lead exposure in an Italian population: Food content, dietary intake and risk assessment [Articolo su rivista]
Malavolti, M.; Fairweather-Tait, S. J.; Malagoli, C.; Vescovi, L.; Vinceti, M.; Filippini, T.
abstract

Background and aim: Lead is a highly toxic heavy metal released into the environment after natural and anthropogenic activities. Excluding populations in occupations where there is possible lead contamination, food is the major source of human exposure. In this study, we determined lead contamination in food and beverages consumed in a Northern Italy community and performed a health risk assessment. Methods: We collected a total of 908 food samples and measured lead levels using inductively coupled plasma mass spectrometry. Using a validated food frequency questionnaire, we assessed the dietary habits and estimated daily lead dietary intakes in a sample of 719 adult individuals. We performed risk assessment using a benchmark dose and margin of exposure approach, based on exposure levels for both adverse effect of systolic blood pressure and chronic kidney disease. Results: Foods with the highest lead levels include non-chocolate confectionery (48.7 µg/kg), leafy (39.0 µg/kg) and other vegetables (42.2 µg/kg), and crustaceans and molluscs (39.0 µg/kg). The estimated mean lead intake was 0.155 µg/kg bw-day in all subjects, with little lower intakes in men (0.151 µg/kg bw-day) compared to women (0.157 µg/kg bw-day). Top food contributors were vegetables, cereals, and beverages, particularly wine. In relation to risk assessment, the estimated dietary intake was lower than levels associated with cardiovascular risk and nephrotoxicity. Conclusions: Our study provides an updated assessment of lead food contamination and dietary exposure in a Northern Italian community. The margin of exposure risk assessment approach suggests that risk of detrimental effects due to dietary lead intake is low in the investigated population. Nonetheless, these exposure levels for adverse effects are not reference health standards, and no safety threshold value can be established for lead. As a consequence, other and more subtle adverse effects may still occur in vulnerable and occupationally exposed individuals, particularly in relation to the nervous system.

2020 - Living near waterbodies as a proxy of cyanobacteria exposure and risk of amyotrophic lateral sclerosis: a population based case-control study [Articolo su rivista]
Fiore, Maria; Parisio, Roberto; Filippini, Tommaso; Mantione, Valerio; Platania, Armando; Odone, Anna; Signorelli, Carlo; Pietrini, Vladimiro; Mandrioli, Jessica; Teggi, Sergio; Costanzini, Sofia; Cristaldi, Antonio; Zuccarello, Pietro; Oliveri Conti, Gea; Nicoletti, Alessandra; Zappia, Mario; Vinceti, Marco; Ferrante, Margherita
abstract

Background: Epidemiological studies highlighted the possibility that exposure to cyanotoxins leads to the development of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Methods: We devised a population-based case-control study in two Italian populations. We used residential proximity of the residence to water bodies as a measure of possible exposure to cyanotoxins. Results: Based on 703 newly-diagnosed ALS cases and 2737 controls, we calculated an ALS odds ratio (OR) of 1.41 (95% CI: 0.72–2.74) for current residence in the vicinity of water bodies, and a slightly lower estimate for historical residence (OR: 1.31; 95% CI: 0.57–2.99). Subjects <65 years and people living in the Northern Italy province of Modena had higher ORs, especially when historical residence was considered. Conclusions: Overall, despite some risk of bias due to exposure misclassification and unmeasured confounding, our results appear to support the hypothesis that cyanotoxin exposure may increase ALS risk.

2020 - Lockdown timing and efficacy in controlling COVID-19 using mobile phone tracking [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Rothman, Kenneth J.; Ferrari, Fabrizio; Goffi, Alessia; Maffeis, Giuseppe; Orsini, Nicola
abstract

Background Italy's severe COVID-19 outbreak was addressed by a lockdown that gradually increased in space, time and intensity. The effectiveness of the lockdown has not been precisely assessed with respect to the intensity of mobility restriction and the time until the outbreak receded. Methods We used processed mobile phone tracking data to measure mobility restriction, and related those data to the number of new SARS-CoV-2 positive cases detected on a daily base in the three most affected Italian regions, Lombardy, Veneto and Emilia-Romagna, from February 1 through April 6, 2020, when two subsequent lockdowns with increasing intensity were implemented by the Italian government. Findings During the study period, mobility restriction was inversely related to the daily number of newly diagnosed SARS-CoV-2 positive cases only after the second, more effective lockdown, with a peak in the curve of diagnosed cases of infection occurring 14 to 18 days from lockdown in the three regions and 9 to 25 days in the included provinces. An effective reduction in transmission must have occurred nearly immediately after the tighter lockdown, given the lag time of around 10 days from asymptomatic infection to diagnosis. The period from lockdown to peak was shorter in the areas with the highest prevalence of the infection. This effect was seen within slightly more than one week in the most severely affected areas. Interpretation It appears that the less rigid lockdown led to an insufficient decrease in mobility to reverse an outbreak such as COVID-19. With a tighter lockdown, mobility decreased enough to bring down transmission promptly below the level needed to sustain the epidemic. Funding No funding sources have been used for this work.

2020 - Metal(loid)s role in the pathogenesis of amyotrophic lateral sclerosis: Environmental, epidemiological, and genetic data [Articolo su rivista]
Tesauro, M.; Bruschi, M.; Filippini, T.; D'Alfonso, S.; Mazzini, L.; Corrado, L.; Consonni, M.; Vinceti, M.; Fusi, P.; Urani, C.
abstract

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. The etiology is still unknown and the pathogenesis remains unclear. ALS is familial in the 10% of cases with a Mendelian pattern of inheritance. In the remaining sporadic cases, a multifactorial origin is supposed in which several predisposing genes interact with environmental factors. The etiological role of environmental factors, such as pesticides, exposure to electromagnetic fields, and metals has been frequently investigated, with controversial findings. Studies in the past two decades have highlighted possible roles of metals, and ionic homeostasis dysregulation has been proposed as the main trigger to motor-neuron degeneration. This study aims at evaluating the possible role of environmental factors in etiopathogenesis of ALS, with a particular attention on metal contamination, focusing on the industrial Briga area in the province of Novara (Piedmont region, North Italy), characterized by: i) a higher incidence of sporadic ALS (sALS) in comparison with the entire province, and ii) the reported environmental pollution. Environmental data from surface, ground and discharge waters, and from soils were collected and specifically analyzed for metal content. Considering the significance of genetic mechanisms in ALS, a characterization for the main ALS genes has been performed to evaluate the genetic contribution for the sALS patients living in the area of study. The main findings of this study are the demonstration that in the Briga area the most common metal contaminants are Cu, Zn, Cr, Ni (widely used in tip-plating processes), that are above law limits in surface waters, discharge waters, and soil. In addition, other metals and metalloids, such as Cd, Pb, Mn, and As show a severe contamination in the same area. Results of genetic analyses show that sALS patients in the Briga area do not carry recurrent mutations or an excess of mutations in the four main ALS causative genes (SOD1, TARDBP, FUS, C9ORF72) and for ATXN2 CAG repeat locus. This study supports the hypothesis that the higher incidence of sALS in Briga area may be related to environmental metal(loid)s contamination, along with other environmental factors. Further studies, implementing analysis of genetic polymorphisms, as well as investigation with long term follow-up, may yield to key aspects into the etiology of ALS. The interplay between different approaches (environmental, chemical, epidemiological, genetic) of our work provides new insights and methodology to the comprehension of the disease etiology.

2020 - Nutritional safety and suitability of a specific protein hydrolysate derived from whey protein concentrate and used in an infant and follow-on formula manufactured from hydrolysed protein by Danone Trading ELN B.V [Articolo su rivista]
Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Castle, L.; Fewtrell, M.; Przyrembel, H.; Dumas, C.; Titz, A.; Turck, D.
abstract

The European Commission asked EFSA to deliver an opinion on the nutritional safety and suitability of a specific protein hydrolysate. It is derived from whey protein concentrate and used in an infant and follow-on formula by Danone Trading ELN B.V, which submitted a dossier to the European Commission to request an amendment of Regulation (EU) 2016/127 with respect to the protein sources that may be used in the manufacture of infant and/or follow-on formula. This opinion does not cover the assessment of the safety of the food enzymes used in the manufacture of the protein hydrolysate. The protein hydrolysate under evaluation is sufficiently characterised with respect to the fraction of the hydrolysed protein. In the pertinent intervention study provided, an infant formula manufactured from the protein hydrolysate with a protein content of 2.3 g/100 kcal and consumed as the sole source of nutrition by infants for 3.5 months led to growth equivalent to a formula manufactured from intact cow's milk protein (2 g protein/100 kcal). No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. However, given that it is consumed with complementary foods and the protein source is considered nutritionally safe and suitable in an infant formula that is the sole source of nutrition of infants, the Panel considers that the protein hydrolysate is also a nutritionally safe and suitable protein source for use in follow-on formula. The Panel concludes that the protein hydrolysate under evaluation is a nutritionally safe and suitable protein source for use in infant and follow-on formula, as long as the formula in which it is used contains a minimum of 2.3 g/100 kcal protein and complies with the compositional criteria of Commission Delegated Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA.

2020 - Orodispersible lozenges containing a combination of Lactobacillus reuteri DSM 17938 and Lactobacillus reuteri ATCC PTA 5289 and normal gum function: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Ildico Hirsch-Ernst, K.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Sanz, Y.; Siani, A.
abstract

Following an application from BioGaia AB submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Sweden, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to orodispersible lozenges containing a combination of Lactobacillus reuteri DSM 17938 and Lactobacillus reuteri ATCC PTA 5289 and normal gum function. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The Panel considers that orodispersible lozenges containing L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289 are sufficiently characterised. Maintenance of normal gum function is a beneficial physiological effect. Out of the two studies from which conclusions could be drawn and that investigated the effect of lozenges containing L. reuteri at the proposed conditions of use (i.e. consumption twice daily) on appropriate gingival outcomes (bleeding on probing (PoB) and gingival index (GI)) in subjects with gingivitis, but without periodontitis, one showed a large effect on BoP and other gingival outcomes and one showed no effect. No effect was found in one study with the use of one lozenge daily. The three studies that investigated, at the proposed conditions of use, modified GI (and not BoP or GI) in subjects with gingivitis, but without periodontitis, or were conducted in patients with periodontitis support an effect of lozenges with L. reuteri on gum function. Some evidence has been provided for mechanisms by which consumption of lozenges containing L. reuteri could improve outcomes of gingivitis in patients with chronic periodontitis but the relevance of such mechanisms for the target population of the claim (i.e. subjects without periodontitis) is unclear. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of orodispersible lozenges containing a combination of L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289 and maintenance of normal gum function.

2020 - Pesticides, cognitive functions and dementia: A review [Articolo su rivista]
Aloizou, A. -M.; Siokas, V.; Vogiatzi, C.; Peristeri, E.; Docea, A. O.; Petrakis, D.; Provatas, A.; Folia, V.; Chalkia, C.; Vinceti, M.; Wilks, M.; Izotov, B. N.; Tsatsakis, A.; Bogdanos, D. P.; Dardiotis, E.
abstract

Pesticides are widely-used chemicals commonly applied in agriculture for the protection of crops from pests. Depending on the class of pesticides, the specific substances may have a specific set of adverse effects on humans, especially in cases of acute poisoning. In past years, evidence regarding sequelae of chronic, low-level exposure has been accumulating. Cognitive impairment and dementia heavily affect a person's quality of life and scientific data has been hinting towards an association between them and antecedent chronic pesticide exposure. Here, we reviewed animal and human studies exploring the association between pesticide exposure, cognition and dementia. Additionally, we present potential mechanisms through which pesticides may act neurotoxically and lead to neurodegeneration. Study designs rarely presented homogeneity and the estimation of the exposure to pesticides has been most frequently performed without measuring the synergic effects and the possible interactions between the toxicants within mixtures, and also overlooking low exposures to environmental toxicants. It is possible that a Real-Life Risk Simulation approach would represent a robust alternative for future studies, so that the safe exposure limits and the net risk that pesticides confer to impaired cognitive function can be examined. Previous studies that evaluated the effect of low dose chronic exposure to mixtures of pesticides and other chemicals intending to simulate real life exposure scenarios showed that hermetic neurobehavioral effects can appear after mixture exposure at doses considered safe for individual compounds and these effects can be exacerbated by a coexistence with specific conditions such as vitamin deficiency. However, there is an overall indication, derived from both epidemiologic and laboratory evidence, supporting an association between exposure to neurotoxic pesticides and cognitive dysfunction, dementia and Alzheimer's disease.

2020 - Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials [Articolo su rivista]
Filippini, T.; Naska, A.; Kasdagli, M. -I.; Torres, D.; Lopes, C.; Carvalho, C.; Moreira, P.; Malavolti, M.; Orsini, N.; Whelton, P. K.; Vinceti, M.
abstract

Background Epidemiologic studies, including trials, suggest an association between potassium intake and blood pressure (BP). However, the strength and shape of this relationship is uncertain. Methods and Results We performed a meta-analysis to explore the dose-response relationship between potassium supplementation and BP in randomized-controlled trials with a duration ≥4 weeks using the recently developed 1-stage cubic spline regression model. This model allows use of trials with at least 2 exposure categories. We identified 32 eligible trials. Most were conducted in adults with hypertension using a crossover design and potassium supplementation doses that ranged from 30 to 140 mmol/d. We observed a U-shaped relationship between 24-hour active and control arm differences in potassium excretion and BP levels, with weakening of the BP reduction effect above differences of 30 mmol/d and a BP increase above differences ≈80 mmol/d. Achieved potassium excretion analysis also identified a U-shaped relationship. The BP-lowering effects of potassium supplementation were stronger in participants with hypertension and at higher levels of sodium intake. The BP increase with high potassium excretion was noted in participants with antihypertensive drug-treated hypertension but not in their untreated counterparts. Conclusions We identified a nonlinear relationship between potassium intake and both systolic and diastolic BP, although estimates for BP effects of high potassium intakes should be interpreted with caution because of limited availability of trials. Our findings indicate an adequate intake of potassium is desirable to achieve a lower BP level but suggest excessive potassium supplementation should be avoided, particularly in specific subgroups.

2020 - RAAS inhibitors are not associated with mortality in COVID-19 patients: findings from an observational multicenter study in Italy and a meta-analysis of 19 studies [Articolo su rivista]
Di Castelnuovo, Augusto; Costanzo, Simona; Antinori, Andrea; Berselli, Nausicaa; Blandi, Lorenzo; Bonaccio, Marialaura; Cauda, Roberto; Gialluisi, Alessandro; Guaraldi, Giovanni; Menicanti, Lorenzo; Mennuni, Marco; Mussinelli, Roberta; My, Ilaria; Parruti, Giustino; Patti, Giuseppe; Perlini, Stefano; Santilli, Francesca; Signorelli, Carlo; Stefanini, Giulio G; Vergori, Alessandra; Abete, Paolo; Ageno, Walter; Agostoni, Piergiuseppe; Aiello, Luca; Al Moghazi, Samir; Arboretti, Rosa; Aucella, Filippo; Barbieri, Greta; Barchitta, Martina; Bartoloni, Alessandro; Bonfanti, Paolo; Cacciatore, Francesco; Caiano, Lucia; Carrozzi, Laura; Cascio, Antonio; Castiglione, Giacomo; Cianfrone, Stefania; Ciccullo, Arturo; Cingolani, Antonella; Cipollone, Francesco; Colomba, Claudia; Colombo, Crizia; Cozzi, Ottavia; Crisetti, Annalisa; Crosta, Francesca; Danzi, Gian Battista; D'Ardes, Damiano; de Gaetano Donati, Katleen; Di Gennaro, Francesco; Di Tano, Giuseppe; D'Offizi, Gianpiero; Fusco, Francesco Maria; Gentile, Ivan; Graziani, Emauele; Guarnieri, Gabriella; Larizza, Giovanni; Leone, Armando; Lio, Veronica; Lucia, Mothanje Barbara; Maccagni, Gloria; Madaro, Ferruccio; Maitan, Stefano; Mancarella, Sandro; Manuele, Rosa; Mapelli, Massimo; Maragna, Riccardo; Marcucci, Rossella; Maresca, Giulio; Marongiu, Silvia; Marotta, Claudia; Marra, Lorenzo; Mastroianni, Franco; Mazzitelli, Maria; Mengozzi, Alessandro; Menichetti, Francesco; Meschiari, Marianna; Milic, Jovana; Minutolo, Filippo; Molena, Beatrice; Mussini, Cristina; Musso, Maria; Odone, Anna; Olivieri, Marco; Palimodde, Antonella; Pasi, Emanuela; Pesavento, Raffaele; Petri, Francesco; Pinchera, Biagio; Pivato, Carlo A; Poletti, Venerino; Ravaglia, Claudia; Rossato, Marco; Rossi, Marianna; Sabena, Anna; Salinaro, Francesco; Sangiovanni, Vincenzo; Sanrocco, Carlo; Scoppettuolo, Giancarlo; Scorzolini, Laura; Sgariglia, Raffaella; Simeone, Paola Giustina; Trecarichi, Enrico Maria; Vettor, Roberto; Vianello, Andrea; Vinceti, Marco; Virano, Alexandra; Vocciante, Laura; Iacoviello, Licia; Caterina, Null
abstract

OBJECTIVE: The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID-19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID-19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies.METHODS: We analyzed 4,069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method.RESULTS: Out of 4,069 COVID-19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID-19 treatments: 0.96, 95% confidence interval 0.77-1.20 and HR=0.89, 0.67-1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N=2,057) patients (HR=1.00, 0.78-1.26 and HR=0.88, 0.65-1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID-19 adult patients, 9,700 with hypertension) confirmed the absence of association.CONCLUSIONS: In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID-19 patients.

2020 - Reply to comment on “environmental and occupational risk factors of amyotrophic lateral sclerosis: A population-based case-control study” [Articolo su rivista]
Filippini, T.; Tesauro, M.; Fiore, M.; Malagoli, C.; Consonni, M.; Violi, F.; Iacuzio, L.; Arcolin, E.; Conti, G. O.; Cristaldi, A.; Zuccarello, P.; Zucchi, E.; Mazzini, L.; Pisano, F.; Gagliardi, I.; Patti, F.; Mandrioli, J.; Ferrante, M.; Vinceti, M.
abstract

We much appreciate the positive comments and interest concerning our study on the environmental and occupational risk factors of amyotrophic lateral sclerosis (ALS) [...].

2020 - Safety of 3’-Sialyllactose (3’-SL) sodium salt as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3’-Sialyllactose (3’-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human identical milk oligosaccharide (HiMO) 3’-SL but also containing D-lactose, sialic acid and a small fraction of other related oligosaccharides resulting in a fully characterised mixture of carbohydrates. The NF is produced by fermentation with a genetically modified strain of Escherichia coli K-12 DH1. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and toddlers, foods for special medical purposes and food supplements. The target population is the general population. The anticipated daily intake of 3’-SL from the NF at the maximum proposed use levels is unlikely to exceed the intake level of naturally occurring 3’-SL in breastfed infants on a body weight basis. The intake of 3’-SL in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to 3’-SL is also considered of no safety concern. Food supplements are not intended to be used if other foods with added NF (as well as breast milk, milk, fermented milk-based products and selected cheeses retaining milk sugar (e.g. curd cheese) for infants and young children) are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use for the proposed target populations.

2020 - Safety of 6′-Sialyllactose (6′-SL) sodium salt as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 6′-Sialyllactose (6′-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 6′-SL but also contains D-lactose, sialic acid and a small fraction of other related oligosaccharides. The NF is produced by fermentation with a genetically modified strain of Escherichia coli K-12 DH1. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and toddlers, foods for special medical purposes and food supplements. The target population is the general population. The anticipated daily intake of 6′-SL from the NF at the maximum proposed use levels is unlikely to exceed the intake level of naturally occurring 6′-SL in breastfed infants on a body weight basis. The intake of 6′-SL in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to 6′-SL is also considered of no safety concern. Food supplements are not intended to be used if other foods with the added NF or breast milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2020 - Safety of Schizochytrium sp. oil as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Ferreira, L.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single-cell microalga. The strain WZU477, used by the applicant (Progress Biotech bv), was found to belong to the species Schizochytrium limacinum and was obtained in a marine environment from rotted mangrove forest leaves. The NF, an oil rich in docosahexaenoic acid (DHA), is isolated from the microalgae by mechanical extraction. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use level defined by the applicant was derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20–50 mg/100 kcal. The intake of DHA resulting from the use of the NF in IF and FOF is not expected to pose safety concerns. The composition of the NF indicates the absence of marine biotoxins in the NF. Furthermore, Schizochytrium limacinum was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’. Based on the information provided, the microalga is not expected to survive the manufacturing process. Toxicological tests conducted with the NF were not performed. However, based on the available toxicological data on various forms of oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process and the composition of the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

2020 - Safety of a botanical extract derived from Panax notoginseng and Astragalus membranaceus (AstraGin™) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on a botanical extract derived from both Panax notoginseng and Astragalus membranaceus (AstraGin™) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a combination of an ethanol extract of the roots of A. membranaceus and a hot water extract of the roots of P. notoginseng. The NF contains 1.5–5% total saponins, 0.1–0.5% ginsenoside Rb1 and 0.01–0.1% astragaloside I. Both plants that are used to produce the NF have a long history of use, especially in traditional Chinese medicine. Information on the production process and the composition of the NF is sufficient and does not raise safety concerns. The applicant proposed to use the NF as a food supplement for the general adult population, excluding pregnant women, at a maximum daily amount of 350 mg. Taking into account these conditions of use, the Panel considers that the consumption of the NF is not nutritionally disadvantageous. The provided genotoxicity studies do not raise concerns for genotoxicity of the NF. Based on the findings of a subchronic toxicity study, supported by a subacute toxicity study, the Panel identified the overall no observed adverse effect level (NOAEL) of the NF at 100 mg/kg body weight (bw) per day. By applying an uncertainty factor of 200, the Panel concludes that the NF is safe at an intake level of 0.5 mg/kg bw per day, corresponding to a maximum daily intake of 35 mg of the NF for the target population, i.e. adults excluding pregnant women.

2020 - Safety of astaxanthin for its use as a novel food in food supplements [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Gelbmann, W.; Steinkellner, H.; Knutsen, H. K.
abstract

Following a request from the European Commission, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of astaxanthin when used as a novel food in food supplements at maximum levels of 8 mg/day, taking into account the overall cumulative intake of astaxanthin from all food sources. In 2014, the NDA Panel assessed the safety of the novel astaxanthin-rich ingredient derived from microalgae Haematococcus pluvialis in the context of an application submitted under Regulation (EC) No 258/1997. In that opinion, the NDA Panel considered that the acceptable daily intake (ADI) for astaxanthin was 0.034 mg/kg body weight (bw) set by the EFSA FEEDAP Panel in 2014. In 2019, the FEEDAP Panel adopted an opinion which concerned the renewal of the authorisation of dimethyldisuccinate-astaxanthin and a new use of the additive for crustaceans and other fish than salmonids. In that assessment, the FEEDAP Panel derived a new ADI of 0.2 mg astaxanthin/kg bw which replaced the ADI of 0.034 mg/kg bw established in 2014. By taking into account an updated exposure assessment for astaxanthin from the background diet (fish and crustaceans) in combination with 8 mg from food supplements, the NDA Panel concludes that (i) such combined exposure to astaxanthin is safe for adults, (ii) 14 to < 18 years old adolescents reach the ADI, and (iii) the ADI is exceeded by 28% in children aged 10 to < 14 years and up to 524% in infants aged 4–6 months.

2020 - Safety of chia seeds (Salvia hispanica L.) subject to thermal processing in relation to the formation of process contaminants as a novel food for extended uses [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Matijevic, L.; Romero, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of chia seeds in foods subject to thermal processing which may result in the formation of process contaminants. The safety assessment of this novel food (NF) is based on previous assessments of chia seeds by the EFSA NDA Panel, information received from a public call for data by EFSA and information retrieved from an extensive literature search performed by EFSA. In 2019, during the overall safety assessment of chia seeds, the NDA panel retrieved one reference which, among others, investigated the formation of process contaminants, i.e. acrylamide, hydroxymethylfurfural and furfural, in wheat flour-based biscuits with added chia seeds flour. Based on this study, the Panel considers that there is a potential for substantial acrylamide formation in biscuits with 10–20% added chia seeds flour with low residual moisture contents (≤ 2%). The Panel is not aware of further scientific evidence corroborating these findings. The extensive new literature searches performed by EFSA did not show any relevant articles regarding either asparagine content or formation of process contaminants in chia seeds and products thereof. Information received from the call for data were either limited or inconclusive. The available evidence does not provide a basis to conclude whether or not the addition of chia seeds to foods undergoing heat treatment (at temperatures above 120°C) results in increased formation of acrylamide as compared to these foods without chia seeds. Reported concentrations of hydroxymethylfurfural and furfural in heat-treated chia seeds do not pose a safety concern. No information on other process contaminants in chia seeds was found.

2020 - Safety of chromium-enriched biomass of Yarrowia lipolytica as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on chromium-enriched biomass of Yarrowia lipolytica as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is the dried and heat-killed chromium-enriched biomass of Y. lipolytica. This yeast species is widespread in nature, can be found in the environment and in foods, and was attributed the qualified presumption of safety (QPS) status for production purposes in 2018, including food and feed products based on biomass of the yeast. The production process, fermentation in the presence of chromium chloride, includes a heat-killing step of the yeast, resulting in the absence of viable Y. lipolytica in the NF. The maximum total chromium content of the NF is 23 μg Cr/g, with the chromium present as Cr(III). The applicant proposed to use the NF as a food supplement. The target population proposed by the applicant is the general population from 3 years of age onwards, with maximum proposed use levels of 2 g/day for children from 3 to 9 years of age and 4 g/day thereafter. At the proposed use levels of the NF, the combined intake of chromium provided by the NF, in addition to a background diet high in chromium, would result in total chromium intakes well below the tolerable daily intake (TDI) for chromium(III) for all target population groups. The Panel concludes that the NF, chromium-enriched biomass of Y. lipolytica, is safe under the proposed conditions of use.

2020 - Safety of dried whole cell Euglena gracilis as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of dried whole cell Euglena gracilis as a novel food (NF) pursuant to Regulation (EU) 2015/2283. E. gracilis is a single-cell microalga which occurs widely in nature and is commonly found in freshwater habitats. The NF, the dried biomass of E. gracilis, is produced by fermentation and its major constituent (> 50%) is a β-glucan polysaccharide. The applicant proposed to use the NF in food supplements, in foods for total diet replacement for weight control and as a food ingredient added to a number of food products. The target population proposed by the applicant is the general population, except for food supplements and for foods for total diet replacement for which the target population is the general population from 12 months of age onwards. In 2019, E. gracilis was attributed the qualified presumption of safety (QPS)-status with the qualification ‘for production purposes only’, which includes food products based on microbial biomass of the microalga. Based on the information provided, E. gracilis is not expected to survive the manufacturing process. The submitted toxicity studies did not raise safety concerns. No adverse effects were observed in the subchronic toxicity study, up to the highest dose tested, i.e. 3,300 mg NF/kg body weight, considered as the no observed adverse effect level (NOAEL). The margins of exposure between this dose and the high (95th percentile) intake estimates, range from 33 for infants to 192 for adults. The Panel considers that in view of the QPS status of the source of the NF, supported by the compositional data and lack of toxicity observed in the 90-day study, the margins of exposure are sufficient. The Panel considers that the NF, i.e. dried whole cell Euglena gracilis, is safe at the proposed uses and use levels.

2020 - Safety of hot water extract of fruits and peduncles of Hovenia dulcis as a novel food pursuant to Regulation 1(EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of ‘Hovenia dulcis fruit extract’ as a novel food (NF) for its use in food supplements. The NF concerns a hot water extract of sliced and dried fruits and peduncles of Hovenia dulcis Thun. The production process is described in sufficient detail but contains contradictory information regarding the mixing with another ingredient of the NF. The NF is comprised of mostly carbohydrates (about 90%), about 2% proteins, 5% moisture, less than 1% fat and about 2% ash. In addition, the NF contains small amounts of flavonoids such as dihydromyricetin, myricetin and quercetin. The Panel notes limitations of the data provided from the batch testing regarding proximate analyses and plant secondary metabolites. Given these limitations, the Panel considers that the data provided by the applicant do not demonstrate that different batches produced with the described production process meet the proposed specifications. The target population is the general adult population excluding pregnant and lactating women and people with a chronic disease, such as liver malfunction. Limited information was provided on a history of consumption of Hovenia dulcis fruits and on an extract approved in South Korea. A number of toxicological studies were performed. However, the study reports did not allow to verify that the test item was representative of the NF. The same applied to a human study provided by the applicant. The Panel concludes that the safety of the NF has not been established.

2020 - Safety of lacto-N-neotetraose (LNnT) produced by derivative strains of E. coli BL21 as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the change in the production process and specifications of lacto-N-neotetraose (LNnT) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) LNnT but also contains lactose, lacto-N-triose II (LNT II), para-lacto-N-neo-hexaose (para-LNnH) and other related carbohydrates. The NF is produced by fermentation with two genetically modified strains of Escherichia coliBL21. LNnT when chemically synthesised or produced by microbial fermentation using another E. coli strain (K-12) is already authorised and included in the EU list of NFs. This application is limited to a change in the manufacturing process and specifications while target population, uses and use levels and consequently the anticipated intake do not change. The information provided on the manufacturing process, including the absence of DNA from the producing microorganisms, composition, identity and specifications of the NF do not raise safety concerns. Particularly, the proposed changes in the specifications are limited to a slightly higher ash content and limits for the presence of yeast and moulds, while specifications for methanol and LNnT fructose isomer have been removed. Food supplements are not intended to be used if other foods with the added NF or breast milk for young children are consumed on the same day. The Panel concludes that lacto-N-neotetraose (LNnT) as a NF when produced by fermentation with two genetically modified strains of E. coliBL21 is safe under the proposed conditions of use.

2020 - Safety of rapeseed powder from Brassica rapa L. and Brassica napus L. as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Dumont, A. F.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of rapeseed powder from Brassica rapa L. and Brassica napus L. as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Rapeseed powder will be produced from the seeds of non-genetically modified double low (00) cultivars that are varieties with a low content of erucic acid and reduced content of glucosinolates compared to older varieties. The applicant developed a production process designed to further reduce the content of glucosinolates and other undesirable compounds such as phytates. The NF will be used as a food ingredient added to a number of food products. The target population is the general population from 1 year of age. The maximum estimated intake of the NF is 18–21 g/day in adolescents, adults and elderly (corresponding to 0.35, 0.23 and 0.25 g/kg body weight (bw) per day, respectively). The levels of undesirable compounds in this NF, such as erucic acid, glucosinolates and phytates, are below levels which would raise concerns. The EFSA NDA Panel has previously assessed the safety of similar products for human consumption and there is extensive experience on the use of rapeseed in animal feed. The applicant provided a human study on the safety and tolerability of the NF and no safety concerns were identified. The Panel considers that the NF, i.e. rapeseed powder from Brassica rapa L. and Brassica napus L., is safe at the proposed conditions of use.

2020 - Safety of selenium-enriched biomass of Yarrowia lipolytica as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on selenium-enriched biomass of Yarrowia lipolytica as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is the dried and heat-killed selenium-enriched biomass of Y. lipolytica. This yeast species is widespread in nature, can be found in the environment and in foods, and was attributed the qualified presumption of safety (QPS) status for production purposes in 2018, including food and feed products based on biomass of the yeast. The production process, fermentation in the presence of sodium selenite, includes a heat-killing step of the yeast, resulting in the absence of viable Y. lipolytica in the NF. The maximum total selenium content in the NF is 200 μg Se/g, mainly present as organic selenium compounds. The applicant proposed to use the NF as a food supplement. The target population proposed by the applicant is the general population from 3 years of age onwards, with maximum proposed use levels of 0.2 g/day for children from 3 to 9 years of age and 1 g/day thereafter. The Panel considers that the yeast biomass is not of safety concern at the proposed use levels. The Panel also considers that the selenium provided by the NF is as safe as selenium from other dietary sources. However, the Panel notes that, at the use levels proposed by the applicant, the intake of the NF could, in combination with a background diet high in selenium, lead to total selenium intakes exceeding the UL for selenium in all target population groups, except for children from 7 to 9 years. Furthermore, the Panel considers that newly emerging data warrant a reassessment of the UL for selenium.

2020 - Safety of the extension of use of plant sterol esters as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use of the novel food ‘plant sterol esters’ when added to vegetable fat spreads and to liquid vegetable fat-based emulsions for cooking and baking purposes pursuant to Regulation (EU) 2015/2283. Member States expressed concerns in relation to plant sterol oxidation products (POP) and consumption by non-target population groups. The median (0.5%) and P90 (2.28%) value of the oxidation rates of plant sterols determined by a wide range of cooking experiments were used together with exposure estimates for plant sterol when added and cooked with vegetable fat spreads and liquids. The no-observed adverse effect level (NOAEL) of a subchronic rat study and an applied default uncertainty factor of 200 served to derive levels (i.e. 0.64 mg POP/kg body weight (bw) per day) considered safe for humans. This safe level of exposure would be exceeded at the P95 by all age groups when considering the P90 oxidation rate and using EFSA's comprehensive food consumption database for assessing the potential exposure. When considering the median oxidation rate, the safe level of 0.64 mg POP/kg bw per day would be exceeded at the highest P95 intake estimates in children below 9 years of age. When considering an intake of the maximum authorised use level of 3 g plant sterols/person per day and oxidation rates of 0.5% and 2.28%, the resulting daily POP intakes per kg bw by an adult weighing 70 kg would be 0.21 and 0.98 mg/kg bw per day, respectively, the latter value exceeding 0.64 mg/kg bw per day. The Panel concludes that the safety of the intended extension of use of plant sterol esters under the proposed conditions of use has not been established.

2020 - Safety of vitamin D2 mushroom powder as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Roldan-Torres, R.; Steinkellner, H.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on vitamin D2 mushroom powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is an ingredient produced from Agaricus bisporus mushrooms that have been exposed to ultraviolet (UV) light to induce the conversion of provitamin D2 (ergosterol) to vitamin D2 (ergocalciferol). The NF contains concentrations of vitamin D provided by vitamin D2 in the ranges of 1,000–1,300 μg/g. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods and beverages, including food for special medical purposes and food supplements. The target population is the general population except for food supplements, for which the target population is individuals above seven months of age. The Panel concludes that the NF, used as an ingredient, is safe for the general population at the proposed condition of use in foods and beverages and that the NF used as a food supplement, is safe for individuals above 1 year. The Panel, however, notes that the UL for infants aged 0–6 months may be exceeded in high consumers of infant formula (IF) and/or follow-on formula (FoF) that may also be high consumers of foods fortified with the NF and for infants aged 7–12 months consuming a daily vitamin D oral supplementation of 10 μg. However, the Panel considers this scenario unlikely as complementary feeding in high consumers of IF and/or FoF may be limited. Furthermore, the combined consumption of vitamin D via fortified foods and supplements does not specifically concern this NF application. The Panel concludes that the NF is safe under the proposed conditions of use for the proposed target populations.

2020 - Satellite-detected tropospheric nitrogen dioxide and spread of SARS-CoV-2 infection in Northern Italy [Articolo su rivista]
Filippini, T.; Rothman, K. J.; Goffi, A.; Ferrari, F.; Maffeis, G.; Orsini, N.; Vinceti, M.
abstract

Following the outbreak of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) last December 2019 in China, Italy was the first European country to be severely affected, with the first local case diagnosed on 20 February 2020. The virus spread quickly, particularly in the North of Italy, with three regions (Lombardy, Veneto and Emilia-Romagna) being the most severely affected. These three regions accounted for >80% of SARS-CoV-2 positive cases when the tight lockdown was established (March 8). These regions include one of Europe's areas of heaviest air pollution, the Po valley. Air pollution has been recently proposed as a possible risk factor of SARS-CoV-2 infection, due to its adverse effect on immunity and to the possibility that polluted air may even carry the virus. We investigated the association between air pollution and subsequent spread of the SARS-CoV-2 infection within these regions. We collected NO2 tropospheric levels using satellite data available at the European Space Agency before the lockdown. Using a multivariable restricted cubic spline regression model, we compared NO2 levels with SARS-CoV-2 infection prevalence rate at different time points after the lockdown, namely March 8, 22 and April 5, in the 28 provinces of Lombardy, Veneto and Emilia-Romagna. We found little association of NO2 levels with SARS-CoV-2 prevalence up to about 130 μmol/m2, while a positive association was evident at higher levels at each time point. Notwithstanding the limitations of the use of aggregated data, these findings lend some support to the hypothesis that high levels of air pollution may favor the spread of the SARS-CoV-2 infection.

2020 - Scientific Opinion related to a notification from Lyckeby Starch AB on barley starch to be used in the manufacturing of several foods as ingredient, of the food additive modified starch and of glucose syrups pursuant to Article 21(2) of Regulation (EU) No 1169/2011 – for permanent exemption from labelling [Articolo su rivista]
Turck, D.; Castenmiller, J.; Hirsch Ernst, K. -I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Marchelli, R.; van Loveren, H.; Martinez, S. V.; de Henauw, S.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on barley starch to be used in the manufacturing of several foods as ingredient, of the food additive modified starch and of glucose syrups pursuant to Article 21(2) of Regulation (EU) No 1169/2011, as notified by Lyckeby Starch AB. The applicant provided information on the manufacturing process and data on the content of total protein, gluten and allergenic proteins in barley starch. The applicant also performed IgE-binding in vitro tests, which were considered inconclusive by the Panel. No human intervention studies with barley starch or food products thereof were provided by the applicant, except for a DBPCFC with barley starch hydrolysate in cereal allergic individuals. The Panel notes that glucose syrups based on barley have been already exempted from allergen labelling as per Annex II of Regulation (EU) No 1169/2011 and that the current application is for the exemption from labelling of all foods manufactured from barley starch. In all the scenarios considered for the anticipated intake, the calculated total protein intake from barley starch was above the MED/MOED for wheat (expressed in mg of wheat protein) in adults (10 mg) and children (2 mg). The Panel concludes that the data available are insufficient to conclude on the likelihood of adverse allergic reactions in cereal-allergic individuals upon consumption of barley starch under the conditions of use proposed by the applicant, and that the consumption of foodstuffs produced from barley starch as starting (raw) material or foodstuffs containing barley starch as an ingredient is unlikely to cause an adverse reaction in individuals with coeliac disease who are not allergic to cereals, provided that the value of gluten for ‘gluten-free’ foods (20 mg/kg) is not exceeded.

2020 - Scientific opinion on the safety of selenite triglycerides as a source of selenium added for nutritional purposes to food supplements [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Germini, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on selenite triglycerides as a novel food (NF) pursuant to Regulation (EU) 2015/2283, their safety when added for nutritional purposes to food supplements as a source of selenium and the bioavailability of selenium from this source, in the context of Directive 2002/46/EC. The proposed NF is the first lipophilic organic form of selenium so far described in the literature. It is composed by a mixture of individual Se-containing lipids which do not occur in nature. The Panel considers that the information provided on the composition of the NF does not allow a complete characterisation of the product. From the data provided to characterise the absorption, distribution, metabolism and excretion of the NF, it cannot be established in which chemical form Se is systemically available and if it can enter the functional Se body pool to fulfil Se physiological functions. The Panel considers that, since it is not demonstrated that the NF is converted to a known form of Se following ingestion and absorption, the NF is to be treated as a xenobiotic with unknown properties in the body. From a subchronic toxicity study in rats, the Panel derives a lowest observed adverse effect level (LOAEL) for general toxicity of 2 mg Se/kg body weight (bw) per day based on findings indicating liver as a target organ, as it has been shown for other studies on dietary Se. The Panel concludes that the NF is absorbed and provides Se, but in an unknown form of which the bioavailability has not been determined. The Panel also concludes that the safety of the NF under the intended conditions of use cannot be established.

2020 - Selenium and Other Trace Elements in the Etiology of Parkinson's Disease: A Systematic Review and Meta-Analysis of Case-Control Studies [Articolo su rivista]
Adani, G.; Filippini, T.; Michalke, B.; Vinceti, M.
abstract

Background: Parkinson's disease (PD) is the most common neurodegenerative disease after Alzheimer's dementia. Whereas the exact etiology of PD remains unknown, risk of developing PD seems to be related to a combination of genetic and environmental factors. This also includes abnormal exposure to trace elements of nutritional and toxicological interest. Objectives: In this systematic review and meta-Analysis, we summarized the results of case-control studies comparing levels of selenium, copper, iron, and zinc in PD patients and controls in either blood (whole blood, serum/plasma) or cerebrospinal fluid (CSF). Methods: We performed a systematic PubMed search selecting studies reporting trace element levels in different specimens of patients and controls. We performed a meta-Analysis using a random-effect model to compute the weighted mean differences (WMD) and corresponding 95% CI of selenium, copper, iron, and zinc levels in the blood or CSF of patients and their matched controls. Results: We retrieved 56 papers reporting data for selenium (cases/controls: 588/721), copper (2,190/2,522), iron (2,956/3,469), and zinc (1,798/1,913) contents in CSF and blood. Cases showed considerably higher levels of selenium in CSF compared with controls (+51.6%; WMD 5.49; 95% CI 2.82 to 8.15), while levels in serum were similar (-0.2%; WMD-0.22; 95% CI-8.05 to 7.62). For copper, cases showed slightly higher levels in CSF and slightly lower concentrations in serum (+4.5%; WMD 1.87; 95% CI-3.59 to 7.33, and-4.5%; WMD-42.79; 95% CI-134.35 to 48.76, respectively). A slight increase was also found for CSF iron-levels (+9.5%; WMD 9.92; 1.23 to 18.61), while levels were-decreased in serum/plasma (-5.7%; WMD-58.19; 95% CI-106.49 to-9.89) and whole blood (-10.8%; WMD-95.69; 95% CI-157.73 to-33.65). Conversely, for zinc cases exhibited lower levels both in CSF (-10.8%; WMD-7.34; 95% CI-14.82 to 0.14) and serum/plasma (-7.5%; WMD-79.93; 95% CI-143.80 to-16.06). A longer duration of the disease tends to be associated with overall lower trace element levels in either CSF or blood. Conclusions: Due to the study findings and the greater relevance of the CSF compartment compared with the circulating peripheral ones, this meta-Analysis suggests that overexposure in the central nervous system to selenium, and possibly to copper and iron, may be a risk factor of the disease, while zinc might have a protective-effect.

2020 - Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity [Articolo su rivista]
Tinkov, Alexey A; Ajsuvakova, Olga P; Filippini, Tommaso; Zhou, Ji-Chang; Lei, Xin Gen; Gatiatulina, Eugenia R; Michalke, Bernhard; Skalnaya, Margarita G; Vinceti, Marco; Aschner, Michael; Skalny, Anatoly V
abstract

Selenium (Se) homeostasis is tightly related to carbohydrate and lipid metabolism, but its possible roles in obesity development and in adipocyte metabolism are unclear. The objective of the present study is to review the current data on Se status in obesity and to discuss the interference between Se and selenoprotein metabolism in adipocyte physiology and obesity pathogenesis. The overview and meta-analysis of the studies on blood Se and selenoprotein P (SELENOP) levels, as well as glutathione peroxidase (GPX) activity in obese subjects, have yielded heterogenous and even conflicting results. Laboratory studies demonstrate that Se may modulate preadipocyte proliferation and adipogenic differentiation, and also interfere with insulin signaling, and regulate lipolysis. Knockout models have demonstrated that the selenoprotein machinery, including endoplasmic reticulum-resident selenoproteins together with GPXs and thioredoxin reductases (TXNRDs), are tightly related to adipocyte development and functioning. In conclusion, Se and selenoproteins appear to play an essential role in adipose tissue physiology, although human data are inconsistent. Taken together, these findings do not support the utility of Se supplementation to prevent or alleviate obesity in humans. Further human and laboratory studies are required to elucidate associations between Se metabolism and obesity.

2020 - Selenium and other trace elements in the etiology of Parkinson’s disease: a systematic review and meta-analysis of case-control studies [Abstract in Rivista]
Adani, G.; Filippini, T.; Michalke, B.; Vinceti, M.
abstract

.INTRODUCTION Parkinson’s disease (PD) is a neurodegenerative illness recognised as the most common neurological disorder after Alzheimer’s dementia. Whereas the exact PD etiology remains unknown, risk of developing PD seems to be related to an interrelation of genetic and environmental factors, including also altered exposure to trace elements. In this systematic review and meta-analysis, we updated and summarized the results of epidemiologic case-control studies comparing levels of selenium, copper, iron and zinc in PD patients with healthy subjects in either blood (as whole blood, serum or plasma) and cerebrospinal fluid (CSF). MATERIALS AND METHODS We performed a systematic PubMed search and we included in our assessment only studies reporting demographic and disease-related characteristics, as well as trace element levels in different specimens (whole blood, serum/plasma and CSF). We then performed a meta-analysis of mean differences of trace element levels between cases and controls, using a random-effect model computing the weighted mean differences (WMD) and corresponding 95% confidence intervals (CI) to assess the association between serum/plasma, whole blood, CSF and selenium, copper, iron and zinc with Parkinson’s disease. RESULTS We retrieved 55 papers reporting data for selenium (588 cases and 721 controls), copper (2190 and 2522), iron (2843 and 3434), and zinc (1798 and 1913). Cases showed higher levels of selenium in CSF compared with controls (WMD=5.49; 95%CI 2.82 to 8.15), while levels in serum were similar (WMD=-0.22; -8.05 to 7.62). For copper cases showed higher levels in CSF and lower in serum compared to controls (WMD=1.87; -3.59 to 7.33, and -42.79, -134.35 to 48.76 respectively). Same results were found for iron in CSF (WMD=6.54; -1.97 to 15.04) and in serum/plasma (WMD=-58.19; -106.49 to -9.89 and whole blood (WMD=-95.69; 157.73 to -33.65). On the converse, cases had lower levels of zinc both in CSF (WMD=-7.34; -14.82 to 0.14) and serum/plasma (WMD=-79.93; -143.80 to -16.06). CONCLUSIONS Results of this systematic review and meta-analysis suggests that overexposure to environmental selenium, copper and iron may be risk factors for PD onset or progression. Alternatively, some variation in levels of these trace elements may occur as a consequence of the disease. Considering the burden of PD in the world population, further investigation of trace element exposure in this disease is therefore warranted, especially to plan possible prevention measures.

2020 - The association between seafood intake and fecundability: Analysis from two prospective studies [Articolo su rivista]
Wise, L. A.; Willis, S. K.; Mikkelsen, E. M.; Wesselink, A. K.; Sorensen, H. T.; Rothman, K. J.; Tucker, K. L.; Trolle, E.; Vinceti, M.; Hatch, E. E.
abstract

Background: Seafood is an important source of omega‐3 fatty acids, which have been associated with improved oocyte quality and embryo morphology in some studies. However, seafood is also a source of persistent organic pollutants and heavy metals, which may adversely affect fecundity. Previous studies of seafood intake and fecundity have generated inconsistent results. Methods: In two prospective cohort studies of 7836 female pregnancy planners from Denmark (Snart Foraeldre, n = 2709) and North America (PRESTO, n = 5127), we evaluated the association of dietary intake of total seafood and marine‐sourced long‐chain omega‐3 fatty acids (eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid) with fecundability. Participants completed a baseline questionnaire on sociodemographics, behavioral factors, anthropometrics, and medical history, and a food frequency questionnaire. Pregnancy status was updated bimonthly for up to 12 months or until reported conception. We estimated fecundability ratios (FRs) and 95% confidence intervals (CIs) using proportional probabilities regression models, adjusted for energy intake and other potential confounders. We restricted analyses to women with ≤6 menstrual cycles of attempt time at enrollment. Results: Intake of total seafood or marine‐sourced long‐chain omega‐3 fatty acids was not appreciably associated with fecundability in either cohort (≥200 vs. <50 g/week total seafood: FR = 0.94, 95% CI: 0.79–1.10 in Snart Foraeldre; FR = 1.00, 95% CI: 0.90–1.13 in PRESTO; marine fatty acids: ≥90th vs. <25th percentile: FR = 1.00, 95% CI: 0.85–1.18 in Snart Foraeldre; FR = 0.97, 95% CI: 0.86–1.09 in PRESTO). In PRESTO, where we collected additional data on seafood preparation, we observed an inverse association between fecundability and fried shellfish (≥10 g/week vs. none: FR = 0.77, 95% CI: 0.61–0.98), but not unfried shellfish (≥20 g/week vs. none: FR = 0.98, 95% CI: 0.89–1.07); in Snart Foraeldre, there was no association with total shellfish intake. Conclusions: We found little association between seafood intake and fecundability overall, but greater intake of fried shellfish was associated with reduced fecundability among North American participants.

2020 - The study of levels from redox-active elements in cerebrospinal fluid of amyotrophic lateral sclerosis patients carrying disease-related gene mutations shows potential copper dyshomeostasis [Articolo su rivista]
Violi, F.; Solovyev, N.; Vinceti, M.; Mandrioli, J.; Lucio, M.; Michalke, B.
abstract

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by a loss of function of motor neurons. The etiology of this disorder is still largely unknown. Gene-environment interaction arises as a possible key factor in the development of amyotrophic lateral sclerosis. We assessed the levels of trace metals, copper (Cu), iron (Fe), and manganese (Mn), of 9 amyotrophic lateral sclerosis cases and 40 controls by measuring their content in cerebrospinal fluid. The following trace element species were quantified using ion chromatography-inductively coupled plasma mass spectrometry: univalent copper (Cu-I), divalent Cu (Cu-II), divalent Fe (Fe-II), trivalent Fe (Fe-III), divalent Mn (Mn-II), trivalent Mn (Mn-III), and also unidentified Mn species (Mn-unknown) were present in some samples. When computing the relative risks for amyotrophic lateral sclerosis through an unconditional logistic regression model, we observed a weak and imprecise positive association for iron (Fe III, adjusted odds ratio 1.48, 95% CI 0.46-4.76) and manganese (total-Mn and Mn-II; adjusted odds ratio 1.11, 95% CI 0.74-1.67, and 1.13, 95% CI 0.79-1.61, respectively). Increased risk for copper was found both in the crude analysis (odds ratio 1.14, 95% CI 0.99-1.31) and in multivariable analysis after adjusting for sex, age, and year of storage (1.09, 95% CI 0.90-1.32). Our results suggest a possible positive association between Cu and genetic amyotrophic lateral sclerosis, while they give little indication of involvement of Fe and Mn in disease, though some correlations found also for these elements deserve further investigation.

2020 - Towards effective COVID‑19 vaccines: Updates, perspectives and challenges (Review) [Articolo su rivista]
Calina, D.; Docea, A. O.; Petrakis, D.; Egorov, A. M.; Ishmukhametov, A. A.; Gabibov, A. G.; Shtilman, M. I.; Kostoff, R.; Carvalho, F.; Vinceti, M.; Spandidos, D. A.; Tsatsakis, A.
abstract

In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS‑COV‑2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID‑19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.

2020 - Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study [Articolo su rivista]
Castelnuovo, A. D.; Costanzo, S.; Antinori, A.; Berselli, N.; Blandi, L.; Bruno, R.; Cauda, R.; Guaraldi, G.; Menicanti, L.; My, I.; Parruti, G.; Patti, G.; Perlini, S.; Santilli, F.; Signorelli, C.; Spinoni, E.; Stefanini, G. G.; Vergori, A.; Ageno, W.; Agodi, A.; Aiello, L.; Agostoni, P.; Moghazi, S. A.; Astuto, M.; Aucella, F.; Barbieri, G.; Bartoloni, A.; Bonaccio, M.; Bonfanti, P.; Cacciatore, F.; Caiano, L.; Cannata, F.; Carrozzi, L.; Cascio, A.; Ciccullo, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Crosta, F.; Pra, C. D.; Danzi, G. B.; D'Ardes, D.; Donati, K. D. G.; Giacomo, P. D.; Gennaro, F. D.; Tano, G. D.; D'Offizi, G.; Filippini, T.; Fusco, F. M.; Gentile, I.; Gialluisi, A.; Gini, G.; Grandone, E.; Grisafi, L.; Guarnieri, G.; Lamonica, S.; Landi, F.; Leone, A.; Maccagni, G.; Maccarella, S.; Madaro, A.; Mapelli, M.; Maragna, R.; Marra, L.; Maresca, G.; Marotta, C.; Mastroianni, F.; Mazzitelli, M.; Mengozzi, A.; Menichetti, F.; Meschiari, M.; Minutolo, F.; Montineri, A.; Mussinelli, R.; Mussini, C.; Musso, M.; Odone, A.; Olivieri, M.; Pasi, E.; Petri, F.; Pinchera, B.; Pivato, C. A.; Poletti, V.; Ravaglia, C.; Rinaldi, M.; Rognoni, A.; Rossato, M.; Rossi, I.; Rossi, M.; Sabena, A.; Salinaro, F.; Sangiovanni, V.; Sanrocco, C.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Spinicci, M.; Trecarichi, E. M.; Venezia, A.; Veronesi, G.; Vettor, R.; Vianello, A.; Vinceti, M.; Vocciante, L.; De Caterina, R.; Iacoviello, L.
abstract

Background: Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective: We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods: In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results: Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions: HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.

2020 - [The Health Examination Survey at regional level: the Emilia-Romagna Region (Northern Italy) example] [Articolo su rivista]
Salvia, Chiara; Donfrancesco, Chiara; Palmieri, Luigi; Lo Noce, Cinzia; Vanuzzo, Diego; Vinceti, Marco; Bargellini, Annalisa; Borella, Paola; Giampaoli, Simona
abstract

to assess time trend of lifestyles, cardiovascular risk factors, and prevalence of high-risk conditions in random samples of the general adult population residing in Emilia-Romagna, examined in two cross-sectional surveys conducted within the Epidemiological Cardiovascular Observatory (OEC 1998-2002) and the Epidemiological Cardiovascular Observatory/Health Examination Survey (OEC/HES 2008-2012).

2019 - A combination of beta-sitosterol and beta-sitosterol glucoside and normal function of the immune system: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from Essential Sterolin Products (Pty) Ltd., submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the European Food Safety Authority (EFSA) Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to a combination of beta-sitosterol and beta-sitosterol glucoside and normal function of the immune system. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is a combination of beta-sitosterol and beta-sitosterol glucoside in a ratio 100:1. The Panel considers that a combination of beta-sitosterol and beta-sitosterol glucoside in a ratio 100:1 is sufficiently characterised. The claimed effect proposed by the applicant is ‘normal function of the immune system by restoring balance between TH1-TH2 mediated immunity’. The Panel notes that the claimed effect ‘normal function of the immune system by restoring balance between TH1- and TH2-mediated immunity’ does not refer to a specific function of the body which can be assessed in vivo in humans by generally accepted methods, but rather to a mechanism of action by which the food/constituent could exert the claimed effect. The Panel considers that the claimed effect does not refer to any specific health claim as required by Regulation (EC) No 1924/2006. The Panel concludes that a cause and effect relationship cannot be established between the consumption of a combination of beta-sitosterol and beta-sitosterol glucoside in a ratio 100:1 and a beneficial physiological effect.

2019 - A risk of bias instrument for non-randomized studies of exposures: A users' guide to its application in the context of GRADE [Articolo su rivista]
Morgan, Rebecca L; Thayer, Kristina A; Santesso, Nancy; Holloway, Alison C; Blain, Robyn; Eftim, Sorina E; Goldstone, Alexandra E; Ross, Pam; Ansari, Mohammed; Akl, Elie; Filippini, Tommaso; Hansell, Anna; Meerpohl, Joerg J; Mustafa, Reem A; Verbeek, Jos; Vinceti, Marco; Whaley, Paul; Schünemann, Holger J
abstract

The objective of this paper is to explain how to apply, interpret, and present the results of a new instrument to assess the risk of bias (RoB) in non-randomized studies (NRS) dealing with effects of environmental exposures on health outcomes. This instrument is modeled on the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) instrument. The RoB instrument for NRS of exposures assesses RoB along a standardized comparison to a randomized target experiment, instead of the study-design directed RoB approach. We provide specific guidance for the integral steps of developing a research question and target experiment, distinguishing issues of indirectness from RoB, making individual-study judgments, and performing and interpreting sensitivity analyses for RoB judgments across a body of evidence. Also, we present an approach for integrating the RoB assessments within the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess the certainty of the evidence in the systematic review. Finally, we guide the reader through an overall assessment to support the rating of all domains that determine the certainty of a body of evidence using the GRADE approach.

2019 - Alimentazione, ambiente e malattie cronico-degenerative: nuove metodologie di valutazione del rischio [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Malavolti, Marcella
abstract

Introduzione La valutazione del rischio sanitario associato a fattori di interesse nutrizionale e/o tossicologico (risk assessment) rappresenta un ambito di grande interesse per la popolazione generale, la comunità scientifica e gli operatori di sanità pubblica. Tale processo mira a definire adeguate misure ed indicazioni di sicurezza alimentare, ambientale e occupazionale, e favorire un’appropriata comunicazione del rischio ed efficaci interventi di medicina preventiva. Alla valutazione dei rischi sanitari attribuibili ai diversi fattori di tipo chimico e fisico presenti negli alimenti e negli ambienti di vita e di lavoro (‘fattori ambientali’ in senso lato) contribuiscono da un lato i singoli ricercatori attraverso i loro lavori originali di ricerca o meta-analisi, dall’altro gli enti e le istituzioni specificatamente deputati al processo di risk assessment, quali nello specifico per l’Unione Europea la European Food Safety Authority (EFSA), con sede nel nostro Paese a Parma. La valutazione del rischio attribuibile ai fattori ambientali e nutrizionali prevede diverse fasi metodologiche, tre delle quali sono state soggette a profonde innovazioni nel corso degli ultimi anni e sono di seguito brevemente analizzate: 1) l’identificazione e la valutazione metodologica della letteratura epidemiologica; 2) l’analisi ed interpretazione dei risultati di tale letteratura; 3) la formulazione di valutazioni finali condivise, superando eventuali differenze di opinione tra gli esperti. Identificazione e valutazione della letteratura pertinente al risk assessment Non vi è dubbio come ogni processo di valutazione del rischio sanitario debba basarsi in primo luogo sull’identificazione della letteratura scientifica pertinente. A tal fine, è naturalmente necessario effettuare una ricerca bibliografica rigorosa, completa ed infine illustrata in modo ‘trasparente’. In questa prospettiva, la metodologia adottata dai processi di valutazione del rischio sanitario si avvicina molto a quella adottata per le rassegne sistematiche, caratterizzandosi per una scelta il più possibile estensiva delle ‘parole chiave’ per identificare la letteratura di interesse, e per una strategia di ricerca e selezione degli studi facilmente riproducibile da chiunque. Ciò comporta l’uso di archivi bibliografici quali PubMed e la nota banca dati da esso contenuta Medline, EMBASE, Scopus e Web of Science (anche quest’ultimi contenenti Medline), ed eventualmente Google Scholar (in realtà più motore di ricerca che archivio bibliografico in senso proprio). Viene talora utilizzata per il risk assessment anche la letteratura ‘grigia’, ritrovabile però mediante ricerche complesse e non facilmente riproducibili attraverso archivi quali Conference Proceedings Citation Indexes di WoS, ERIC, PsycINFO, CINHAL, ProQuest Dissertations & Theses Global, International Guideline Library, e l’URL http://www.opengrey.eu/. L’appropriatezza dell’uso di tale letteratura grigia è tuttavia controversa, trattandosi di materiale bibliografico talora di limitata qualità e non sottoposto a valutazione ‘tra pari’. Dopo aver identificato gli articoli di interesse, occorre valutarne la pertinenza mediante l’esame del loro testo integrale, ed infine compiere una valutazione della qualità metodologica (critical appraisal o risk of bias assessment). Quest’ultimo processo è estremamente delicato ed influenza in modo sostanziale l’intero processo di valutazione del rischio. Esso prevede la valutazione delle principali distorsioni metodologiche degli studi, quali errori nella stima espositiva, presenza di confondimento, distorsione di selezione e di classificazione degli esiti sanitari, descrizione incompleta dei risultati e improprietà dell’elaborazione statistica. Valutazioni di questo tipo vengono frequentemente effettuate mediante l’uso di ‘griglie’ precodificate (quali il Risk of Bias della Cochrane Coll

2019 - Aluminum and tin: Food contamination and dietary intake in an Italian population [Articolo su rivista]
Filippini, Tommaso; Tancredi, Stefano; Malagoli, Carlotta; Cilloni, Silvia; Malavolti, Marcella; Violi, Federica; Vescovi, Luciano; Bargellini, Annalisa; Vinceti, Marco
abstract

Aluminum and tin are ubiquitous in the environment. In normal biological systems, however, they are present only in trace amounts and have no recognized biological functions in humans. High exposure to these metals can result in adverse health effects such as neurodegenerative diseases. In non-occupationally exposed subjects, diet is the primary source of exposure. In this study, we aimed at estimating dietary aluminum and tin intake in an Italian adult population. We measured aluminum and tin concentrations through inductively-coupled plasma mass spectrometry in 908 food samples. We also estimated dietary intake of these two metals, by using a validated semi-quantitative food-frequency questionnaire administered to 719 subjects (319 men and 400 women) recruited from the general population of the Emilia Romagna region, Northern Italy. We found the highest aluminum levels in legumes, sweets, and cereals, while the highest tin levels were in sweets, meat and seafood. The estimated median daily dietary intake of aluminum was 4.1 mg/day (Interquartile range – IQR: 3.3–5.2), with a major contribution from beverages (28.6%), cereals (16.9%), and leafy vegetables (15.2%). As for tin, we estimated a median intake of 66.8 μg/day (IQR: 46.7–93.7), with a major contribution from vegetables (mainly tomatoes) (24.9%), fruit (15.5%), aged cheese (12.2%), and processed meat (10.4%). This study provides an updated estimate of the dietary intake of aluminum and tin in a Northern-Italy adult population, based on data from a validated food-frequency questionnaire. The intake determined for this population does not exceed the established thresholds of tolerable intake.

2019 - Amyotrophic lateral sclerosis incidence following exposure to inorganic selenium in drinking water [Abstract in Atti di Convegno]
Vinceti, M; Filippini, T; Malagoli, C; Violi, F; Mandrioli, J; Consonni, D; Rothman, Kj; Wise, La
abstract

Background and aim. Some laboratory and epidemiologic studies have documented an association between high intake of the trace element selenium and risk of amyotrophic lateral sclerosis (ALS), a degenerative disease of the motor neurons. There have been few epidemiologic studies of the association. Methods. From 1986 through 2015, we followed a community cohort in northern Italy that had been inadvertently exposed in the 1974-86 period to drinking water with unusually high levels of selenium, around 8 µg/ml, in its inorganic hexavalent form (selenate). In this cohort, we previously identified a high incidence of ALS during 1986-94. Here we report extended follow-up of this exposed cohort, as well as of an unexposed cohort including over 95,000 municipal residents, for an additional 21 years. We identified incident cases through administrative sources and a specialized registry. Results. During follow-up, 7 and 112 ALS cases were newly diagnosed in the exposed and unexposed cohorts, respectively, yielding incidence rates of 14 and 5 per 100,000 person-years. A Poisson regression analysis adjusting for age, sex, and calendar year produced an overall rate ratio (RR) for ALS of 2.8 (95% confidence interval (CI) 1.3 - 6) in the entire period of follow-up. The association was stronger earlier than later in follow-up (1986-1994 vs. 1994-2015), and among women than men. All exposed cases were of the sporadic, non-familial form for the disease. Conclusion. Overall, results from this ‘natural experiment’ indicate a positive association between chronic exposure to inorganic selenium and ALS incidence, with rates in the exposed cohort declining over time after cessation of exposure. Also taking into account the recognized neurotoxicity of selenium, particularly its selective toxicity on motor neurons observed in animal studies, the present study provides additional support for the hypothesis that selenium in its inorganic form increases ALS risk.

2019 - Amyotrophic lateral sclerosis incidence following exposure to inorganic selenium in drinking water: A long-term follow-up [Articolo su rivista]
Vinceti, M.; Filippini, T.; Malagoli, C.; Violi, F.; Mandrioli, J.; Consonni, D.; Rothman, K. J.; Wise, L. A.
abstract

Some studies have reported an association between overexposure to selenium and risk of amyotrophic lateral sclerosis (ALS), a rare degenerative disease of motor neurons. From 1986 through 2015, we followed a cohort in Northern Italy that had been inadvertently consuming tap water with unusually high concentrations of inorganic hexavalent selenium from 1974 to 1985. We had previously documented an excess incidence of ALS in this cohort during 1986-1994. Here, we report extended follow-up of the cohort for an additional 21 years, encompassing 50,100 person-years of the exposed cohort and 2,233,963 person-years of the unexposed municipal cohort. We identified 7 and 112 incident ALS cases in the exposed and unexposed cohorts, respectively, yielding crude incidence rates of 14 and 5 cases per 100,000 person-years. A Poisson regression analysis, adjusting for age, sex and calendar year, produced an overall incidence rate ratio (IRR) for ALS of 2.8 (95% confidence interval (CI) 1.3, 6), with a substantially stronger IRR in 1986-1994 (8.2, 95% CI 2.7, 24.7) than in 1995-2015 (1.5, 95% CI 0.5, 4.7), and among women (5.1, 95% CI 1.8, 14.3) than men (1.7, 95% CI 0.5, 5.4). Overall, these results indicate an association between high exposure to inorganic selenium, a recognized neurotoxicant, and ALS incidence, with declining rates after cessation of exposure and stronger effects among women.

2019 - Appropriate age range for introduction of complementary feeding into an infant's diet [Articolo su rivista]
Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Fewtrell, M.; Kersting, M.; Przyrembel, H.; Dumas, C.; Titz, A.; Turck, D.
abstract

Following a request from the European Commission, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) revised its 2009 Opinion on the appropriate age for introduction of complementary feeding of infants. This age has been evaluated considering the effects on health outcomes, nutritional aspects and infant development, and depends on the individual's characteristics and development. As long as foods have an age-appropriate texture, are nutritionally appropriate and prepared following good hygiene practices, there is no convincing evidence that at any age investigated in the included studies (< 1 to < 6 months), the introduction of complementary foods (CFs) is associated with adverse health effects or benefits (except for infants at risk of iron depletion). For nutritional reasons, the majority of infants need CFs from around 6 months of age. Infants at risk of iron depletion (exclusively breastfed infants born to mothers with low iron status, or with early umbilical cord clamping (< 1 min after birth), or born preterm, or born small-for-gestational age or with high growth velocity) may benefit from earlier introduction of CFs that are a source of iron. The earliest developmental skills relevant for consuming pureed CFs can be observed between 3 and 4 months of age. Skills for consuming finger foods can be observed in some infants at 4 months, but more commonly at 5–7 months. The fact that an infant may be ready from a neurodevelopmental perspective to progress to a more diversified diet before 6 months of age does not imply that there is a need to introduce CFs. There is no reason to postpone the introduction of potentially allergenic foods (egg, cereals, fish and peanut) to a later age than that of other CFs as far as the risk of developing atopic diseases is concerned. Regarding the risk of coeliac disease, gluten can be introduced with other CFs.

2019 - Association between Outdoor Air Pollution and Childhood Leukemia: A Systematic Review and Dose-Response Meta-Analysis [Articolo su rivista]
Filippini, T.; Hatch, E. E.; Rothman, K. J.; Heck, J. E.; Park, A. S.; Crippa, A.; Orsini, N.; Vinceti, M.
abstract

BACKGROUND: A causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our knowledge, no systematic reviews have summarized the most recently published evidence and no analyses have examined the dose-response relation. OBJECTIVE: We investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia. METHODS: We searched all case-control and cohort studies that have investigated the risk of childhood leukemia in relation to exposure either to motorized traffic and related contaminants, based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or to measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. We carried out a meta-analysis of all eligible studies, including nine studies published since the last systematic review and, when possible, we fit a dose-response curve using a restricted cubic spline regression model. RESULTS: We found 29 studies eligible to be included in our review. In the dose-response analysis, we found little association between disease risk and traffic indicators near the child's residence for most of the exposure range, with an indication of a possible excess risk only at the highest levels. In contrast, benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 y of age, and when exposure assessment at the time of diagnosis was used. Exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels. DISCUSSION: Overall, the epidemiologic literature appears to support an association between benzene and childhood leukemia risk, with no indication of any threshold effect. A role for other measured and unmeasured pollutants from motorized traffic is also possible. https://doi.org/10.1289/EHP4381.

2019 - Blood pressure levels and hypertension prevalence in a high selenium environment: results from a cross-sectional study [Articolo su rivista]
Vinceti, M.; Chawla, R.; Filippini, T.; Dutt, C.; Cilloni, S.; Loomba, R.; Bargellini, A.; Orsini, N.; Dhillon, K. S.; Whelton, P.
abstract

Background and aims: Recent human and laboratory studies have suggested the possibility that selenium overexposure may increase blood pressure. We sought to ascertain whether adults living in a seleniferous area exhibit an association between selenium exposure and both blood pressure levels as well as prevalence of hypertension. Methods and results: We measured selenium levels in blood (serum), hair and nail samples obtained from 680 adult volunteers (267 men and 413 women), living in seven Punjabi villages in a seleniferous area and related them to health outcomes, including systolic and diastolic blood pressure and presence of hypertension. In a multivariable restricted cubic spline regression model, adjusted for age, sex and history of hypertension, we found a positive association between systolic blood pressure and both serum (P = 0.004) and hair (P = 0.058) selenium levels, but not with nail selenium content. Little association emerged between the three selenium biomarkers and diastolic blood pressure. Hypertension prevalence was positively associated with the three exposure indicators (P < 0.001). The associations we found were generally stronger in women than in men. Conclusions: Overall, these findings suggest that chronic overexposure to environmental selenium may increase blood pressure, though there were inconsistencies for this association according to the choice of exposure indicator, the study endpoint and the sex.

2019 - Cadmium exposure and breast cancer risk: a systematic review and dose-response meta-analysis of cohort studies [Abstract in Atti di Convegno]
Filippini, T; Kasdagli, Mi; Naska, A; Torres, D; Lopes, C; Carvalho, C; Moreira, P; Malavolti, M; Orsini, N; Vinceti, M
abstract

Background and aim: Cadmium is a heavy metal which has been implicated in breast cancer etiology because of its toxic properties such as endocrine disruption. The general population is exposed to cadmium through dietary intake, cigarette smoking, emissions of motorized traffic and industrial facilities. We carried out a systematic review and dose-response meta-analysis of the cohort studies investigating the association between cadmium exposure and breast cancer risk, for which inconsistent results have been reported in the literature. Methods: Following online database search up to January 2019, we carried out a dose-response meta-analysis to identify the relation between cadmium exposure and disease risk. We used a restricted cubic spline model and the ‘one-stage’ approach, stratifying for exposure assessment method and menopausal status. Results: We identified 12 studies, 9 using breast cancer incidence and 3 mortality as an outcome. In six studies cadmium exposure was assessed through dietary questionnaires, in five through urinary excretion levels, and in one based on environmental air levels. Seven studies included post-menopausal women only. Overall, we observed a positive linear relation between breast cancer risk and dietary cadmium intake (relative risk (RR) 1.04, 95% confidence interval (CI) 0.81-1.33 at 10 µg/day, and RR 1.12, 95% CI 0.80-1.56 at 20 µg/day). On the converse, risk was not associated with urinary excretion. Analysis restricted to post-menopausal women showed a positive association between cadmium exposure assessed through either dietary intake and urinary excretion, for levels higher than 20 µg/day and 1.65 µg/g creatinine, respectively.

2019 - Cadmium exposure and risk of breast cancer: a dose-response meta-analysis of cohort studies [Abstract in Atti di Convegno]
Filippini, T; Torres, D; Lopes, C; Carvalho, C; Moreira, P; Naska, A; Kasdagli, M-I; Malavolti, M; Orsini, Nicola; Vinceti, M
abstract

Background: Cadmium is a toxic heavy metal that has been implicated in breast cancer etiology, albeit with inconsistent results. The general population is exposed to cadmium through dietary intake, cigarette smoking, emissions of motorized traffic and industrial facilities. We carried out a systematic review and dose-response meta-analysis of the cohort studies investigating the association between cadmium exposure and breast cancer risk. Methods: Following a literature search through September 10, 2019, we carried out a systematic review and a dose-response meta-analysis to investigate the relation between cadmium exposure and disease risk. We used a restricted cubic spline model and the ‘one-stage’ approach, stratifying for exposure assessment method and menopausal status. Results: We identified eleven studies on breast cancer risk, six based on cadmium dietary intake, and five on urinary excretion levels. In dose-response analysis, we observed a positive, statistically imprecise linear relation between dietary cadmium intake and disease risk. The risk ratio at 20 µg/day compared with no intake was 1.12 (95% confidence interval 0.80-1.56). Conversely, we detected a very imprecise negative association between urinary cadmium excretion and risk (risk ratio=0.89, 95% confidence interval 0.37-2.14 at 2 µg/g creatinine of cadmium excretion). Analysis restricted to post-menopausal women showed substantially no association, as was true for all meta-analyses carried out by comparing the highest versus the lowest exposure category. Conclusions: Overall, we found scant evidence of positive association between cadmium and breast cancer. Available data were too limited to carry out stratified analyses according to age, smoking and hormone receptor status. Therefore, possible associations between cadmium exposure and breast cancer risk in selected subgroups cannot be entirely ruled out. Keywords: cadmium, breast cancer, dietary intake, urine excretion, dose-response meta-analysis

2019 - Capitolo 3: Determinanti di salute e malattia [Capitolo/Saggio]
Vinceti, M; Balzarini, F; Filippini, T; Malagoli, C; Bossi, E
abstract

2019 - Compliance with Tuberculosis Screening in Irregular Immigrants [Articolo su rivista]
Bonvicini, Francesca; Cilloni, Silvia; Fornaciari, Rossano; Casoni, Carmen; Marchesi, Cristina; Greci, Marina; Monici, Lucia; Nicolini, Fausto; Vinceti, Marco
abstract

Tuberculosis (TB) is a serious public health problem in many regions of the world, especially in the poorest areas. For this reason, screening for active and latent forms must be considered when dealing with high-risk groups such as irregular immigrants in Western countries. We conducted a retrospective cohort study by recruiting subjects aged ≥15 years who underwent a tuberculin skin test at a dedicated National Health Service Centre in a northern Italian province between 1 January 2012 and 31 December 2013. These participants were followed up until 31 December 2016. We aimed at evaluating an experimental protocol for active and latent tuberculosis screening, focusing on patient compliance, feasibility, and capability to detect clinical forms of the disease. We enrolled 368 irregular immigrants, i.e., immigrants not having a valid residence permit and who were therefore not entitled to choose a general practitioner. In total, 90.22% of these completed all the steps for the screening of active TB, while 87.33% also undertook screening for the latent form of the disease. Homelessness, self-reported prostitution, female sex, and employment status adversely affected compliance. Chronic alcohol consumption was associated with increased risk of no beginning or interruption of the procedures. All of the five patients with active TB successfully completed the treatment. Overall, adherence to the screening program was high compared to other studies in immigrants, possibly owing to organizational factors such as the availability of cultural mediators, the network between the different health services, the presence of dedicated nursing staff and a free-of-charge service. In addition, selected vulnerable subgroups should be targeted using tailored screening and follow-up programs.

2019 - Deficient calcium, zinc, and iron intake on absorption of cadmium from diet [Abstract in Atti di Convegno]
Upson, K; Filippini, T; Vinceti, M; Wegienka, G; Wise, LAUREN ANNE; Tokar, Ej; Baird, Dd
abstract

Background/Aim: In vitro and in vivo studies have demonstrated that deficient calcium, zinc, and iron dietary intake upregulates metal ion transporters to increase intestinal absorption. However, these gut transporters are not specific and bind to other metals, including cadmium. Few human studies have investigated whether deficient calcium, zinc, and iron intake increases intestinal absorption of dietary cadmium. Methods: We used enrollment data (2010-2012) from the Study of Environment, Lifestyle & Fibroids, a cohort of 1693 African American women ages 23-35 who reside in the Detroit, Michigan area. Whole blood cadmium concentrations (proxy for cadmium absorption) were measured in 1548 participants. Dietary and supplemental calcium, zinc, and iron intake was estimated using Block 2005 Food Frequency Questionnaire data; deficient intake was defined as <80% of the recommended daily allowance. Daily dietary intake of total grains was used as the proxy for dietary cadmium intake as grains are a major source of cadmium exposure in U.S. diet. We estimated the percent difference in blood cadmium concentrations per median daily intake of total grains (4.55 ounce equivalents) using multivariable linear regression, stratified by deficient and sufficient calcium, zinc, and/or iron intake. We restricted the analyses to never smokers with plausible values for total energy intake (>400 and <5000 kcal/day) (n=1087). We adjusted for age at enrollment, total energy intake, body mass index, height, education, and natural log-transformed blood lead concentrations. Results: The observed percent difference in blood cadmium concentrations in relation to intake of total grains was stronger among those with deficient intake of calcium, zinc, and/or iron (28%, 95% CI; 6, 53%) than among those with sufficient intake of all 3 essential nutrients (5%, 95% CI: -7, 19%). Conclusions: Our preliminary findings suggest that women with deficient calcium, zinc, and/or iron intake have increased absorption of cadmium from the diet.

2019 - Dietary cadmium and risk of breast cancer subtypes defined by hormone receptor status: a prospective cohort study [Articolo su rivista]
Grioni, Sara; Agnoli, Claudia; Krogh, Vittorio; Pala, Valeria; Rinaldi, Sabina; Vinceti, Marco; Contiero, Paolo; Vescovi, Luciano; Malavolti, Marcella; Sieri, Sabina
abstract

Diet is the primary source of cadmium - a proven Group 1 human carcinogen - for non-smokers. Observational studies investigating the effect of cadmium from food sources on breast cancer risk have produced inconsistent results. We examined the association between dietary cadmium and risk of breast cancer defined by estrogen receptor (ER), progesterone receptor (PR) and HER2 status, in 8,924 women recruited to a prospective study between 1987 and 1992. Dietary cadmium intake was estimated using a semi-quantitative food frequency questionnaire at baseline. During a median of 22 years of follow-up, 451 incident cases of breast cancer were identified through the Varese Cancer Registry. Multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for breast cancer and receptor-defined breast cancer subtypes were estimated for quintiles of dietary cadmium intake, adjusting for confounding factors. Mean dietary cadmium intake was 7.8 (standard deviation 1.4) μg/day. Women with highest quintile of cadmium intake had a greater risk of breast cancer (HR 1.54; 95% CI, 1.06 - 2.22; p-trend = 0.028) than those with lowest quintile of intake. Women premenopausal at recruitment had HR = 1.73 (95% CI, 1.10 - 2.71, highest vs. lowest quintile); postmenopausal women had HR = 1.32 (95% CI, 1.05 - 1.66 for each standard deviation increase in cadmium). Cadmium-related risk of breast cancer did not vary with ER, PR or HER2 status (p-heterogeneity not significant). These findings support the hypothesis that dietary cadmium is a risk factor for breast cancer. This article is protected by copyright. All rights reserved.

2019 - Dietary cadmium exposure and risk of melanoma: an Italian population-based case-control study [Abstract in Atti di Convegno]
Filippini, T; Malagoli, C; Malavolti, M; Vinceti, M
abstract

Background and aim. The heavy metal cadmium could be highly toxic to humans, and its environmental exposure has been linked to many adverse health effects, such as atherosclerosis, diabetes, and cancer, including melanoma. Although the underlying mechanisms need yet to be clearly identified, recent findings suggested that cadmium can specifically promote the malignant transformation of melanoma cells through the aberrant DNA methylation inducing dysregulation of specific gene expression. Since in the non-occupationally exposed population, in addition to smoking, food intake is the major source of cadmium exposure, we aimed at assessing the risk of cutaneous melanoma in relation to dietary cadmium intake. Methods. Using a population-based study design, we recruited 380 incident cases of newly-diagnosed melanoma and 719 sex- and age-matched controls in the Emilia-Romagna Region, Northern Italy. We evaluated their dietary habits through a semi-quantitative food frequency questionnaire and we computed the odds ratio (OR) and its 95% confidence interval (CI) for melanoma according to quintile distribution of cadmium intake, using a conditional logistic regression model, matching by sex, age and province of residence, and adjusting also for phototype, non-alcoholic energy intake, body mass index, and Italian Mediterranean Diet Index. Results: Median intake of cadmium was 5.81 µg/day (interquartile range 4.46-7.59) in cases, and 5.63 µg/day (4.46-7.34) in controls. OR of melanoma associated with 1-unit increase in cadmium intake was 1.11 (95% CI 1.00-1.24). Melanoma risk increased with increasing quintile of cadmium exposure, with ORs of 1.55 (95% CI 0.99-2.42), 1.54 (95% CI 0.99-2-40), 1.75 (95% CI 1.12-2.75), and 1.65 (95% CI 1.05-2.61) in the second to the highest quintile compared to the lowest quintile. Sex-stratified analysis showed substantially comparable results and a generally higher risk in female population, with continuous ORs of 1.10 (95% CI 0.93-1-29), and 1.15 (95% CI 0.99-1.33) in men and women, respectively. Conclusions: Our results suggest a positive association between cadmium exposure through diet and risk of cutaneous melanoma in a Northern Italy population. Such association started to occur at a level of exposure lower than the tolerable intake established by the World Health Organization, and considered to be safe for humans.

2019 - Dietary cadmium intake and fecundability in a North American preconception cohort study [Abstract in Rivista]
Filippini, Tommaso; Willis, Sydney K.; Wesselink, Amelia K.; Hatch, Elizabeth E.; Rothman, Kenneth J.; Vinceti, Marco; Wise, Lauren A.
abstract

Objective To evaluate the association between dietary cadmium intake (D-Cd) and fecundability. Diet is one of the main sources of cadmium, and D-Cd is often used as indicator of cadmium exposure, particularly in non-smoking populations. In a previous preconception cohort study of 501 couples,1 high female cadmium concentrations measured in whole blood were associated with reduced fecundability. Design Prospective cohort study (2013-2018). Materials and Methods Pregnancy Online Study (PRESTO) is a North American prospective preconception cohort of pregnancy planners. At baseline, female participants aged 21-45 years completed a web-based questionnaire on demographic, lifestyle, medical and reproductive factors. Ten days after enrollment, participants completed the National Cancer Institute Dietary History Questionnaire II, a validated food frequency questionnaire (FFQ) of average intake during the previous year. D-Cd (μg/day) was estimated by combining FFQ responses with US Food and Drug Administration data on food cadmium content. Participants were then followed for up to 12 months or until reported pregnancy, whichever came first. The analysis included 4,768 women attempting to conceive for ≤6 cycles at study entry and not using fertility treatment. We used a proportional probabilities regression model to estimate fecundability ratios (FR) and 95% confidence intervals (CI), adjusted for age, body mass index (BMI), smoking history, parity, physical activity, last method of contraception, daily use of multivitamins, race/ethnicity, education, income, geographic region, and the 2010 healthy eating index score. We used the nutrient residual approach to adjust for energy intake. Results Median D-Cd was 8.0 μg/day (interquartile range: 7.0-9.1 μg/day). The top 5 contributors to D-Cd were nuts and seeds; fried potatoes; dark green lettuce; cooked greens; and white potatoes. Compared with an average D-Cd of <6.8 μg/day, FRs for D-Cd quintiles of 6.8-7.6, 7.7-8.4, 8.5-9.5, and ≥9.6 μg/day were 1.03 (CI: 0.92-1.14), 1.07 (CI: 0.96-1.18), 1.07 (CI: 0.96-1.19), and 1.08 (0.97-1.20), respectively. Results were not appreciably different among never smokers with no current passive smoke exposure, for whom cadmium exposure from other sources (e.g., cigarettes) would be lower (respective FRs: 1.02, 1.05, 1.06 and 1.02). Results did not differ materially by age (<30 vs. ≥30 years), BMI (<30 vs. ≥30 kg/m2), total fiber intake (<25 vs. ≥25 g/day), geographic region of residence (West, Midwest, Northeast, South, Canada), or attempt time at study entry (<3 vs. ≥3 cycles). Conclusions Dietary intake of cadmium was not appreciably associated with fecundability, though exposure misclassification and confounding could explain the null results. References 1 Buck Louis GM, Sundaram R, Schisterman EF, Sweeney AM, Lynch CD, Gore-Langton RE, Chen Z, Kim S, Caldwell KL, Barr DB. Heavy metals and couple fecundity, the LIFE Study. Chemosphere. 2012 Jun;87(11):1201-7. https://doi.org/10.1016/j.chemosphere.2012.01.017. Epub 2012 Feb 4. PubMed PMID: 22309709; PubMed Central PMCID: PMC3327819.

2019 - Dietary cadmium intake and risk of cutaneous melanoma: An Italian population-based case-control study [Articolo su rivista]
Filippini, T.; Malagoli, C.; Wise, L. A.; Malavolti, M.; Pellacani, G.; Vinceti, M.
abstract

Introduction: Exposure to the heavy metal cadmium has been associated with many adverse health effects, such as atherosclerosis, diabetes, and cancer, possibly melanoma. In non-occupationally exposed individuals, food intake is a major source of cadmium exposure, after smoking. We aimed to assess the risk of melanoma in relation to dietary cadmium intake. Methods: Using a population-based case-control study design, we recruited 380 incident cases of newly-diagnosed cutaneous melanoma and 719 matched controls in the Emilia-Romagna Region, Northern Italy in the years 2005-2006. We evaluated dietary intake using a semi-quantitative food frequency questionnaire. We used conditional logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs) for melanoma according to quintiles of dietary cadmium intake, adjusting for several potential confounders, and we modeled the association non-parametrically, using restricted cubic splines. Results: Median energy-adjusted intake of cadmium was 6.11 μg/day (interquartile range 5.38–6.91) among cases and 5.97 μg/day (5.15–6.79) among controls. For each 1 μg/day-increase in cadmium intake, the OR for melanoma was 1.11 (95% CI 1.00–1.24). Melanoma risk generally increased with increasing quintile of cadmium exposure, with ORs of 1.55 (95% CI 0.99–2.42), 1.54 (95% CI 0.99-2-40), 1.75 (95% CI 1.12–2.75), and 1.65 (95% CI 1.05–2.61) for the second through fifth quintiles, compared with the lowest quintile. Sex-stratified analysis showed ORs per 1 μg/day-increase in cadmium intake of 1.10 (95% CI 0.93-1-29) among men and 1.15 (95% CI 0.99–1.33) among women. Using spline regression analysis, we observed a generally linear increase in melanoma risk up to 6 μg/day of cadmium intake, after which the risk appeared to plateau. Conclusions: We observed a positive non-linear association between dietary cadmium intake and risk of cutaneous melanoma in a Northern Italy population. However, further studies are needed to elucidate this association, due to concerns about exposure misclassification, unmeasured confounding, and the limited and conflicting evidence from epidemiological findings.

2019 - Dietary cadmium intake and risk of cutaneous melanoma: a population-based case-control study in Northern Italy [Abstract in Rivista]
Filippini, T; Malagoli, C; Malavolti, M; Vinceti, M
abstract

BACKGROUND AND AIM. Cadmium is a toxic heavy metal for humans, and its environmental exposure has been linked to many adverse health effects, including cancer, atherosclerosis and diabetes. In particular, recent findings suggest that cadmium may increase risk of cutaneous melanoma, possibly through the promotion of the malignant transformation of melanoma cells through aberrant DNA methylation and by inducing gene expression dysregulation. Since in non-occupational exposed and non-smoking subjects dietary exposure is the major source of cadmium exposure, we aimed to assess melanoma risk in relation to dietary cadmium intake. METHODS. We recruited 380 newly-diagnosed incident cases of cutaneous melanoma and 719 sex- and age-matched population controls in four North Italian provinces (Parma, Reggio Emilia, Modena, and Bologna) of Emilia-Romagna Region. We estimated their dietary habits using a semi-quantitative food frequency questionnaire and we evaluated melanoma risk by computing the odds ratio (OR) and its 95% confidence interval (CI) according to quintile distribution of cadmium intake. We used a conditional logistic regression model to compute ORs, matching by sex, age and province of residence, and adjusting also for phototype, non-alcoholic energy intake, body mass index, and Italian Mediterranean Diet Index. Also a spline regression model was used in order to evaluated possible dose-response relation. RESULTS: Median cadmium intake was 5.81 µg/day (interquartile range 4.46-7.59) in cases, and 5.63 µg/day (4.46-7.34) in controls. OR of melanoma associated with 1-unit increase in cadmium intake was 1.11 (95% CI 1.00-1.24). Melanoma risk increased with increasing quintile of cadmium exposure, with ORs of 1.55 (95% CI 0.99-2.42), 1.54 (95% CI 0.99-2-40), 1.75 (95% CI 1.12-2.75), and 1.65 (95% CI 1.05-2.61) from second to highest quintile compared to lowest quintile. Sex-stratified analysis showed substantially comparable results and a generally higher risk in women, with continuous ORs of 1.10 (95% CI 0.93-1-29), and 1.15 (95% CI 0.99-1.33) in men and women, respectively. Spline regression analysis showed a non-linear risk increase, with possible plateau at 5-6 µg/day of cadmium intake. Slightly higher risk estimates in women and older subjects were detected. CONCLUSIONS: Our results seem to point out a positive association between dietary cadmium exposure and melanoma risk in the study population. Such association started to occur at a level of exposure lower than the tolerable intake established for food safety by international authorities.

2019 - Dietary exposure estimates to fifteen trace elements in an adult population of Emilia Romagna region, Northern Italy [Abstract in Atti di Convegno]
Filippini, T; Tancredi, S; Malagoli, C; Malavolti, M; Vescovi, L; Bargellini, A; Vinceti, M
abstract

The health effects and the exposure levels of trace elements in humans are important public health topics. Assessing their dietary intake is fundamental to evaluate the long-term risks for public health and for food safety assessment. Since a priority of food safety regulatory agencies is to ensure the protection of consumers and to assess the health risks for the general population, to estimate the actual dietary intake of trace elements for comparison with the upper and lower tolerable levels is very important. In this study, we aimed to evaluate the dietary intake of several trace elements in an Italian community, namely of antimony, barium, beryllium, boron, cobalt, lithium, molybdenum, nickel, silver, strontium, tellurium, thallium, titanium, uranium, and vanadium. To do that, in 2016-2017 we collected a total of 908 food samples available in Italian markets and groceries from two Northern Italy provinces (Modena and Reggio Emilia), and we measured their trace element content through inductively-coupled plasma mass spectrometry. We also administered a validated semi-quantitative food frequency questionnaire to 708 residents (300 men and 48 women) in the Emilia-Romagna Region, to assess their dietary habits and eventually to estimate their dietary intake of the aforementioned trace elements. Overall, study results showed that in our population the dietary exposure levels to selected trace elements could be considered similar to that observed in other European and non-European populations. Though we cannot rule out the possibility that the dietary exposure estimates in the present study may not be representative of the population as a whole, our results provide a good and updated assessment of trace elements far frequently evaluated in a sample of Italian adult consumers from the Emilia Romagna region. Our findings finally suggest that our population should not be at risk of adverse health effects in relation to excess or deficiency of the investigated trace elements since the estimated dietary intake generally point out exposure levels within the safe range as far as indicated by recommendations of international agencies.

2019 - Dietary intake of acrylamide and risk of breast, endometrial and ovarian cancer: a systematic review and dose-response meta-analysis [Poster]
Filippini, T; Adani, G; Wise, La; Vinceti, M
abstract

Background: Acrylamide is probable human carcinogen that occurs naturally in starchy foods during cooking processes at high temperatures. Aside from occupational exposures and smoking, main source of human exposure is diet, particularly consumption of potatoes, grain products, and coffee. High acrylamide intake has been associated with altered sex-steroid hormone concentrations and increased risk of hormone-dependent gynecologic neoplasms. Objective: We performed a systematic review of the papers investigating the association between acrylamide intake and risk of breast, endometrial and ovarian cancer. We also examined a possible dose-response relation by carrying out a dose-response meta-analysis of these studies. Methods: We searched in PubMed up to September 10, 2019 the non-experimental human studies investigating risk of breast, endometrial, or ovarian cancer in relation to dietary intake of acrylamide. We also carried out a dose-response meta-analysis using a restricted cubic spline model. Results: We retrieved 18 studies: 11 cohort, 5 case-cohort, and 2 case-control studies. Since some studies assessed more than one cancer type, we found a total of ten studies on risk of breast cancer, seven on endometrial cancer, and seven on ovarian cancer. In the dose-response meta-analysis, acrylamide intake was associated with slightly increased risks of endometrial and ovarian cancers, with a stronger and almost linear increased risk among never smokers. Conversely, for breast cancer we found no evidence to support an increased risk following acrylamide exposure, except for a positive association among premenopausal women exposed to at least 20 µg/day of acrylamide. Conclusions: Based on the relatively small number of studies published to date, acrylamide intake was associated with increased risk of endometrial and ovarian cancer in a dose-response fashion, with a slightly stronger association observed among never smokers. Acrylamide intake was associated with an increased risk of breast cancer only among premenopausal women and at intakes greater than 20 µg/day.

2019 - Dietary intake of acrylamide and risk of breast, endometrial and ovarian cancer: a systematic review and dose-response meta-analysis. [Abstract in Atti di Convegno]
Filippini, T; Adani, Giorgia; Wise, LAUREN ANNE; Vinceti, M
abstract

Background: Acrylamide is a probable human carcinogen that occurs naturally in starchy foods during cooking processes at high temperatures. Aside from occupational exposures and smoking, the main source of human exposure is diet, particularly consumption of potatoes, grain products, and coffee. High acrylamide intake has been associated with altered sex-steroid hormone concentrations and increased risk of hormone-dependent gynecologic neoplasms. Objective: We performed a systematic review of the papers investigating the association between acrylamide intake and risk of breast, endometrial and ovarian cancer in humans. We also examined a possible dose-response relation by carrying out a dose-response meta-analysis of these studies. Methods: We searched in PubMed up to September 10, 2019 the non-experimental human studies investigating risk of breast, endometrial, or ovarian cancer in relation to dietary intake of acrylamide. We also carried out a dose-response meta-analysis using a restricted cubic spline model. Results: We retrieved 18 studies: 11 cohort, 5 case-cohort, and 2 case-control studies. Since some studies assessed more than one cancer type, we found a total of ten studies on risk of breast cancer, seven on endometrial cancer, and seven on ovarian cancer. In the dose-response meta-analysis, acrylamide intake was associated with slightly increased risks of endometrial and ovarian cancers, with a stronger and almost linear increased risk among never smokers. Conversely, for breast cancer we found no evidence to support an increased risk following acrylamide exposure, except for a positive association among premenopausal women exposed to at least 20 µg/day of acrylamide. Conclusions: Based on the relatively small number of studies published to date, acrylamide intake was associated with increased risk of endometrial and ovarian cancer in a dose-response fashion, with a slightly stronger association observed among never smokers. Acrylamide intake was associated with an increased risk of breast cancer only among premenopausal women and at intakes greater than 20 µg/day. Keywords: acrylamide; dietary intake; breast cancer; endometrial cancer; ovarian cancer.

2019 - Dietary reference values for chloride [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aggett, P.; Fairweather-Tait, S.; Martin, A.; Przyrembel, H.; de Sesmaisons-Lecarre, A.; Naska, A.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) has derived dietary reference values (DRVs) for chloride. There are no appropriate biomarkers of chloride status, no balance studies and no adequate evidence on the relationship between chloride intake and health outcomes that can be used to set DRVs for chloride. There is a close relationship between sodium and chloride balances in the body. Sodium chloride is the main source of both electrolytes in European diets and similar urinary excretion levels of sodium and chloride (on a molar basis) are typically observed in Western populations. Hence, the Panel considered that reference values for chloride can be set at values equimolar to the reference values for sodium for all population groups, and are as follows: 1.7 g/day for children aged 1–3 years, 2.0 g/day for children aged 4–6 years, 2.6 g/day for children aged 7–10 years, 3.1 g/day for children aged 11–17 years and 3.1 g/day for adults including pregnant and lactating women. Consistent with the reference values for sodium, these levels of chloride intake are considered to be safe and adequate for the general EU population, under the consideration that the main dietary source of chloride intake is sodium chloride. For infants aged 7–11 months, an adequate intake of 0.3 g/day is set.

2019 - Dietary reference values for sodium [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aggett, P.; Fairweather-Tait, S.; Martin, A.; Przyrembel, H.; Ciccolallo, L.; de Sesmaisons-Lecarre, A.; Valtuena Martinez, S.; Martino, L.; Naska, A.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) derived dietary reference values (DRVs) for sodium. Evidence from balance studies on sodium and on the relationship between sodium intake and health outcomes, in particular cardiovascular disease (CVD)-related endpoints and bone health, was reviewed. The data were not sufficient to enable an average requirement (AR) or population reference intake (PRI) to be derived. However, by integrating the available evidence and associated uncertainties, the Panel considers that a sodium intake of 2.0 g/day represents a level of sodium for which there is sufficient confidence in a reduced risk of CVD in the general adult population. In addition, a sodium intake of 2.0 g/day is likely to allow most of the general adult population to maintain sodium balance. Therefore, the Panel considers that 2.0 g sodium/day is a safe and adequate intake for the general EU population of adults. The same value applies to pregnant and lactating women. Sodium intakes that are considered safe and adequate for children are extrapolated from the value for adults, adjusting for their respective energy requirement and including a growth factor, and are as follows: 1.1 g/day for children aged 1–3 years, 1.3 g/day for children aged 4–6 years, 1.7 g/day for children aged 7–10 years and 2.0 g/day for children aged 11–17 years, respectively. For infants aged 7–11 months, an Adequate Intake (AI) of 0.2 g/day is proposed based on upwards extrapolation of the estimated sodium intake in exclusively breast-fed infants aged 0–6 months.

2019 - Does outdoor air pollution cause childhood leukemia? A systematic review and dose-response meta-analysis [Poster]
Filippini, Tommaso; Orsini, Nicola; Vinceti, Marco
abstract

A causal link between outdoor air pollution from motorized traffic and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks and no analyses have examined the dose-response relation. In this review, we investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia. We performed online database search up to October 10, 2019, including also snowballing methods to retrieve all possible case-control and cohort eligible studies. We carried out a meta-analysis, whenever possible with a dose-response approach using a restricted cubic spline regression model, our intent being to investigate the extent to which air pollution, especially in regard to traffic-related contaminants, affects the risk of childhood leukemia. We found 30 studies eligible to be included in our review. Exposure assessment either to motorized traffic and related contaminants was based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or on measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. In the dose-response analysis, we found an indication of increased but imprecise association between disease risk and traffic indicators, measured as number of vehicles in the closest roads, road density, and distance from major roads near the child’s residence, only at the highest levels of exposure. Similarly, exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels. Conversely, we found that benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 years of age, and when exposure assessment at the time of diagnosis was used. Overall, the summarized epidemiologic literature appears to support an association between benzene emissions from traffic exhausts and childhood leukemia risk, especially the myeloid subtype and in the youngest children, with no indication of any threshold.

2019 - Effect modification of smoking status and menopausal status on the association between die- tary intake of acrylamide and risk of breast cancer [Abstract in Rivista]
Adani, Giorgia; Filippini, Tommaso; Vinceti, Marco
abstract

Introduction Acrylamide is a probable human carcinogen 1 that occurs natu- rally in starchy foods during cooking processes at high tempera- tures 2. Aside from occupational exposures and smoking 3, main source of human exposure is diet, particularly consumption of potatoes, grain products, and coffee 4 5. High acrylamide intake has been associated with altered sex-steroid hormone concen- trations and increased risk of hormone-dependent cancers, such breast neoplasm with inconsistent findings 6-9. Since this cancer type represent a major cause of death among both premenopau- sal and postmenopausal women 10, investigating its environmen- tal and life-style risk factors, including for instance acrylamide intake, is of key relevance under a public health perspective. Materials and methods We performed a systematic review of the association between estimated dietary intake of acrylamide and risk of female breast cancer. Using PubMed, we performed a systematic search for non-experimental studies published through October 20, 2019 and we first performed a meta-analysis of the overall measure of association. Subsequently, we carried out a dose-response meta- analysis of these associations using restricted cubic spline models which allow to estimate the summary relative risk (sRR) across a large exposure range of acrylamide intake alongside with their approximate pointwise 95% confidence interval (CI) 11 12. Results We identified 10 papers covering 8 different study populations: 9 cohorts and 1 case-control studies, with a total of 18100 cases of breast cancer. Acrylamide dietary intake ranged from 3.6 μg/ day to 44 μg/day, with both mean and median values of 21 μg/ day (range 6.3 to 29.8 μg/day). In the meta-analysis summarizing the RR in the highest category of exposure versus the lowest, we found no evidence of cancer risk at any levels of acrylamide ex- posure. After restricting the analysis to never smokers, we found similar results, if not a reverse correlation. In analyses stratified by menopausal status, we found no appreciable association be- tween exposure and risk of breast cancer among premenopau- sal women, and an inverse association in postmenopausal par- ticipants. Results among never-smoking premenopausal women was available only for one study, which reported a positive as- sociation between acrylamide intake and breast cancer risk. Con- versely, among postmenopausal women, we found no associa- tion for breast cancer in never-smokers. In the dose-response me- ta-analysis, we found evidence of a null or even inverse relation between exposure to dietary acrylamide and breast cancer risk, particularly in never smokers and in post-menopausal women. Interestingly, in subgroup analysis limited to pre-menopausal women, breast cancer risk linearly increased starting from 20 μg/ day of acrylamide intake. Conclusions In conclusion, there was limited evidence for an association between acrylamide intake and breast cancer risk, with the ex- ception of increased risks at the highest levels of acrylamide exposure among premenopausal women, which warrants further investigation.

2019 - Environment and health: Risk perception and its determinants among Italian university students [Articolo su rivista]
Carducci, A.; Fiore, M.; Azara, A.; Bonaccorsi, G.; Bortoletto, M.; Caggiano, G.; Calamusa, A.; De Donno, A.; De Giglio, O.; Dettori, M.; Di Giovanni, P.; Di Pietro, A.; Facciola, A.; Federigi, I.; Grappasonni, I.; Izzotti, A.; Libralato, G.; Lorini, C.; Montagna, M. T.; Nicolosi, L. K.; Paladino, G.; Palomba, G.; Petrelli, F.; Schiliro, T.; Scuri, S.; Serio, F.; Tesauro, M.; Verani, M.; Vinceti, M.; Violi, F.; Ferrante, M.
abstract

Among the determinants of environmental health risk perception, health literacy and social media messages have been generally neglected. This study details the environmental health risk perception and its determinants in Italian university students, including a measure of functional health literacy and an analysis of newspapers and social media. A cross sectional survey was carried out among students from 15 Italian universities and different disciplines (grouped into Scientific-Health and Humanistic-Legal-Social sectors) using a self-administered anonymous questionnaire, divided into six sections: socio-demographic characteristics, information on health and environment, environmental health risk perception, trust, attitudes and behaviors and functional health literacy. Local newspapers and tweets in the same areas and period were analyzed in relation to quantity and topics. The study population included 4778 students (65.1% female) aged 21 ± 4.3 years, and functional health literacy was low (below the cutoff value) for 44.4% of students. A new outcome of the survey is that the detected association between high functional health literacy a higher global health risk perception and trust in institutions both as sources of information and as actors for protection against environmental risks. The internet and social networks were the most frequently consulted sources of information (77.7%), which was predictive of a higher risk perception. The possible relation between environmental health risk perception and tweet communication was highlighted by a comparison between the risk perception in the city with the highest number of tweets (Modena) and another one similar for socio-demographic characteristics (Pisa). In conclusion, the results of our study may be of help to strengthen information and education programs: functional health literacy should be taken into account in school programs, to produce a basic knowledge for a better understanding of health and environment. Moreover, mass and social media should be included in planning communication intervention and in verifying their results.

2019 - Epidemiology and social impact of early onset dementia in the province of Modena, Northern Italy [Abstract in Atti di Convegno]
Fiondella, Luigi; Galli, C.; Tondelli, M.; Vinceti, G.; Filippini, T.; Garuti, Caterina; Vinceti, M.; Chiari, A.; Zamboni, G.; Molinari, MARIA ANGELA; COSTA (Modena), M.
abstract

Aims of the study. Early onset dementia (EOD), defined as onset of dementia <65 years, has a much higher social impact compared to the more common late onset dementia. EOD epidemiologic data in Italy are extremely scarce, and international estimates of prevalence are considerably variable, ranging between 15.1 and 153/100.000 in the age 45-65. We present data from an ongoing study aimed at establishing EOD epidemiology in a Northern Italy community (Modena province, around 700.000 inhabitants). Materials. We retrospectively recruited all patients residing in Modena province referred to the Modena Baggiovara Hospital Neurologic Clinic CDCD (Centro disturbi cognitivi e demenze), by family practitioners and geriatricians of the province. Eligible patients were those affected by EOD from 2012 to January 2019. EOD was diagnosed in patients <65 years presenting with cognitive/behavioral symptoms, following a comprehensive neurological examination by a cognitive neurologist, as well as brain MRI, FDG PET scanning and CSF analyses when appropriate. Methods. We collected clinical data such as age at onset, disease severity at time of diagnosis, time delay from onset to diagnosis, and epidemiologic data including residence and occupational status. Results. We identified 223 patients with an EOD diagnosis from 2012 to January 2019. Of these, 103 are males (46,2%). 97 patients have AD (21 lvPPA, 13 PCA, 2 frontal variant), 47 have FTD (33 bvFTD, 14 svPPA), 6 have leucoencephalopathy. Mean onset age was 58,6 years (SD 5,1). Median time from symptoms onset to diagnosis was 3.1 years (SD 29,83). Mean MMSE score at diagnosis was 22,63/30 (SD 5,2). 24 patients were working at time of diagnosis (10,76%) and had to quit working due to the cognitive impairment. Two patients (0,89%) had young children (<18) at time of diagnosis. Discussion. We provide the first epidemiological data on EOD in Italy. These are consistent with the estimates calculated by transposing European data to the population of Modena province (estimated prevalence=200 patients, detected prevalence=223 patients)1. Our data show a higher percentage of atypical AD phenotypes and FTD in the EOD group compared to late onset disease2. Also, CAA and leucoencephalopaties were over-represented compared to LOD. From a social perspective, EOD has significant impacts on patients and their families: patients are generally forced to leave work, and their children are expected to need psychological support, currently not routinely available. Conclusions. Our population study provides the first data regarding EOD epidemiology and social impact in Italy.

2019 - Exposure to inorganic selenium in drinking water and incidence of amyotrophic lateral sclerosis: a long-term follow-up of a natural experiment [Poster]
Vinceti, Marco; Filippini, Tommaso; Malagoli, Carlotta; Violi, Federica; Mandrioli, Jessica; Consonni, Dario; Rothman, Kenneth; Wise, LAUREN ANNE
abstract

Background: Some studies have reported an association between overexposure to selenium and risk of amyotrophic lateral sclerosis (ALS), a rare degenerative disease of motor neurons. From 1986 through 2015, we followed a cohort in Northern Italy that had been inadvertently consuming tap water with unusually high concentrations of inorganic hexavalent selenium from 1974 to 1985. Methods: We had previously documented an excess incidence of ALS in this cohort during 1986-1994. Here, we report extended follow-up of the cohort for an additional 21 years, encompassing 50,100 person-years of the exposed cohort and 2,233,963 person-years of the unexposed municipal cohort. We assessed ALS risk using a Poisson regression analysis, adjusting for age, sex and calendar year. Results: We identified 7 and 112 incident ALS cases in the exposed and unexposed cohorts, respectively, yielding crude incidence rates of 14 and 5 cases per 100,000 person-years. The Poisson regression analysis produced an overall incidence rate ratio (IRR) for ALS of 2.8 (95% confidence interval (CI) 1.3, 6), with a substantially stronger IRR in 1986-1994 (8.2, 95% CI 2.7, 24.7) than in 1995-2015 (1.5, 95% CI 0.5, 4.7), and among women (5.1, 95% CI 1.8, 14.3) than men (1.7, 95% CI 0.5, 5.4). Conclusions: Overall, these results indicate an association between high exposure to inorganic selenium, a recognized neurotoxicant, and ALS incidence, with declining rates after cessation of exposure and stronger effects among women.

2019 - Food and beverage consumption and melanoma risk: a population-based case-control study in Northern Italy [Articolo su rivista]
Malagoli, C; Malavolti, M; Agnoli, C; Farnetani, F; Longo, C; Filippini, T; Pellacani, G; Vinceti, M
abstract

It has been suggested that diet may influence the risk of melanoma, but few studies are available on this topic. We assessed the relation between food consumption and the risk of cutaneous melanoma in a Northern Italy population. We carried out a population-based case-control study involving 380 cases of melanoma and 719 age- and sex-matched controls. Dietary habits were established through a self-administered semi-quantitative food frequency questionnaire. We computed the odds ratios (ORs) of melanoma and the corresponding 95% confidence intervals (CIs) according to tertiles of daily intake of each food item, using multiple logistic regression models adjusted for major confounding factors. We observed an indication of a positive association between melanoma risk and consumption of cereals and cereal products (OR = 1.32; 95% CI 0.89–1.96, higher vs. lowest tertile), sweets (OR = 1.22; 95% CI 0.84–1.76), chocolate, candy bars. etc., (OR = 1.51; 95% CI 1.09–2.09) and cabbages (OR = 1.51; 95% CI 1.09–2.09). Conversely, an inverse association with disease risk was found for the intake of legumes (OR = 0.77; 95% CI 0.52–1.13), olive oil (OR = 0.77; 95% CI 0.51–1.16), eggs (OR = 0.58; 95% CI 0.41–0.82), and onion and garlic (OR = 0.80; 95% CI 0.52–1.14). No relationship was observed with beverage consumption. Our results suggest potentially adverse effects on melanoma risk of foods characterized by high contents of refined flours and sugars, while suggesting a protective role for eggs and two key components of the Mediterranean diet, legumes and olive oil. These associations warrant further investigation and, if confirmed, they might have important public health implications for the reduction of melanoma incidence through dietary modification.

2019 - GlycoLite™ and helps to reduce body weight: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from analyze & realize GmbH submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Ireland, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to GlycoLite™. The Panel considers that the food, an aqueous extract from white kidney bean (Phaseolus vulgaris L.) standardised by its in vitro α-amylase inhibitory activity (GlycoLite™) which is the subject of the health claim, is sufficiently characterised. The claimed effect proposed by the applicant is ‘helps to reduce body weight’. The proposed target population is ‘overweight people from the age of 18 years who want to lose or manage their weight’. The Panel considers that a reduction in body weight is a beneficial physiological effect for overweight individuals. Two human intervention studies, carried out in the same centres and by the same research group, showed an effect of 3 g of GlycoLite™ on body weight when consumed daily for 12 weeks in the context of an energy restricted diet. The results have not been replicated in a different setting. One study of short duration and methodological limitations showed an effect of GlycoLite™ on body weight when eating ad libitum. No evidence for a plausible mechanism by which GlycoLite™ could exert a reduction in body weight in vivo in humans has been provided. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of an aqueous extract from white kidney bean (P. vulgaris L.) standardised by its in vitro α-amylase inhibitory activity (GlycoLite™) and a reduction of body weight either under energy restriction or when eating ad libitum.

2019 - Green tea consumption and risk of cancer: a systematic review and meta-analysis of observational studies [Abstract in Rivista]
Filippini, Tommaso; Malavolti, Marcella; Vinceti, Marco
abstract

Introduction Tea is one of the most highly consumed drink in the world after water. Between 2007 and 2016, world tea production grew by an average annual rate of 4.4%. Global tea consumption was 5.53 million tonnes in 2016 with an annual growth rate of 4.5 percent between 2007 and 2016 1. Brewed tea is obtained from the infu- sion of leaves and buds of Camellia sinensis. The most common- ly consumed type of tea varies cross-culturally, but green and black tea are the main ones. It has been described that Camellia sinensis contains polyphenols, particularly green tea that contain a high amount of catechins, powerful antioxidants. Laboratory studies have suggested that these compounds may inhibit cancer cell proliferation and 2 and some experimental and nonexperi- mental epidemiologic studies have suggested that green tea may have cancer-preventative effects 3 4. We aimed to assess associa- tions between green tea consumption and the risk of cancer incidence and mortality. Materials and methods We searched eligible studies up to January 2019 online databases as well as from reference lists of previous reviews and included studies. We included all observational epidemiological stud- ies (both cohort and case-control studies), that investigated the association of green tea consumption with cancer risk. Two or more authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We also per- formed a meta-analysis using a random effects model comparing the highest category of green tea intake with the lowest, and us- ing the most adjusted multivariable model. We summarized the results according to cancer type diagnosis Results In this review update, we included 131 studies, including 46 co- hort and 85 case-control studies with over 1,100,000 participants., we found a lower overall cancer incidence. Regarding overall cancer mortality we found no difference in risk For most of the site-specific cancers we observed a decreased sRR. However, af- ter stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: esophageal, prostate and urinary tract cancer showed an increased sRR in co- hort studies and a decreased/null sRR in case-control studies. Conclusions Overall, findings from observational epidemiological studies yielded inconsistent and even contrasting results for the effect of green tea consumption on cancer risk. In addition, since observa- tional studies generally suffered from the inherent limitation of this study design, potential unmeasured confounding and expo- sure misclassification, well conducted and adequately powered experimental studies are clearly needed to elucidate the possible beneficial effects of green tea consumption on cancer risk in hu- mans.

2019 - High‐frequency motor rehabilitation in amyotrophic lateral sclerosis: a randomized clinical trial [Articolo su rivista]
Zucchi, Elisabetta; Vinceti, Marco; Malagoli, Carlotta; Fini, Nicola; Gessani, Annalisa; Fasano, Antonio; Rizzi, Romana; Sette, Elisabetta; Cavazza, Stefano; Fiocchi, Alena; Buja, Sergio; Faccioli, Tiziana; Storani, Simone; Mandrioli, Jessica
abstract

.

2019 - Influence of selenium on the emergence of neuro tubule defects in a neuron-like cell line and its implications for amyotrophic lateral sclerosis [Articolo su rivista]
Maraldi, T.; Beretti, F.; Anselmi, L.; Franchin, C.; Arrigoni, G.; Braglia, L.; Mandrioli, J.; Vinceti, M.; Marmiroli, S.
abstract

Impairment of the axonal transport system mediated by intracellular microtubules (MTs) is known to be a major drawback in neurodegenerative processes. Due to a growing interest on the neurotoxic effects of selenium in environmental health, our study aimed to assess the relationship between selenium and MTs perturbation, that may favour disease onset over a genetic predisposition to amyotrophic lateral sclerosis. We treated a neuron-like cell line with sodium selenite, sodium selenate and seleno-methionine and observed that the whole cytoskeleton was affected. We then investigated the protein interactome of cells overexpressing αTubulin-4A (TUBA4A) and found that selenium increases the interaction of TUBA4A with DNA- and RNA-binding proteins. TUBA4A ubiquitination and glutathionylation were also observed, possibly due to a selenium-dependent increase of ROS, leading to perturbation and degradation of MTs. Remarkably, the TUBA4A mutants R320C and A383 T, previously described in ALS patients, showed the same post-translational modifications to a similar extent. In conclusion this study gives insights into a specific mechanism characterizing selenium neurotoxicity.

2019 - Intake of Mediterranean Foods [Capitolo/Saggio]
Siotos, C.; Vinceti, M.; Naska, A.
abstract

The traditional Mediterranean diet is characterized by: (a) high consumption of cereals, vegetables, fruit, nuts, legumes, fish, and seafood; (b) the use of olive oil as the main, if not the only, added lipid; (c) moderate consumption of milk and dairy products; (d) moderate intake of alcohol, in the form of wine and preferably during meals; and (e) low consumption of meat and meat products. The prevalent consumption of olive oil and the low consumption of animal products are reflected in the high ratio of monounsaturated to saturated fat intake, typical of the dietary pattern in the region. There is increasing evidence from observational and experimental epidemiological studies, further enriched by the conclusions of their systematic reviews and meta-analyses, that adherence to the Mediterranean dietary pattern promotes health and reduces the risk of premature death from chronic degenerative diseases. Mediterranean countries and especially the European ones have experienced a “westernization” process of their food habits, and have increased the per capita supply of non-Mediterranean foods (animal fats, vegetable oils other than olive oil, sugar, and meat) and decreased the supply of legumes and alcoholic beverages, including wine. The evidence that Mediterraneans are gradually departing from their traditional eating habits does not only refer to the adult population in the region, but it has also been reproduced in large-scale nutritional surveys among children, adolescents, and young adults – the trend-setters for future generations. Next to the effect on people’s health, the gradual abandoning of the traditional Mediterranean diet cannot support sustainable development in the way the Mediterranean diet does. Being adjusted to the cultural, climatic, and other environmental characteristics of the region, the Mediterranean diet is protective and helpful to biodiversity, accessible and economically affordable, and contributes to food and nutrition security.

2019 - Iron consumption is not consistently associated with fecundability among north American and danish pregnancy planners [Articolo su rivista]
Hahn, K. A.; Wesselink, A. K.; Wise, L. A.; Mikkelsen, E. M.; Cueto, H. T.; Tucker, K. L.; Vinceti, M.; Rothman, K. J.; Sorensen, H. T.; Hatch, E. E.
abstract

Background: Infertility is an important public health problem with few known modifiable risk factors. Dietary factors including folic acid have been associated with improved fertility, but the association between iron and fertility is understudied. One study among US nurses found a 40% lower risk of ovulatory infertility with higher intake of nonheme iron and iron supplements. Objectives: The aim of this study was to determine the extent to which iron intake from diet and supplements reported on structured questionnaires is associated with fecundability. Methods: We conducted parallel analyses that used data from 2 prospective cohort studies of pregnancy planners from Denmark (Snart Foraeldre; n = 1693) and North America (PRESTO; n = 2969) during 2013-2018. Follow-up comprised menstrual cycles at risk until pregnancy or censoring for fertility treatment, stopped trying to conceive, withdrawal, loss to follow-up, or 12 cycles of attempt. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, adjusting for confounders. Results: We found little association between dietary heme iron intake and fecundability in either cohort. The FR for nonheme iron intake (≥11 mg/d compared with <9 mg/day) was 1.11 for Snart Foraeldre participants (95% CI: 0.92, 1.34) and 1.01 for PRESTO participants (95% CI: 0.89, 1.14). The FR for iron-containing supplements was 1.01 in Snart Foraeldre (95% CI: 0.90, 1.13) and 1.19 in PRESTO (95% CI: 1.03, 1.38). In PRESTO, but not Snart Foraeldre, stronger positive associations were found for nonheme iron intake and iron supplement use among women with heavy menses or short menstrual cycles. Conclusions: Overall, dietary intake of iron was not consistently associated with fecundability, although there was some evidence for a positive association among women with risk factors for iron deficiency. We also found a small positive association between supplemental iron intake and fecundability among North American, but not Danish, pregnancy planners.

2019 - Maternal pregestational diabetes and risk of acute lymphoblastic leukemia in the offspring: A population-based study in Northern Italy [Articolo su rivista]
Borsari, L.; Malagoli, C.; Della Torre, F.; Cellini, M.; Rodolfi, R.; Pession, A.; Vinceti, M.
abstract

Introduction: This population-based study aims to evaluate the association between maternal pregestational diabetes and risk of acute lymphoblastic leukemia (ALL) in the offspring. Methods: All 241,958 children born in three Northern Italy provinces 1998–2010 were followed from birth until first cancer diagnosis (National Childhood Cancer Register), age 15 years, or 31 December 2017. We computed hazard ratio (HR) and 95% CI of ALL in relation to the presence of maternal diabetes through Cox proportional regression models. Results: We observed 145 cases of ALL, with a higher incidence in children born to women with pregestational diabetes compared to the others (12.4 vs 4.6). Adjusted hazard ratio of ALL was 2.6 (CI, 0.6–10.5) for maternal diabetes. Discussion: We estimated higher risks of ALL in the offspring of women with pregestational diabetes. These results are consistent with previous findings and compatible with a role of prenatal glycaemic environment in childhood cancer aetiology.

2019 - Nutrimune and immune defence against pathogens in the gastrointestinal and upper respiratory tracts: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from H.J. Heinz Supply Chain Europe B.V. submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Nutrimune and immune defence against pathogens in the gastrointestinal (GI) tract and upper respiratory tract (URT). The food Nutrimune (a pasteurised cow's skim milk fermented with Lactobacillus paracasei CBA L74) which is the subject of the health claim is sufficiently characterised. The Panel considers that immune defence against pathogens in GI tract and URT is a beneficial physiological effect. Two human intervention studies were submitted as being pertinent to the claim, which were evaluated by the Panel in the previous application. One human intervention study from which conclusions could be drawn showed an effect of Nutrimune on immune defence against pathogens in the GI tract and the URT. The post hoc re-analysis of the two human studies combined does not address the methodological limitations of the second study raised in the previous opinion, i.e. that the study was not planned, designed, randomised and analysed as a multicentre study, and that the large disparity of subjects in the three centres was not duly justified. The results from one animal study could support an effect of Nutrimune on defence against pathogens in the GI tract. No evidence was provided for a plausible mechanism by which Nutrimune could exert the claimed effect in vivo in humans. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of Nutrimune and immune defence against pathogens in the GI tract and URT.

2019 - Occupational risk factors for early onset dementia (EOD) in the Modena population: a case-control study [Abstract in Rivista]
Adani, Giorgia; Filippini, Tommaso; Garuti, Caterina; Vinceti, Giulia; Chiara, Galli; Zamboni, Giovanna; Tondelli, Manuela; Manuela, Costa; Malavolti, Marcella; Vinceti, Marco; Chiari, Annalisa
abstract

Introduction Dementia is a clinical condition generally affecting subjects in the elderly. However, it may occur also at younger age, yielding a condition called early-onset dementia (EOD) characterized by an onset before 65 years 1 2. Despite the limited epidemiological data and the paucity of information regarding possible risk fac- tors 3 4, there is a general agreement that clinical presentation and consequences on daily life are different than late-onset demen- tia, due to the occurrence when subjects are still involved within occupational activities as well as familiar responsibilities 5. The aim of this work is to assess the epidemiological, clinical and prognostic role of occupational risk factors in EOD. Materials and methods Using a case-control design, we recruited newly-diagnosed EOD cases from the two Centers of Cognitive Disease of the Neurol- ogy Units of Modena-Baggiovara and Carpi Hospitals, as well as from the community health centers and general practitioners, October 1, 2016 to May 31, 2019. Referent population have been recruited from care-givers of EOD and LOD (late onset demen- tia) subjects. We investigated as possible risk factors of the dis- ease the occupational history, by administering a questionnaire collecting information about personal characteristics, family his- tory of diseases, clinical history and comorbidities, occupation activities, hobbies and other leisure activities, residential history, domestic use of pesticides, and dental care. We computed the odds ratios (ORs) of EOD risk, and the corresponding 95% con- fidence intervals (CIs), according to exposure to the investigated risk factors using an unconditional logistic regression model ad- justing for sex, age, and educational attainment. Results Fifty-six cases and fifty-three controls agreed to participate, with generally higher number of women (60% cases and 55% controls) and people over 65 (60% cases compared to 49% con- trols). About occupational factors, working in the agricultural sector seemed to be only slightly associated with risk of EOD (OR 1.31, 95% CI 0.26-6.59), while an increased risk was found for industrial sector (OR 2.23, 95% CI 0.85-5.88). Occupational exposure to contaminants showed positive association for occupational exposure to selenium (OR 2.23, 95% CI 0.11-46.42), aluminum (OR 2.75, 95% CI 0.42-18.11), pesticides (OR 2.10, 95% CI 0.60-7.36), dyes, paints or thinners (OR 2.07, 95% CI 0.70-6.05), while no association was found for exposure to or use of electric and electronic system or electromagnetic fields. Conclusions Results of this study suggest that some occupational factors, namely use of pesticides, dyes/paints, and metalloids such as alu- minum and selenium, could be associated with increased disease risk. Despite study limitations due to case-control design, includ- ing possible occurrence of selection and recall bias, our findings support the hypothesis of an environmental etiology of EOD.

2019 - Proximity to petrol station and risk of childhood leukemia: systematic review and meta-analysis [Poster]
Filippini, Tommaso; Malagoli, Carlotta; Vinceti, Marco
abstract

Motorized traffic exposure and particularly benzene have been associated to childhood leukemia. In particular, living next to a petrol station or repair garage may increase the opportunity for benzene exposure. In this review, we investigated the extent to which living in proximity to petrol stations is associated with risk of childhood leukemia. We searched all observational studies that have investigated the risk of childhood leukemia in relation to exposure to petrol station using either proximity of children residence or modelled exposure. We performed online database search up to October 10, 2019, including also snowballing methods to retrieve all possible eligible studies. We carried out a meta-analysis of all eligible studies using a random effect model. We found six studies eligible to be included in our review published from 1999 to 2019 and all with all with a case-control design. We identified two additional studies compared to the last published systematic review, including one conference abstract. Exposure assessment was performed using questionnaire or face-to-face interview asking for distance of residence to petrol station in three studies (in one case with external validation), while georeferencing method was used using either distance (two studies) or petrol station density (one study). We eventually included 3632 cases and 21874 controls in the analysis. Summary relative risk (sRR) was 1.63 (95% CI 1.11 to 2.50). After exclusion of one study in which exposure to either petrol station and automotive repair was considered, we still found an increased sRR of 1.48 (95% CI 1.03 to 2.12). Comparable risk was reported after stratification of exposure assessment method. Estimates were slightly higher for ALL (sRR=3.31, 95% CI 0.92 to 11.86) compared with AML (sRR=2.06, 95% CI 0.90 to 4.70), although based on only two studies. Overall, the epidemiologic literature appears to support an association between living in proximity to petrol station and childhood leukemia risk, particularly ALL, supporting previous findings regarding motorized traffic and particularly benzene.

2019 - Risk of early onset dementia (EOD) in relation to fruit and vegetable consumption: a case-control study [Abstract in Rivista]
Filippini, Tommaso; Garuti, Caterina; Adani, Giorgia; Vinceti, Giulia; Chiara, Galli; Zamboni, Giovanna; Tondelli, Manuela; Manuela, Costa; Malavolti, Marcella; Vinceti, Marco; Chiari, Annalisa
abstract

Introduction Early onset dementia (EOD) is a condition characterized by the onset of severe cognitive impairment before 65 year 1. There is a general agreement that clinical presentation and conse- quences on daily life are different than late-onset dementia, due to the occurrence when subjects are still involved within occupational activities as well as familiar responsibilities 2. Previous studies have raised the possibility that the risk factors may also differ between the two forms, including the role of environmental and life-style determinants such as diet 3. There is some epidemiologic evidence of an association between dietary habits and protective relations to cognitive decline and incident dementia 4 5. The aim of this study is to evaluate, for the first time to our knowledge, the association between diet and EOD risk. Materials and methods Using a case-control design, we recruited newly-diagnosed EOD cases from 2016 to 2019 in Modena province, Northern Italy. We recruited controls from care-givers of dementia patients referring the Neurology Units of Modena-Baggiovara and Carpi Hospi- tals. We investigated dietary habits through a self-administered semi-quantitative food frequency questionnaire, designed and validated to capture eating behaviors in Italy, and specifically developed as part of the European Prospective Investigation into Cancer and Nutrition (EPIC) study for the Northern Italy pop- ulation 6. Participants were asked to respond to 248 questions about 188 different food items, in order to assess frequency and quantity of daily consumption for each food item. We specifically focused on consumption of fruits and vegetables that were categorized into major and sub-group categories as previously reported 7. We computed the odds ratios (ORs) of EOD risk, and the corresponding 95% confidence intervals (CIs), according to increasing tertile of intake using an unconditional logistic regres- sion model and we also modeled the relation using restricted cu- bic splines with three knots (10, 50 and 90%). We implemented a model adjusted for sex, age (years), educational attainment (years), and total energy intake (kcal/day). Results We recruited 56 (men/women: 22/34) and 53 (men/women: 24/29) controls who agreed to participate and returned study ma- terial. Regarding food intake, cases showed a lower intake than controls of vegetables (119 g/day versus 148 g/day), pulses (19 g/day versus 22 g/day), potatoes (15 g/day versus 23 g/day), and dry fruits (2.6 g/day versus 4.0 g/day). Conversely cases showed a higher intake than controls of fresh fruits (256 g/day versus 240 g/day). In the analysis of EOD risk according to increasing tertile we found an inverse association with all vegetables overall considered and also for individual subgroup, particularly leafy vegetables and other vegetables (e.g. eggplant, zucchini or sweet pepper). Also, an inverse association was found for potatoes and slightly for legumes. Conversely, the higher tertile of intake of fresh fruits was associated with no difference in EOD risk, but in the stratified analysis for non-citrus and citrus fruits we found inverse association for the latter. Interestingly, for non-citrus fruits we found inverse association in the second tertile of consumption, and an opposite positive association in the third tertile. Finally, with increasing tertile of dry fruits intake, we found a strong inverse association with EOD risk. Similarly in the spline analysis, the increasing consumption of vegetables, particularly leafy vegetables showed a strong inverse association, as simi- larly also increased pulse intake. Regarding fruit consumption, fresh fruit overall considered showed ambivalent relation, while higher consumption of citrus fruits only, as well as dry fruits, showed a negative association with EOD risk. Conclusions In this study, we found an association of consumption of vegeta- bles and to some extent fruit with EOD risk in an Italian popula- tio

2019 - Safety of 2’-fucosyllactose/difucosyllactose mixture as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Sun, Q.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 2’-fucosyllactose/difucosyllactose (2’-FL/DFL) mixture as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a powdered mixture mainly composed of two oligosaccharides, 2’-FL and DFL, which are produced together by fermentation with a genetically modified strain of Escherichia coli K12. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and young children, foods for special medical purposes and food supplements. The target population is the general population except for food supplements, for which the target population is individuals above 1 year of age. Since the intake of 2’-FL and DFL from the NF at the proposed use levels is unlikely to exceed the intake level of naturally occurring 2’-FL and DFL in breastfed infants per kilogram body weight, the Panel concludes that the NF, a mixture of 2’-FL and DFL, is safe under the proposed conditions of use for the proposed target population.

2019 - Safety of Yarrowia lipolytica yeast biomass as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; de Henauw, Stefaan; Hirsch‐ernst, Karen‐ildico; Kearney, John; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Engel, Karl‐heinz; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser‐berthold, Monika; Pöting, Annette; Poulsen, Morten; Sanz, Yolanda; Schlatter, Josef Rudolf; van Loveren, Henk; Ackerl, Reinhard; Knutsen, Helle Katrine
abstract

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2019 - Safety of betaine as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

In 2017, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) concluded that betaine as a novel food (NF) is safe to be used at a maximum intake level of 6 mg/kg body weight per day in addition to the intake from the background diet. Following the present request from the European Commission, the EFSA NDA Panel was asked to deliver a scientific opinion on betaine by carrying out the assessment for the revised uses and use levels of betaine as proposed by the applicant. Thus, EFSA performed an intake assessment based on individual data from the EFSA Comprehensive European Food Consumption Database and the new proposed uses of the NF for the general population. The resulting ranges for the mean and high-level estimated intakes of betaine for the general population do not exceed the safe level of intake previously established. The Panel concludes that the NF, betaine, is safe under the new proposed conditions of use.

2019 - Safety of chia seeds (Salvia hispanica L.) as a novel food for extended uses pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Matijevic, L.; Romero, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel foods and Food Allergens (NDA) was asked to deliver an opinion on overall safety assessment for chia seeds (Salvia hispanica L.) as a novel food (NF) pursuant to Regulation (EU) 2015/2283 in the light of the increasing dietary intake from the growing number of authorised uses in recent years. The safety assessment of this NF is based on data supplied in seven applications, previous safety assessments of chia seeds and information retrieved from an extensive literature search done by EFSA. Since none of the applications addressed the possible formation of process contaminants, the present assessment is limited to those proposed extended uses which do not raise safety concerns regarding the formation of such contaminants. These include the use of whole and ground chia seeds added to chocolate, fruit spreads, fruit desserts, mixed fruit with coconut milk in twin pot, fruit-preparations to underlay a dairy product, fruit-preparations to be mixed with dairy products, confectionary (excluding chewing gums), dairy products and analogues, edible ices, fruit and vegetables products, non-alcoholic beverages and compotes from fruit and/or vegetables and/or with cereals. In addition, this assessment also concerns uses of chia seeds without specific restrictions and precautions regarding their use levels in other foods which usually do not include heat treatment during processing and cooking. Apart from allergenicity, the Panel did not identify any hazard which causes safety concerns. Lacking the basis and need to establish safe maximum intake levels for chia seeds, no exposure assessment was conducted. The Panel concludes that chia seeds are safe under the assessed conditions of use.

2019 - Safety of chia seeds (Salvia hispanica L.) powders, as novel foods, pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Matijevic, L.; Katrine Knutsen, H.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel foods and Food Allergens (NDA) was asked to deliver an opinion on chia seeds (Salvia hispanica L.) powders as novel foods (NFs) pursuant to Regulation (EU) 2015/2283. The NFs are partially defatted chia seed powders, obtained by extrusion of whole seeds of S. hispanica L. with the main differences between two powders in particle sizes and the content of some macronutrients. The information provided on the production processes, composition, batch-to-batch variability, stability and specifications of the NFs is sufficient and does not raise safety concerns. The applicant proposed to market the NFs as food supplements and as ingredients in a variety of foods. The target population for the NFs is the general population. Noting that no hazard raising safety concerns (except for allergenicity) could be identified from the information available on the source (i.e. chia seeds), the production processes, composition, specifications and proposed uses of the NFs, irrespectively of the maximum use levels at the proposed uses, the Panel considers that intake estimates and additional toxicological data for the NFs are not needed for this assessment. The Panel concludes that the NFs, partially defatted powders of whole chia seeds, are safe under the assessed conditions of use.

2019 - Safety of heat-killed Mycobacterium setense manresensis as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Sun, Q.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on heat-killed Mycobacterium setense manresensis as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is an encapsulated ingredient composed of 200 mg mannitol and ≤ 105 heat-killed, freeze-dried M. setense manresensis. The information provided on the efficacy of the heat inactivation process demonstrates that the applied thermal process effectively kills all M. setense manresensis. The Panel considers that the NF is sufficiently described and characterised. The NF is intended by the applicant to be marketed exclusively in food supplements (gelatine capsules) for the general adult population excluding, children, pregnant and lactating women. The NF is not intended to be an alternative to standard treatment against tuberculosis. The applicant proposed an intake of one capsule (with ≤ 105 heat-killed, freeze-dried M. setense manresensis) for 14 consecutive days and a minimum of 6 months with no consumption of the NF, before another intake for fourteen days may follow. M. setense is not considered to be a suitable microorganism species for the qualified presumption of safety (QPS). Genetic analyses of the genome indicate the absence of the ability to produce exotoxins. The Panel considers that consumption of heat-killed M. setense manresensis would not contribute to the pool of transmissible antimicrobial resistance genes already present in the intestinal microbiota. The Panel concludes that the NF is safe under the proposed conditions of use.

2019 - Safety of lacto-N-tetraose (LNT) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on lacto-N-tetraose (LNT) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a powdered mixture mainly composed by LNT, but also containing d-lactose and other oligosaccharides such as para-lacto-N-hexaose-2 (para-LNH-2), lacto-N-triose II and a small fraction of other carbohydrates. It is produced by fermentation with a genetically modified strain of Escherichia coli K-12. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and toddlers, foods for special medical purposes and food supplements. The target population is the general population except for food supplements, for which the target population is individuals above 1 year of age. The intake of LNT from the NF at the proposed use levels is unlikely to exceed the intake level of naturally occurring LNT in breastfed infants on a body weight basis. The intake of other carbohydrate-type compounds structurally related to LNT is considered of no safety concern. The Panel concludes that the NF is safe under the proposed conditions of use for the proposed target populations.

2019 - Safety of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren Agnes de Sesmaisons-Lecarre, H.; Germini, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Allergens (NDA) was asked to deliver an opinion on nicotinamide riboside chloride as a novel food (NF) pursuant to Regulation (EU) 2015/2283, including an evaluation of the safety of its use in food supplements as a source of niacin, and the bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC. The NF, a synthetic form of nicotinamide riboside, is proposed to be used in food supplements for the healthy adult population at levels up to 300 mg/day. The production process, composition, specifications, batch-to-batch variability and stability of the NF do not raise safety concerns. Animal and human data indicate that the NF contributes to the nicotinamide body pool. There are no concerns regarding genotoxicity. Human studies do not raise safety concerns. The proposed maximum use level corresponds to an amount of nicotinamide, which is sixfold lower than the tolerable upper intake level (UL) set for adults, excluding pregnant and lactating women. The margin of exposure (MoE) of 70 derived from repeated dose toxicity studies with rats and dogs is considered sufficient for the adult population, excluding pregnant and lactating women. Regarding these two population groups, the MoE of 76 derived from a developmental toxicity study in rats is considered insufficient in the absence of data which could justify accepting a MoE lower than 100. The Panel concludes that the NF is safe under the proposed conditions of use for the healthy adult population, excluding pregnant and lactating women, and that an intake of the NF up to 230 mg/day is safe for pregnant and lactating women. The Panel also concludes that the NF is a source from which nicotinamide, a form of niacin, is bioavailable.

2019 - Safety of phenylcapsaicin as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Amundsen, M.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on phenylcapsaicin as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Phenylcapsaicin is a chemically synthesised analogue of capsaicin intended to be marketed in food supplements and in foods for special medical purposes to the general population above the age of 11 years old at a maximum level of 2.5 mg/day. The highest intake of the NF is 2.5 mg/day which corresponds to 36 μg/kg body weight (bw) per day for adults, and 58 μg/kg bw per day for adolescents (10–14 years). The Panel considers that there is no concern with respect to genotoxicity of the NF. The reference point derived based on a 13-week rat study was the lowest of the model averaged BMDL20 values of 37.2 mg/kg bw per day in females for increased plasma alanine aminotransferase (ALAT) levels. The Panel concludes that the NF, phenylcapsaicin, is safe under the proposed uses and use levels.

2019 - Safety of viable embryonated eggs of the whipworm Trichuris suis as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Fernandez Dumont, A.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on viable embryonated eggs of the whipworm Trichuris suis as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The applicant proposes to use the NF as a food supplement in the format of a 15-mL bottle containing 250 viable embryonated eggs of T. suis. The target population for the NF is the general population. Considering the compositional data and proposed conditions of use, the consumption of the NF is considered of no nutritional relevance. Available data suggest that most larvae of T. suis after hatching in the intestinal tract of humans remain immature and live for several weeks in the gastrointestinal tract of the human host. Nevertheless, under certain circumstances, T. suis can be invasive in human, being able to mature into adult size and reproduce in humans. Human studies have also shown that administration of T. suis ova may increase the incidence of adverse gastrointestinal reactions. The Panel considers that there are no studies available that demonstrate the safety of this NF intended for the general population at a proposed intake of 250 viable embryonated eggs of T. suis ova per day. Based on the available information, the Panel cannot establish a safe dose at which no safety concerns would be expected. The Panel concludes that the safety of the NF has not been established.

2019 - Safety of whey basic protein isolate for extended uses in foods for special medical purposes and food supplements for infants pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Amundsen, M.; Knutsen, H. K.
abstract

In 2018, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) concluded that whey basic protein isolate obtained by ion exchange chromatography from skimmed cow's milk is safe for human consumption under the proposed conditions of use as infant and follow on formula, meal replacement beverages, foods for special medical purposes and food supplements. Following a request from the European Commission, the EFSA NDA Panel was asked to deliver a scientific opinion on whey basic protein isolate for extended uses in foods for special medical purposes and food supplements for infants as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The applicant seeks to extend the conditions of use to infant (powder 30 mg/100 g and reconstituted 3.9 mg/100 mL) and follow on formulae (powdered 30 mg/100 g and reconstituted 4.2 mg/100 mL) as foods for special medical purposes as well as in food supplements for infants (25 mg/day). The Panel considers that the proposed extended uses would not increase the potential intake of the NF compared to that assessed in its 2018 opinion. The Panel concludes that whey basic protein isolate is safe at the extended uses and use levels.

2019 - Selenium and selenium species in the etiology of Alzheimer's dementia: The potential for bias of the case-control study design [Articolo su rivista]
Vinceti, Marco; Michalke, Bernhard; Malagoli, Carlotta; Eichmüller, Marcel; Filippini, Tommaso; Tondelli, Manuela; Bargellini, Annalisa; Vinceti, Giulia; Zamboni, Giovanna; Chiari, Annalisa
abstract

Several human studies imply that the trace element selenium and its species may influence the onset of neurological disease, including Alzheimer's dementia (AD). Nevertheless, the literature is conflicting, with reported associations between exposure and risk in opposite direction, possibly due to biases in exposure assessment. After conducting a cohort study that detected an excess AD risk associated with higher levels of inorganic-hexavalent selenium in subjects with mild cognitive impairment (MCI), we investigated the relation between selenium and AD using a case-control study design. We determined cerebrospinal fluid levels of selenium species in 56 MCI participants already included in the cohort study, considered as referents, and in 33 patients with established AD. AD risk was inversely correlated with inorganic selenium species and with the organic form bound to selenoprotein P. Selenium bound to other organo-selenium species was positively correlated with AD risk, suggesting compensatory selenoprotein upregulation following increased oxidative stress. The finding of an increased AD risk associated with inorganic-hexavalent selenium from the cohort study was not replicated. This case-control study yielded entirely different results than those generated by a cohort study with a partially overlapping participant population, suggesting that case-control design does not allow to reliably assess the role of selenium exposure in AD etiology. This inability appears to be due to exposure misclassification, falsely indicating an etiologic role of selenium deficiency likely due to reverse causation, and involving most selenium species. The case-control design may instead lend insights into the pathologic process underlying disease progression.

2019 - [The dose-response relationship between potassium intake and blood pressure levels. Results of meta-analysis of randomized clinical trials] [Abstract in Rivista]
Kasdagli, Μι; Filippini, T; Lopes, C; Carvalho, C; Moreira, P; Malavolti, M; Orsini, N; Vinceti, M; Naska, A
abstract

2018 - A GIS-based atmospheric dispersion model for pollutants emitted by complex source areas [Articolo su rivista]
Teggi, Sergio; Costanzini, Sofia; Ghermandi, Grazia; Malagoli, Carlotta; Vinceti, Marco
abstract

Gaussian dispersion models are widely used to simulate the concentrations and deposition fluxes of pollutants emitted by source areas. Very often, the calculation time limits the number of sources and receptors and the geometry of the sources must be simple and without holes. This paper presents CAREA, a new GIS-based Gaussian model for complex source areas. CAREA was coded in the Python language, and is largely based on a simplified formulation of the very popular and recognized AERMOD model. The model allows users to define in a GIS environment thousands of gridded or scattered receptors and thousands of complex sources with hundreds of vertices and holes. CAREA computes ground level, or near ground level, concentrations and dry deposition fluxes of pollutants. The input/output and the runs of the model can be completely managed in GIS environment (e.g. inside a GIS project). The paper presents the CAREA formulation and its applications to very complex test cases. The tests shows that the processing time are satisfactory and that the definition of sources and receptors and the output retrieval are quite easy in a GIS environment. CAREA and AERMOD are compared using simple and reproducible test cases. The comparison shows that CAREA satisfactorily reproduces AERMOD simulations and is considerably faster than AERMOD.

2018 - Adverse pregnancy outcomes in women with changing patterns of exposure to the emissions of a municipal waste incinerator [Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; Werler, Martha M.; Filippini, Tommaso; De Girolamo, Gianfranco; Ghermandi, Grazia; Fabbi, Sara; Astolfi, Gianni; Teggi, Sergio
abstract

Municipal solid waste incinerators emissions contain pollutants that, despite their low concentration, might adversely affect reproductive health. In the present study, we examined rates of miscarriage and birth defects among women who resided or were employed in the vicinity of a municipal solid waste incinerator plant from 2003-2013. In 2009, a progressive shutdown of the old incineration lines and operation of a new line caused considerably higher atmospheric release of polycyclic aromatic hydrocarbons, particularly of dioxins, due to these irregular operating conditions, technological renovation, and increased capacity. We used dioxin emission levels, based on a dispersion model, as a marker of air pollution due to waste incineration. In women who resided in areas characterized by higher emission exposures compared with a referent area, the relative risk (RR) of miscarriage was 1.04 (95% confidence interval (CI) 0.80-1.32) based on 62 cases overall, with little evidence of a dose-response relation. RRs were similarly null for both 2003-2008 and 2010-2013 periods (RR 1.12 (95% CI 0.80-1.53) and 0.98 (95% CI 0.63-1.48), respectively). Concerning birth defects in the offspring of women residing in the exposed area, no evidence of increased risk emerged, since the prevalence ratio at birth was 0.64 (95% CI 0.29-1.26), with comparable results in the 2003-2008 and 2010-2013 period. Corresponding analyses carried out in municipal residents who worked in the exposed area confirmed these findings. We also did not detect abnormally high rates of miscarriage and birth defects in the exposed cohorts in the single year 2009. Overall, these results do not suggest an effect of exposure to the emissions of the municipal solid waste incinerator we investigated on two indicators of reproductive health. However, the limited statistical stability of the estimates and the absence of individual-based information on some potential confounders suggest caution in the interpretation of study findings.

2018 - Assessment of food contamination and dietary intake of lead and thallium in a Northern Italy population. [Abstract in Atti di Convegno]
Filippini, T; Malavolti, M; Cilloni, S; Violi, F; Malagoli, C; Vescovi, L; Vinceti, M.
abstract

Lead and thallium are heavy metals released in the environment after natural and anthropogenic activities. Food and water intake are the major sources of human exposure to these elements. In this study, we aimed at characterizing lead and thallium content in foods consumed in Northern Italy population, in order to estimate the dietary intake of these metals. To do that we bought food samples in markets and groceries collected during the period from October 2016 to February 2017 in the Emilia Romagna region, and we measured their element content using inductively coupled plasma-mass spectrometry. Finally, after assessing dietary habits of an Emilia-Romagna community by using a validated food frequency questionnaire, we eventually estimated dietary intake of these metals in that community. In the 890 analyzed food samples, the highest lead contamination levels were found in seafood, vegetables, sweets and beverages. The estimated dietary intake of lead was 5.758 (interquartile range-IQR: 4.547-7.427) µg/day, corresponding to 0.089 (IQR: 0.069-0.113) µg/kg of body weight per day, with cereals, beverages and vegetables as major contributors. About thallium, one third of specimens showed very low levels below the limit of detection, with the highest contamination levels in vegetables, dry fruits and sweets. The dietary intake of thallium was 0.236 (IQR: 0.183-0.312) µg/day, mainly from vegetables, beverages, cereals and sweets. In conclusion, our study provides an estimation of lead and thallium intake in a Northern Italian community and shows a generally low exposure levels from dietary sources.

2018 - Assessment of residential exposure to pesticides and risk of amyotrophic lateral sclerosis: methodological issue in the use of different versions of Land Use Chart. [Abstract in Atti di Convegno]
Filippini, T; Fiore, M; Violi, F; Malagoli, C; Cilloni, S; Odone, A; Signorelli, C; Ferrante, Michele; Vinceti, M.
abstract

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2018 - Atmospheric Dispersion Modelling and Spatial Analysis to Evaluate Population Exposure to Pesticides from Farming Processes [Articolo su rivista]
Costanzini, Sofia; Teggi, Sergio; Bigi, Alessandro; Ghermandi, Grazia; Filippini, Tommaso; Malagoli, Carlotta; Nannini, Roberta; Vinceti, Marco
abstract

This work originates from an epidemiological study aimed to assess the correlation between population exposure to pesticides used in agriculture and adverse health effects. In support of the population exposure evaluation two models implemented by the authors were applied: a GIS-based proximity model and the CAREA atmospheric dispersion model. In this work, the results of the two models are presented and compared. Despite the proximity analysis is widely used for these kinds of studies, it was investigated how meteorology could affect the exposure assessment. Both models were applied to pesticides emitted by 1519 agricultural fields and considering 2584 receptors distributed over an area of 8430 km2. CAREA output shows a considerable enhancement in the percentage of exposed receptors, from the 4% of the proximity model to the 54% of the CAREA model. Moreover, the spatial analysis of the results on a specific test site showed that the effects of meteorology considered by CAREA led to an anisotropic exposure distribution that differs considerably from the symmetric distribution resulting by the proximity model. In addition, the results of a field campaign for the definition and planning of ground measurement of concentration for the validation of CAREA are presented. The preliminary results showed how, during treatments, pesticide concentrations distant from the fields are significantly higher than background values.

2018 - Black tea and improvement of attention: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean-Louis; Burlingame, Barbara; Dean, Tara; Fairweather-Tait, Susan; Heinonen, Marina; Hirsch-Ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser-Berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (JJ); Siani, Alfonso
abstract

Following an application from Unilever NV, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Ireland, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to black tea and improvement of attention. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is black tea. The Panel considers that black tea characterised by its content of tea solids, caffeine and l-theanine, which is the subject of the health claim, is sufficiently characterised in relation to the claimed effect. The claimed effect proposed by the applicant is ‘improves attention’. The Panel considers that improvement of attention is a beneficial physiological effect. Three human intervention studies provided by the applicant show an effect of black tea on attention under the conditions of used proposed by the applicant. The applicant proposed that the claimed effect depends on the concerted action of two substances, caffeine and l-theanine, both of which are present in black tea. The Panel considers that the effect of black tea on attention observed in the three human intervention studies provided by the applicant can be explained by its caffeine content. The Panel concludes that a cause and effect relationship has been established between the consumption of black tea and improvement of attention. The Panel considers that the effect of black tea on attention can be explained by its caffeine content. The following wording reflects the scientific evidence: ‘Owing to its caffeine content, black tea improves attention’. In order to obtain the claimed effect, 2–3 servings of black tea providing at least 75 mg of caffeine in total should be consumed within 90 min.

2018 - Black tea and maintenance of normal endothelium‐dependent vasodilation: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdor, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (J. J. ); Siani, Alfonso
abstract

ollowing an application from Unilever NV, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Ireland, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to black tea and maintenance of normal endothelium-dependent vasodilation. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is black tea beverages, either freshly prepared or reconstituted from water extract powders of black tea, characterised by the content of flavanols (expressed as catechins plus theaflavins) of at least 30mg per 200mL serving. The Panelconsiders that black tea characterised by the content of flavanols (expressed as catechins plus theaflavins) is sufficiently characterised. The claimed effect proposed by the applicant is improvement of endothelium-dependent vasodilation'. The Panelconsiders that maintenance of normal endothelium-dependent vasodilation is a beneficial physiological effect. Of the five human intervention studies provided on the chronic effect of black tea consumption on endothelium-dependent vasodilation, two investigated the effect after regular consumption of black tea for a sufficiently long time period (i.e. at least 4weeks). These two studies did not allow an effect of black tea on endothelium-dependent vasodilation to be established. The Panelconcludes that a cause and effect relationship has not been established between the consumption of black tea and maintenance of normal endothelium-dependent vasodilation.

2018 - Cadmium and atherosclerosis: A review of toxicological mechanisms and a meta-analysis of epidemiologic studies [Articolo su rivista]
Tinkov, Alexey A; Filippini, Tommaso; Ajsuvakova, Olga P; Skalnaya, Margarita G; Aaseth, Jan; Bjørklund, Geir; Gatiatulina, Eugenia R; Popova, Elizaveta V; Nemereshina, Olga N; Huang, Pai-Tsang; Vinceti, Marco; Skalny, Anatoly V
abstract

Cadmium has been proposed to be the one of the factors of atherosclerosis development, although the existing data are still controversial. The primary objective of the present study is the review and the meta-analysis of studies demonstrating the association between Cd exposure and atherosclerosis as well as review of the potential mechanisms of such association. We performed a systematic search in the PubMed-Medline database using the MeSH terms cadmium, cardiovascular disease, atherosclerosis, coronary artery disease, myocardial infarction, stroke, mortality and humans up through December 20, 2017. Elevated urinary Cd levels were associated with increased mortality for cardiovascular disease (HR = 1.34, 95% CI: 1.07-1.67) as well as elevated blood Cd levels (HR = 1.78, 95% CI: 1.24-2.56). Analysis restricted to never smokers showed similar, though more imprecise, results. Consistently, we also observed an association between Cd exposure markers (blood and urine) and coronary heart disease, stroke, and peripheral artery disease. Moreover, Cd exposure was associated with atherogenic changes in lipid profile. High Cd exposure was associated with higher TC levels (OR = 1.48, 95% CI: 1.10-2.01), higher LDL-C levels (OR = 1.31, 95% CI 0.99-1.73) and lower HDL-C levels (OR = 1.96, 95% CI: 1.09-3.55). The mechanisms of atherogenic effect of cadmium may involve oxidative stress, inflammation, endothelial dysfunction, enhanced lipid synthesis, up-regulation of adhesion molecules, prostanoid dysbalance, as well as altered glycosaminoglycan synthesis.

2018 - Cancer incidence following long-term consumption of drinking water with high inorganic selenium content [Articolo su rivista]
Vinceti, Marco; Vicentini, Massimo; Wise, Lauren A.; Sacchettini, Claudio; Malagoli, Carlotta; Ballotari, Paola; Filippini, Tommaso; Malavolti, Marcella; Rossi, Paolo Giorgi
abstract

Selenium, a trace element to which humans are exposed mainly through diet, has been involved in the etiology of human cancer. We investigated the long-term effects of selenium exposure on cancer incidence using data from a natural experiment in Northern Italy. During the 1970s–1980s, in a part of the Italian municipality of Reggio Emilia, residents were inadvertently exposed to unusually high levels of inorganic hexavalent selenium (selenate) through drinking water. We followed the exposed residents for 28 years, generating data on incidence (when available) and mortality rates for selected cancer sites; the remaining municipal residents comprised the unexposed (reference) group. We observed no substantial difference in overall cancer incidence comparing exposed and unexposed cohorts. We detected, however, a higher incidence of cancer at some sites, and for a few of them, namely cancers of the buccal cavity and pharynx, melanoma, urinary tract and lymphoid tissue, the excess incidence was particularly evident in the first period of follow-up but decreased over time. Overall, these results suggest that consumption of water with levels of selenium in its inorganic hexavalent form close to the European standard, 10 μg/L, may have unfavourable effects on cancer incidence.

2018 - Carbohydrate solutions and contribute to the improvement of physical performance during a high‐intensity and long‐lasting physical exercise: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (JJ); Siani, Alfonso
abstract

Following an application from Specialised Nutrition Europe (SNE), submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to carbohydrate solutions and contribute to the improvement of physical performance during a high-intensity and long-lasting physical exercise. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is carbohydrate solutions containing glucose, mixtures of glucose and fructose, sucrose and/or maltodextrins. The Panel considers that carbohydrate solutions are sufficiently characterised in relation to the claimed effect. The claimed effect proposed by the applicant is 'contribute to the improvement of physical performance during a high-intensity and long-lasting physical exercise', which is considered by the Panel as a beneficial physiological effect. The Panel concludes that a cause and effect relationship has been established between the consumption of carbohydrate solutions and the improvement of physical performance during high-intensity and long-lasting physical exercise. The target population is healthy trained adults performing high-intensity (at least at 65% of the VO2max) and long-lasting (at least 60 min) physical exercise. (c) 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2018 - Cerebrospinal Fluid Neurofilaments May Discriminate Upper Motor Neuron Syndromes: A Pilot Study [Articolo su rivista]
Zucchi, Elisabetta; Bedin, Roberta; Fasano, Antonio; Fini, Nicola; Gessani, Annalisa; Vinceti, Marco; Mandrioli, Jessica
abstract

Patients presenting with upper motor neuron (UMN) signs may widely diverge in prognosis, ranging from amyotrophic lateral sclerosis (ALS) to primary lateral sclerosis (PLS) and hereditary spastic paraplegia (hSP). Neurofilaments are emerging as potential diagnostic and prognostic biomarkers for ALS, but the diagnosis of UMN syndromes still relies mostly on clinical long-term observation and on familiarity or genetic confirmation.

2018 - Comparison of two alternative methodologies to estimate the weekly intake of cadmium in an italian population [Abstract in Rivista]
Filippini, Tommaso; Malagoli, Carlotta; Michalke, Bernhard; Vinceti, Marco
abstract

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2018 - Congenital anomalies and risk of childhood leukemia: a pooled analysis from the childhood leukemia international consortium (clic) [Abstract in Atti di Convegno]
Lupo, Pj; Mueller, Ba; Clavel, J; Dockerty, Jd; Ezzat, S; Hansen, J; Heck, Je; Infante-Rivard, C; Magnani, C; Metayer, C; Milne, E; Mora, Am; Petridou, Et; Malagoli, C; Pombo-de-Oliveira, Ms; Roman, E; Schüz, J; Vinceti, M; Spector, Lg; Scheurer, Me
abstract

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2018 - Contaminazione alimentare da piombo e stima dell’assunzione giornaliera in una popolazione del Nord Italia. [Abstract in Atti di Convegno]
Cilloni, S; Filippini, T; Violi, F; Malavolti, M; Malagoli, C; Ferrari, A; Vescovi, L; Vinceti, M.
abstract

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2018 - Correlation between dietary cadmium exposure with biochemical and metabolic parameters: A cross-sectional study in Northern Italy population [Abstract in Atti di Convegno]
Filippini, T; Lasagni, D; Bruzziches, F; Baraldi, C; Malagoli, C; Grioni, S; Sieri, S; Santachiara, A; De Luca, T; Pertinhez, T; Baricchi, R; Vinceti, M.
abstract

Background and aim: Cadmium is a heavy metal classified as carcinogen for humans. It accumulates in the organism, especially in kidney and liver. Recent findings suggested that cadmium could influence human metabolism acting as endocrine disruptor and high cadmium exposure has been associated with impairment of cardiovascular and endocrine systems. This study aims at assessing the dietary intake of cadmium in an Italian community of Northern Italy and to evaluate its correlation with endocrine and metabolic factors. Methods: In a sample adult population of ever smokers from Reggio Emilia Province we estimated dietary cadmium intake through a food frequency questionnaire, validated for the Northern Italy population. From each participant we collected a fasten blood sample for determination of biochemical parameters and hormones levels, including alanine transaminase, blood glucose, total cholesterol, high-density lipoproteins (HDL), and thyroid-stimulating hormone (TSH). All subjects who participated to this study signed a written informed consent. Results: We eventually recruited 104 participants (men/women: 46/58), with mean (standard deviation) dietary intake of cadmium of 16.0 (8.5) μg/day. Correlation between cadmium intake and biochemical factors demonstrated a positive association with total cholesterol levels, blood glucose and TSH. Adjustment for main confounders, including sex, age, and bass index did not substantially alter the results. No clear correlation emerged with other parameters under investigation. Discussion: The results show that in our sampled population, dietary intake of cadmium is similar with other Italian and European populations. They also suggest that cadmium intake could influence the levels of metabolic and other biochemical factor which are important risk factors for chronic cardiovascular and endocrine system diseases. Acknowledgements We acknowledge the collaboration of the personnel of Transfusion Medicine Unit of AUSL-IRCCS of Reggio Emilia, staff and volunteers of AVIS – Section of Reggio Emilia, and all blood donors who participated to this study.

2018 - Correlation between dietary selenium exposure with biochemical and metabolic parameters: a cross-sectional study in Northern Italy population. [Abstract in Atti di Convegno]
Vinceti, M; Lasagni, D; Bruzziches, F; Baraldi, C; Malagoli, C; Grioni, S; Sieri, S; Santachiara, A; De Luca, T; Pertinhez, T; Baricchi, R; Filippini, T.
abstract

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2018 - Diagnostic medical radiation exposure and risk of childhood leukaemia: results from an Italian population-based case-control study. [Abstract in Atti di Convegno]
Cilloni, S; Arcolin, E; Malagoli, C; Filippini, T; Violi, F; Borsari, L; Vinceti, M.
abstract

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2018 - Diagnostic medical radiation exposure and risk of childhood leukemia: results from an Italian population-based case-control study. [Abstract in Atti di Convegno]
Filippini, T; Arcolin, E; Malagoli, C; Cilloni, S; Violi, F; Borsari, L; Vinceti, M.
abstract

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2018 - Diet composition and serum levels of selenium species: A cross-sectional study [Articolo su rivista]
Filippini, Tommaso; Michalke, Bernhard; Wise, Lauren A.; Malagoli, Carlotta; Malavolti, Marcella; Vescovi, Luciano; Salvia, Chiara; Bargellini, Annalisa; Sieri, Sabina; Krogh, Vittorio; Ferrante, Margherita; Vinceti, Marco
abstract

Selenium is a trace element of both nutritional and toxicological interest, depending on its dose and chemical form. Diet is the primary source of exposure for most individuals. We sought to investigate the influence of food intake on serum levels of selenium species. Among fifty subjects randomly selected from a Northern Italian population, we assessed dietary habits using a validated semi-quantitative food frequency questionnaire. We also measured circulating levels of selenium species in serum using high pressure liquid chromatography associated with inductively-coupled plasma dynamic reaction cell mass spectrometer. Circulating levels of inorganic selenium, the most toxic selenium species, were positively associated with intake of fish, legumes and dry fruits, and inversely associated with intake of dairy products and mushrooms. Concerning the organic selenium species, selenoproteinP-bound selenium was inversely associated with intake of fish, fresh fruits, vegetables, and legumes, while selenocysteine-bound selenium positively associated with intake of fresh fruit, potato, legume and mushroom. In the present study, intakes of different foods were correlated with different types of selenium species. These results have important public health implications when assessing the nutritional and toxicological potential of diet composition with reference to selenium exposure.

2018 - Dietary intake of cadmium, chromium, copper, manganese, selenium and zinc in a Northern Italy community [Articolo su rivista]
Filippini, T; Cilloni, S; Malavolti, M; Violi, F; Malagoli, C; Tesauro, M; Bottecchi, I; Ferrari, A; Vescovi, L; Vinceti, M
abstract

This study provides the dietary intakes of six trace elements (cadmium, chromium, copper, manganese, selenium and zinc), generally characterized by both nutritional and toxicological features depending on their exposure. Being diet the most relevant source of exposure to trace elements in non-professionally exposed subjects, we measured content of these trace elements in foods composing the typical Italian diet using inductively coupled plasma-mass spectrometry, and assessing dietary habits using a validated semi-quantitative food frequency questionnaire we eventually estimated dietary daily intake of trace elements in a Northern Italian community. In the 890 analyzed food samples, the main contributors to cadmium intake are cereals, vegetables and sweets, while cereals, beverages and vegetable are to primary source of manganese. The primary contributors for copper are cereals, fresh fruits and vegetables, while for chromium are beverages, cereals and meat. The main source of selenium intake are cereals and meat, followed by fish, seafood and milk and dairy products, while of zinc intake are meat, cereals, milk and dairy products. In our Italian population sample, the estimated median (interquartile range) dietary daily intakes are 5.00 (3.17-7.65), 56.70 (36.08-86.70) and 66.53 (40.04-101.32) µg/day for cadmium, chromium and selenium, and corresponding figures are 0.98 (0.61-1.49), 2.34 (1.46-3.52) and 8.50 (5.21-12.48) mg/day for copper, manganese and zinc. The estimated intakes are generally within the average intake reported in other European populations, and in such cases well above the daily dietary intakes recommended by national international agencies, avoiding the risk of excess or deficiency. The present estimated intake data can be used to examine a specific trace element of interest and would afford enhanced health protection from those trace elements characterized by both nutritional and toxicological effects.

2018 - Dietary intake of calcium, phosphorus and magnesium in a Northern Italian community. [Abstract in Atti di Convegno]
Malavolti, M; Filippini, T; Malagoli, C; Cilloni, S; Violi, F; Vescovi, L; Vinceti, M.
abstract

Minerals are essential micronutrients for growth, development, and maintenance of healthy tissues, the long term insufficient intake of minerals may lead to bone demineralization and often requires the use of food supplements. The ratios of certain minerals intake like calcium and phosphorus are also proved to can affect the bioavailability of calcium and even lead to adverse health consequence. This study was designed to explore the dietary sources of calcium (Ca), phosphorus (P), and magnesium (Mg) and the ratios between different minerals (Ca/P). We measured the content of these elements in foods composing typical Italian diet using inductively coupled plasma-mass spectrometry and we estimated their daily dietary intakes assessing through a semi-quantitative food frequency questionnaire specifically developed within the European Prospective Investigation into Cancer and Nutrition (EPIC) study in a Northern Italian Community. In 890 analyzed food samples the main contributors to calcium are milk and dietary products, dry fruits, legumes and sweet products. Important sources of phosphorus are represented by dry fruits, legumes, milk and dairy products and meat. While dry fruits, legumes, cereals and fish symbolized the most important sources for magnesium. In our Italian population sample, the estimated median (interquartile range) dietary daily intakes are 786.3 (592.2-1062.7) μg/day for calcium; 1291.7 (1017.2-1591.4) mg/day for phosphorus and 323.2 (260.3-396.6) mg/day for magnesium. The calcium-phosphorus (Ca/P) ratio in this study was 0.63 (0.52-0.73). These values are in agreement with those suggested by European and International recommended intake for adult population, with the exception of calcium which is slightly lower than recommended values and suggest that this population does not present nutritional deficiencies requiring any supplementation.

2018 - Environmental Selenium and Human Health: an Update [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Wise, Lauren A
abstract

Selenium, a trace element, is ubiquitous in the environment. The main source of human exposure is diet. Despite its nutritional benefits, it is one of the most toxic naturally occurring elements. Selenium deficiency and overexposure have been associated with adverse health effects. Its level of toxicity may depend on its chemical form, as inorganic and organic species have distinct biological properties.

2018 - Exposure to electromagnetic fields and risk of childhood leukemia: a population-based case-control study in two Italian provinces. [Abstract in Atti di Convegno]
Malagoli, C; Filippini, T; Storani, S; Violi, F; Fabbi, S; Teggi, S; Ballotti, E; Zanichelli, P; Poli, M; Bruni, M; Sesti, D; Notari, B; Palazzi, G; Vinceti, M.
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2018 - Exposure to high voltage power lines and risk of childhood leukaemia: an Italian population-based case-control study. [Abstract in Atti di Convegno]
Violi, F; Malagoli, C; Filippini, T; Fabbi, S; Teggi, S; Ballotti, E; Zanichelli, P; Poli, M; Bruni, M; Sesti, D; Notari, B; Vinceti, M.
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2018 - Food contamination from the food packaging metals aluminum and tin: estimation of their dietary exposure in an Italian adult community. [Abstract in Atti di Convegno]
Filippini, T; Tancredi, Stefano; Malagoli, C; Cilloni, S; Malavolti, M; Violi, F; Vescovi, L; Bargellini, A; Vinceti, M.
abstract

2018 Scientific meeting Italian Association for the Study of Trace Elements in living Organisms – AISETOV. Ozzano Emilia, Bologna, October 12, 2018 (ISBN: 9788894309812)

2018 - Genetic polymorphisms in amyotrophic lateral sclerosis: Evidence for implication in detoxification pathways of environmental toxicants [Articolo su rivista]
Dardiotis, Efthimios; Siokas, Vasileios; Sokratous, Maria; Tsouris, Zisis; Michalopoulou, Amalia; Andravizou, Athina; Dastamani, Metaxia; Ralli, Styliani; Vinceti, Marco; Tsatsakis, Aristidis; Hadjigeorgiou, Georgios M.
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2018 - Guidance for the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Heng, Leng; Valtueña Martínez, Silvia; Siani, Alfonso
abstract

EFSA asked the Panelon Dietetic Products, Nutrition and Allergies (NDA) to update the guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health published in 2011. The update takes into accounts experiences gained with evaluation of additional health claim applications related to antioxidants, oxidative damage and cardiovascular health, and the information collected from a Grant launched in 2014. This guidance is intended to assist applicants in preparing applications for the authorisation of health claims related to the antioxidants, oxidative damage and cardiovascular health. The document was subject to public consultation (from 12 July to 3 September 2017). This document supersedes the guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health published in 2011. It is intended that the guidance will be further updated as appropriate in the light of experience gained from the evaluation of health claims.

2018 - Guidance on the scientific requirements for health claims related to muscle function and physical performance: (Revision 1) [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Bresson, Jean-Louis; Burlingame, Barbara; Dean, Tara; Fairweather-Tait, Susan; Heinonen, Marina; Neuhäuser-Berthold, Monika; Nowicka, Grażyna; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Heng, Leng; Valtueña Martínez, Silvia; Siani, Alfonso
abstract

EFSA has asked the Panel on Nutrition, Novel Foods and Food Allergens (NDA) to update the guidance on the scientific requirements for health claims related to physical performance published in 2012. The update takes into account the experience gained by the NDA Panel with the evaluation of additional health claim applications, changes introduced to the general scientific guidance for stakeholders for health claims applications and information collected from a grant launched in 2014 which aimed at gathering information in relation to claimed effects, outcome variables and methods of measurement in the context of the scientific substantiation of health claims. The guidance is intended to assist applicants in preparing applications for the authorisation of health claims related to muscle function and physical performance. The draft guidance was subject to public consultation from 16 July to 2 September 2018. This document supersedes the guidance on the scientific requirements for health claims related to physical performance published in 2012. It is intended that the guidance will be further updated as appropriate in the light of experience gained from the evaluation of health claims.

2018 - I fattori ambientali di rischio delle malattie neurodegenerative: prospettive e metodologie di ricerca epidemiologica. [Abstract in Atti di Convegno]
Vinceti, M; Malagoli, C; Filippini, T
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2018 - Impact of referral sources and waiting times on the failure to quit smoking: One-year follow-up of an italian cohort admitted to a smoking cessation service [Articolo su rivista]
Borsari, Lucia; Storani, Simone; Malagoli, Carlotta; Filippini, Tommaso; Tamelli, Marco; Malavolti, Marcella; Nicolini, Fausto; Vinceti, Marco
abstract

In Italy, the National Health Service offers specialized evidence-based support to smokers who would like to quit through smoking cessation (SC) services. We conducted a two-year prospective study, involving all 288 subjects treated for smoking cessation at the SC service of Reggio Emilia, to assess the association of referral sources and waiting times with the risk of treatment failure, by following participants up to one year after the quit date. We performed Cox-regression analysis, including demographic and smoking-related characteristics as confounding variables. The treatment failure rate at 12 months was 59.4% (171/288), including only 12 subjects lost to follow-up. The main mode of entry was self-referral (42.4%), followed by 32.6% from general practice, 17.4% from hospital and 7.6% from other sources. Only 27.8% participants were involved in the SC-program within 60 days of the first contact, as the guidelines suggest. The risk of treatment failure at 12 months showed little association with the type of referral source, while it correlated with waiting times ≥ 60 days (hazard ratio = 1.59; 95% confidence interval 1.10-2.29). This study provides evidence of long-term high quit rates from a SC service, with few subjects lost to follow-up and biochemical verification of almost all abstinent subjects. Timeliness in care provision could further improve the outcome.

2018 - Intake of arsenic and mercury from fish and seafood in a Northern Italy community [Articolo su rivista]
Filippini, Tommaso; Malavolti, Marcella; Cilloni, Silvia; Wise, Lauren A.; Violi, Federica; Malagoli, Carlotta; Vescovi, Luciano; Vinceti, Marco
abstract

Regular consumption of fish is generally recommended by authorities because fish is an important source of essential nutrients. However, the presence of potentially toxic contaminants in fish has raised many concerns about the food's safety for human health. In the present study, we used a validated semi-quantitative food frequency questionnaire to assess the dietary habits of a representative sample of 719 individuals (319 males and 400 females) aged 18–87 years residing in Northern Italy. We estimated weekly dietary intakes of Arsenic (As) and Mercury (Hg), and we compared them with safety standards set by the European Food Safety Authority. In this population, fish was the main contributor to As and Hg intake. The highest levels of As were in sardine, sole/flounder and cephalopods, and of Hg in the biggest, predatory fish. About the other foods, cereals were the second contributor to the intake of these elements, especially rice for As and bread for Hg, and high levels of As and Hg were also found in mushrooms, coffee and wine. Average weekly intake of both contaminants was below recommended safety limits.

2018 - Investigating the environmental risk factors for childhood leukaemia: the research activity at the University of Modena and Reggio Emilia, Northern Italy. [Abstract in Atti di Convegno]
Vinceti, M; Malagoli, C; Filippini, T; Violi, F; Cilloni, S; Malavolti, M; Borsari, L; Storani, S; Arcolin, E; Palazzi, G; Teggi, S; Fabbi, S; Costanzini, Sofia; Ghermandi, G; Bagni, Enrico
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2018 - Is there a relation between birth of month and risk of childhood leukaemia? A case-control study in two Italian provinces. [Abstract in Atti di Convegno]
Malavolti, M; Filippini, T; Malagoli, C; Cilloni, S; Borsari, L; Vinceti, M.
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2018 - Joint Effect of Maternal Tobacco Smoking and Pregestational Diabetes on Preterm Births and Congenital Anomalies: A Population-Based Study in Northern Italy [Articolo su rivista]
Borsari, Lucia; Malagoli, Carlotta; Werler, Martha M.; Rothman, Kenneth J.; Malavolti, Marcella; Rodolfi, Rossella; De Girolamo, Gianfranco; Nicolini, Fausto; Vinceti, Marco
abstract

Smoking and pregestational diabetes (PGD) are recognized risk factors for adverse pregnancy outcomes, but to date, no population-based study has investigated their joint effects. Using hospital discharges, we identified all women with PGD delivering in Emilia-Romagna region during 2007-2010 matched 1: 5 with parturients without diabetes. Our study endpoints were preterm births and congenital anomalies. We measured interaction between PGD and maternal smoking, by calculating excess prevalence and prevalence ratio due to interaction, relative excess risk due to interaction (RERI), attributable proportion (AP), and the synergy index (S). Analyses were performed in the overall study population and in the subgroup whose PGD was validated through diabetes registers. The study included 992 women with PGD (10.5% smokers) and 4788 comparison women (11.9% smokers). The effects of PGD and maternal tobacco smoking were greater than additive for both preterm birth (excess prevalence due to interaction = 11.7%, excess ratio due to interaction = 1.5, RERI = 2.39, AP = 0.51, S = 2.82) and congenital anomalies (excess prevalence due to interaction = 2.2%, excess ratio due to interaction = 1.3, RERI = 1.33, AP = 0.49, S = 5.03). Joint effect on both endpoints was confirmed in the subgroup whose PGD status was validated. In conclusion, we found that maternal tobacco smoking and PGD intensify each other's effect on preterm birth and congenital anomalies.

2018 - Livelli di assunzione di selenio in un campione di popolazione italiana e correlazione con parametri metabolici ed ormonali: uno studio trasversale in Emilia Romagna. [Abstract in Atti di Convegno]
Vinceti, M; Lasagni, D; Bruzziches, F; Baraldi, C; Malagoli, C; Grioni, S; Sieri, S; Santachiara, Alessia; De Luca, T; Pertinez, T; Baricchi, R; Filippini, T.
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2018 - Livelli di esposizione alimentare a cadmio e correlazione con parametri metabolici ed ormonali: uno studio cross-sectional in una popolazione emiliana. [Abstract in Atti di Convegno]
Filippini, T; Lasagni, D; Bruzziches, F; Baraldi, C; Malavolti, M; Grioni, S; Sieri, S; Santachiara, A; De Luca, T; Pertinez, T; Baricchi, R; Vinceti, M
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2018 - L‐carnitine and contribution to normal lipid metabolism: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (J. J. ); Siani, Alfonso
abstract

Following an application from Lonza Ltd., submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No1924/2006 via the Competent Authority of Germany, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to L-carnitine and normal lipid metabolism. The food that is proposed as the subject of the health claim is L-carnitine. The Panelconsiders that L-carnitine is sufficiently characterised. The claimed effect proposed by the applicant is normal lipid metabolism'. The target population proposed by the applicant is the general population. The Panelconsiders that contribution to normal lipid metabolism is a beneficial physiological effect. The applicant proposes that the claim submitted with this application is based on the essentiality of a nutrient. The Panelconsiders that the evidence provided does not establish that dietary L-carnitine is required to maintain normal lipid metabolism in the target population, for which the claim is intended. The Panelconcludes that a cause and effect relationship has not been established between the consumption of L-carnitine and contribution to normal lipid metabolism in the target population.

2018 - Magnesium citrate malate as a source of magnesium added for nutritional purposes to food supplements [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Dean, Tara; Engel, Karl-Heinz; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser-Berthold, Monika; Poulsen, Morten; Pöting, Annette; Sanz, Yolanda; Schlatter, Josef Rudolf; Germini, Andrea; van Loveren, Henk
abstract

The present scientific opinion deals with the assessment of the bioavailability of magnesium, from the proposed nutrient source, magnesium citrate malate (MgCM), when added for nutritional purposes to food supplements. MgCM is a mixed salt consisting of magnesium cations and citrate and malate anions, and with a magnesium content of 12–15%. MgCM is proposed to be used in food supplements that are intended to provide up to 300–540 mg/day magnesium. The data provided demonstrate that the production process results in batches of MgCM that comply with the product specifications and that the product is stable throughout its proposed shelf life. The human studies provided demonstrate that magnesium from MgCM is bioavailable. However, the extent of its bioavailability per se or compared to other magnesium sources cannot be established due to the lack of an appropriate magnesium source as a comparator in the studies provided or relevant kinetic data for magnesium. One publication provided in the dossier reported that supplementation with MgCM decreases calcium absorption, but this finding was not supported by publications on different magnesium salts and therefore the Panel could not draw conclusions from this finding. The Panel concludes that MgCM is a source from which magnesium is bioavailable, but the extent of its bioavailability cannot be established. The Panel notes that at the proposed maximum use levels of MgCM, the existing tolerable upper intake level for magnesium in nutritional supplements, water, or added to food and beverages (250 mg/day) is exceeded.

2018 - Maternal pregestational diabetes and risk of childhood leukaemia in the offspring: a population-based study in Northern Italy. [Abstract in Atti di Convegno]
Borsari, L; Malagoli, C; della Torre, F; Palazzi, G; Rodolfi, R; Filippini, T; Violi, F; Cilloni, S; Malavolti, M; Nicolini, F; Vinceti, M.
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2018 - NWT‐02, a fixed combination of lutein, zeaxanthin and docosahexaenoic acid in egg yolk and reduction of the loss of vision: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (J. J. ); Siani, Alfonso
abstract

Following an application from Newtricious R&D B.V., submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to NWT-02 and a reduction of the loss of vision. The food proposed by the applicant as the subject of the health claim is NWT-02. NWT-02 is standardised by its content in lutein (>= 1.10 mg), zeaxanthin (>= 0.20 mg) and docosahexaenoic acid (DHA) (>= 170 mg). The Panel considers that the food/constituent that is the subject of the health claim, NWT-02, a fixed combination of lutein, zeaxanthin and docosahexaenoic acid in egg yolk, is sufficiently characterised. The claimed effect proposed by the applicant is 'reduces loss of vision'. The target population proposed by the applicant is 'healthy adults over 50 years of age'. The Panel considers that a reduction of the loss of vision is a beneficial physiological effect. The applicant provided two human intervention studies for the scientific substantiation of the claim. The Panel considers that the only study from which conclusions can be drawn for the scientific substantiation of the claim did not show an effect of NWT-02 on vision. The Panel concludes that a cause and effect relationship has not been established between the consumption of NWT-02, a fixed combination of lutein, zeaxanthin and docosahexaenoic acid in egg yolk, and a reduction of the loss of vision.

2018 - Non-chromosomal congenital anomalies and risk of childhood leukaemia: An Italian population-based case-control study [Abstract in Atti di Convegno]
Malagoli, C; Filippini, T; Malavolti, M; Volpato, S; Astolfi, G; Palazzi, G; Vinceti, M
abstract

Introduction: The association between chromosomal conditions such as Down syndrome and increased CL risk of childhood leukemia (CL) is well established, while the association between non-chromosomal birth defects is far less clear. We conducted a population-based case-control study in two provinces of Northern Italy to evaluate CL risk in children born with non-chromosomal anomalies. Methods: We identified all leukemia cases diagnosed in children (<15 years) in the Modena and Reggio Emilia provinces through the Italian National Childhood Cancer Register in the period 1998-2013. For each case, we randomly selected four population controls matched by age, sex, province of residence and calendar year. Through the Emilia-Romagna Region population-based Birth Defects Registry, we retrieved information about occurrence and type of congenital malformations for each study subject. We computed the odds ratio (OR) of CL for children affected by non-chromosomal birth defects using a multivariable conditional logistic regression model. Results: We eventually included 132 cases and 528 controls, 5 of which (2 cases and 3 controls) were affected by a non-chromosomal congenital malformation. We found an increased risk of CL in children born with non-chromosomal anomalies, with an OR of 2.7 (95% confidence interval 0.4–16.0). Conclusions: Despite the limited stability of the risk estimates and the risk of unmeasured and residual confounding, our study appears to suggest an association between non-chromosomal birth defects and risk of childhood leukemia.

2018 - Non-chromosomal congenital anomalies and risk of childhood leukaemia: a Italian population-based case-control study. [Abstract in Atti di Convegno]
Malagoli, C; Filippini, T; Malavolti, M; Volpato, S; Astolfi, G; Palazzi, G; Vinceti, M.
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2018 - Outdoor air pollution and risk of conversion from mild cognitive impairment to dementia: a cohort study. [Abstract in Atti di Convegno]
Filippini, T; Chiari, A; Zamboni, G; Tondelli, M; Vinceti, G; Maffeis, G; Cherubini, A; Malagoli, C; Vinceti, M.
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2018 - Proximity to Overhead Power Lines and Childhood Leukemia: An International Pooled Analysis [Abstract in Atti di Convegno]
Amoon, A; Crespi, Cm; Ahlbom, A; Bhatnagar, M; Bray, I; Bunch, K; Clavel, J; Feychting, M; Hemon, D; Johansen, C; Kreis, C; Malagoli, C; Marquant, F; Pedersen, C; Raaschou-Nielsen, O; Roosli, M; Spycher, B; Sudan, M; Swanson, J; Tittarelli, A; Tuck, D; Tynes, T; Vergara, X; Vinceti, M; Wünsch-Filho, V; Kheifets, L.
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2018 - Proximity to overhead power lines and childhood leukemia: an international pooled analysis [Articolo su rivista]
Amoon, Aryana; Crespi, Catherine; Ahlbom, Anders; Bhatnagar, Megha; Bray, Issy; Bunch, Kathryn; Clavel, Jacqueline; Feychting, Maria; Hemon, Denis; Johansen, Christoffer; Kreis, Christian; Malagoli, Carlotta; Marquant, Fabienne; Pedersen, Camilla; Raaschou-Nielsen, Ole; Roosli, Martin; Spycher, Ben; Sudan, Madhuri; Swanson, John; Tittarelli, Andrea; Tuck, Dierdre; Tynes, Tore; Vergara, Ximena; Vinceti, Marco; Wunsch Filho, Victor; Kheifets, Leeka
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2018 - Residence near electrical transformer rooms and risk of childhood leukaemia: an Italian population-based case-control study. [Abstract in Atti di Convegno]
Filippini, T; Storani, S; Malagoli, C; Fabbi, S; Teggi, S; Sesti, D; Notari, B; Zanichelli, P; Poli, M; Palazzi, G; Vinceti, M.
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2018 - Riluzole and other prognostic factors in ALS: a population-based registry study in Italy [Articolo su rivista]
Mandrioli, Jessica; Malerba, Sara Angela; Beghi, Ettore; Fini, Nicola; Fasano, Antonio; Zucchi, Elisabetta; De Pasqua, Silvia; Guidi, Carlo; Terlizzi, Emilio; Sette, Elisabetta; Ravasio, Alessandro; Casmiro, Mario; Salvi, Fabrizio; Liguori, Rocco; Zinno, Lucia; Handouk, Yasmin; Rizzi, Romana; Borghi, Annamaria; Rinaldi, Rita; Medici, Doriana; Santangelo, Mario; Granieri, Enrico; Mussuto, Vittoria; Aiello, Marina; Ferro, Salvatore; Vinceti, Marco
abstract

In this prospective population-based registry study on ALS survival, we investigated the role of riluzole treatment, together with other clinical factors, on the prognosis in incident ALS cases in Emilia Romagna Region (ERR), Italy.

2018 - Risk of amyotrophic lateral sclerosis and passive residential exposure to pesticides: comparison of questionnaire-based with gis-based exposure assessment methods [Abstract in Rivista]
Filippini, Tommaso; Malagoli, Carlotta; Costanzini, Sofia; Violi, Federica; Cilloni, Silvia; Teggi, Sergio; Fiore, Maria; Ferrante, Margherita; Vinceti, Marco
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2018 - Safety of Allanblackia seed oil for extended uses in vegetable oils and milk and in yellow fat and cream-based spreads up to 30% (w/w) [Articolo su rivista]
Turck, Dominique; Bresson, Jean-Louis; Burlingame, Barbara; Dean, Tara; Fairweather-Tait, Susan; Heinonen, Marina; Hirsch-Ernst, Karen Ildico; Mangelsdorf, Inge; McArdle, Harry J; Naska, Androniki; Neuhäuser-Berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl-Heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef; Gelbmann, Wolfgang; van Loveren, Henk
abstract

In 2007, the EFSA NDA Panel concluded that Allanblackia seed oil obtained from the seeds of Allanblackia trees is safe for human consumption under the proposed conditions of use. Due to its high contents of stearic-oleic-stearic and stearic-oleic-oleic triglycerides, which made the oil suitable as a ‘hardstock’ component, the applicant applied for its use as a novel food (NF) ingredient in yellow fat and cream-based spreads at a level of 20% (w/w). In this application, the applicant seeks (1) to increase the authorised maximum use level (i.e. 20% w/w) in yellow fat spreads and cream-based spreads to 30% (w/w) and (2) the use of this NF in mixes of vegetable oils and milk up to a maximum use level of 30% (w/w). (3) The applicant proposes also some changes in the specifications of the NF, although he noted that the oil is collected, extracted and refined using the same processes that are currently used for other edible vegetable oils and which have been evaluated in the original application assed by EFSA in 2007. According to the information provided by the applicant, the production process and the composition of the NF do not change. The Panel notes that the revised specification limits on trans-fatty acid (TFA), unsaponifiable matter, peroxide value are similar to those for other edible oils and fats. The applicant also indicated that he had performed an updated comprehensive literature search using several different databases, but no preclinical studies or human studies on Allanblackia seed oil were identified which have not been provided for the previous EFSA assessment in 2007. The Panel notes that the proposed extended uses would increase the potential intake of the NF, which is considered not to be nutritionally disadvantageous. The Panel concludes that Allanblackia seed oil is safe at the extended uses and use level.

2018 - Safety of Whey basic protein isolates as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl–heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef Rudolf; Amundsen, Mathias; van Loveren, Henk
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2018 - Safety of d-ribose as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Bresson, Jean-Louis; Burlingame, Barbara; Dean, Tara; Fairweather-Tait, Susan; Heinonen, Marina; Hirsch-Ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry; Naska, Androniki; Neuhäuser-Berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl-Heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef Rudolf; Germini, Andrea; Van Loveren, Henk
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on D-ribose as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The applicant intends to market the NF as ingredient in a variety of foods, food supplements and in certain foods for specific groups. The NF is produced by fermentation using a transketolase-deficient strain of Bacillus subtilis and marketed as Bioenergy Ribose™. The information provided on the batch-to-batch variability, specifications, stability, production process and history of the organism used as a source of the NF is sufficient and does not raise safety concerns. The Panel considers that the effects observed in a subchronic toxicity study in rats could be the consequence of nutritional imbalances, but toxicological effects could not be ruled out; from this study, the Panel derived a No observed adverse effect level (NOAEL) of 3.6 g/kg body weight (bw) per day. From the human studies indicating a potential decrease in glucose levels and/or the occurrence of transient symptomatic hypoglycaemia at intakes of 10 g of d-ribose, the Panel defined 70 mg/kg bw per day as the NOAEL with respect to hypoglycaemia that can be considered applicable for adults. For children, the Panel acknowledges the lack of human data directly relevant for this population group. Based on the NOAEL derived from the subchronic toxicity study in rats, an acceptable level of intake of 36 mg/kg bw per day was defined that would also take into account the potentially increased sensitivity of certain population groups to hypoglycaemia. The Panel concludes that the NF is safe for the general population at intake levels up to 36 mg/kg bw per day and considers that the safety of the NF at the intended uses and use levels as proposed by the applicant has not been established.

2018 - Safety of egg membrane hydrolysate as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl‐heinz; Marchelli, Rosangela; Pöting, Annette; Schlatter, Josef Rudolf; Ackerl, Reinhard; van Loveren, Henk
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2018 - Safety of shrimp peptide concentrate as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Bresson, Jean-Louis; Burlingame, Barbara Ann; Dean, Tara; Fairweather-Tait, Susan; Heinonen, Marina; Hirsch-Ernst, Karen Ildico; Mangelsdorf, Inge; McArdle, Harry J; Naska, Androniki; Neuhäuser-Berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl-Heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef Rudolf; Matijević, Leonard; van Loveren, Henk
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on shrimp peptide concentrate as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a peptide mixture obtained by an enzymatic proteolysis from northern shrimp (Pandalus borealis) shells and heads. The information provided on the composition, specifications, batch-to-batch variability, stability and production process of the NF is sufficient and does not raise safety concerns. The intention of the applicant is to use this NF as an ingredient in food supplements and to market it to adult consumers at a maximum proposed level of intake of 1,200 mg/day (corresponding to 17 mg/kg body weight (bw) per day for a 70 kg person). There are no concerns with regard to genotoxicity. The available human data do not raise safety concerns. Considering the no observed adverse effect level (NOAEL) of 2,000 mg/kg bw per day from a 90-day repeated-dose oral toxicity study, the maximum proposed level of intake and the nature of the NF, the Panel concludes that the margin of exposure (of 117) is sufficient. The Panel concludes that the NF, shrimp peptide concentrate, is safe to be used as a food supplement at the proposed maximum dose of 1,200 mg/day. The target population is adults. The Panel considered that the conclusion on the safety of the NF could not have been reached without the data from the unpublished study report on repeated-dose 90-day oral toxicity and from the unpublished study reports on two human studies.

2018 - Safety of xylo‐oligosaccharides (XOS) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl‐heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef Rudolf; Turla, Emanuela; van Loveren, Henk
abstract

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2018 - Selenium Neurotoxicity and Amyotrophic Lateral Sclerosis: An Epidemiologic Perspective [Capitolo/Saggio]
Filippini, Tommaso; Michalke, Bernhard; Mandrioli, Jessica; Tsatsakis, Aristidis M.; Weuve, Jennifer; Vinceti, Marco
abstract

.Selenium exposure has been proposed as possible risk factor for amyotrophic lateral sclerosis (ALS), due to the selective toxicity of the trace element, especially in its inorganic forms, toward motor neurons. The epidemiological evidence, in association with laboratory and veterinary findings, linking selenium exposure and ALS risk was originally suggested by the increased ALS mortality in an area characterized by high selenium content in soil, and subsequently confirmed in an Italian community. The latter was unintentionally exposed to high levels of inorganic hexavalent selenium through drinking water, and subsequently showed an increased incidence for neurodegenerative diseases, including ALS and Parkinson’s disease. Review of the epidemiological studies addressing the association between selenium exposure and ALS risk points out important lessons that should be considered in future research, in order to avoid misleading and biased evaluations of selenium’s effects. These include the use of central nervous system indicator of exposure such as cerebrospinal fluid, and the implementation of speciation analysis, due to the different toxic and nutritional properties of the various selenium compounds.

2018 - Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Rothman, Kenneth J
abstract

In 2007, supplementation with the trace element selenium in a trial was unexpectedly found to be associated with an excess risk of type 2 diabetes. Given the concerns raised by these findings and the large number of recent studies on this topic, we reviewed the available literature with respect to this possible association. In this paper, we assessed the results of both experimental and nonexperimental epidemiologic studies linking selenium with type 2 diabetes incidence. Through a systematic literature search, we retrieved 50 potentially eligible nonexperimental studies and 5 randomized controlled trials published through June 11, 2018. To elucidate the possible dose-response relation, we selected for further analysis those studies that included multiple exposure levels and serum or plasma levels. We computed a pooled summary risk ratio (RR) of diabetes according to selenium exposure in these studies. We also computed a RR for diabetes incidence following supplementation with 200 µg/day of selenium compared with placebo in trials. In the nonexperimental studies, we found a direct relation between selenium exposure and risk of diabetes, with a clear and roughly linear trend in subjects with higher plasma or serum selenium levels, with RR at 140 µg/L of selenium exposure compared with a referent category of < 45 µg/L equal to 3.6 [95% confidence interval (CI) 1.4-9.4]. A dose-response meta-analysis focusing on studies with direct assessment of dietary selenium intake showed a similar trend. In experimental studies, selenium supplementation increased the risk of diabetes by 11% (RR 1.11, 95% CI 1.01-1.22) compared with the placebo-allocated participants, with a higher RR in women than in men. Overall, results from both nonexperimental and experimental studies indicate that selenium may increase the risk of type 2 diabetes across a wide range of exposure levels. The relative increase in risk is small but of possible public health importance because of the high incidence of diabetes and the ubiquity of selenium exposure.

2018 - Selenium for preventing cancer [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Del Giovane, Cinzia; Dennert, Gabriele; Zwahlen, Marcel; Brinkman, Maree; Zeegers, Maurice P. A.; Horneber, Markus; D'Amico, Roberto; Crespi, Catherine M.
abstract

Background: This review is the third update of the Cochrane review "Selenium for preventing cancer". Selenium is a naturally occurring element with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancer. Objectives: To gather and present evidence needed to address two research questions: 1. What is the aetiological relationship between selenium exposure and cancer risk in humans?2. Describe the efficacy of selenium supplementation for cancer prevention in humans. Search methods: We updated electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE (Ovid, 2013 to January 2017, week 4), and Embase (2013 to 2017, week 6), as well as searches of clinical trial registries. Selection criteria: We included randomised controlled trials (RCTs) and longitudinal observational studies that enrolled adult participants. Data collection and analysis: We performed random-effects (RE) meta-analyses when two or more RCTs were available for a specific outcome. We conducted RE meta-analyses when five or more observational studies were available for a specific outcome. We assessed risk of bias in RCTs and in observational studies using Cochrane's risk assessment tool and the Newcastle-Ottawa Scale, respectively. We considered in the primary analysis data pooled from RCTs with low risk of bias. We assessed the certainty of evidence by using the GRADE approach. Main results: We included 83 studies in this updated review: two additional RCTs (10 in total) and a few additional trial reports for previously included studies. RCTs involved 27,232 participants allocated to either selenium supplements or placebo. For analyses of RCTs with low risk of bias, the summary risk ratio (RR) for any cancer incidence was 1.01 (95% confidence interval (CI) 0.93 to 1.10; 3 studies, 19,475 participants; high-certainty evidence). The RR for estimated cancer mortality was 1.02 (95% CI 0.80 to 1.30; 1 study, 17,444 participants). For the most frequently investigated site-specific cancers, investigators provided little evidence of any effect of selenium supplementation. Two RCTs with 19,009 participants indicated that colorectal cancer was unaffected by selenium administration (RR 0.99, 95% CI 0.69 to 1.43), as were non-melanoma skin cancer (RR 1.16, 95% CI 0.30 to 4.42; 2 studies, 2027 participants), lung cancer (RR 1.16, 95% CI 0.89 to 1.50; 2 studies, 19,009 participants), breast cancer (RR 2.04, 95% CI 0.44 to 9.55; 1 study, 802 participants), bladder cancer (RR 1.07, 95% CI 0.76 to 1.52; 2 studies, 19,009 participants), and prostate cancer (RR 1.01, 95% CI 0.90 to 1.14; 4 studies, 18,942 participants). Certainty of the evidence was high for all of these cancer sites, except for breast cancer, which was of moderate certainty owing to imprecision, and non-melanoma skin cancer, which we judged as moderate certainty owing to high heterogeneity. RCTs with low risk of bias suggested increased melanoma risk. Results for most outcomes were similar when we included all RCTs in the meta-analysis, regardless of risk of bias. Selenium supplementation did not reduce overall cancer incidence (RR 0.99, 95% CI 0.86 to 1.14; 5 studies, 21,860 participants) nor mortality (RR 0.81, 95% CI 0.49 to 1.32; 2 studies, 18,698 participants). Summary RRs for site-specific cancers showed limited changes compared with estimates from high-quality studies alone, except for liver cancer, for which results were reversed. In the largest trial, the Selenium and Vitamin E Cancer Trial, selenium supplementation increased risks of alopecia and dermatitis, and for participants with highest background selenium status, supplementation also increased risk of high-grade prostate cancer. RCTs showed a slightly increased risk of type 2 diabetes associated with supplementation. A hypothesis generated by the Nutritional Prevention of Cancer Trial - that individu

2018 - Statement on the safety of d-ribose [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Dean, Tara; Engel, Karl Heinz; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser-Berthold, Monika; Poulsen, Morten; Pöting, Annette; Sanz, Yolanda; Schlatter, Josef Rudolf; Germini, Andrea; van Loveren, Henk
abstract

In 2018, the EFSA NDA Panel adopted the Scientific Opinion on the safety of d-ribose as a novel food pursuant to Regulation (EU) 2015/2283 when used in a variety of food, concluding that d-ribose is safe for the general population at intake levels up to 36 mg/kg body weight (bw) per day, but that its safety at the intended uses and use levels as proposed by the applicant could not be established. Following a request from the European Commission, the EFSA NDA Panel was asked to carry out a supplementary safety assessment for d-ribose by considering the new proposed uses and use levels submitted by the applicant. In order to address the present mandate, an intake assessment was carried out based on individual data from the EFSA Comprehensive European Food Consumption Database. Intakes were estimated for all age groups of the general population. The resulting ranges for the mean and high-level estimated intakes of d-ribose for all the population groups, including the target population groups, did not exceed the acceptable level of intake for the general population previously defined, i.e. 36 mg/kg bw per day, except for one survey on adolescents where the mean and 95th percentile of the intake estimates were 8.6 and 39.4 mg/kg bw per day, respectively. The Panel concludes that the novel food, d-ribose, is safe under the new proposed conditions of use.

2018 - Symbiosal® and lowering of blood pressure and reduced risk of hypertension: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (J. J. ); Siani, Alfonso
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2018 - The new-old exposure to lead: assessment of food contamination and estimation of dietary intake in a Northern Italy population. [Abstract in Atti di Convegno]
Filippini, T; Malavolti, M; Cilloni, S; Violi, F; Malagoli, C; Vescovi, L; Vinceti, M.
abstract

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2018 - Traffic-related air pollution and risk of childhood leukaemia: A systematic review and dos-response meta-analysis [Abstract in Atti di Convegno]
Vinceti, M; Filippini, T
abstract

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2018 - Traffic-related air pollution and risk of childhood leukaemia: A systematic review and dose-response meta-analysis. [Abstract in Atti di Convegno]
Vinceti, M; Filippini, T
abstract

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2018 - Update of the tolerable upper intake level for vitamin D for infants [Articolo su rivista]
Turck, Dominique; Bresson, Jean-Louis; Burlingame, Barbara; Dean, Tara; Fairweather-Tait, Susan; Heinonen, Marina; Hirsch-Ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Loveren, Henk Van; Vinceti, Marco; Willatts, Peter; Fewtrell, Mary; Lamberg-Allardt, Christel; Przyrembel, Hildegard; Arcella, Davide; Dumas, Céline; Fabiani, Lucia; Martino, Laura; Tomcikova, Daniela; Neuhäuser-Berthold, Monika
abstract

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to revise the tolerable upper intake level (UL) for vitamin D for infants (≤ 1 year) set in 2012. From its literature review, the Panel concluded that the available evidence on daily vitamin D intake and the risk of adverse health outcomes (hypercalciuria, hypercalcaemia, nephrocalcinosis and abnormal growth patterns) cannot be used alone for deriving the UL for infants. The Panel conducted a meta-regression analysis of collected data, to derive a dose–response relationship between daily supplemental intake of vitamin D and mean achieved serum 25(OH)D concentrations. Considering that a serum 25(OH)D concentration of 200 nmol/L or below is unlikely to pose a risk of adverse health outcomes in infants, the Panel estimated the percentage of infants reaching a concentration above this value at different intakes of vitamin D. Based on the overall evidence, the Panel kept the UL of 25 μg/day for infants aged up to 6 months and set a UL of 35 μg/day for infants 6–12 months. The Panel was also asked to advise on the safety of the consumption of infant formulae with an increased maximum vitamin D content of 3 μg/100 kcal (Commission Delegated Regulation (EU) 2016/127 repealing Directive 2006/141/EC in 2020). For infants aged up to 4 months, the intake assessment showed that the use of infant formulae containing vitamin D at 3 μg/100 kcal may lead some infants to receive an intake above the UL of 25 μg/day from formulae alone without considering vitamin D supplemental intake. For infants aged 4–12 months, the 95th percentile of vitamin D intake (high consumers) estimated from formulae and foods fortified or not with vitamin D does not exceed the ULs, without considering vitamin D supplemental intake.

2018 - Xanthohumol in XERME®, a xanthohumol‐enriched roasted malt extract, and protection of DNA from oxidative damage: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (JJ); Siani, Alfonso
abstract

Following an application from TA-XAN AG, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to xanthohumol in XERME (R), a xanthohumol-enriched roasted malt extract, and protection of DNA from oxidative damage. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is xanthohumol in XERME (R), a xanthohumol-enriched roasted malt extract. The Panel considers that xanthohumol in XERME (R), a xanthohumol-enriched roasted malt extract, is sufficiently characterised. The claimed effect proposed by the applicant is helps to maintain the integrity of DNA and protects against oxidative damage in the cells of the body'. The Panel considers that protection of DNA from oxidative damage is a beneficial physiological effect. The only human study from which conclusions can be drawn for the scientific substantiation of the claim did not show an effect of xanthohumol in XERME (R) on the protection of DNA from oxidative damage. In the absence of evidence for an effect of xanthohumol in XERME (R) on the protection of DNA from oxidative damage, the studies provided by the applicant on the proposed mechanisms by which the food/constituent could exert the claimed effect were not considered by the Panel for the scientific substantiation of the claim. The Panel concludes that a cause and effect relationship has not been established between the consumption of xanthohumol in XERME (R), a xanthohumol-enriched roasted malt extract, and protection of DNA from oxidative damage.

2017 - 112. Bonvicini F, Fornaciari R, Casoni C, Marchesi C, Monici L, Cilloni S, Malagoli C, Greci M, Vinceti M. Epidemiologia della forma attiva e latente di tubercolosi in un gruppo di immigrati irregolari visitati presso il centro della salute per la famiglia straniera (CSFS) dell’azienda Ausl di Reggio Emilia. 50° Congresso Nazionale SItI. Torino 20-22 Novembre 2017 [Abstract in Atti di Convegno]
Bonvicini, F; Fornaciari, R; Casoni, C; Marchesi, C; Monici, L; Cilloni, S; Malagoli, C; Greci, M; Vinceti, M.
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2017 - A fixed carbohydrate: protein ratio <= 1.8 on an energy basis consumed in the context of an energy-restricted diet and reduction of body weight: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006. [Articolo su rivista]
Turck, D; Bresson, Jl; Burlingame, B; Dean, T; Fairweather Tait, S; Heinonen, M; Hirsch Ernst, Ki; Mangelsdorf, I; Mcardle, Hj; Naska, A; Neuhauser Berthold, M; Nowicka, G; Pentieva, K; Sanz, Y; Sjodin, A; Stern, M; Tome, D; Van Loveren, H; Vinceti, Marco; Willatts, P; Martin, A; Joseph, J; Siani, A.
abstract

Following an application from Marks and Spencer PLC, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the United Kingdom, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to a CHO:P ratio &lt;= 1.8 on an energy basis in the context of an energy-restricted diet and body weight. The Panel considers that the food/constituent that is the subject of the health claim is sufficiently characterised. The Panel also considers that reduction of body weight in the context of an energy-restricted diet is a beneficial physiological effect. The target population proposed by the applicant is 'adults between the ages of 18 and 70 years with excess body weight'. No conclusions could be drawn from two unpublished studies investigating the effect of ready-to-eat meals with a CHO: P ratio &lt;= 1.8 on body weight. The remaining 14 human intervention studies investigated the effect of diets targeting a CHO: P ratio &lt;= 1.8 as compared to diets targeting a CHO: P ratio &gt;= 3.0 on overweight and obese adults in the context of energy restriction. Four out of seven studies lasting &lt; 12 weeks reported an effect of a CHO: P ratio &lt;= 1.8 on body weight in overweight/obese subjects, whereas no significant effect was observed in six out of the seven studies lasting 12 weeks or more. The Panel considers that these studies do not provide evidence for a sustained effect of the food/constituent on body weight. The Panel concludes that a cause and effect relationship has not been established between the consumption of a fixed CHO: P ratio &lt;= 1.8 on an energy basis consumed in the context of an energy-restricted diet and reduction of body weight. (C) 2017 European Food Safety Authority.

2017 - A selenium species in cerebrospinal fluid predicts conversion to Alzheimer's dementia in persons with mild cognitive impairment [Articolo su rivista]
Vinceti, Marco; Chiari, Annalisa; Eichmüller, Marcel; Rothman, Kenneth J; Filippini, Tommaso; Malagoli, Carlotta; Weuve, Jennifer; Tondelli, Manuela; Zamboni, Giovanna; Nichelli, Paolo F; Michalke, Bernhard
abstract

Little is known about factors influencing progression from mild cognitive impairment to Alzheimer's dementia. A potential role of environmental chemicals and specifically of selenium, a trace element of nutritional and toxicological relevance, has been suggested. Epidemiologic studies of selenium are lacking, however, with the exception of a recent randomized trial based on an organic selenium form.

2017 - Air dispersion modelling for the evaluation of population exposure to pollutants emitted by complex areal sources. [Abstract in Atti di Convegno]
Costanzini, Sofia; Teggi, Sergio; Bigi, Alessandro; Ghermandi, Grazia; Filippini, Tommaso; Malagoli, Carlotta; Vinceti, Marco; Nannini, R.
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2017 - Assessment of selenium levels and risk factors for stroke and other cardiovascular disease: a cross sectional study in a seleniferous area of Punjab, India [Abstract in Atti di Convegno]
Chawla, R; Cilloni, S; Loomba, R; Rohit, C; Chander, D; Dhillon, Ks; Filippini, T; Vinceti, M
abstract

Background and aims: Rural areas of Punjab in India have been found to have soil rich in selenium (Se); about 2160 hectare area is seleniferous and is populated by about 10,000 inhabitants. Selenium concentrations in these villages were reported to be as high as 65 times over non-seleniferous areas. The aim of this cross-sectional study was to evaluate selenium levels in blood, hair and nails in a group of subjects living in this area, and to evaluate the correlation between selenium exposure levels and a relevant cardiovascular risk factor and blood pressure. Methods: In a random sample of rural residents in three districts of a seleniferous area of Punjab, we determined selenium concentration in hair, nail clippings and serum samples. Analyses were carried out using atomic absorption spectrophotometry at National Dairy Research Institute (NDRI), Karnal, India. Data analysis was performed using the STATA 15.0 software (STATA Corp. TX). Results: A total of 680 human subjects were recruited in this study, with a male/female ratio of 0.65 and a median age of 43 (IQR 32-52). Medium selenium levels in blood, hair and nail were 86.7 µg/l (IQR 55.9-200.3), 20.7 µg/g (IQR 12.6-40.3) and 56.9 µg/g (IQR 42.8-83.9), respectively, with lower levels in women in all three kind of samples. Concerning systolic blood pressure, Pearson’s correlation coefficients were 0.102 (95 % CI -0.025 to 0.226, p=0.116); 0.076 (95% CI -0.010 to 0.160, p=0.085); 0.072 (95% CI -0.015 to 0.157, p=0.104) with blood, hair and nail, respectively. For diastolic blood pressure, Pearson’s correlation coefficients are 0.106 (95% CI -0.022 to 0.230, p=0.104), 0.036 (95% CI -0.050 to 0.122, p=0.409), 0.049 (95% CI -0.038 to 0.135, p=0.272), respectively. Conclusions: Our findings indicate a positive correlation between selenium content in blood, hair and nails and increasing systolic and diastolic pressure levels, in line with previous epidemiologic findings, indicating a possible health concern for this highly exposed population. The possible relation between selenium over-exposure and onset of hypertension and other cardiovascular diseases deserves further investigation.

2017 - Assunzione di potassio e rischio cardiovascolare [Articolo su rivista]
Filippini, Tommaso; Salvia, Chiara; Vinceti, Marco
abstract

Il potassio è un minerale essenziale che interviene a diversi livelli nella regolazione di molti processi fisiologici. • Il potassio viene principalmente introdotto con la dieta. La dose giornaliera attualmente raccomandata per il soggetto sano è dell’ordine di 3.500 mg; tuttavia in buona parte della popolazione si riscontrano livelli di assunzione subottimali. • L’associazione tra assunzione di potassio e rischio di stroke potrebbe essere rappresentata con un andamento a U, in cui si evidenzia un effetto protettivo maggiore per livelli sovrapponibili alla dose raccomandata; per un’assunzione superiore, ci potrebbe essere addirittura un aumento di tale rischio.

2017 - Capitolo 3: Determinanti di salute e malattia [Capitolo/Saggio]
Vinceti, M; Balzarini, F; Filippini, T; Malagoli, C
abstract

2017 - Comparative methods to estimate cadmium intake in an Italian population [Abstract in Atti di Convegno]
Filippini, T; Malagoli, C; Michalke, B; Vinceti, M.
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2017 - Comparison of questionnaire exposure data to land cover map from geographical information system to assess passive exposure to pesticides: a methodological study [Abstract in Rivista]
Filippini, T; Malagoli, C; Fiore, M; Violi, F; Costanzini, S; Ledda, C; Mauceri, C; Dimartino, A; Mandrioli, J; Fini, N; Patti, F; Teggi, S; Ferrante, M; Vinceti, M
abstract

Background: Exposure assessment based on questionnaires is frequently implemented in case-control studies, but possible information and recall bias could lead to misclassification of exposure. Methods: We evaluated passive exposure to pesticides as possible environmental risk factors for amyotrophic lateral scle-rosis (ALS) using a questionnaire mailed to participants in a case-control study in Emilia Romagna and Sicily. Results from questionnaire assessment were com-pared with a remote sensing methodology based on geographical information system, i.e. the land use within a circular 100-meter area around subjects' residence. Since land cover maps were made available only about once every ten years, we used the 2003 and 2009 maps for Emilia-Romagna and Sicily, respectively. Thus, we estimated the percent-age of 'recent' total crop density close to each participant's home, setting positive exposure above 10% of land use. Finally, we calculated the agreement between the two different methodologies using Cohen‟s kappa coefficients for all subjects, cases and controls. Results and Conclusions: Cohen's kappa was 0.364 (95% CI 0.158-0.569) in total population, 0.378 (0.056-0.700) in cases and 0.354 (0.090-0.618) in controls using the most recent land use map available close to year of case diagnosis. Although a moderate-to-low agreement could be seen between two exposure methods, similar results were found in both cases and controls, suggesting that no recall bias occurred in the most recent period. In the future, we plan to compare such agreement using historical residence over the 20-30 years prior to diagnosis, in order to validate the long-term exposure to pesticides in subjects.

2017 - Condensyl® and decreases sperm DNA damage which is a risk factor for male infertility: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Panel on Dietetic Products, Efsa; Allergies, Nutrition and; Turck, Dominique; Bresson, Jean Louis; Burlingame, Barbara; Dean, Tara; Fairweather Tait, Susan; Heinonen, Marina; Hirsch Ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuh€auser Berthold, Monika; Nowicka, Gra_zyna; Pentieva, Kristina; Sanz, Yolanda; Sj€odin, Anders; Stern, Martin; Tome, Daniel; Loveren, Henk Van; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Siani, Alfonso
abstract

Following an application from Laboratoire Nurilia submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to ‘Condensyl® and decreases sperm DNA damage. High sperm DNA damage is a risk factor for male subfertility/infertility’. Condensyl® is a fixed combination of opuntia fruit dry extract, N-acetyl cysteine, zinc, nicotinamide, vitamins B2, B6, B12 and E, and folic acid. The Panel considers that Condensyl® is sufficiently characterised. The Panel assumes that the disease that is the subject of the application is male infertility and that the target population for the claim includes males wishing to increase their fertility but excludes males with clinical infertility. The Panel considers that the reduction of DNA sperm damage is a beneficial physiological effect in the context of reducing the risk of male infertility. The applicant provided four human intervention studies conducted in males with clinical infertility, from which no conclusions could be drawn for the scientific substantiation of the claim. The Panel concludes that a cause and effect relationship has not been established between the consumption of Condensyl® and reduction of DNA sperm damage in the context of reducing the risk of male infertility.

2017 - Correlation between intake and biomarker levels of cadmium and selenium in an Italian population: implications for biomonitoring studies. [Abstract in Atti di Convegno]
Malavolti, M; Filippini, T; Malagoli, C; Cilloni, S; Venturelli, M; Michalke, B; Vinceti, M.
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2017 - Correlazione tra cadmio e selenio in un campione di popolazione modenese: implicazioni per studi di biomonitoraggio [Abstract in Atti di Convegno]
Malavolti, M; Filippini, T; Malagoli, C; Cilloni, S; Venturelli, M; Michalke, B; Vinceti, M.
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2017 - Curcumin and normal functioning of joints: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Siani, Alfonso
abstract

Following an application from Suomen Terveysravinto Oy, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Finland, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to curcumin and normal functioning of joints. The food that is proposed as the subject of the health claim is curcumin. The Panel considers that curcumin is sufficiently characterised. The claimed effect proposed by the applicant is 'normal functioning of joints by reducing the biomarkers of inflammation'. The target population proposed by the applicant is the general population. Upon a request from EFSA to clarify whether the claimed effect is related to the normal function of joints or rather to the reduction of inflammation, the applicant did not address this issue in the reply. The Panel assumes that the claimed effect refers to the maintenance of joint function. The Panel considers that maintenance of joint function is a beneficial physiological effect. The Panel considers that no conclusions can be drawn from 15 human intervention studies conducted in patients with osteoarthritis or rheumatoid arthritis and from one study in obese subjects on serum cytokines for the scientific substantiation of the claim. In the absence of evidence for an effect of curcumin on the normal function of joints in humans, the results of the human studies on curcumin pharmacokinetics, safety and mechanistic studies, the animal studies and the in vitro studies submitted by the applicant cannot be used as a source of data for the scientific substantiation of the claim. The Panel concludes that a cause and effect relationship has not been established between the consumption of curcumin and maintenance of joint function. (C) 2017 European Food Safety Authority.

2017 - Determinants of serum manganese levels in an Italian population. [Articolo su rivista]
Filippini, Tommaso; Michalke, B; Grill, P; Malagoli, Carlotta; Malavolti, Marcella; Vescovi, L; Sieri, S; Krogh, V; Cherubini, A; Maffeis, G; Lucchini, R; Ferrante, M; Vinceti, Marco
abstract

Manganese (Mn) is both essential and toxic for humans, mainly depending on the total levels and its species. Main sources of exposure include food and air pollution, particularly motorized traffic. We sought to determine the potential influence of these sources on serum total levels of Mn and Mn species. We selected a random sample of municipality residents from an Italian urban municipality, from whom we collected detailed personal information, dietary habits and a blood sample for serum Mn determination. We also assessed outdoor air Mn exposure, by modeling levels of particulate matter ≤10 µm (PM10) from motorized traffic at the residence of geocoded subjects. Serum Mn species generally showed higher levels in males and positive correlation with age, while no such differences were found according to smoking habits or use of dietary supplements. Among nutrients, only iron intake showed a relation with Mn [an inverse correlation with Mn‑ferritin (Mn‑Fer) and a direct one with inorganic‑Mn (Inorg‑Mn)]. Meat consumption directly correlated and fish and seafood inversely correlated with total Mn, Mn‑transferrin (Mn‑Tf) and Mn-citrate (Mn-Cit). Fruits and vegetables, including legumes and nuts, generally showed a positive correlation with all Mn species, especially Mn‑Cit, and an inverse one with Inorg‑Mn. Odds ratios (ORs) of having serum Mn levels above median value increased with increasing PM10 tertiles, with an OR for highest‑to‑lowest tertile of 7.40 (1.36‑40.25) in multivariate analysis. Analyses for Mn species did not highlight a clear comparable pattern. In conclusion, our results seem to demonstrate that PM10 exposure positively influences total Mn serum levels, while single Mn species show conflicting results.

2017 - Dietary Reference Values for riboflavin [Articolo su rivista]
Turck, D; Bresson, Jl; Burlingame, B; Dean, T; Fairweather-Tait, S; Heinonen, M; Hirsch-Ernst, Ki; Mangelsdorf, I; Mcardle, Hj; Naska, A; Nowicka, G; Pentieva, K; Sanz, Y; Siani, A; Sjodin, A; Stern, M; Tome, D; Van Loveren, H; Vinceti, M; Willatts, P; Lamberg-Allardt, C; Przyrembel, H; Tetens, I; Dumas, C; Fabiani, L; Forss, Ac; Ioannidou, S; Neuhauser-Berthold, M
abstract

Following a request from the European Commission, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) derives dietary reference values (DRVs) for riboflavin. The Panelconsiders that the inflection point in the urinary riboflavin excretion curve in relation to riboflavin intake reflects body saturation and can be used as a biomarker of adequate riboflavin status. The Panelalso considers that erythrocyte glutathione reductase activation coefficient is a useful biomarker, but has limitations. For adults, the Panelconsiders that average requirements (ARs) and population reference intakes (PRIs) can be determined from the weighted mean of riboflavin intake associated with the inflection point in the urinary riboflavin excretion curve reported in four intervention studies. PRIs are derived for adults and children assuming a coefficient of variation of 10%, in the absence of information on the variability in the requirement and to account for the potential effect of physical activity and the methylenetetrahydrofolate reductase 677TT genotype. For adults, the AR and PRI are set at 1.3and 1.6mg/day. For infants aged 7-11months, an adequate intake of 0.4mg/day is set by upward extrapolation from the riboflavin intake of exclusively breastfed infants aged 0-6months. For children, ARs are derived by downward extrapolation from the adult AR, applying allometric scaling and growth factors and considering differences in reference body weight. For children of both sexes aged 1-17years, ARs range between 0.5 and 1.4mg/day, and PRIs between 0.6 and 1.6mg/day. For pregnant or lactating women, additional requirements are considered, to account for fetal uptake and riboflavin accretion in the placenta during pregnancy or the losses through breast milk, and PRIs of 1.9 and 2.0mg/day, respectively, are derived.

2017 - Dietary determinants of serum selenium species in Italian populations [Abstract in Rivista]
Filippini, Tommaso; Michalke, Bernhard; Salvia, Chiara; Malagoli, Carlotta; Malavolti, Marcella; Grill, Peter; Vescovi, Luciano; Sieri, Sabina; Krogh, Vittorio; Vinceti, Marco
abstract

We investigated the correlation between dietary habits with serum levels of selenium (Se) species collected from an Italian community. Consumption of food items was assessed using a food frequency questionnaire. Cereal intake showed a positive relation with total and organic Se, but null/negative with inorganic Se. Fish and seafood positively correlated with inorganic Se and negatively with organic Se. Correlations were generally negative/null in vegetables (only Se-Cys was positively correlated), while in fruits they were positive with organic species, mainly Se-Cys. Legumes showed inverse relation with overall organic Se, but positive with Se-Cys, Se-TrXr and inorganic Se. Correlation of potatoes intake was negative with Se forms, except a positive one with Se-Cys and selenate. Our results show highly specific associations between intake of selected foods and circulating Se species levels.

2017 - Dietary reference values for vitamin K [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Lamberg‐allardt, Christel; Przyrembel, Hildegard; Tetens, Inge; Dumas, Céline; Fabiani, Lucia; Ioannidou, Sofia; Neuhäuser‐berthold, Monika
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derives dietary reference values (DRVs) for vitamin K. In this Opinion, the Panel considers vitamin K to comprise both phylloquinone and menaquinones. The Panel considers that none of the biomarkers of vitamin K intake or status is suitable by itself to derive DRVs for vitamin K. Several health outcomes possibly associated with vitamin K intake were also considered but data could not be used to establish DRVs. The Panel considers that average requirements and population reference intakes for vitamin K cannot be derived for adults, infants and children, and therefore sets adequate intakes (AIs). The Panel considers that available evidence on occurrence, absorption, function and content in the body or organs of menaquinones is insufficient, and, therefore, sets AIs for phylloquinone only. Having assessed additional evidence available since 1993 in particular related to biomarkers, intake data and the factorial approach, which all are associated with considerable uncertainties, the Panel maintains the reference value proposed by the Scientific Committee for Food (SCF) in 1993. An AI of 1 mu g phylloquinone/kg body weight per day is set for all age and sex population groups. Considering the respective reference body weights, AIs for phylloquinone are set at 70 mu g/day for all adults including pregnant and lactating women, at 10 mu g/day for infants aged 7-11 months, and between 12 mu g/day for children aged 1-3 years and 65 mu g/day for children aged 15-17 years. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2017 - Dual role of selenium in health and disease [Abstract in Rivista]
Vinceti, Marco; Filippini, Tommaso; Wise, Lauren A.
abstract

The relation between selenium and the etiology of human diseases is still partially unclear, appears to have a Janus-faced nature and is influenced by the chemical form of the element. While selenium was suggested to decrease cancer risk by observational studies and a randomized controlled trial (RCT), recent large RCTs showed no effect or even adverse effects of selenium on cancer risk, suggesting that the earliest studies were affected by exposure misclassification or unmeasured confounding. RCTs also showed no influence of selenium on cardiovascular risk and an adverse effect on diabetes risk. Conversely, RCTs indicated a beneficial effect of selenium on Keshan disease, a cardiomyopathy described in low-selenium areas in China, though the etiology of this disease is still not entirely elucidated. Selenium may also be involved in the etiology of neurological disease. This dual and intriguing activity of selenium on human health shown by epidemiologic studies is mirrored by laboratory studies. Thus, there is the need of a reassessment of what constitutes a safe intake of selenium in humans.

2017 - Elevated levels of selenium species in cerebrospinal fluid of amyotrophic lateral sclerosis patients with disease-associated gene mutations. [Articolo su rivista]
Mandrioli, Jessica; Michalke, B; Solovyev, N; Grill, P; Violi, Federica; Lunetta, C; Conte, A; Sansone, Va; Sabatelli, M; Vinceti, Marco
abstract

BACKGROUND: Although an increasing role of genetic susceptibility has been recognized, the role of environmental risk factors in amyotrophic lateral sclerosis (ALS) etiology is largely uncertain; among neurotoxic chemicals, epidemiological and biological plausibility has been provided for pesticides, the heavy metal lead, the metalloid selenium, and other persistent organic pollutants. Selenium involvement in ALS has been suggested on the basis of epidemiological studies, in vitro investigations, and veterinary studies in which selenium induced a selective toxicity against motor neurons. OBJECTIVE: Hypothesizing a multistep pathogenic mechanism (genetic susceptibility and environmental exposure), we aimed to study selenium species in ALS patients carrying disease-associated gene mutations as compared to a series of hospital controls. METHODS: Using advanced analytical techniques, we determined selenium species in cerebrospinal fluid sampled at diagnosis in 9 ALS patients carrying different gene mutations (C9ORF72, SOD1, FUS, TARDBP, ATXN2, and TUBA4A) compared to 42 controls. RESULTS: In a patient with the tubulin-related TUBA4A mutation, we found highly elevated levels (in μg/L) of glutathione-peroxidase-bound selenium (32.8 vs. 1.0) as well as increased levels of selenoprotein-P-bound selenium (2.4 vs. 0.8), selenite (1.8 vs. 0.1), and selenate (0.9 vs. 0.1). In the remaining ALS patients, we detected elevated selenomethionine-bound selenium levels (0.38 vs. 0.06). CONCLUSIONS: Selenium compounds can impair tubulin synthesis and the cytoskeleton structure, as do tubulin-related gene mutations. The elevated selenium species levels in the TUBA4A patient may have a genetic etiology and/or represent a pathogenic pathway through which this mutation favors disease onset, though unmeasured confounding cannot be excluded. The elevated selenomethionine levels in the other patients are also of interest due to the toxicity of this nonphysiological selenium species. Our study is the first to assess selenium exposure in genetic ALS, suggesting an interaction between this environmental factor and genetics in triggering disease onset.

2017 - Environmental and occupational exposure to heavy metals and metalloid and development of amyotrophic lateral sclerosis: a population-based case control study in Emilia-Romagna and Sicily. [Abstract in Atti di Convegno]
Violi, F; Filippini, T; Malagoli, C; Fiore, M; Ledda, C; Mauceri, C; Dimartino, A; Mandrioli, J; Fini, N; Patti, F; Ferrante, M; Vinceti, M.
abstract

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2017 - Environmental metal contamination and health impact assessment in two industrial regions of Romania [Articolo su rivista]
Nedelescu, Mirela; Baconi, Baconi; Neagoe, Aurora; Iordache, Virgil; Stan, Miriana; Constantinescu, Paula; Ciobanu, Anne Marie; Vardavas, Alexander I; Vinceti, Marco; Tsatsakis, Aristidis M.
abstract

.We investigated two Romanian industrial regions- Copşa Mică and Zlatna, to assess the current situation of soil pollution and bioaccumulation of Pb, Cd, Cu and Zn in different vegetable species and possible risks to consumers. Both total and mobile forms of the metals were determined in soil samples, and metal content in the edible parts of root vegetable samples was also assessed. The concentrations of Pb and Zn in soil were higher in Copşa Mică than in Zlatna (566mg/kg vs 271mg/kg for Pb and 1143mg/kg vs 368mg/kg for Zn)·The metal mobility in soil from Copsa Mica decreases in the order Zn&gt;Cu&gt;Cd&gt;Pb (1.88mg/kg, 0.40mg/kg, 0.22mg/kg, 0.16mg/kg, respectively), while in Zlatna, the order was Cu&gt;Zn&gt;Pb&gt;Cd (0.88mg/kg, 0.29mg/kg, 0.04mg/kg, 0.01mg/kg, respectively), apparently depending on metal and soil conditions. In Copsa Mica, the amount of Pb and Cd in vegetable samples exceeded the maximum permissible limits in carrots (median concentration 0.32mg/kg for Pb and Cd) and in yellow onions (median concentration 0.24mg/kg for Cd). In Zlatna region, the content of Cd exceeded the maximum limits in yellow onions (median concentration 0.11mg/kg). The amount of Pb was higher than the maximum acceptable level in carrots from the Zlatna region (median concentration 0.12mg/kg). Cu and Zn levels were within the normal range in all vegetable samples. In the Zlatna region, the transfer factors for Pb and Cd were higher in carrots (median values of 9.9 for Pb and 21.0 for Cd) compared to carrots harvested in Copsa Mica (median values of 4.0 for Pb and 2.0 for Cd). Daily intake rates of metals through local vegetable consumption exceeded the limit values established by the European Food Safety Authority for Pb (1.2 to 2.4 times) and Cd (5.5 to 9.1 times) in both regions, with potential adverse health effects for the local population. The results highlight the need for total soil remediation action before fruit and vegetables produced in these polluted areas can be safely consumed.

2017 - Fattori di rischio ambientali e occupazionali per la sclerosi laterale amiotrofica: uno studio caso-controllo di popolazione in Emilia Romagna e Sicilia [Abstract in Atti di Convegno]
Violi, F; Filippini, T; Malagoli, C; Fiore, M; Ledda, C; Mauceri, Mc; Dimartino, A; Mandrioli, J; Fini, N; Patti, F; Ferrante, M; Vinceti, M.
abstract

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2017 - Fattori di rischio ambientali e occupazionali per la sclerosi laterale amiotrofica: uno studio caso-controllo di popolazione in Emilia Romagna e Sicilia. [Abstract in Atti di Convegno]
Filippini, T; Fiore, M; Violi, F; Malagoli, C; Ledda, C; Mauceri, C; Dimartino, A; Mandrioli, J; Fini, N; Patti, F; Ferrante, M; Vinceti, M.
abstract

Introduzione La Sclerosi Laterale Amiotrofica (SLA) è una malattia neurodegenerativa che colpisce sia i motoneuroni inferiori del tronco encefalico e del midollo spinale, sia i motoneuroni superiori della corteccia motoria. La perdita di questi neuroni conduce ad atrofia e debolezza muscolare, fascicolazioni e spasticità. Ad eccezione di alcune forme genetiche, l’eziologia rimane tutt’ora ignota. Obiettivi Abbiamo realizzato uno studio caso-controllo di popolazione in due province emiliane (Modena, Reggio Emilia) e in una provincia siciliana (Catania), al fine di valutare il ruolo di alcuni fattori ambientali e occupazionali sul rischio di SLA. Metodi Al fine di identificare tutti i casi incidenti di SLA diagnosticati nel periodo 2008-2011 nelle tre province in studio sono stati utilizzati i dati provenienti dal Registro SLA della Regione Emilia-Romagna integrato con i flussi informativi degli archivi della banca dati SDO, delle prescrizioni farmacologiche e delle schede di morte. I controlli sono stati estratti con procedura casuale dalla popolazione generale mediante gli archivi degli assistiti AUSL. A ciascun paziente (o alle loro famiglie nel caso di decesso) ed ai relativi controlli è stato inviato per via postale un questionario che prevedeva la raccolta di informazioni personali, cliniche e generali. Risultati In totale sono stati raccolti 162 questionari (61 casi e 101 controlli, tasso di risposta medio di 18,5%). I risultati ottenuti dall’analisi dei questionari mostrano un aumentato rischio per aver svolto attività lavorativa in ambito agricolo (odds ratio- OR = 2.44 (intervallo di confidenza – IC 95% 1.02-5.79), per chi avesse svolto attività lavorativa da saldatore OR = 1.25 (IC 95% 0.27-5.80). In riferimento alla storia occupazionale, abbiamo evidenziato un aumentato rischio derivante da esposizione a metalli pesanti, tra cui piombo (OR=3.40, IC 95% 1.40-8.56) e mercurio (OR=6.86, IC 95% 0.75-62.88), e pesticidi, tra cui insetticidi (OR=1.61, IC 95% 0.77-3.34), erbicidi (OR=1.89, IC 95% 0.75-4.77) e fungicidi (OR=1.93, IC 95% 0.70-5.30). Conclusioni Sebbene tali risultati debbano essere considerati con cautela per l’eventualità della presenza di bias di selezione e di informazione, tuttavia suggeriscono un potenziale ruolo eziologico nello sviluppo della forma sporadica di SLA di due categorie di sostanze dal potenziale neurotossico come metalli pesanti e pesticidi

2017 - Fattori di rischio ambientali e sclerosi laterale amiotrofica: studio caso-controllo in provincia di Novara [Abstract in Atti di Convegno]
Tesauro, M; Filippini, T; Consonni, M; Fontana, A; Mazzini, L; Gagliardi, I; Pisano, F; Chiò, A; Vinceti, M
abstract

La Sclerosi Laterale Amiotrofica (SLA) è una malattia neurodegenerativa a decorso progressivo. Ad eccezione di alcune forme genetiche (mutazioni dei geni SOD1, C9orf72, FUS/TLS e TARDBP), l’eziologia rimane ignota e si ipotizza che la SLA sia una malattia multifattoriale dove fattori genetici predisponenti interagiscano con fattori ambientali, quali metalli, solventi, pesticidi e campi elettromagnetici e/o esposizioni professionali (saldatore, elettricista e agricoltore). Obiettivo di questo studio è valutare il ruolo di alcuni fattori ambientali e occupazionali sul rischio di SLA nella provincia di Novara. Nell’ambito di un disegno di studio caso-controllo sono stati identificati i nuovi casi di SLA diagnosticati tra il 2002 ed il 2012 tra i residenti nella provincia di Novara utilizzando le Schede di Dimissione Ospedaliere dei reparti di Neurologia della provincia di Novara, le schede di morte e il Registro Piemontese di SLA. I controlli sono stati selezionati in modo casuale dall’anagrafe sanitaria dell’ASL di Novara. Un questionario realizzato ad hoc per la valutazione di fattori di rischio ambientali e occupazionali è stato somministrato direttamente (o tramite i familiari) ai casi, mentre i controlli hanno ricevuto il questionario per via postale. Tramite regressione logistica non condizionata, aggiustata per età e sesso, è stato calcolato l’odds ratio (OR) con intervallo di confidenza (IC) al 95% senza cutpoints fissi di significatività. In totale sono stati raccolti 68 questionari (34 casi e 34 controlli). Le attività lavorative o esposizioni associate ad un incremento del rischio di SLA sono state: lavoro agricolo (OR 9,32; IC 95% 1,02-85,23 ; P=0,048), attività di saldatore (OR 5,89; IC 95% 0,57-60,81; P=0,136), esposizione professionale a piombo (OR 4,43; IC 95% 0,88-22,29; P=0,071) e solventi (OR 4,11; IC 95% 1,29-13,05; P=0,016), shock elettrici (OR 4,70; IC 95% 0,44-50,28; P=0,200), residenza vicino a linee elettriche a alta tensione (OR 3,28; IC 95% 0,85-12,68; P=0,085) e residenza vicino a specchi d’acqua (OR 3,09; IC 95% 0,92-10,33; P=0,067). I risultati dello studio mostrano un incremento di rischio in associazione ad alcuni fattori ambientali e occupazionali, ma a causa della limitata numerosità, non sono in grado di confermarne il ruolo eziopatogenetico nella SLA.

2017 - Glycaemic index, glycaemic load and risk of cutaneous melanoma in a population-based, case-control study [Articolo su rivista]
Malavolti, Marcella; Malagoli, Carlotta; Crespi, Cm; Brighenti, F; Agnoli, C; Sieri, S; Krogh, V; Fiorentini, Chiara; Farnetani, Francesca; Longo, Caterina; Ricci, C; Albertini, G; Lanzoni, A; Veneziano, L; Virgili, A; Pagliarello, C; Feliciani, C; Fanti, Pa; Dika, E; Pellacani, Giovanni; Vinceti, Marco
abstract

Glycaemic index (GI) and glycaemic load (GL) are indicators of dietary carbohydrate quantity and quality and have been associated with increased risk of certain cancers and type 2 diabetes. Insulin resistance has been associated with increased melanoma risk. However, GI and GL have not been investigated for melanoma. We present the first study to examine the possible association of GI and GL with melanoma risk. We carried out a population-based, case-control study involving 380 incident cases of cutaneous melanoma and 719 age- and sex-matched controls in a northern Italian region. Dietary GI and GL were computed for each subject using data from a self-administered, semi-quantitative food frequency questionnaire. We computed the odds ratio (OR) for melanoma according to quintiles of distribution of GL and GL among controls. A direct association between melanoma risk and GL emerged in females (OR 2·38; 95 % CI 1·25, 4·52 for the highest v. the lowest quintile of GL score, P for trend 0·070) but not in males. The association in females persisted in the multivariable analysis after adjusting for several potential confounders. There was no evidence of an association between GI and melanoma risk. GL might be associated with melanoma risk in females.

2017 - Health Risk Assessment per esposizione occupazionale a sostanze chimiche cancerogene e non cancerogene nel riciclo di rifiuti di apparecchiature elettriche e elettroniche (RAEE): dati dal progetto WeeenModels. [Abstract in Atti di Convegno]
Modenese, A; Ferrari, Am; Gamberini, R; Grasselli, L; Neri, P; Pini, M; Rimini, B; Vinceti, M; Violi, F; Gobba, F.
abstract

Health Risk Assessment per esposizione occupazionale a sostanze chimiche cancerogene e non cancerogene nel riciclo di rifiuti di apparecchiature elettriche e elettroniche (RAEE): dati dal progetto WeeenModels.

2017 - Health risk assessment of environmental selenium: Emerging evidence and challenges (Review) [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Cilloni, Silvia; Bargellini, Annalisa; Vergoni, Anna Valeria; Tsatsakis, A; Ferrante, M.
abstract

New data have been accumulated in the scientific literature in recent years which allow a more adequate risk assessment of selenium with reference to human health. This new evidence comes from environmental studies, carried out in populations characterized by abnormally high or low selenium intakes, and from high-quality and large randomized controlled trials with selenium recently carried out in the US and in other countries. These trials have consistently shown no beneficial effect on cancer and cardiovascular risk, and have yielded indications of unexpected toxic effects of selenium exposure. Overall, these studies indicate that the minimal amount of environmental selenium which is source of risk to human health is much lower than anticipated on the basis of older studies, since toxic effects were shown at levels of intake as low as around 260 µg/day for organic selenium and around 16 µg/day for inorganic selenium. Conversely, populations with average selenium intake of less than 13-19 µg/day appear to be at risk of a severe cardiomyopathy, Keshan disease. Overall, there is the need to reconsider the selenium standards for dietary intake, drinking water, outdoor and indoor air levels, taking into account the recently discovered adverse health effects of low-dose selenium overexposure, and carefully assessing the significance of selenium-induced proteomic changes.

2017 - Implications of different methods for literature searching and assessment in systematic reviews and meta-analyses: A case study. [Abstract in Rivista]
Vinceti, Marco; Filippini, Tommaso; Cilloni, Silvia; Platt, J; Jess, C.
abstract

Implications of different methods for literature searching and assessment in systematic reviews and meta-analyses: A case study.

2017 - Incidence of amyotrophic lateral sclerosis in the province of Novara, Italy, and possible role of environmental pollution. [Articolo su rivista]
Tesauro, M; Consonni, M; Filippini, Tommaso; Mazzini, L; Pisano, F; Chiò, A; Esposito, A; Vinceti, Marco
abstract

OBJECTIVE AND METHODS: Based on nationwide death certificates, a cluster of amyotrophic lateral sclerosis (ALS) has been reported in the area of Briga (Novara province, northern Italy), known for its severe environmental contamination. We further investigated this finding, by following up with the collection of recent incidence ALS data in 2002-2012 of Novara province, also to assess the possible long-term effects of environmental pollution in that area. RESULTS: In the whole Novara province we identified 106 ALS cases, of which 35 were from the Briga area. Incidence rates of Novara province were 3.98, 5.14 and 2.97 for the total population, males and females, respectively, compared with the Briga area where they were 4.65, 4.27 and 4.98, respectively. The ratio of observed-to-expected ALS cases in the Briga area, using incidence of the rest of Novara province as a reference, was 1.17 (95% CI 0.81-1.62), with a value of 0.83 (95% CI 0.47-1.37) in males and 1.68 (95% CI 1.03-2.60) in females. CONCLUSIONS: Overall, our study did not confirm previous findings of an excess ALS incidence in an area characterised by severe environmental heavy metal pollution, and it suggests the need to interpret with caution clusters identified through mortality data.

2017 - Inorganic selenium exposure in drinking water and cancer incidence: a natural experiment [Abstract in Atti di Convegno]
Vinceti, M; Malagoli, C; Malavolti, M; Filippini, T; Cilloni, S; Wisen, L; Sacchettini, C; Vicentini, M; Ballotari, Paola; Giorgi Rossi, P.
abstract

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2017 - Intake of Mediterranean foods [Capitolo/Saggio]
Siotos, Charalampos; Vinceti, Marco; Naska, Androniki
abstract

The traditional Mediterranean diet is characterized by: (a) high consumption of cereals, vegetables, fruit, nuts, legumes, fish, and seafood; (b) the use of olive oil as the main, if not the only, added lipid; (c) moderate consumption of milk and dairy products; (d) moderate intake of alcohol, in the form of wine and preferably during meals; and (e) low consumption of meat and meat products. The prevalent consumption of olive oil and the low consumption of animal products are reflected in the high ratio of monounsaturated to saturated fat intake, typical of the dietary pattern in the region. There is increasing evidence from observational and experimental epidemiological studies, further enriched by the conclusions of their systematic reviews and meta-analyses, that adherence to the Mediterranean dietary pattern promotes health and reduces the risk of premature death from chronic degenerative diseases. Mediterranean countries and especially the European ones have experienced a “westernization” process of their food habits, and have increased the per capita supply of non-Mediterranean foods (animal fats, vegetable oils other than olive oil, sugar, and meat) and decreased the supply of legumes and alcoholic beverages, including wine. The evidence that Mediterraneans are gradually departing from their traditional eating habits does not only refer to the adult population in the region, but it has also been reproduced in large-scale nutritional surveys among children, adolescents, and young adults – the trend-setters for future generations. Next to the effect on people’s health, the gradual abandoning of the traditional Mediterranean diet cannot support sustainable development in the way the Mediterranean diet does. Being adjusted to the cultural, climatic, and other environmental characteristics of the region, the Mediterranean diet is protective and helpful to biodiversity, accessible and economically affordable, and contributes to food and nutrition security.

2017 - Lactobacillus fermentum CECT 5716 and a reduction of the Staphylococcus load in breast milk which reduces the risk of infectious mastitis: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Siani, Alfonso
abstract

Following an application from Biosearch Life, submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No1924/2006 via the Competent Authority of France, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Lactobacillusfermentum CECT 5716 and decreases the Staphylococcus load in breast milk. High Staphylococcus load in breast milk is a risk factor for infectious mastitis. The scope of the application was proposed to fall under a health claim referring to disease risk reduction. The Panelconsiders that Lactobacillusfermentum CECT 5716 is sufficiently characterised. In the context of this application, the Staphylococcus load in breast milk can be considered a risk factor for the development of infectious mastitis, as long as evidence is provided that the consumption of Lactobacillusfermentum CECT 5716 reduces the Staphylococcus load in breast milk as well as the incidence of infectious mastitis. Three human intervention studies investigated the effect of Lactobacillus fermentum CECT 5716 on the Staphylococcus load of breast milk in lactating women. One of these studies was conducted in lactating women free of infectious mastitis at baseline. The Panelconsiders that no conclusions can be drawn from this study for the scientific substantiation of the claim owing to important methodological limitations. The other two studies were conducted in lactating women with infectious mastitis and, therefore, the effect of the intervention on the incidence of infectious mastitis cannot be assessed. The Panelconcludes that a cause and effect relationship has not been established between the consumption of Lactobacillusfermentum CECT 5716 and a reduction of the Staphylococcus load in breast milk which reduces the risk of infectious mastitis.

2017 - Lead, cadmium and mercury in cerebrospinal fluid and risk of amyotrophic lateral sclerosis: A case-control study [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Mandrioli, Jessica; Violi, Federica; Bargellini, Annalisa; Weuve, Jennifer; Fini, Nicola; Grill, Peter; Michalke, Bernhard
abstract

Exposure to neurotoxic chemicals such as pesticides, selenium, and heavy metals have been suggested toplay a role in the etiology of amyotrophic lateral sclerosis (ALS). We assessed exposure to lead, cadmium,and mercury in 38 ALS patients (16 men and 22 females) and 38 hospital-admitted controls by using theircerebrospinal fluid (CSF) content as biomarker. We determined CSF heavy metal levels with inductivelycoupled plasma sector field mass spectrometry, according to a methodology specifically developed forthis biological matrix. ALS patients had higher median values for Pb (155 vs. 132 ng/L) but lower levelsfor Cd (36 vs. 72 ng/L) and Hg (196 vs. 217 ng/L). In the highest tertile of exposure, ALS odds ratio was1.39 (95% CI 0.48–4.25) for Pb, 0.29 (0.08–1.04) for Cd and 3.03 (0.52–17.55) for Hg; however, no dose-response relation emerged. Results were substantially confirmed after conducting various sensitivityanalyses, and after stratification for age and sex. Though interpretation of these results is limited by thestatistical imprecision of the estimates, and by the possibility that CSF heavy metal content may notreflect long-term antecedent exposure, they do not lend support to a role of the heavy metals cadmium,lead and mercury in ALS etiology.

2017 - Magnetic fields exposure from high-voltage power lines and risk of amyotrophic lateral sclerosis in two Italian populations [Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; Fabbi, Sara; Kheifets, Leeka; Violi, Federica; Poli, Maurizio; Caldara, Salvatore; Sesti, Daniela; Violanti, Silvia; Zanichelli, Paolo; Notari, Barbara; Fava, Roberto; Arena, Alessia; Calzolari, Roberta; Filippini, Tommaso; Iacuzio, Laura; Arcolin, Elisa; Mandrioli, Jessica; Fini, Nicola; Odone, Anna; Signorelli, Carlo; Patti, Francesco; Zappia, Mario; Pietrini, Vladimiro; Oleari, Paola; Teggi, Sergio; Ghermandi, Grazia; Dimartino, Angela; Ledda, Caterina; Mauceri, Cristina; Sciacca, Salvatore; Fiore, Maria; Ferrante, Margherita
abstract

The aetiology of amyotrophic lateral sclerosis (ALS), a rare and extremely severe neurodegenerative disease, has been associated with magnetic fields exposure. However, evidence for such a relation in the general population is weak, although the previous null results might also be due to exposure misclassification, or a relationship might exist only for selected subgroups. To test such a hypothesis we carried out a population-based case-control study in two Northern and Southern Italy regions, including 703 ALS cases newly diagnosed from 1998 to 2011 and 2737 controls randomly selected from the residents in the study provinces. Overall, we found that a residence near high-voltage power lines, within the corridors yielding a magnetic fields of 0.1 lT, was not associated with an excess disease risk, nor did we identify a dose-response relationship after splitting the exposed corridor according to the 0.1, 0.2 and 0.4 lT cut-points of exposure. These results were confirmed taking into account age at onset, period of diagnosis, sex, geographical area, and length of exposure. Overall, despite the residual possibility of unmeasured confounding or small susceptible subgroups not identified in our study, these results appear to confirm that the exposure to magnetic fields from power lines occurring in the general population is not associated with increased ALS risk.

2017 - Methods to assess cadmium intake in biomonitoring surveys [Abstract in Atti di Convegno]
Filippini, T; Michalke, B; Malagoli, C; Vinceti, M.
abstract

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2017 - Metodologie per la valutazione dell’intake del cadmio a partire da studi di biomonitoraggio. [Abstract in Atti di Convegno]
Filippini, T; Malagoli, C; Michalke, B; Vinceti, M.
abstract

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2017 - Percutaneous endoscopic gastrostomy, body weight loss and survival in amyotrophic lateral sclerosis: a population-based registry study [Articolo su rivista]
Fasano, Antonio; Fini, Nicola; Ferraro, Diana; Ferri, Laura; Vinceti, Marco; Errals, ; Mandrioli, Jessica
abstract

Abstract Objective: To assess the role of percutaneous endoscopic gastrostomy (PEG) insertion, and its timing, on ALS survival, and to study prognostic factors of survival before and after PEG placement in a population-based setting. Methods: In this observational population-based, registry study, we enrolled patients with newly- diagnosed ALS, according to the El Escorial revised criteria, who were resident in the Emilia Romagna Region, and who developed severe dysphagia needing enteral nutritional support. The primary outcome measure was tracheostomy-free survival after PEG recommendation. Results: There were 210 patients needing PEG, out of an incident cohort of 545 patients from the Emilia Romagna Registry for ALS, who were diagnosed between 2009 and 2013. One hundred and ninety-three patients were included in the study, and 17 were excluded because they were already tracheostomized at the time of PEG placement. Of the 193 patients included in the study, 152 underwent PEG, whereas 41 did not undergo the procedure. Patients who did not undergo PEG, among the eligible ones, had the same tracheostomy-free survival from onset as patients who did (25 vs. 32 months, p¼0.21). Tracheostomy-free survival from PEG recommendation was greater in patients who underwent PEG placement than in patients who did not (6 vs. 2 months, p¼0.008). Median tracheostomy-free survival from PEG insertion was eight months (95% CI5–12); 30 days after PEG placement, survival was 89.60%. At Cox multivariable analysis, the hazard of death or tracheostomy after PEG insertion was significantly influenced by the difference between BMI at the time of the PEG procedure and BMI at diagnosis (HR 1.05, 95% CI 1.02–1.08; p¼0.002). The hazard of death or tracheostomy was not affected by the timing of PEG insertion. Conclusions: The present study, although it has some limitations, suggests a gain of tracheostomy-free survival from the time of PEG recommendation for patients who undergo PEG placement, and, among patients who undergo PEG, a greater survival if PEG is inserted before a significant weight loss occurs, and if nutritional support avoids further weight loss. Should this association between prevention of weight loss and better clinical outcome be confirmed by further studies, it would have important implications for disease management.

2017 - Pesticide exposure assessed through agricultural crop proximity and risk of amyotrophic lateral sclerosis [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Violi, Federica; Rothman, Kenneth J.; Costanzini, Sofia; Malagoli, Carlotta; Wise, Lauren A.; Odone, Anna; Signorelli, Carlo; Iacuzio, Laura; Arcolin, Elisa; Mandrioli, Jessica; Fini, Nicola; Patti, Francesco; Fermo, Salvatore Lo; Pietrini, Vladimiro; Teggi, Sergio; Ghermandi, Grazia; Scillieri, Renato; Ledda, Caterina; Mauceri, Cristina; Sciacca, Salvatore; Fiore, Maria; Ferrante, Margherita
abstract

Background: Epidemiologic studies have raised the possibility that some pesticide compounds induce the neurodegenerative disease amyotrophic lateral sclerosis (ALS), though the available evidence is not entirely consistent. Methods: We conducted a population-based case-control study in two Italian populations to assess the extent to which residence in the vicinity of agricultural crops associated with the application of neurotoxic pesticides is a risk factor for ALS, using crop acreage in proximity to the residence as an index of exposure. Results: Based on 703 cases and 2737 controls, we computed an ALS odds ratio of 0.92 (95% confidence interval 0.78-1.09) for those in proximity to agricultural land. Results were not substantially different when using alternative exposure categories or when analyzing specific crop types, with the exception of a higher risk related to exposure to citrus orchards and olive groves in Southern Italy, though based on few exposed subjects (N = 89 and 8, respectively). There was little evidence of any dose-response relation between crop proximity and ALS risk, and using long-term residence instead of current residence did not substantially change our estimates. Conclusions: Though our index of exposure is indirect and subject to considerable misclassification, our results offer little support for the hypothesis that neurotoxic pesticide exposure increases ALS risk.

2017 - Pesticides, polychlorinated biphenyls and polycyclic aromatic hydrocarbons in cerebrospinal fluid of amyotrophic lateral sclerosis patients: a case-control study. [Articolo su rivista]
Vinceti, Marco; Violi, Federica; Tzatzarakis, M; Mandrioli, J; Malagoli, Carlotta; Hatch, Ee; Fini, N; Fasano, Antonio; Rakitskii, Vn; Kalantzi, Oi; Tsatsakis, A.
abstract

Neurotoxic chemicals including several pesticides have been suggested to play a role in the etiology of amyotrophic lateral sclerosis (ALS). We investigated the relation between organochlorine pesticides and their metabolites (OCPs), polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) in the etiology of sporadic ALS, determining for the first time their levels in cerebrospinal fluid as indicator of antecedent exposure. We recruited 38 ALS patients and 38 controls referred to an Italian clinical center for ALS care, who underwent a lumbar puncture for diagnostic purposes between 1994-2013, and had 1mL of cerebrospinal fluid available for the determination of OCPs, PCBs and PAHs. Many chemicals were undetectable in both case and control CSF samples, and we found little evidence of any increased disease risk according to higher levels of exposure. Among males &gt;60 years, we found a slight but statistically very unstable increased ALS risk with higher levels of the congener PCB 28 and the OCP metabolite p,p'-DDE. Overall, these results do not suggest an involvement of the neurotoxic chemicals investigated in this study in disease etiology, although small numbers limited the precision of our results.

2017 - Redox speciation of iron, manganese, and copper in cerebrospinal fluid by strong cation exchange chromatography e sector field inductively coupled plasma mass spectrometry. [Articolo su rivista]
Solovyev, N; Vinceti, Marco; Grill, P; Mandrioli, Jessica; Michalke, B.
abstract

Abstract A new method of simultaneous redox speciation of iron (II/III), manganese (II/III), and copper (I/II) in cerebrospinal fluid (CSF) has been designed. For the separation of redox species strong cation exchange chromatography (SCX) with isocratic elution was employed. Species were detected using inductively coupled plasma sector field mass spectrometry (ICP-sf-MS), operating at medium resolution. The following parameters were optimized: analytical column, eluent composition and pH, CSF injection volume and dilution factor. Analytical column Dionex IonPac CS5A RFIC 4*250 mm was found to retain and separate species of interest the most effectively under the isocratic elution with a buffer, containing 50 mM ammonium citrate, 7.0 mM pyridine-2,6-dicarboxylic acid at pH = 4.2 and flow rate of 0.8 L min−1. Injection volume of 50 μL with CSF sample dilution of 1/3 (v/v) with the eluent was shown to result in minimal matrix suppression. For species identification, retention time matching with standards was used. The stability of metalloproteins (ferritin, transferrin, and ceruloplasmin) under elution conditions was evaluated. For the quantification of redox species, external calibration was employed. To avoid column contamination, a blank was run after measurement and all quantification values were blank subtracted. For recovery checks, species quantification data was verified against total content of an element, measured by dynamic reaction cell ICP-MS. Recoveries (sum of quantified species vs. total element determinations) were 82.5 ± 22% (Mn), 92 ± 11% (Fe), and 88.7 ± 12% (Cu). The method was tested using 38 real CSF samples. Limits of detection (3σ) for the CSF samples were 0.5 μg L−1, 0.6 μg L−1, and 0.8 μg L−1 for Fe, Mn, and Cu species, respectively. Retention time precision was 1–7.5% (as RSD), whereas peak area RSDs were in the range 5–11%, both depending on the species.

2017 - Safety of 1-methylnicotinamide chloride (1-MNA) as a novel food pursuant to Regulation (EC) No258/97 [Articolo su rivista]
Turck, D; Bresson, Jl; Burlingame, B; Dean, T; Fairweather-Tait, S; Heinonen, M; Hirsch-Ernst, Ki; Mangelsdorf, I; Mcardle, Hj; Naska, A; Neuhauser-Berthold, M; Nowicka, G; Pentieva, K; Sanz, Y; Siani, A; Sjodin, A; Stern, M; Tome, D; Vinceti, Marco; M, Willatts; P, ; Engel, Kh; Marchelli, R; Poting, A; Poulsen, M; Schlatter, Jr; Gelbmann, W; Ververis, E; van Loveren, H
abstract

Following a request from the European Commission, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on 1-methylnicotinamide chloride (1-MNA) as a novel food (NF) ingredient submitted pursuant to Regulation (EC) No258/97 of the European Parliament and of the Council, taking into account the comments and objections of a scientific nature raised by Member States. 1-MNA is a substance present naturally in the human body as a normal downstream product of niacin metabolism. The Panelconsiders that the information provided on the composition, the specification and the batch-to-batch variability of the NF is sufficient. The applicant intends to use 1-MNA in food supplements and proposes a maximum intake of 58mg/day. 1-MNA is not genotoxic. In a subchronic rat study, epithelium degeneration of the non-glandular stomach was observed at all dose levels with increasing frequency. The Panelnotes that the human stomach does not have non-glandular epithelium and considers this finding is toxicologically not relevant for humans. At doses of 500 and 1,000mg/kg body weight (bw), changes of the urine pH, that did not reverse in the recovery period, were reported. As adversity of this finding cannot be ruled out, the Panelselected 250mg/kg bw in this rat study as the reference point. The Margin of Exposure to humans weighing 70kg and consuming 58mg would be about 300. The Panelnotes the upper level for nicotinamide, i.e. 900mg/day for adults. Taking into account that 1-MNA is a main metabolite from nicotinamide, the Panelconsiders that it is unlikely that an intake of 58mg 1-MNA from food supplements would result in adverse health outcomes in humans. The Panelconcludes that the NF, 1-MNA, is safe under the proposed uses and use levels. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2017 - Safety of Ecklonia cava phlorotannins as a novel food pursuant to Regulation (EC) No 258/97 [Articolo su rivista]
Turck, D; Bresson, Jl; Burlingame, B; Dean, T; Fairweather-Tait, S; Heinonen, M; Hirsch-Ernst, Ki; Mangelsdorf, I; Mcardle, Hj; Naska, A; Neuhauser-Berthold, M; Nowicka, G; Pentieva, K; Sanz, Y; Siani, A; Sjodin, A; Stern, M; Tome, D; Vinceti, M; Willatts, P; Engel, Kh; Marchelli, R; Poting, A; Poulsen, M; Schlatter, Jr; Ackerl, R; van Loveren, H
abstract

Following a request from the European Commission, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on the safety of Ecklonia cava phlorotannins (marketed as SeaPolynol) as a novel food submitted pursuant to Regulation (EC) No258/97. The novel food is a phlorotannin-rich alcohol extract of Ecklonia cava, which is an edible marine brown alga species. The information provided on the composition, the specifications, the production process and the batch-to-batch variability of the novel food is sufficient and does not raise safety concerns. The intention is to market the novel food as a food supplement for healthy individuals over the age of 12years. A subchronic repeated dose oral toxicity study in rodents tested the novel food at daily doses of 0, 375, 750 and 1,500mg/kg body weight (bw). The Panelconsiders the mid-dose as the no-observed-adverse-effect-level (NOAEL) of the study. Taking into account this NOAEL of 750mg/kg bw per day and by applying an uncertainty factor of 200, the Panelconsiders an intake level of 3.75mg/kg bw per day as safe. The Panelconcludes that the novel food, Ecklonia cava phlorotannins, is safe for the use in food supplements at a maximum daily intake level of 163mg/day for adolescents from 12 to 14years of age, 230mg/day for adolescents above 14years of age and 263mg/day for adults. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2017 - Safety of alginate‐konjac‐xanthan polysaccharide complex (PGX) as a novel food pursuant to Regulation (EC) No 258/97 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl‐heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef Rudolf; Turla, Emanuela; Van Loveren, Henk
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on alginate-konjac- xanthan polysaccharide complex (PGX) as a novel food (NF) submitted pursuant to Regulation (EC) No 258/97. The NF is an off-white granular powder composed of three non- starch polysaccharides: konjac glucomannan, xanthan gum and sodium alginate. The information provided on the composition, the specifications, the batch-to-batch variability and the stability of the NF is sufficient and does not raise safety concerns. The production process is sufficiently described and does not raise concerns about the safety of the NF. The applicant intends to add the NF to a variety of foods as well as to market the NF in capsules. The recommended maximum daily intake of the NF from fortified foods and food supplements is 15 g. The target population proposed by the applicant is adults from 18 to 64 years of age. Considering the no observed adverse effect level of 1.8 g/kg body weight (bw) per day in a subchronic toxicity study with PGX and the highest mean and 95th percentile anticipated daily intake of NF from fortified foods, the margin of exposure (MoE) is 12 and 6, respectively, whereas the MoE for the NF from food supplements is 9. The Panel concludes that the safety of the novel food, PGX, for the intended uses and use levels as proposed by the applicant, has not been established. (C) 2017 European Food Safety Authority.

2017 - Safety of betaine as a novel food pursuant to Regulation (EC) No 258/97 [Articolo su rivista]
Turck, D; Bresson, Jl; Burlingame, B; Dean, T; Fairweather-Tait, S; Heinonen, M; Hirsch-Ernst, Ki; Mangelsdorf, I; Mcardle, Hj; Naska, A; Neuhauser-Berthold, M; Nowicka, G; Pentieva, K; Sanz, Y; Siani, A; Sjodin, A; Stern, M; Tome, D; Vinceti, M; Willatts, P; Engel, Kh; Marchelli, R; Poting, A; Poulsen, M; Schlatter, Jr; Turla, E; van Loveren, H
abstract

Following a request from the European Commission, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on betaine as a novel food (NF) pursuant to Regulation (EC) No 258/97. The information provided on the composition, the specifications, the batch-to-batch variability, stability and production process of the NF is sufficient and does not raise concerns about the safety of the NF. The NF is proposed to be used in foods intended to meet additional requirements for intense muscular effort with a maximum intake of 2.5 g/day of betaine for sports people above 10 years of age. Based on the lowest BMDL05, which was derived from a chronic toxicity study in rats in which a dose-related increase in platelet counts was observed, and the anticipated daily intake of the NF in the target population, the Margins of Exposure are 3.6 and 5, which are generally regarded as not sufficient. However, the total exposure to betaine from the diet (about 830 mg/day) is not known to be associated with adverse effects. Moreover, no adverse effects on platelet counts were noted in human intervention studies with exposure levels of 4 g/day of betaine for up to 6 months. A significant increase in total and low-density lipoprotein (LDL)-cholesterol concentrations was noted at intakes of 4 g/day of betaine in overweight subjects with metabolic syndrome but not in healthy subjects, nor at intakes of 3 g/day. Thus, considering 4 g/day of betaine as a reference point and applying an uncertainty factor of 10 to account for interindividual variability, an amount of 400 mg/day of betaine in addition to the background exposure is considered as safe. The Panelconsiders that the NF is safe to be used at maximum intake of 400 mg/day in the target population.

2017 - Safety of cranberry extract powder as a novel food ingredient pursuant to Regulation (EC) No 258/97 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl‐heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef; Gelbmann, Wolfgang; Van Loveren, Henk
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on 'cranberry extract powder' as a novel food (NF)submitted pursuant to Regulation (EC) No 258/97 of the European Parliament and of the Council. The NF contains about 55-60% proanthocyanidins ( PACs). The Panel considers that the information provided on the composition, the specifications, batch-to-batch variability and stability of the NF is sufficient and does not raise safety concerns. Cranberry extract powder is produced from cranberry juice concentrate through an ethanolic extraction using an adsorptive resin column to retain the phenolic components. The Panel considers that the production process is sufficiently described and does not raise concerns about the safety of the novel food. The NF is intended to be added to beverages and yogurts to provide 80 mg PACs per serving. The target population is the adult general population. The mean and 95th percentile estimates for the all-user intakes from all proposed food-uses are 68 and 192 mg/day, respectively, for female adults, and 74 mg/day and 219 mg/day, respectively, for male adults. Taking into account the composition of the novel food and the intended use levels, the Panel considers that the consumption of the NF is not nutritionally disadvantageous. While no animal toxicological studies have been conducted on the NF, a number of human clinical studies have been conducted with cranberry products. Considering the composition, manufacturing process, intake, history of consumption of the source and human data, the Panel considers that the data provided do not give reasons for safety concerns. The Panel concludes that the cranberry extract powder is safe as a food ingredient at the proposed uses and use levels. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2017 - Safety of dried aerial parts of Hoodia parviflora as a novel food pursuant to Regulation (EC) No258/97 [Articolo su rivista]
Turck, D; Bresson, Jl; Burlingame, B; Dean, T; Fairweather-Tait, S; Heinonen, M; Hirsch-Ernst, Ki; Mangelsdorf, I; Mcardle, Hj; Naska, A; Neuhauser-Berthold, M; Nowicka, G; Pentieva, K; Sanz, Y; Siani, A; Sjodin, A; Stern, M; Tome, D; Vinceti, M; Willatts, P; Engel, Kh; Marchelli, R; Poting, A; Poulsen, M; Schlatter, Jr; Ackerl, R; van Loveren, H
abstract

Following a request from the European Commission, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on the dried aerial parts of Hoodiaparviflora as a novel food (NF) submitted pursuant to Regulation (EC) No258/97. The information provided on the composition, the specifications, the production process, the batch-to-batch variability and the stability of the NF is sufficient and does not raise safety concerns. The applicant intends to use the NF in a number of energy-reduced/sugar-free/no-added-sugar foods in quantities of up to 15mg per serving. The applicant also proposes to provide the NF as a food supplement. The target population proposed by the applicant is adults. The highest intake estimates were found in the group of elderly (65years) individuals, with a high intake of 1.0mg/kg body weight (bw) per day. One 90-day toxicity study in rodents was provided from which a benchmark dose lower confidence limit (BMDL05) of 53.5mg/kg bw per day was derived for effects of the NF on bodyweight. The Panelconcludes that the addition of the NF to foods as a food ingredient at the uses and use levels as proposed by the applicant would exceed intake levels considered safe in humans. The Panelconsiders that the NF is safe to be used as a food supplement at a maximum dose of 9.4mg/day. The target population is adults. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2017 - Safety of hydroxytyrosol as a novel food pursuant to Regulation (EC) No 258/97 [Articolo su rivista]
EFSA Panel on Dietetic, Products; Nutrition, Allergies; Dominique, Turck; Jean Louis, Bresson; Barbara, Burlingame; Tara, Dean; Susan Fairweather, Tait; Marina, Heinonen; Karen Ildico Hirsch, Ernst; Inge, Mangelsdorf; Harry J., Mcardle; Androniki, Naska; Monika Neuhäuser, Berthold; Grażyna, Nowicka; Kristina, Pentieva; Yolanda, Sanz; Alfonso, Siani; Anders, Sjödin; Martin, Stern; Daniel, Tomé; Vinceti, Marco; Peter, Willatts; Karl–heinz, Engel; Rosangela, Marchelli; Annette, Pöting; Morten, Poulsen; Josef, Schlatter; Emanuela, Turla; Henk van, Loveren
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on hydroxytyrosol, which is chemically synthesised, as a novel food (NF) pursuant to Regulation (EC) No 258/97. The information provided on the composition, specifications, batch-to-batch variability, stability and production process of the NF is sufficient and does not raise concerns about the safety of the NF. The applicant intends to add hydroxytyrosol to fish and vegetable oils up to 215 mg/kg and to margarines up to 175 mg/kg. The target group is the general population which excludes children under 36 months of age, pregnant women and breastfeeding women. Considering the no observed adverse effect level (NOAEL) of 50 mg/kg body weight per day from a subchronic oral toxicity study with the NF and the maximum anticipated daily intake for the NF, the margin of exposure (MoE) would result in 100 for children (3–9 years of age) and at least 200 for adolescents, adults (excluding pregnant and breastfeeding women) and elderly. Taking into account that the anticipated daily intake of the NF would be in the range of or even less than the exposure of hydroxytyrosol from the consumption of olive oils and olives, which has not been associated with adverse effects, and considering the similar kinetics of hydroxytyrosol in rats and humans, the Panel considers that the MoE for the NF at the intended uses and use levels is sufficient for the target population. The Panel concludes that the novel food, hydroxytyrosol, is safe under the proposed uses and use levels.

2017 - Safety of proline-specific oligopeptidase as a novel food pursuant to Regulation (EC) No 258/97 [Articolo su rivista]
Panel on Dietetic Products, Efsa; Allergies, Nutrition and; Turck, Dominique; Bresson, Jean Louis; Burlingame, Barbara; Dean, Tara; Fairweather Tait, Susan; Heinonen, Marina; Hirsch Ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Neuh€auser Berthold, Monika; Nowicka, Gra_zyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sj€odin, Anders; Stern, Martin; Tome, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl Heinz; Marchelli, Rosangela; P€oting, Annette; Poulsen, Morten; Schlatter, Josef; Gelbmann, Wolfgang; Loveren, Henk Van
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on proline-specific oligopeptidase (Tolerase® G) as a novel food ingredient submitted pursuant to Regulation (EC) No 258/97 of the European Parliament and of the Council, taking into account the comments and objections of a scientific nature raised by Member States. The novel food is an enzyme preparation of prolyl-oligopeptidase produced with a genetically modified Aspergillus niger self clone strain. The target population is the general adult population. The results from a bacterial reverse mutation test and of an in vitro chromosome aberration test did not indicate genotoxicity. The Panel considers that the reported effects observed in a 90-day rat study are treatment-related effects and can be attributed to the higher energy consumption by these animals. Taking into account the intended maximum use level for Tolerase® G, its daily consumption would correspond to 2,746 mg TOS/person or to 39.2 mg TOS/kg body weight (bw) per day, when considering a default body weight of 70 kg for an adult person. The margin between this value and the dose in the rats, which caused effects attributable to the excess energy intake, is approximately 45. Noting this margin, the Panel considers that it is unlikely that such effects would occur in human at the intended use levels. The Panel concludes that the NF, Tolerase® G, is safe for the intended use at the intended use level.

2017 - Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC)No 258/97 [Articolo su rivista]
Turck, D; Bresson, Jl; Burlingame, B; Dean, T; Fairweather-Tait, S; Heinonen, M; Hirsch-Ernst, Ki; Mangelsdorf, I; Mcardle, Hj; Naska, A; Neuhauser-Berthold, M; Nowicka, G; Pentieva, K; Sanz, Y; Siani, A; Sjodin, A; Stern, M; Tome, D ); Vinceti, M; Willatts, P; Engel, Kh; Marchelli, R; Poting, A; Poulsen, M; Schlatter, Jr; de Sesmaisons, A; Van Loveren, H
abstract

Following a request from the European Commission, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on pyrroloquinoline quinone disodium salt (PQQ), trade name BioPQQ, as a novel food pursuant to Regulation (EC) No 258/97. PQQ is produced by fermentation using Hyphomicrobiumdenitrificans CK-275 and purification process. PQQ has a minimum purity of 99.0%. The information provided on the composition, specifications, batch-to-batch variability, stability and production process of PQQ is sufficient and does not raise safety concerns. The applicant intends to market PQQ for use in food supplements for healthy adults, except pregnant and lactating women, at a maximum proposed level of consumption of 20 mg/day (corresponding to 0.29 mg/kg bw per day for a 70-kg person). The proposed level of consumption is at least 250 times higher than the estimated background intake of PQQ occurring naturally in foods. Information on the absorption, distribution, metabolism and excretion of PQQ in animals and humans is limited. Considering the no-observed-adverse-effect-level (NOAEL) of 100mg/kg bw per day from a 90-day repeated dose oral toxicity study with BioPQQ, and the maximum proposed level of consumption, the Panelconcludes that the margin of exposure (of 344) is sufficient. The Panelconcludes that the novel food, pyrroloquinoline quinone disodium salt (BioPQQ (TM)), is safe under the intended conditions of use as specified by the applicant.

2017 - Safety of synthetic N‐acetyl‐d‐neuraminic acid as a novel food pursuant to Regulation (EC) No 258/97 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl‐heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef Rudolf; Turla, Emanuela; van Loveren, Henk
abstract

Following a request from the European Commission, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on synthetic N-acetyl-d-neuraminic acid (NANA) as a novel food (NF) submitted pursuant to Regulation (EC) No258/97. The information on the composition, the specifications, the batch-to-batch variability, stability and production process of the NF is sufficient and does not raise concerns about the safety of the NF. The NF is intended to be marketed as an ingredient in formulae and foods for infants and young children as well as an ingredient in a variety of foods and in food supplements for the general population. NANA is naturally present in human milk, in a bound and free form. The Margin of Exposure, which was based on the no-observed-adverse effect level (NOAEL) of 493mg/kg body weight (bw) per day from a subchronic study and the anticipated daily intake of the NF, was considered to be sufficient for fortified foods for the general population and for food supplements for individuals above 10years of age, as the anticipated daily intake was in the range of the exposure to free NANA from the consumption of early human milk, which is considered to be safe. The Panelconcludes that the NF is safe when added to foods other than food supplements at the proposed uses and use levels for the general population; is safe in food supplements alone at the proposed uses and use levels for individuals above 10years of age; is safe at the combined intake from fortified foods plus food supplements in individuals above 10years of age; the safety of the NF is not established in food supplements alone at the proposed uses and use levels for individuals below 10years of age.

2017 - Scientific Opinion on taxifolin-rich extract from Dahurian Larch (Larix gmelinii) [Articolo su rivista]
Panel on Dietetic Products, Efsa; Allergies, Nutrition and; Turck, Dominique; Bresson, Jean Louis; Burlingame, Barbara; Dean, Tara; Fairweather Tait, Susan; Heinonen, Marina; Hirsch Ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Neuh€auser Berthold, Monika; Nowicka, Gra_zyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sj€odin, Anders; Stern, Martin; Tome, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl–heinz; Marchelli, Rosangela; P€oting, Annette; Poulsen, Morten; Schlatter, Josef; Gelbmann, Wolfgang; Loveren, Henk Van
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to carry out the additional assessment for taxifolin-rich extract from Dahurian Larch as a food ingredient in the context of Regulation (EC) No 258/97. The novel food (NF) is a taxifolin-rich water–ethanol extract from the wood of the Dahurian Larch and contains a minimum of 90% taxifolin. The Panel considers that the taxifolin-rich extract is sufficiently characterised and that its compositional data and specifications do not raise safety concerns. The NF is intended to be added to non-alcoholic beverages, to yogurt and to chocolate confectionery. The Panel considers that the data on genotoxicity do not raise concern. In a subchronic rat study performed in accordance with OECD standards, the highest dose tested (i.e. 1,500 mg/kg bw) was considered to be the NOAEL. The margin of exposure (MOE) of the combined intake (158 mg) from the intended food uses (including 100 mg from food supplements) would result to about 660 for an adult weighing 70 kg. For adolescents, taking into account a default body weight of 45 kg, the MOE of the combined intake (146 mg) would be about 460. In the absence of a high percentile intake estimate for children between 9 and 14 years of age, the Panel considers the P97.5 intake estimate from the intended food uses (except from food supplements) for children between 10 and 17 years, i.e. 46 mg/day. Taking into account a default body weight of 29.4 kg (P5 body weight for children aged 10–14 years as suggested by EFSA Scientific Committee (2012)), the resulting MOE would be about 960.

2017 - Scientific Opinion on the safety and suitability for use by infants of follow‐on formulae with a protein content of at least 1.6 g/100 kcal [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Fewtrell, Mary; Przyrembel, Hildegard; Titz, Ariane; Valtueña Martínez, Silvia
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on the safety and suitability for use by infants of follow-on formulae (FOF) based on cow's milk intact protein with a protein content of at least 1.6 g/100 kcal (rounded value) that meet otherwise the requirements of relevant EU legislation. If the formula under evaluation is considered to be safe and suitable for use by infants, the NDA Panel is also asked to advise on whether FOF based on goat's milk intact protein, soy protein isolates or protein hydrolysates are also safe and suitable for infants under the same conditions. The Panel concludes that the use of FOF with a protein content of at least 1.6 g/100 kcal from either intact cow's milk protein or intact goat's milk protein otherwise complying with the requirements of relevant EU legislation is safe and suitable for healthy infants living in Europe with an intake of complementary foods of a sufficient quality. This conclusion does not apply to infant formula (IF). The Panel also concludes that the safety and suitability of FOF with a protein content of at least 1.6 g/100 kcal manufactured from either protein hydrolysates or soy protein isolates cannot be established with the available data. The same conclusion applies to IF. The NDA Panel endorsed a draft of this scientific opinion on 14 December 2016 for public consultation. The draft document has been revised and updated according to the comments received, where appropriate. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2017 - Scientific and technical guidance for the preparation and presentation of a health claim application (Revision 2) [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Heng, Leng; Valtueña Martínez, Silvia; Siani, Alfonso
abstract

EFSA asked the Panel on Dietetic Products, Nutrition and Allergies (NDA) to update the scientific and technical guidance for the preparation and presentation of an application for authorisation of a health claim published in 2011. Since then, the NDA Panel has gained considerable experience in the evaluation of health claims. Lessons learnt from these experiences have been translated into a new General scientific guidance for stakeholders on health claim applications (published in January 2016). In this context, it is noted the need to adapt the existing guidance to the new scientific and technical developments in this area. This guidance document presents a common format for the organisation of information for the preparation of a well-structured application for authorisation of health claims which fall under Articles 13(5), 14 and 19 of Regulation (EC) No 1924/2006. This guidance outlines the information and scientific data which must be included in the application, the hierarchy of different types of data and study designs, and the key issues which should be addressed in the application to substantiate the health claim. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2017 - Scientific and technical guidance for the preparation and presentation of an application for authorisation of an infant and/or follow‐on formula manufactured from protein hydrolysates [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Fewtrell, Mary; Przyrembel, Hildegard; Titz, Ariane; Valtueña Martínez, Silvia
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to provide scientific and technical guidance for the preparation and presentation of applications for authorisation of infant and/or follow-on formula manufactured from protein hydrolysates. This guidance document addresses the information and data to be submitted to EFSA on infant and follow-on formulae manufactured from protein hydrolysates with respect to the safety and suitability of the specific formula and/or the formula's efficacy in reducing the risk of developing allergy to milk proteins. The guidance will be further reviewed and updated with the experience gained from the evaluation of specific applications for authorisation, and in the light of future Community guidelines and legislation. The NDA Panel endorsed a draft of this scientific opinion on 14 December 2016 for public consultation. The draft document has been revised and updated according to the comments received, where appropriate. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2017 - Se-speciation investigations at neural barrier (NB) [Abstract in Atti di Convegno]
Solovyev, Nikolay; Vinceti, Marco
abstract

Introduction: Se-speciation helps for deeper insight into Se-metabolism and transport, important at NB or under neurological diseases. Analytical set-up of hyphenated speciation techniques with 2-D-identification of Se-compounds is described. Then applications at NB in paired serum and cerebrospinal fluid (CSF) samples are reported, finishing with comparison of Se-speciation of neurologically diseased persons vs. controls. Method: Serum and CSF samples were subject to speciation analysis by HPLC-ICP-DRC-MS. For improved species identification Se-species were analysed serially after HPLC by CE-ICP-DRC-MS (2D approach). Result: Paired samples had 58.39 (serum) or 0.86 (CSF , each μg Se/L). Prominent Se-species were selenoprotein-P (SePP), glutathione-peroxidase (GPx), thioredoxinreductase (TrxR), Se(IV) and Se-albumin (Se-HSA). Relationships between Se-species from serum and CSF allowed evaluating Se-species passage across NB: SePP-serum correlated with total Se-serum when > 65 μg/L. SePP-CSF appeared independent from SePP-serum. For anti-oxidative Seenzymes higher correlation factors (r2) were calculated: GPx-serum/GPx-CSF: r2=0.3837 and TrxR-serum/TrxR-CSF: r2=0.6293. No correlation for inorganic Se-compounds was found proving limited representativeness of their circulating levels beyond NB[1]. Se-species-ratios (CSF/serum) were 21.4*10-3 (TrxR) or 8.3*10-3 (GPx), being significantly elevated compared to NB permeability factor 3.8*10-3 (HSA). In a hospital-referred cases-control we investigated Se-species in CSF of patients with amyotrophic lateral sclerosis, compared to reference neurological patients. We found an excess concentration of inorganic Se(IV) and reduced levels of organic Se-compounds among ALS patients[2]. Discussion: ROS-protecting enzymes GPx and TrxR seem to be shuttled across NB to brain/CSF. In ALS etiology overexposure of inorganic Se(IV) together with decreased organic Se-species may be involved in ALS etiology.

2017 - Selenium in human neurodegenerative diseases: friend or foe? [Abstract in Atti di Convegno]
Vinceti, M; Filippini, T; Malagoli, C.
abstract

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2017 - Selenium levels in patients with mild cognitive impairment and Alzheimer’s disease [Abstract in Atti di Convegno]
Vinceti, M; Chiari, A; Eichmüller, M; Rothman K., J; Filippini, T; Malagoli, C; Weuve, J; Tondelli, M; Zamboni, G; Nichelli P., F; Michalke, B.
abstract

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2017 - Selenium, zinc and copper content of foods consumed in an Italian community [Abstract in Rivista]
Cilloni, Silvia; Malavolti, Marcella; Malagoli, Carlotta; Violi, Federica; Filippini, Tommaso; Vescovi, Luciano; Vinceti, Marco
abstract

This study aimed to determine the concentrations of selenium, zinc and copper in foods generally composing the diet of Northern Italy population in order to implement a database of the quantitative content for each of the three trace elements, according to food category intake. Food samples were collected from (small to large) distribution markets in triplicates and trace elements determination was performed with ICP-MS after sample mineralization. We found the highest levels of selenium in meat (202g/kg), fish and seafood (489), dry fruits (314) and legumes (220). The level of zinc was higher in cereal products (11.7 mg/kg), meat (28.4), dairy products (18.8), legumes (21.2) and dry fruits (37.8). Finally, the highest concentration of copper was found in dry fruits (14.9 mg/kg), legumes (6.2), sweets (4.1) and meat (3.7). Our findings will allow to estimate dietary trace elements exposure which could be useful for both toxicological and epidemiological studies.

2017 - Stablor® and reduction of visceral fat while maintaining lean mass: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Panel on Dietetic Products, Efsa; Allergies, Nutrition and; Turck, Dominique; Bresson, Jean Louis; Burlingame, Barbara; Dean, Tara; Fairweather Tait, Susan; Heinonen, Marina; Hirsch Ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuh€auser Berthold, Monika; Nowicka, Gra_zyna; Pentieva, Kristina; Sanz, Yolanda; Sj€odin, Anders; Stern, Martin; Tome, Daniel; Loveren, Henk Van; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John J; Siani, Alfonso
abstract

Following an application from Laboratoires Nutrition et Cardiometabolisme, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Stablor® and decrease in visceral fat while preserving lean mass. The food Stablor®, a drink preparation with defined macro- and micronutrient composition and a specific proportion of amino acids (tryptophan to neutral amino acids ratio) which is the subject of the health claim, is sufficiently characterised. The Panel considers that reduction of visceral fat while maintaining lean body mass in the context of an energy restricted diet is a beneficial physiological effect in overweight or obese subjects with abdominal fat and cardiometabolic risk factors. Four human studies were submitted by the applicant as pertinent to the claimed effect. In weighing the evidence, the Panel took into account that one human study from which conclusions could be drawn for scientific substantiation of the claimed effect did not show an effect of Stablor® on visceral fat mass in the context of an energy restricted diet. The Panel concludes that a cause and effect relationship has not been established between the consumption of Stablor® and reduction of visceral fat while maintaining lean body mass in the context of an energy restricted diet.

2017 - Statement on the safety of EstroG‐100™ as a novel food pursuant to Regulation (EC) No 258/97 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl‐heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef Rudolf; Turla, Emanuela; van Loveren, Henk
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to update its scientific opinion on the safety of EstroG-100 (TM) as a novel food (NF) in the light of additional information submitted by the applicant. In its previous scientific opinion of 2016, the Panel concluded that EstroG-100 (TM), which is a hot-water extract of a mixture of three herbal roots, is safe for the use in food supplements at the maximum intake level of 175 mg/day in post-menopausal women, which is lower than the maximum intake level proposed by the applicant (514 mg/day). The Panel reached its conclusions based on the effects of EstroG-100 (TM) on liver and haematology as observed in several oral toxicity studies, the lack of information on liver and haematological parameters in human studies and the absence of chronic toxicity data. In view of the Panel's conclusion on the safety of EstroG-100 (TM), the applicant has now provided additional information on haematological and liver parameters for the human intervention study with EstroG-100 (TM) and historical control data related to the subchronic 90-day oral toxicity study with EstroG-100 (TM). After assessing the additional information provided by the applicant, the Panel considers that the conclusion of the scientific opinion on the safety of EstroG-100 (TM) does not need to be revised, and thus, the Panel reconfirms that the NF is safe for the use in food supplements at the maximum intake level of 175 mg/day in post-menopausal women. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2017 - Statement on the safety of synthetic L-ergothioneine as a novel food - supplementary dietary exposure and safety assessment for infants and young children, pregnant and breastfeeding women [Articolo su rivista]
Turck, D; Bresson, Jl; Burlingame, B; Dean, T; Fairweather-Tait, S; Heinonen, M; Hirsch-Ernst, Ki; Mangelsdorf, I; Mcardle, Hj; Naska, A; Neuhauser-Berthold, M; Nowicka, G; Pentieva, K; Sanz, Y; Siani, A; Sjodin, A; Stern, M; Tome, D; Vinceti, M; Willatts, P; Engel, Kh; Marchelli, R; Poting, A; Poulsen, M; Schlatter, Jr; Ackerl, R; van Loveren, H
abstract

Following a request from the European Commission, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to provide a supplementary dietary exposure and safety assessment of synthetic l-ergothioneine for those groups of the population which had been excluded by the applicant in the original application, i.e. infants and young children (i.e. toddlers), pregnant and breastfeeding women. Thus, intake estimates were calculated for these population groups and the following maximum anticipated daily intakes of l-ergothioneine from the NF, in addition to the background diet, were calculated: 2.82 mg/kg body weight (bw) per day for infants, 3.39 mg/kg bw per day for toddlers and 1.31 mg/kg bw per day for adults including pregnant and breastfeeding women. The Panelconsiders that based on the overall toxicological data the no-observed-adverse-effect level (NOAEL) of 800 mg/kg bw per day as established in the original assessment also pertains to pregnant and breastfeeding women as well as to young children (i.e. toddlers) and infants. The corresponding margins of exposure (i.e. the ratio between the NOAEL and the maximum anticipated daily intakes) are 284 for infants, 236 for young children and 610 for pregnant and breastfeeding women. These margins of exposure are considered sufficient. The Panelconcludes that the novel food, synthetic l-ergothioneine, is safe under the proposed uses and use levels for infants, young children (i.e. toddlers) and pregnant and breastfeeding women.

2017 - Statement on the safety of taxifolin-rich extract from Dahurian Larch (Larix gmelinii) [Articolo su rivista]
Turck, D; Bresson, Jl; Burlingame, B; Dean, T; Fairweather-Tait, S; Heinonen, M; Hirsch-Ernst, Ki; Mangelsdorf, I; Mcardle, Hj; Naska, A; Neuhauser-Berthold, M; Nowicka, G; Pentieva, K; Sanz, Y; Siani, A; Sjodin, A; Stern, M; Tome, D; Vinceti, M; Willatts, P; Engel, Kh; Marchelli, R; Poting, A; Poulsen, M; Schlatter, J; Gelbmann, W; van Loveren, H
abstract

Following a request from the European Commission, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to carry out a supplementary safety assessment for taxifolin by considering also those population groups which were originally excluded at the request of the applicant (i.e. infants, young children and children up to 9 years) for the food categories set out in the application, and by taking into the extension of use of taxifolin from yogurt to a wider range of dairy products. In 2016, the EFSA NDA Paneladopted the Scientific Opinion on the safety of taxifolin-rich extract from Dahurian Larch (Larix gmelinii) as a novel food ingredient in non-alcoholic beverages, yogurts, chocolate confectionery and food supplements pursuant to Regulation (EC) No 258/97. In order to address the present mandate, an intake assessment was carried out by taking into account all population groups (including now also children below 9years of age) and by considering the food intended categories for which the applicant provided maximum use levels of taxifolin. Intakes were estimated for all age groups of the general population. The highest 95 th percentile intakes per kg bw per day among all population groups are 0.94 and 1.54 mg, respectively, derived for toddlers. Noting that the no-observed-adverse effect level (NOAEL) of the subchronic study was 1,500 mg/kg body weight (bw), the resulting margin of exposure (MOE) would be almost 1,000. For adults weighing 70 kg, the MOE to the combined intake from fortified foods and food supplements would be about 772. For adolescents, taking into account a default mean body weight of 61 kg, the MOE to the combined intake (including 100 mg from food supplements) would be about 627. The Panelconsiders that these MOEs are sufficient. The Panelconcludes that the NF food, taxifolin-rich extract from Dahurian Larch, is safe under the proposed conditions of use.

2017 - Stima dell’assunzione settimanale di cadmio in un campione di popolazione italiana: metodologie a confronto [Abstract in Atti di Convegno]
Filippini, T; Malagoli, C; Michalke, B; Vinceti, M.
abstract

Introduzione: Il cadmio (Cd) è un metallo carcinogeno per l’uomo introdotto principalmente con la dieta nei soggetti non fumatori e non esposti professionalmente. La dose settimanale ammissibile di Cd è stata recentemente abbassata a 2,5 μg/kg di peso corporeo (bw) a settimana dall’Agenzia Europea per la Sicurezza Alimentare (EFSA) al fine di assicurare un alto livello di protezione per la popolazione. Nella presente indagine abbiamo messo a confronto due differenti modelli atti a stimare l’assunzione settimanale di Cd. Materiali e Metodi In un campione casuale di residenti adulti del comune di Modena è stato somministrato un questionario al fine di raccogliere informazioni sulle caratteristiche individuali, gli stili di vita e le abitudini alimentari. Inoltre è stato misurato il livello di Cd in un campione di siero. Sono stati dunque costruiti in base ai dati di letteratura due modelli per stimare la dose settimanale di Cd a partire rispettivamente dall’intake calcolato tramite il questionario alimentare e dai livelli nel biomarcatore, tenendo in considerazione il rapporto tra Cd sierico e totale, la percentuale di assorbimento del Cd assunto con la dieta e il contributo relativo del fumo di sigaretta. Risultati Nei 51 soggetti reclutati, l’intake giornaliero medio (deviazione standard: DS) di Cd è risultato pari a 14,1 µg/die (DS 6,5) e la concentrazione media di Cd sierico a 45 ng/L (DS 24,0). Abbiamo in tal modo potuto stimare un’assunzione settimanale media pari a 1,38 (DS 0,41; range 0,26-3,18) µg/kg/bw a partire dalla dieta e di 0,78 (DS 0,68; range 0,27-2,47) µg/kg/bw a partire dai livelli del biomarcatore. Conclusioni Nel campione di popolazione esaminato abbiamo riscontrato un livello medio di assunzione settimanale di Cd più elevato nel caso di stima effettuata tramite questionario alimentare rispetto a quella con il biomarcatore. Le differenze riscontrate confrontando i due modelli sottolineano la necessità di valutare con attenzione il rapporto tra l’intake alimentare e i livelli di Cd nei biomarcatori, soprattutto al fine di valutare l’esposizione individuale. Sulla base delle stime effettuate mediante la somministrazione del questionario, per alcuni soggetti la dose di Cd è risultata superiore al valore di riferimento stabilito dall’EFSA, mettendo in luce un possibile rischio per la salute.

2017 - Sugar‐free hard confectionery with at least 90% erythritol and reduction of dental plaque which reduces the risk of dental caries: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Siani, Alfonso
abstract

Following an application from Cargill R&amp;D Centre Europe, submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No1924/2006 via the Competent Authority of Belgium, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to sugar-free hard confectionery with at least 90% erythritol and reduction of dental plaque which reduces the risk of caries. The food proposed by the applicant as the subject of the health claim, sugar-free hard confectionery with at least 90% erythritol, is sufficiently characterised. In the context of this application, the weight of dental plaque, and/or the counts of Streptococcusmutans in dental plaque, and/or the concentration of organic acids in plaque (primarily acetic acid and lactic acid) can be considered as risk factor(s) in the development of dental caries, as long as evidence is provided that the consumption of the food that is the subject of the health claim reduces one or more of the proposed risk factors and the incidence of dental caries. One human intervention study did not show an effect of sugar-free hard confectionery with at least 90% erythritol on the incidence of dental caries in children on either mixed or permanent dentition. The Panelconcludes that a cause and effect relationship has not been established between the consumption of sugar-free hard confectionery with at least 90% erythritol and reduction of dental plaque which reduces the risk of dental caries.

2017 - The Epidemiology of Selenium and Human Cancer [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Cilloni, Silvia; Crespi, Catherine M.
abstract

The relation between selenium and cancer has been one of the most hotly debated topics in human health over the last decades. Early observational studies reported an inverse relation between selenium exposure and cancer risk. Subsequently, randomized controlled trials showed that selenium supplementation does not reduce the risk of cancer and may even increase it for some types, including advanced prostate cancer and skin cancer. An increased risk of diabetes has also been reported. These findings have been consistent in the most methodologically sound trials, suggesting that the early observational studies were misleading. Other studies have investigated selenium compounds as adjuvant therapy for cancer. Though there is currently insufficient evidence regarding the utility and safety of selenium compounds for such treatments, this issue is worthy of further investigation. The study of selenium and cancer is complicated by the existence of a diverse array of organic and inorganic selenium compounds, each withdistinct biological properties, and this must be taken into consideration in the interpretation of both observational and experimental human studies.

2017 - The effect of potassium supplementation on blood pressure in hypertensive subjects: A systematic review and meta-analysis. [Articolo su rivista]
Filippini, Tommaso; Violi, Federica; D'Amico, Roberto; Vinceti, Marco
abstract

BACKGROUND: Several intervention studies have investigated the relation between potassium intake and blood-pressure, particularly in hypertensive subjects. However, uncertainties still exist about the existence and the amount of such an effect, and about the role of some potential effect-modifiers, including the baseline potassium intake and geographical area. METHODS: We carried out a systematic review of the evidence concerning such relation in hypertensive subjects, performing a meta-analysis and a meta-regression of RCT with selective and validated long-term (≥4weeks) potassium supplementation. We also implemented 'unconventional' search strategies in order to identify all potentially interesting studies. RESULTS: Overall, potassium supplementation decreased systolic blood pressure of 4.48mmHg (95% CI 3.07-5.90) and diastolic blood pressure of 2.96mmHg (1.10-4.82). There was little evidence of dose-response relation between blood-pressure decrease and potassium supplementation, as assessed through total achieved potassium intake in the intervention groups, difference in achieved potassium intake, and study duration. However, lower (&lt;90mmol/day) potassium intake at baseline was associated with a higher blood-pressure lowering effect, as were higher sodium intake (particularly ≥4g/day), higher sodium-to-potassium ratio and the absence of any anti-hypertensive drug treatment. Trials conducted in Southern Europe showed the highest blood-pressure lowering effect compared with the remaining regions. CONCLUSIONS: Potassium supplementation in hypertensives was generally associated with decreased blood pressure, particularly in high sodium consumers, subjects not on hypertensive drug treatment, and those in the lowest category of potassium intake. An adequate dietary intake of potassium, in the order of 90mmol/day, should be achieved for blood pressure control.

2017 - The role of cadmium in obesity and diabetes [Articolo su rivista]
Tinkov, Alexey A.; Filippini, Tommaso; Ajsuvakova, Olga P.; Aasethe, Jan; Gluhcheva, Yordanka G.; Ivanova, Juliana M.; Bjørklundi, Geir; Skalnaya, Margarita G.; Gatiatulina, Eugenia R.; Popoval, Elizaveta V.; Nemereshina, Olga N.; Vinceti, Marco; Skalny, Anatoly V.
abstract

Multiple studies have shown an association between environmental exposure to hazardous chemicals including toxic metals and obesity, diabetes, and metabolic syndrome. At the same time, the existing data on the impact of cadmium exposure on obesity and diabetes are contradictory. Therefore, the aim of the present work was to review the impact of cadmium exposure and status on the risk and potential etiologic mechanisms of obesity and diabetes. In addition, since an effect of cadmiumexposure on incidence of diabetesmellitus and insulin resistance was suggested by several epidemiologic studies, we carried out a meta-analysis of all studies assessing risk of prevalence and incidence of diabetes. By comparing the highest versus the lowest cadmium exposure category, we found a high risk of diabetes incidence (odds ratio = 1.38, 95% confidence interval 1.12–1.71), which was higher for studies using urine as exposure assessment. On the converse, results of epidemiologic studies linking cadmium exposure and overweight or obesity are far less consistent and even conflicting, also depending ondifferences in exposure levels and the specific marker of exposure (blood, urine, hair, nails). In turn, laboratory studies demonstrated that cadmium adversely affects adipose tissue physiopathology through several mechanisms, thus contributing to increased insulin resistance and enhancing diabetes. However, intimate biological mechanisms linking Cd exposure with obesity and diabetes are still to be adequately investigated.

2017 - Toenail selenium as an indicator of environmental exposure: A cross-sectional study. [Articolo su rivista]
Filippini, Tommaso; Ferrari, Angela; Michalke, B; Grill, P; Vescovi, L; Salvia, Chiara; Malagoli, Carlotta; Malavolti, Marcella; Sieri, S; Krogh, V; Bargellini, Annalisa; Martino, Antonio; Ferrante, M; Vinceti, Marco
abstract

The relation between toxicity and essentiality of selenium (Se) is of growing interest in human health, as the effects may widely differ depending of its different chemical species and the exposure levels. Toenail Se has been proposed as a reliable biomarker of long-term Se exposure, but few studies investigated the correlation between its toenail content and environmental determinants (i.e., dietary food intake). We aimed to determine the relation of toenail Se levels with serum Se species as well as food items. We recruited a random sample of Modena (Northern Italy) municipal residents, from whom we collected detailed personal information, dietary habits, toenail specimen for Se determination and a blood sample for serum Se speciation analysis. Toenail Se mean value was 0.96 µg/g (range, 0.47‑1.60), with slightly higher levels in females, in non-obese subjects and in Se supplements users, while it was lower in current smokers. Toenail Se positively correlated with organic Se forms, mainly selenoprotein P and selenocysteine, and inversely with the inorganic forms (selenite and selenate). Toenail Se was not associated with meat, cereals and dairy products consumption, positively correlated with fruit and slightly with vegetable intake, and negatively with fish and seafood consumption. Finally, no clear association emerged with estimated air Se exposure.

2017 - Trace element speciation in the cerebrospinal fluid samples from the patients with amyotrophic lateral sclerosis? [Abstract in Atti di Convegno]
Solovyev, N; Mandrioli, J; Vinceti, M; Malagoli, C; Lucio, M; Michalke, B.
abstract

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2017 - Trace element species and amyotrophic lateral sclerosis with disease associated genetic mutations [Abstract in Atti di Convegno]
Nikolay, Solovyev; Mandrioli, Jessica; Vinceti, Marco; Malagoli, Carlotta; Marianna, Lucio; Bernhard, Michalke
abstract

Introduction: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with mostly unknown eti-ology. Certain genetic mutations are associated with the disease; however, the role of environmental factors, such as exposure to metals and organic pollutants is also widely discussed in the literature. ALS, as other neurodegenerative disorders, is related to the brain oxidative stress, so the disturbance of redox homeostasis may be anticipated for such elements as selenium (Se), copper (Cu), iron (Fe), and manganese (Mn). Aim: The aim of the study was to evaluate a possible alteration of trace element (Se, Cu, Mn, and Fe) homeostasis in the ALS patients with disease associated gene mutations. Methods: We analyzed cerebrospinal fluid (CSF) samples from 9 patients with ALS-associated muta-tions (C9ORF72, SOD1, FUS, TARDBP, ATXN2, and TUBA4A) and 42 age- and gender-matched controls. Advanced speciation techniques were used to quantify redox forms of Cu (I/II), Mn (II/III), and Fe (II/III) and Se species (selenoprotein P, glutathione peroxidase, thioredoxin reductase, selenite, selenate, and human serum bound-Se). For the separation of Se species strong anion exchange chromatography (SAX) was used, whereas Cu, Mn, and Fe redox forms were separated by strong cation exchange (SCX). For the species detection, inductively coupled plasma sector field mass spectrometry (ICP-sf-MS), op-erated at high resolution for Se or medium resolution for Cu, Fe, and Mn was employed. Standard compounds and spikings were used for peak assignment. External calibration vs. matching to the total content of the elements, measured by inductively coupled plasma dynamic reaction cell mass spec-trometry, was used for species quantification. Results: The analytical schemes of species quantification, using SAX-ICP-sf-MS [1] and SCX-ICP-sf-MS [2], have been optimized. The difference in Cu(II) and some Se species were found to be altered in the CSF of the ALS patients with disease-associated mutations. Also, since multi-element speciation had been performed for the same set of CSF samples, some inter-element correlations were observed (be-tween Fe and Se species, Mn and Fe, Mn and Cu). Conclusion: Despite the limited sample size, we could presume a distortion in trace element metabo-lism, reflected the altered speciation of Cu and Se in the CSF. However, more insight is required to understand if these findings are an innocent bystander to the pathological changes in the ALS brain or has its own relevant role in the etiopathogenesis of the disease.

2017 - Validity of hospital discharge records to identify pregestational diabetes in an Italian population [Articolo su rivista]
Borsari, Lucia; Malagoli, Carlotta; Ballottari, Paola; De Girolamo, Gianfranco; Bonora, Karin; Violi, Federica; Capelli, Oreste; Rodolfi, Rossella; Nicolini, Fausto; Vinceti, Marco
abstract

.AIMS: In recent years, the prevalence of pregestational diabetes (PGDM) and the concern about the possibility of adverse pregnancy outcomes in affected women have been increasing. Routinely collected health data represent a timely and cost-efficient approach in PGDM epidemiological research. This study aims to evaluate the reliability of hospital discharge (HD) coding to identify a population-based cohort of pregnant women with PGDM and to assess trends in prevalence in two provinces of Northern Italy. METHODS: We selected all deliveries occurred in the period 1997-2010 with ICD-9-CM codes for PGDM in HD record and we matched up to 5 controls from mothers without diabetes. We used Diabetes Registers (DRs) as the gold standard for validation analysis. RESULTS: We selected 3800 women, 653 with diabetes and 3147 without diabetes. The agreement between HD records and DRs was 90.7%, with K=0.58. We detected 350 false positives and only 1 false negative. Sensitivity was 99.3%, specificity 90.0%, positive predictive value 46.4% and negative predictive value 99.9%. Of the false positives, 48.6% had gestational diabetes and 2.3% impaired glucose tolerance. After the validation process, PGDM prevalence decreased from 4.4 to 2.0 per 1000 deliveries. CONCLUSIONS: Our results show that HD facilitate detection of almost all PGDM cases, but they also include a large number of false positives, mainly due to gestational diabetes. This misclassification causes a large overestimation of PGMD prevalence. Our findings require accuracy evaluation of ICD-9-CM codes, before they can be widely applied to epidemiological research and public health surveillance related to PGDM.

2017 - Vibigaba (germinated brown rice) and maintenance of long‐term normal blood glucose concentration: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Siani, Alfonso
abstract

Following an application from Loc Troi group, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No1924/2006 via the Competent Authority of the Netherlands, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Vibigaba (germinated brown rice) and maintenance of long-term normal blood glucose concentration. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is Vibigaba. The Panelconsiders that the germinated brown rice Vibigaba is sufficiently characterised. The claimed effect proposed by the applicant is contribution to the maintenance of normal glycated haemoglobin level'. The Panelconsiders that maintenance of long-term normal blood glucose concentration is a beneficial physiological effect. The Panelnotes that the applicant did not perform a comprehensive literature search to identify human intervention studies which could be pertinent to the claim. The applicant did not reply to a specific request from EFSA to provide this information. The applicant identified one human intervention study as being pertinent to the claim. The Panelnotes the important methodological limitations of the study (e.g. statistical methods used for data analysis not appropriate for the study design) and that the information provided on the design and conduct of the study is insufficient for a complete scientific evaluation. The Panelconsiders that no conclusions can be drawn from this study for the scientific substantiation of the claim. The Panelconcludes that a cause and effect relationship has not been established between the consumption of Vibigaba (germinated brown rice) and maintenance of long-term normal blood glucose concentration.

2017 - Vibigaba (germinated brown rice) and maintenance of normal blood cholesterol concentration: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Siani, Alfonso
abstract

Following an application from Loc Troi group, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No1924/2006 via the Competent Authority of the Netherlands, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Vibigaba (germinated brown rice) and contribution to the maintenance of normal blood cholesterol concentrations. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is Vibigaba. The Panelconsiders that the germinated brown rice Vibigaba is sufficiently characterised. The claimed effect proposed by the applicant is contribution to the maintenance of normal blood cholesterol levels'. The Panelconsiders that maintenance of normal blood cholesterol concentrations is a beneficial physiological effect. The Panelnotes that the applicant did not perform a comprehensive literature search to identify human intervention studies which could be pertinent to the claim. The applicant did not reply to a specific request from EFSA to provide this information. The applicant identified one human intervention s being pertinent to the claim. The Panelnotes the important methodological limitations of the study study a(e.g. statistical methods used for data analysis not appropriate for the study design) and that the information provided on the design and conduct of the study is insufficient for a complete scientific evaluation. The Panelconsiders that no conclusions can be drawn from this study for the scientific substantiation of the claim. The Panelconcludes that a cause and effect relationship has not been established between the consumption of Vibigaba (germinated brown rice) and maintenance of normal blood cholesterol concentration.

2017 - Vibigaba (germinated brown rice) and maintenance of normal blood pressure: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Siani, Alfonso
abstract

Following an application from Loc Troi group, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No1924/2006 via the Competent Authority of the Netherlands, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Vibigaba (germinated brown rice) and contribution to the maintenance of normal blood pressure. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is Vibigaba. The Panelconsiders that the germinated brown rice Vibigaba is sufficiently characterised. The claimed effect proposed by the applicant is contribution to the maintenance of normal blood pressure'. The Panelconsiders that maintenance of normal blood pressure is a beneficial physiological effect. The Panelnotes that the applicant did not perform a comprehensive literature search to identify human intervention studies which could be pertinent to theclaim. The applicant did not reply to a specific request from EFSA to provide this information. The applicant identified one human intervention study as being pertinent to the claim. The Panelnotes theimportant methodological limitations of the study (e.g. statistical methods used for data analysis not appropriate for the study design) and that the information provided on the design and conduct of the study is insufficient for a complete scientific evaluation. The Panelconsiders that no conclusions can be drawn from this study for the scientific substantiation of the claim. The Panelconcludes that a cause and effect relationship has not been established between the consumption of Vibigaba (germinated brown rice) and maintenance of normal blood pressure.

2017 - Vibigaba (germinated brown rice) and reduction of body weight in the context of an energy‐restricted diet: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Siani, Alfonso
abstract

Following an application from Loc Troi group, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No1924/2006 via the Competent Authority of the Netherlands, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Vibigaba (germinated brown rice) and reduction of body weight in the context of an energy-restricted diet. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is Vibigaba. The Panelconsiders that the germinated brown rice Vibigaba is sufficiently characterised. The claimed effect proposed by the applicant is in the context of an energy-restricted diet contributes to weight loss'. The Panelconsiders that reduction of body weight in the context of an energy-restricted diet is a beneficial physiological effect. The Panelnotes that the applicant did not perform a comprehensive literature search to identify human intervention studies which could be pertinent to the claim. The applicant identified one human intervention study as being pertinent to the claim. The Panelnotes the important methodological limitations of the study (e.g. statistical methods used for data analysis not appropriate for the study design) and that the information provided on the design and conduct of the study is insufficient for a complete scientific evaluation. The Panelconsiders that no conclusions can be drawn from this study for the scientific substantiation of the claim. The Panelconcludes that a cause and effect relationship has not been established between the consumption of Vibigaba (germinated brown rice) and reduction of body weight in the context of an energy-restricted diet.

2017 - Vitamin C and protection of DNA, proteins and lipids from oxidative damage: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen‐ildico; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John J.; Ciok, Janusz; Siani, Alfonso
abstract

Following an application from Specialised Nutrition Europe (formerly IDACE), submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to vitamin C and protection of DNA, proteins and lipids from oxidative damage. The Panel considers that vitamin C is sufficiently characterised and that protection of DNA, proteins and lipids from oxidative damage is a beneficial physiological effect. The target population proposed by the applicant is infants (from birth) and young children up to 3 years of age. The Panel has previously assessed a claim on vitamin C and protection of DNA, proteins and lipids from oxidative damage with a favourable outcome. The target population was the general population. The Panel considers that the role of vitamin C in protection of DNA, proteins and lipids from oxidative damage applies to all ages, including infants and young children up to 3 years of age. The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin C and protection of DNA, proteins and lipids from oxidative damage. (C) 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2017 - ‘Nutrimune®’ and immune defence against pathogens in the gastrointestinal and upper respiratory tracts: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Panel on Dietetic Products, Efsa; Allergies, Nutrition and; Turck, Dominique; Bresson, Jean Louis; Burlingame, Barbara; Dean, Tara; Fairweather Tait, Susan; Heinonen, Marina; Hirsch Ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuh€auser Berthold, Monika; Nowicka, Gra_zyna; Pentieva, Kristina; Sanz, Yolanda; Stern, Martin; Tome, Daniel; Loveren, Henk Van; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John J; Siani, Alfonso
abstract

Following an application from H.J. Heinz Supply Chain Europe B.V., submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to ‘Nutrimune®’ and immune defence against pathogens in the gastrointestinal (GI) tract and upper respiratory tract (URT). The food ‘Nutrimune®’ (a pasteurised cow’s skim milk fermented with Lactobacillus paracasei CBA L74) which is the subject of the health claim is sufficiently characterised. The Panel considers that immune defence against pathogens in GI tract and URT is a beneficial physiological effect. One human intervention study from which conclusions can be drawn showed an effect of ‘Nutrimune®’ on immune defence against pathogens in the GI tract and the URT, and the results from one animal study could support an effect of ‘Nutrimune®’ on defence against pathogens in the GI tract. However, there were inconsistencies in the reporting of the process and criteria used for the diagnosis of URTI in the human intervention study, the results of this study have not been replicated, and no evidence was provided for a plausible mechanism by which ‘Nutrimune®’ could exert the claimed effect in vivo in humans. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of ‘Nutrimune®’ and immune defence against pathogens in the gastrointestinal and upper respiratory tracts.

2016 - A CASE-CONTROL STUDY OF NEUROTOXIC METALS IN CEREBROSPINAL FLUID AND RISK OF AMYOTROPHIC LATERAL SCLEROSIS [Abstract in Atti di Convegno]
Vinceti, Marco; Filippini, Tommaso; Mandrioli, Jessica; Fini, Nicola; Salvia, Chiara; Grill, Peter; Michalke, Bernhard
abstract

Many studies have investigated the possible relation between exposure to heavy metals and risk of amyotrophic lateral sclerosis (ALS). We aimed at assessing the levels of two neurotoxic metals, cadmium (Cd), lead (Pb) and mercury (Hg) in cerebrospinal fluid (CSF) of ALS patients and hospital controls. CSF heavy metal content was determined using inductively coupled plasma sector field mass spectrometry (ICP-SF-MS) according to methodologies previously established for biological matrices and specifically for CSF. We obtained CSF samples from 38 ALS cases, including 16 men and 22 women, and from 38 hospital-referred subjects undergoing lumbar puncture because of suspected but later unconfirmed neurological disease, with mean age of 55.5 and 52.26 respectively (range 30– 85). Median heavy metal concentrations were higher in ALS cases compared to controls for Pb (155 vs. 132 ng/l) but lower for Cd (36 vs. 72) and Hg (196 vs. 217). In unconditional multiple logistic regression analysis adjusting for age and sex, we found a disease odds ratio (OR) for the middle and the upper exposure tertiles of 0.8 (0.2-2.6) and 1.4 (95% CI 0.5 to 4.2) for Pb, 0.9 (0.3-2.8) and 0.3 (0.1 to 1.0) for Cd, and 12.4 (2.7-57.3) and 3.03 (0.52-17.55) for Hg. We also conducted sensitivity analyses with log transformed values and with winsorized values by setting data exceeding the 95th percentile to the 95th percentile, but the risk estimates did not substantially change. Our results and particularly the lack of dose-response relations give little support for an involvement of these heavy metals in ALS etiology, with the possible exception of Hg. However, caution should be used in the interpretation of these results due to some study limitations, such as the statistical imprecision of the risk estimates, the hospital-based design of the study, and the potential for unmeasured confounding.

2016 - Air pollution and childhood leukemia [Abstract in Atti di Convegno]
Vinceti, Marco; Filippini, Tommaso; Heck Julia, E; Hatch Elizabeth, E; Rothman Kenneth, J; Crippa, Alessio; Orsini, Nicola
abstract

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2016 - Assessing Cancer Risk from Heavy Metals in Recycling Waste Electrical and Electronic Equipment: Preliminary Results from the WEENMODELS European Life Programme [Abstract in Rivista]
Violi, Federica; Modenese, Alberto; Gobba, Fabriziomaria; Ferrari, Anna Maria; Rimini, Bianca; Gamberini, Rita; Pini, Martina; Neri, Paolo; Filippini, Tommaso; Grasselli, Luigi; Montanari, Pinuccia; Vinceti, Marco
abstract

Introduction The growing amount of waste derived from electrical and electronic equipment (WEEE) poses significant challenges to waste management, due to the presence of toxic chemicals with environmental and health implications for the general population and for occupationally-exposed workers. Methods Based on an toxicological and epidemiologic evaluation, we carried out a health risk assessment to evaluate the cancer risk deriving from environmental and occupational exposure to heavy metals released during different WEEE recycling procedures (electronic scrap in blister copper, treatment of metals recovery in copper smelter, treatment of shredding, pyrometallurgical treatment of Li-ion battery). We considered the typical WEEE production in a municipality of 150.0000 inhabitants, carrying out a Life Cycle Assessment. Outdoor (1 square km around a treatment plant) and indoor (for a factory volume of 3200 m3) emissions generated during the WEEE recycling procedures were computed. In particular, we estimated the amount of Cd, Ni and As inhaled by the potentially exposed population. We computed the cancer risk due to inhalation of these heavy metals in residents and workers using the methodology proposed by the California Office of Environmental Health and Hazard Assessment Results For the metals considered, our results showed negligible cancer risk (from 2,21x10-11 to 4,31x10-08) for the general population around the plant. On the converse, occupational exposures linked to specific procedures were associated with a cancer risk of 1,42x10-3 for workers in the shredding procedures mainly due to Ni exposure, and of 4,68x10-4 for workers with electronic scrap and exposed to As. Conclusions Based on our preliminary results from an integrated toxicological and epidemiologic approach, WEEE life cycle may be linked to health risks for workers in the recycling procedures, while it does not seem to adversely affect health of the general population around the treatment plants.

2016 - Assessing cancer risk from heavy metal exposure in recycling waste of electrical and electronic equipment: preliminary results from the Weeenmodels European Life Programme. [Abstract in Atti di Convegno]
Violi, Federica; Modenese, Alberto; Gobba, Fabriziomaria; Ferrari, Anna Maria; Rimini, Bianca; Gamberini, Rita; Pini, M; Neri, P; Filippini, Tommaso; Grasselli, Luigi; Montanari, P; Vinceti, Marco
abstract

Introduction The growing amount of waste derived from electrical and electronic equipment (WEEE) poses significant challenges to waste management, due to the presence of toxic chemicals with environmental and health implications for the general population and for occupationally-exposed workers. Methods Based on an toxicological and epidemiologic evaluation, we carried out a health risk assessment to evaluate the cancer risk deriving from environmental and occupational exposure to heavy metals released during different WEEE recycling procedures (electronic scrap in blister copper, treatment of metals recovery in copper smelter, treatment of shredding, pyrometallurgical treatment of Li-ion battery). We considered the typical WEEE production in a municipality of 150.0000 inhabitants, carrying out a Life Cycle Assessment. Outdoor (1km2 around a treatment plant) and indoor (for a factory volume of 3200m3) emissions generated during the WEEE recycling procedures were computed. In particular, we estimated the amount of Cd, Ni and As inhaled by the potentially exposed population. We computed the cancer risk due to inhalation of these heavy metals in residents and workers using the methodology proposed by the California Office of Environmental Health and Hazard Assessment Results For the metals considered, our results showed negligible cancer risk (from 2,21x10-11 to 4,31x10-08) for the general population around the plant. On the converse, occupational exposures linked to specific procedures were associated with a cancer risk of 1,42x10-3 for workers in the shredding procedures mainly due to Ni exposure, and of 4,68x10-4 for workers with electronic scrap and exposed to As. Conclusions Based on our preliminary results from an integrated toxicological and epidemiologic approach, WEEE life cycle may be linked to health risks for workers in the recycling procedures, while it does not seem to adversely affect health of the general population around the treatment plants.

2016 - CANCER RISK FROM HEAVY METAL EXPOSURE IN RECYCLING WASTE OF ELECTRICAL AND ELECTRONIC EQUIPMENT: PRELIMINARY RESULTS FROM THE WEEENMODELS EUROPEAN LIFE PROGRAM [Abstract in Atti di Convegno]
Violi, Federica; Modenese, Alberto; Gobba, Fabriziomaria; Ferrari, Anna Maria; Rimini, Bianca; Gamberini, Rita; Pini, Martina; Neri, Paolo; Filippini, Tommaso; Grasselli, Luigi; Montanari, Pinuccia; Vinceti, Marco
abstract

Background and objectives: When electrical and electronic equipment reaches its end of life, it becomes ‘Waste Electrical and Electronic Equipment’ (WEEE). The growing amount of this type of waste has posed significant challenges to waste management, since WEEE contains a whole range of toxic chemicals having relevant environmental and health implications. The WEEE life cycle may expose the general population and workers to various toxic chemicals, such as heavy metals. We conducted a health risk assessment to evaluate the cancer risk derived from environmental and occupational exposure to trace elements from different recycling procedures (electronic scrap in blister copper, treatment of metals recovery in copper smelter, treatment of shredding, pyrometallurgical treatment of Li-ion battery). We considered the typical production of WEEE in a municipality of 150.0000 inhabitants, where a Life Cycle assessment (LCA) was carried out. Methods: Outdoor (1km2 around a WEEE treatment plant) and indoor (factory volume of 3200m3) emissions generated from the above-mentioned procedures were computed, to perform a health risk assessment for occupationally-exposed workers and for the general population around the plant. Dose of the heavy metals cadmium, nickel, arsenic inhaled by the potentially exposed population was estimated using the values obtained through a toxicological model. Cancer risk due to inhalation was calculated using the method proposed by the California Office of Environmental Health and Hazard Assessment. Results and Conclusions: For the heavy metals considered, generated from WEEE treatment, these preliminary results show negligible cancer risk for the general population. On the converse, some risks may be present for occupational exposures linked to specific procedures (from cancer risk of 1,42x10-3 for men working in shredding procedure and exposed to nickel to cancer risk of 4,68x10- 4 for women working with electronic scrap and exposed to arsenic).

2016 - Cardiovascular Risk Assessment in People Affected with Diabetes in Primary Care. [Capitolo/Saggio]
Borsari, Lucia; Lorenzini, M; Riccomi, S; Solfrini, V; Vinceti, Marco; Capelli, O.
abstract

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2016 - Determinants of serum cadmium levels in a Northern Italy community: A cross-sectional study. [Articolo su rivista]
Filippini, Tommaso; Michalke, B; Malagoli, Carlotta; Grill, P; Bottecchi, Iliaria; Malavolti, Marcella; Vescovi, L; Sieri, S; Krogh, V; Cherubini, A; Maffeis, G; Modenesi, M; Castiglia, P; Vinceti, Marco
abstract

Introduction Cadmium (Cd) is a heavy metal and a serious environmental hazard to humans. Some uncertainties still exist about major sources of Cd exposure in non-occupationally exposed subjects in addition to cigarette smoking, such as diet and outdoor air pollution. We sought to determine the influence of these sources on a biomarker of exposure, serum Cd concentration. Methods We recruited 51 randomly selected residents from an Italian urban community, from whom we obtained detailed information about dietary habits and smoking habits, and a blood sample for serum Cd determination. We also assessed outdoor air Cd exposure, by modeling outdoor air levels of particulate matter ≤10 µm (PM10) from motorized traffic at geocoded subjects’ residence. Results In crude analysis, regression beta coefficients for dietary Cd, smoking and PM10 on serum Cd levels were 0.03 (95% CI -0.83 to 0.88), 6.96 (95% CI -0.02 to 13.95) and 0.62 (95% CI -0.19 to 1.43), respectively. In the adjusted analysis, regression beta coefficients were -0.34 (95% CI -1-40 to 0.71), 5.81 (95% CI -1.43 to 13.04) and 0.47 (95% CI -0.35 to 1.29), respectively. Conclusion Cigarette smoking was the most important factor influencing serum Cd in our non-occupationally exposed population, as expected, while dietary Cd was not associated with this biomarker. Outdoor air pollution, as assessed through exposure to particulate matter generated by motorized traffic, was an additional source of Cd exposure.

2016 - Dietary reference values for potassium [Articolo su rivista]
EFSA NDA, Panel; Dominique, Turck; Jean Louis, Bresson; Barbara, Burlingame; Tara, Dean; Susan Fairweather, Tait; Marina, Heinonen; Karen Ildico Hirsch, Ernst; Inge, Mangelsdorf; Harry, Mcardle; Monika Neuhäuser, Berthold; Grażyna, Nowicka; Kristina, Pentieva; Yolanda, Sanz; Alfonso, Siani; Anders, Sjödin; Martin, Stern; Daniel, Tomé; Henk Van, Loveren; Vinceti, Marco; Peter, Willatts; Peter, Aggett; Ambroise, Martin; Hildegard, Przyrembel; Anja, Brönstrup; Janusz, Ciok; Agnès de Sesmaisons, Lecarré; Androniki, Naska
abstract

Scientific opinion on Dietary Reference Values for potassium.

2016 - Dietary reference values for thiamin [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Ildico Hirsch‐Ernst, Karen; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Lamberg‐allardt, Christel; Przyrembel, Hildegard; Tetens, Inge; Gudelj Rakic, Jelena; Ioannidou, Sofia; Sesmaisons‐lecarré, Agnès; Forss, Annette Cecilia; Neuhäuser‐berthold, Monika
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derived dietary reference values (DRVs) for thiamin (vitamin B1). The Panel considers that data from depletion–repletion studies in adults on the amount of dietary thiamin intake associated with the erythrocyte transketolase activity coefficient (αETK) &lt; 1.15, generally considered to reflect an adequate thiamin status, or with the restoration of normal (baseline) erythrocyte transketolase activity, without a sharp increase in urinary thiamin excretion, can be used to estimate thiamin requirement. In the absence of new scientific evidence, the Panel endorses the average requirement (AR) of 0.072 mg/MJ (0.3 mg/1,000 kcal) for all adults proposed by the Scientific Committee for Food (SCF) in 1993 on the basis of one depletion–repletion study, in which both αETK and urinary thiamin excretion were measured. Results from other depletion–repletion studies are in agreement with this value. The Panel agrees on the coefficient of variation of 20% used by the SCF to cover uncertainties related to distribution of thiamin requirements in the general population, and endorses the population reference intake (PRI) of 0.1 mg/MJ (0.4 mg/1,000 kcal) set by the SCF for all adults. The same AR and PRI as for adults, expressed in mg/MJ, are proposed for infants aged 7–11 months, children aged 1 to &lt; 18 years, and during pregnancy and lactation, under the assumption that the relationship between thiamin requirement and energy requirement is the same in all population groups.

2016 - Dietary reference values for vitamin D [Articolo su rivista]
Bresson, J. L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K. I.; Mangelsdorf, I.; McArdle, H.; Naska, A.; Neuhauser-Berthold, M.; Nowicka, G.; Pentieva, K.; Sanz, Y.; Siani, A.; Sjodin, A.; Stern, M.; Tome, D.; Turck, D.; Van Loveren, H.; Vinceti, M.; Willatts, P.
abstract

Following a request from the European Commission, the EFSA Panel&nbsp;on Dietetic Products, Nutrition and Allergies (NDA) derived dietary reference values (DRVs) for vitamin D. The Panel&nbsp;considers that serum 25(OH)D concentration, which reflects the amount of vitamin D attained from both cutaneous synthesis and dietary sources, can be used as a biomarker of vitamin D status in adult and children populations. The Panel&nbsp;notes that the evidence on the relationship between serum 25(OH)D concentration and musculoskeletal health outcomes in adults, infants and children, and adverse pregnancy-related health outcomes, is widely variable. The Panel&nbsp;considers that Average Requirements and Population Reference Intakes for vitamin D cannot be derived, and therefore defines adequate intakes (AIs), for all population groups. Taking into account the overall evidence and uncertainties, the Panel&nbsp;considers that a serum 25(OH)D concentration of 50&nbsp;nmol/L is a suitable target value for all population groups, in view of setting the AIs. For adults, an AI for vitamin D is set at 15&nbsp;μg/day, based on a meta-regression analysis and considering that, at this intake, the majority of the population will achieve a serum 25(OH)D concentration near or above the target of 50&nbsp;nmol/L. For children aged 1–17&nbsp;years, an AI for vitamin D is set at 15&nbsp;μg/day, based on the meta-regression analysis. For infants aged 7–11&nbsp;months, an AI for vitamin D is set at 10&nbsp;μg/day, based on trials in infants. For pregnant and lactating women, the Panel&nbsp;sets the same AI as for non-pregnant non-lactating women, i.e. 15&nbsp;μg/day. The Panel&nbsp;underlines that the meta-regression was done on data collected under conditions of assumed minimal cutaneous vitamin D synthesis. In the presence of cutaneous vitamin D synthesis, the requirement for dietary vitamin D is lower or may even be zero.

2016 - Does maternal exposure to benzene and PM10 during pregnancy increase the risk of congenital anomalies? A population-based case-control study [Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; Malavolti, Marcella; Cherubini, Andrea; Maffeis, Giuseppe; Rodolfi, Rossella; Heck, Julia E; Astolfi, Gianni; Calzolari, Elisa; Nicolini, Fausto
abstract

A few studies have suggested an association between maternal exposure to ambient air pollution from vehicular traffic and risk of congenital anomalies in the offspring, but epidemiologic evidence is neither strong nor entirely consistent. In a population-based case-control study in a Northern Italy community encompassing 228 cases of birth defects and 228 referent newborns, we investigated if maternal exposure to PM10 and benzene from vehicular traffic during early pregnancy, as estimated through a dispersion model, was associated with excess teratogenic risk. In conditional logistic regression analysis, and with adjustment for the other pollutant, we found that higher exposure to PM10 but not benzene was associated with increased risk of birth defects overall. Anomaly categories showing the strongest dose-response relation with PM10 exposure were musculoskeletal and chromosomal abnormalities but not cardiovascular defects, with Down syndrome being among the specific abnormalities showing the strongest association, though risk estimates particularly for the less frequent defects were statistically very unstable. Further adjustment in the regression model for potential confounders did not considerably alter the results. All the associations were stronger for average levels of PM10 than for their maximal level. Findings of this study give some support for an excess teratogenic risk following maternal exposure during pregnancy to PM10, but not benzene. Such association appears to be limited to some birth defect categories.

2016 - Environmental and occupational risk factors of amyotrophic lateral sclerosis: a population-based case control study [Abstract in Atti di Convegno]
Violi, Federica; Fiore, Maria; Filippini, Tommaso; Malagoli, Carlotta; Ledda, Caterina; Mauceri, Cristina; Dimartino, Angela; Mandrioli, Jessica; Fini, Nicola; Patti, Francesco; Ferrante, Margherita; Vinceti, Marco
abstract

Background and aims Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor neuron. Its etiology is still largely unknown, except for some rare forms of genetic origin, but environmental factors may have an important role. Methods We performed a population case-control study in three Italian provinces (Modena, Reggio Emilia and Catania) in order to assess the possible etiologic role of some environmental factors. We administered 877 questionnaires by mail or by person in a neurological office to collect information about personal, clinical and professional history to ALS cases newly diagnosed in the 2008-2011 period and age- and sex-matched population controls. Results Analysis of the returned questionnaires (18,5%, 61 cases and 101 controls) showed an increased risk when examining clinical information for reported trauma (OR 1.20, 95%CI 0.63-2.30), head (OR 3.04, 1.23-7.55) and chest trauma (OR 2.65, 95%CI 0.72-9.78). History of previous fractures has an OR of 1.10 (95%CI 0.58-2.11), but for head fracture OR raised to 5.17 (95%CI 0.53-50.88). With reference to occupational history an excess of risk was found for employment in agriculture (OR 2.44, 95%CI 1.03-5.79) and for welding (OR 1.25, 95%CI 0.27-5.80). Occupational exposure to lead (OR 1.27, 95%CI 0.74-2.17), thinners (OR 1.12, 95%CI 0.66-1.91) and solvents (toluene/xylene) (OR 1.24, 95%CI 0.72-2.13) provide some excess risk. Considering 'extra-working' activities, we found an excess disease risk for hunting (OR 1.69, 95%CI 0.33-8.65), painting (OR 1.46, 95%CI 0.47-4.58), modelling with glue (OR 1.72, 95%CI 0.57-5.17), gardening (OR 1.15, 95%CI 0.64-2.08), football (OR 1.04, 95%CI 0.44-2.47) and pesticides (OR 1.98, 95%CI 0.76-5.12) and herbicides use (OR 2.27, 95%CI 0.72-7.19). Conclusions Thoughthese results must be assessed with caution for the risk of selection and information bias, they suggest potential etiologic clues to ALS etiology which are worthy of further study.

2016 - Epidemiologia, fattori di rischio e caratteristiche cliniche e socio-assistenziali delle early-onset dementia (EOD): metodologia di uno studio nella provincia di Modena. [Abstract in Atti di Convegno]
Salvia, C; Chiari, A; Tondelli, Manuela; Vinceti, Marco
abstract

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2016 - Esposizione occupazionale negli addetti alle attività di riciclo e riuso dei rifiuti di apparecchiature elettriche e elettroniche (RAEE): dati preliminari dal progetto WEEENMODELS. [Abstract in Atti di Convegno]
Modenese, A.; Violi, F.; Pini, M.; Gioia, T. C.; Ferrari, A. M.; Gamberini, R.; Grasselli, L.; Montanari, G.; Neri, P.; Rimini, B.; Vinceti, M.; Gobba, F.
abstract

Esposizione occupazionale negli addetti alle attività di riciclo e riuso dei rifiuti di apparecchiature elettriche e elettroniche (RAEE): dati preliminari dal progetto WEEENMODELS.

2016 - Esposizione passiva a pesticidi e rischio di leucemia infantile. [Abstract in Atti di Convegno]
Malagoli, Carlotta; Malavolti, Marcella; Costanzini, Sofia; Fabbi, Sara; Teggi, Sergio; Arcolin, Elisa; De Girolamo, G; Oleari, P; Palazzi, G; Vinceti, Marco
abstract

Esposizione passiva a pesticidi e rischio di leucemia infantile.

2016 - FOOD INTAKE OF ZINC AND CADMIUM IN NORTHERN ITALY POPULATION [Abstract in Atti di Convegno]
Malagoli, Carlotta; Malavolti, Marcella; Sieri, Sabina; Krogh, Vittorio; Bottecchi, Ilaria; Filippini, Tommaso; Modenesi, Marina; Vescovi, Luciano; Vinceti, Marco
abstract

Background: Some trace elements are essential for humans; their deficiency may cause abnormal biological functions, whereas excessive intakes may produce adverse health effects. The aim of this study was to estimate the daily intake through diet of zinc (Zn) and cadmium (Cd) in a Northern Italy population and verify the compliance with recommended levels of intake for Italian population recently updated by Italian Society of Human Nutrition (SINU). Methods: We investigated dietary intake of Zn, and Cd in 719 residents of five provinces of Emilia Romagna region in Northern Italy, using a validated semi-quantitative food frequency questionnaire designed to capture eating behaviors in Italy, specifically developed as part of the European Prospective Investigation into Cancer and Nutrition study, for the Northern Italy population. Results: We analyzed the diet of 319 men and 400 women, mean (±SD) aged 59.0 (± 14.0) and 52.3 (±14.1) respectively. The daily average (±SD) intake of Zn and Cd was 11.99 (±4.31) mg/day and 15.06 (±8.41) μg/day in men and 10.83 (±4.06) mg/day and 13.23 (±7.23) μg/day in women. Dietary intake levels of Zn were above the recommended values and well below the upper safe levels set by SINU for healthy adults. Cd intake did not exceed the safety limits established by European Food Safety Authority (EFSA). Conclusions: Our analysis suggested that dietary intake of the above-mentioned essential and toxic trace elements characterizing this Northern Italy population is within the range defined as safe by SINU and EFSA.

2016 - GASTROSTOMY, BODY WEIGHT LOSS AND SURVIVAL IN AMYOTROPHIC LATERAL SCLEROSIS: A POPULATIONBASED STUDY [Abstract in Rivista]
Fasano, A; Fini, N; Ferraro, D; Ferri, L; Vinceti, M; Mandrioli, J
abstract

2016 - General scientific guidance for stakeholders on health claim applications [Articolo su rivista]
Bresson, J. L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K. I.; Mangelsdorf, I.; Mcardle, H.; Naska, A.; Neuhauser-Berthold, M.; Nowicka, G.; Pentieva, K.; Sanz, Y.; Siani, A.; Sjodin, A.; Stern, M.; Tome, D.; Turck, D.; Van Loveren, H.; Vinceti, M.; Willatts, P.
abstract

The European Food Safety Authority (EFSA) asked the Panel on Dietetic Products Nutrition and Allergies (NDA) to update the General guidance for stakeholders on the evaluation of Article 13.1, 13.5 and 14 health claims published in March 2011. Since then, the NDA Panel has completed the evaluation of Article 13.1 claims except for claims put on hold by the European Commission, and has evaluated additional health claim applications submitted pursuant to Articles 13.5, 14 and also 19. In addition, comments received from stakeholders indicate that general issues that are common to all health claims need to be further clarified and addressed. This guidance document aims to explain the general scientific principles applied by the NDA Panel for the evaluation of all health claims and outlines a series of steps for the compilation of applications. The general guidance document represents the views of the NDA Panel based on the experience gained to date with the evaluation of health claims, and it may be further updated, as appropriate, when additional issues are addressed.

2016 - Guidance on the preparation and presentation of an application for authorisation of a novel food in the context of Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bresson, J. -L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K. I.; Mangelsdorf, I.; Mcardle, H.; Naska, A.; Neuhauser-Berthold, M.; Nowicka, G.; Pentieva, K.; Sanz, Y.; Siani, A.; Sjodin, A.; Stern, M.; Tome, D.; Vinceti, M.; Willatts, P.; Engel, K. -H.; Marchelli, R.; Poting, A.; Poulsen, M.; Salminen, S.; Schlatter, J.; Arcella, D.; Gelbmann, W.; de Sesmaisons-Lecarre, A.; Verhagen, H.; van Loveren, H.
abstract

Following the adoption of Regulation (EU) 2015/2283 of the European Parliament and of the Council on novel foods, the European Commission requested EFSA to update and develop scientific and technical guidance for the preparation and presentation of applications for authorisation of novel foods. This guidance presents a common format for the organisation of the information to be presented in order to assist the applicant in preparing a well-structured application to demonstrate the safety of the novel food. The application should be comprehensive and complete. This guidance outlined the data needed for the safety assessments of novel foods. Requirements which should be covered in all applications relate to the description of the novel food, production process, compositional data, specification, proposed uses and use levels, and anticipated intake of the novel food. Further sections on the history of use of the novel food and/or its source, absorption, distribution, metabolism, excretion, nutritional information, toxicological information and allergenicity should be considered by the applicant by default. If not covered in the application, this should be justified. The applicant should integrate the data presented in the different sections to provide their overall considerations on how the information supports the safety of the novel food under the proposed conditions of use. Where potential health hazards have been identified, they should be discussed in relation to the anticipated intakes of the novel food and the proposed target populations. On the basis of the information provided, EFSA will assess the safety of the novel food under the proposed conditions of use.

2016 - Guidance on the preparation and presentation of thenotification and application for authorisation of traditionalfoods from third countries in the context of Regulation(EU) 2015/2283 [Articolo su rivista]
Dominique, Turck; Jean Louis, Bresson; Barbara, Burlingame; Tara, Dean; Susan, Fairweather Tait; Marina, Heinonen; Karen, Ildico Hirsch Ernst; Inge, Mangelsdorf; Harry, Mcardle; Androniki, Naska; Monika, Neuhäuser Berthold; Grażyna, Nowicka; Kristina, Pentieva; Yolanda, Sanz; Alfonso, Siani; Anders, Sjödin; Martin, Stern; Daniel, Tomé; Vinceti, Marco; Peter, Willatts; Karl Heinz, Engel; Rosangela, Marchelli; Annette, Pöting; Morten, Poulsen; Josef, Schlatter; Wolfgang, Gelbmann; Agnès, de Sesmaisons Lecarré; Hans, Verhagen; Hendrik van, Loveren
abstract

Following the adoption of Regulation (EU) 2015/2283 of the European Parliament and of the Councilon Novel Foods, the European Commission requested EFSA to develop a scientific and technicalguidance for the preparation and presentation of notifications for traditional foods from third countries.This guidance presents a common format for the organisation of the information to be presented inorder to assist the applicant in the preparation of a well-structured dossier. The safety of a traditionalfood should be substantiated by reliable data on its composition, its experience of continued use andits proposed conditions of use. Besides, its normal consumption should not be nutritionallydisadvantageous. To that end, information is requested on the description, production process,composition, stability data, specifications, data from experience of continued use in a third country andon the proposed conditions of use of the traditional food for the EU market. The structure of thenotification dossier should follow the sections presented in this guidance. This guidance is alsointended to support applicants in provi ding the type and quality of information EU Member States andEFSA need for the assessments of traditional foods from third countries. The applic ation should becomprehensive and complete. The applicant should integrate the information on the compo sition andthe experience of continued use and provide a concise overall conside ration on how this substantiatesthe history of safe use of the traditional food and how this relates to the proposed conditions of usefor the EU. Where potential health hazards have been identified on the basis of the composition and/ordata from the experience of continu ed use, they should be discussed. On the basis of the informationprovided, EFSA will assess the safety related to the consumption of the traditional food under theproposed conditions of use.

2016 - Health risks related to environmental exposure in WEEE management [Capitolo/Saggio]
Vinceti, Marco; Violi, Federica
abstract

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2016 - INTAKE OF IRON IN A NORTHERN ITALY POPULATION [Abstract in Atti di Convegno]
Malavolti, Marcella; Malagoli, Carlotta; Sieri, Sabina; Krogh, Vittorio; Vinceti, Marco
abstract

Backgrounds: Globally an estimated two billion people suffer from a chronic deficiency of micronutrients. Iron deficiency and related anaemia is a significant public health problem in several countries, and it becomes a very serious condition in poor resources countries. Methods: We investigated dietary iron intake of 719 residents of five provinces of the Emilia Romagna region in Northern Italy, using a validated semi-quantitative food frequency questionnaire designed to capture eating behaviors in Italy. This questionnaire was specifically developed as part of the European Prospective Investigation into Cancer and Nutrition study for the Northern Italy population. We focused our attention especially in non-menopausal women (considered as aged <50), a population at high risk for anemia, to assess if their iron intake is adequate taking into account the population reference intake (PRI) recently established by the European Food Safety Authority (EFSA). Results: We found an average iron intake of 13.68 (±4.43) mg/day in males and 11.93 (±4.12) mg/day in females without any differences between younger and older women (<50 or ≥ 50). These intakes by young women were lower the intakes recommended by EFSA for non-menopausal women (16 mg/day). Conclusions: Our analysis suggested that women iron intake in this northern Italy population is much lower than the recommended levels. Public health interventions should be considered to increase iron intake in this population and counteract the risk of iron deficiency anaemia.

2016 - Livelli di piombo, cadmio e mercurio nel liquido cerebrospinale e rischio di sclerosi laterale amiotrofica: uno studio caso-controllo. [Abstract in Atti di Convegno]
Filippini, Tommaso; Violi, Federica; Mandrioli, Jessica; Bargellini, Annalisa; Weuve, J; Fini, N; Grill, P; Michalke, B; Vinceti, Marco
abstract

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2016 - Long-term mortality patterns in a residential cohort exposed to inorganic selenium in drinking water. [Articolo su rivista]
Vinceti, Marco; Ballotari, P; Steinmaus, C; Malagoli, Carlotta; Luberto, F; Malavolti, Marcella; Rossi Giorgi, P.
abstract

Selenium (Se) is a metalloid of considerable nutritional and toxicological importance in humans. To date, limited epidemiologic evidence exists about the health effects of exposure to this trace element in drinking water. We investigated the relationship between Se levels in water and mortality in the municipality of Reggio Emilia, Italy, where high levels of Se were previously observed in drinking water. From 1974 to 1985, 2065 residents consumed drinking water with Se levels close to the European standard of 10 μg/l, in its inorganic hexavalent form (selenate). Follow-up was conducted for the years 1986–2012 in Reggio Emilia and a lesser exposed comparison group of around 100,000 municipal residents, with comparable socio-demographic characteristics. Overall mortality from all causes, cardiovascular disease and cancer showed little evidence of differences. However, excess rate ratios were seen for some site specific cancers such as neoplasms of buccal cavity and pharynx, urinary tract, lymphohematopoietic tissue, melanoma, and two neurodegenerative diseases, Parkinson's disease and amyotrophic lateral sclerosis. Excess mortality in the exposed cohort for specific outcomes was concentrated in the first period of follow-up (1986–1997), and waned starting 10 years after the high exposure ended. We also found lower mortality from breast cancer in females during the first period of follow-up. When we extended the analysis to include residents who had been consuming the high-selenium drinking water for a shorter period, mortality rate ratios were also increased, but to a lesser extent. Overall, we found that the mortality patterns related to long-term exposure to inorganic hexavalent selenium through drinking water were elevated for several site-specific cancers and neurodegenerative disease.

2016 - Meta-Analysis of Potassium Intake and the Risk of Stroke [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Crippa, Alessio; de Sesmaisons, Agnes; Wise, Lauren; Orsini, Nicola
abstract

Background-—The possibility that lifestyle factors such as diet, specifically potassium intake, may modify the risk of stroke has been suggested by several observational cohort studies, including some recent reports. We performed a systematic review and meta-analysis of existing studies and assessed the dose–response relation between potassium intake and stroke risk. Methods and Results-—We reviewed the observational cohort studies addressing the relation between potassium intake, and incidence or mortality of total stroke or stroke subtypes published through August 6, 2016. We carried out a meta-analysis of 16 cohort studies based on the relative risk (RR) of stroke comparing the highest versus lowest intake categories. We also plotted a pooled dose–response curve of RR of stroke according to potassium intake. Analyses were performed with and without adjustment for blood pressure. Relative to the lowest category of potassium intake, the highest category of potassium intake was associated with a 13% reduced risk of stroke (RR=0.87, 95% CI 0.80–0.94) in the blood pressure–adjusted analysis. Summary RRs tended to decrease when original estimates were unadjusted for blood pressure. Analysis for stroke subtypes yielded comparable results. In the spline analysis, the pooled RR was lowest at 90 mmol of potassium daily intake (RRs=0.78, 95% CI 0.70–0.86) in blood pressure–adjusted analysis, and 0.67 (95% CI 0.57–0.78) in unadjusted analysis. Conclusions-—Overall, this dose–response meta-analysis confirms the inverse association between potassium intake and stroke risk, with potassium intake of 90 mmol (!3500 mg)/day associated with the lowest risk of stroke.

2016 - More results but no clear conclusion on selenium and cancer. [Articolo su rivista]
Vinceti, Marco; Rothman, Kj
abstract

More results but no clear conclusion on selenium and cancer.

2016 - Passive exposure to agricultural pesticides and risk of childhood leukemia in an Italian community [Articolo su rivista]
Malagoli, Carlotta; Costanzini, Sofia; Heck, Julia E.; Malavolti, Marcella; De Girolamo, Gianfranco; Oleari, Paola; Palazzi, Giovanni; Teggi, Sergio; Vinceti, Marco
abstract

Background Exposure to pesticides has been suggested as a risk factor for childhood leukemia, but definitive evidence on this relation and the specific pesticides involved is still not clear. Objective We carried out a population-based case-control study in a Northern Italy community to assess the possible relation between passive exposure to agricultural pesticides and risk of acute childhood leukemia. Methods We assessed passive pesticide exposure of 111 childhood leukemia cases and 444 matched controls by determining density and type of agricultural land use within a 100-m radius buffer around children's homes. We focused on four common crop types, arable, orchard, vineyard and vegetable, characterized by the use of specific pesticides that are potentially involved in childhood induced leukemia. The use of these pesticides was validated within the present study. We computed the odds ratios (OR) of the disease and their 95% confidence intervals (CI) according to type and density of crops around the children's homes, also taking into account traffic pollution and high-voltage power line magnetic field exposure. Results Childhood leukemia risk did not increase in relation with any of the crop types with the exception of arable crops, characterized by the use of 2.4-D, MCPA, glyphosate, dicamba, triazine and cypermethrin. The very few children (n&nbsp;=&nbsp;11) residing close to arable crops had an OR for childhood leukemia of 2.04 (95% CI 0.50–8.35), and such excess risk was further enhanced among children aged &lt;5 years. Conclusions Despite the null association with most crop types and the statistical imprecision of the estimates, the increased leukemia risk among children residing close to arable crops indicates the need to further investigate the involvement in disease etiology of passive exposure to herbicides and pyrethroids, though such exposure is unlikely to play a role in the vast majority of cases.

2016 - Pesticidi organoclorurati, bifenili policlorurati e idrocarburi aromatici policiclici nel liquido cefalorachidiano di pazienti con sclerosi laterale amiotrofica: uno studio caso-controllo [Abstract in Atti di Convegno]
Violi, Federica; Tzatzarakis, M; Mandrioli, Jessica; Fini, N; Fasano, Antonio; Malagoli, Carlotta; Tsatsakis, A; Vinceti, Marco
abstract

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2016 - Reduced levels of alpha-1-antitrypsin in cerebrospinal fluid of amyotrophic lateral sclerosis patients: a novel approach for a potential treatment [Articolo su rivista]
Wormser, Uri; Mandrioli, Jessica; Vinceti, Marco; Fini, Nicola; Sintov, Amnov; Brodsky, Berta; Proskura, Elena; Finkelstein, Yoram
abstract

Abstract Background: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative motor neuron disease that involves activation of the immune system and inflammatory response in the nervous system. Reduced level of the immuno-modulatory and anti-inflammatory protein alpha-1-antitrypsin (AAT) is associated with inflammation-related pathologies. The objective of the present is to determine AAT levels and IL-23 in the cerebrospinal fluid (CSF) of ALS patients and control group. Findings: CSF samples from newly diagnosed ALS patients and age-matched controls were analyzed for AAT and IL-23 by ELISA and magnetic luminex screening, respectively. A statistically significant reduction of 45 % in mean AAT levels was observed in the CSF of ALS patients (21.4 μg/ml) as compared to the control group (mean 38.8 μg/ml, p = 0.013). A statistically significant increase of 30.8 % in CSF mean levels of the pro-inflammatory cytokine IL-23 was observed in ALS patients (1647 pg/ml) in comparison to the controls (1259 pg/ml, p = 0.012). A negative correlation coefficient (r = −0.543) was obtained by linear regression analysis of the two measured parameters (p = 0.036). Conclusions: Reduced AAT and elevated IL-23 CSF levels support the notion of neuroinflammatory process occurring in ALS patients. Increasing AAT levels in the patients’ nervous system should be further investigated as a new therapeutic approach and a novel potential tool for ALS treatment.

2016 - Rischio di leucemia infantile in relazione al mese di nascita: studio caso-controllo basato sui dati del Registro AIEOP. [Abstract in Atti di Convegno]
Malavolti, Marcella; Filippini, Tommaso; Malagoli, Carlotta; Arcolin, Elisa; De Girolamo, G; Oleari, P; Palazzi, G; Vinceti, Marco
abstract

Rischio di leucemia infantile in relazione al mese di nascita: studio caso-controllo basato sui dati del Registro AIEOP.

2016 - Risk of childhood leukemia and exposure to outdoor air pollution. Updated review and dose-response meta-analysis [Abstract in Atti di Convegno]
Filippini, Tommaso; Crippa, Alessio; Orsini, Nicola; Vinceti, Marco
abstract

Leukemia is the most frequent malignant disease of childhood. Most epidemiologic studies have suggested that exposure to traffic pollutants may increase the risk of childhood leukemia. We updated our previous review and metaanalysis as some recent studies have now available, and we also performed a dose-response metaanalysis using traffic estimators.

2016 - Safety of EstroG-100™ as a novel food pursuant to Regulation (EC) No 258/97 [Articolo su rivista]
Dominique, Turck; Jean Louis, Bresson; Barbara, Burlingame; Tara, Dean; Susan, Fairweather Tait; Marina, Heinonen; Karen, Ildico Hirsch Ernst; Inge, Mangelsdorf; Harry, Mcardle; Androniki, Naska; Monika, Neuhäuser Berthold; Grażyna, Nowicka; Kristina, Pentieva; Yolanda, Sanz; Alfonso, Siani; Anders, Sjödin; Martin, Stern; Daniel, Tomé; Vinceti, Marco; Peter, Willatts; Karl Heinz, Engel; Rosangela, Marchelli; Annette, Pöting; Morten, Poulsen; Josef, Schlatter; Emanuela, Turla; Hendrik van, Loveren
abstract

ollowing a request from the European Commission, the EFSA Panel on Dietetic Products, Nutritionand Allergies (NDA ) was asked to deliver an opinion on EstroG-100TMas a novel food (NF) submittedpursuant to Regulation (EC) No 258/97 of the European Parliament and of the Council. The NF isEstroG-100TM, a hot-water extract of a mixture of three herbal roots (Cynanchum wilfordii Hemsley,Phlomis umbrosa Turcz. and Angelica gigas Nakai), which is concentrated and spray-dried. Theinformation provided on the composition, specifications and sta bility of the NF is sufficient, and doesnot raise safety concerns. The applicant intends to use EstroG-100TMin food supplements, with aproposed maximum intake level of 514 mg/day. The target population is post-menopausal women. ThePanel considers that the information provided does not raise safety concerns as regards thegenotoxicity of the NF. The Panel considers that the no-observed-adverse effect level (NOAEL) derivedfrom the subchronic 90-day oral toxicity study with EstroG-100TM, which was supported by observationsin other studies, is 500 mg/kg body weight (bw) per day. Taking into account the NOAEL and theproposed maximum intake level, the Panel considers that the margin of safety of 68 is not sufficient.Based on the absence of chronic toxicity data, increase in effects with exposure duration in toxicitystudies, and the absence of investigatio ns of liver parameters and haematology in human studies, thePanel applies the uncertainty factor of 200 to derive the maximum safe intake level for the NF. Thus,the Panel concludes that the NF, EstroG-100TM, is safe for the use in food supplements at the maximumintake level of 175 mg/day for an adult of 70 kg bw.

2016 - Safety of synthetic l‐ergothioneine (Ergoneine®) as a novel food pursuant to Regulation (EC) No 258/97 [Articolo su rivista]
Dominique, Turck; Jean‐louis, Bresson; Barbara, Burlingame; Tara, Dean; Susan, Fairweather‐tait; Marina, Heinonen; Karen, Ildico Hirsch‐Ernst; Inge, Mangelsdorf; Harry, J. McArdle; Androniki, Naska; Monika, Neuhäuser‐berthold; Grażyna, Nowicka; Kristina, Pentieva; Yolanda, Sanz; Alfonso, Siani; Anders, Sjödin; Martin, Stern; Daniel, Tomé; Vinceti, Marco; Peter, Willatts; Karl–heinz, Engel; Rosangela, Marchelli; Annette, Pöting; Morten, Poulsen; Josef, Schlatter; Reinhard, Ackerl; Henk, van Loveren
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on synthetic l-ergothioneine, marketed as Ergoneine®, as a novel food submitted pursuant to Regulation (EC) No 258/97 of the European Parliament and of the Council. The novel food, synthetic l-ergothioneine, is produced by a one-pot patented manufacturing process. Chemically, l-ergothioneine is a derivative of thiolhistidine, and it is naturally present in a number of foodstuffs such as mushrooms, some varieties of black and red beans, offal and cereals. The production process for the novel food is sufficiently described and does not raise concerns about the safety of the novel food. The information on the composition, specifications, batch-to-batch variability and stability of the novel food is sufficient and does not raise safety concerns. The applicant intends to use the novel food in quantities of up to 5 mg per serving in alcohol-free beverages, cereal bars, milk, fresh dairy products and chocolate. The applicant also proposes to provide the novel food as a food supplement, with a daily dose of up to 30 mg/day for adults and 20 mg/day for children. The target population is children above 3 years of age and the general adult population, except pregnant and breastfeeding women. Considering the NOAEL of 800 mg/kg bw per day, which was based on two subchronic toxicity studies in rats, and the maximum estimated intake levels for l-ergothioneine from all sources, the Panel concludes that the margins of safety of 470 for adults (except pregnant and breastfeeding women) and of 216 for children above 3 years of age are sufficient. The Panel concludes that the novel food, synthetic l-ergothioneine (marketed as Ergoneine®), is safe under the intended conditions of use as specified by the applicant.

2016 - Scientific Opinion on the energy conversion factor of d‐tagatose for labelling purposes [Articolo su rivista]
Dominique, Turck; Jean‐louis, Bresson; Barbara, Burlingame; Susan, Fairweather‐tait; Marina, Heinonen; Karen, Ildico Hirsch‐Ernst; Inge, Mangelsdorf; Harry, J. McArdle; Androniki, Naska; Grażyna, Nowicka; Kristina, Pentieva; Yolanda, Sanz; Alfonso, Siani; Anders, Sjödin; Martin, Stern; Daniel, Tomé; Hendrik, Van Loveren; Vinceti, Marco; Peter, Willatts; Monika, Neuhäuser‐berthold
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutritionand Allergies (NDA) was asked to deliver a scientific opinion on the energy conversion factor ofD-tagatose to be used for calculating the energy value of foods to be declared in nutrition labelling.Energy conversion factors for nutrients for the purpose of nutrition labelling have been set based onthe concept of metabolisable energy (ME). The same methodology has been applied to calculate theenergy conversion factor forD-taga tose in this opinion. The assessment is based on a dossier preparedfor Nutrilab NV and submitted by Bioresco Ltd. At present, data are insufficient to derive an accurateME value forD-tagatose. Relying on the human data indicating a mean absorption rate of 80% (range69–88%) and a urinary excretion of either 1% or 5%, the corresponding energy values forD-tagatosewould be 2.8 kcal/g (11.8 kJ/g) and 2.96 kcal/g (12.4 kJ/g), respectively. Taking into account that theremaining 20% ofD-tagatose which is not absorbed in the sma ll intestine is fermented in the colonand may deliver at least some energy, e.g. in form of short-chain fatty acids, the Panel concludes thata rounded estimate of the energy conversion factor forD-tagatose based on the available data andcalculated as ME would be 3 kcal/g (12.5 kJ/g). The Panel considers that additional data on theabsorption, distribution, metabolism and excretion ofD-tagatose in humans w ould help in thecalculation of a more accurate energy conversion factor forD-tagatose based on the concept of ME.

2016 - Scientific Opinion related to a notification from DuPontNutrition Biosciences Aps on behenic acid from mustardseeds to be used in the manufacturing of certain emulsifierspursuant to Article 21(2) of Regulation (EU) No 1169/2011– for permanent exemption from labelling [Articolo su rivista]
Dominique, Turck; Jean‐louis, Bresson; Barbara, Burlingame; Susan, Fairweather‐tait; Marina, Heinonen; Karen, Ildico Hirsch‐Ernst; Inge, Mangelsdorf; Harry, J. McArdle; Androniki, Naska; Monika, Neuhäuser‐berthold; Grażyna, Nowicka; Kristina, Pentieva; Yolanda, Sanz; Alfonso, Siani; Anders, Sjödin; Martin, Stern; Daniel, Tomé; Hendrik, Van Loveren; Vinceti, Marco; Peter, Willatts; Rosangela, Marchelli; Patrizia, Restani; Tara, Dean
abstract

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition andAllergies (NDA) was asked to deliver a scientific opinion related to a notification from DuPont NutritionBiosciences Aps on behenic acid from mustard seeds to be used in the manufacturing of certainemulsifiers pursuant to Article 21(2) of Regulation (EU) No 1169/2011 – for permanent exemptionfrom labelling. Behenic acid is produced from rapeseed–mustard seed variants prevalent in India,namely Brassica juncea (L.) Czern. (oriental mustard), Brassica rapa (L.) (brown/yellow Sarson orToria), Brassica napus (L.) (rapeseed) and Brassica nigra (L.) W.D.J.Koch (black mustard). No humanor animal allergenicity data were provided by the applic ant for either behenic acid or the emulsifiersmanufactured from beheni c acid. Based on enzyme-linke d immunosorbent assay (ELISA) data, thePanel considers that proteins and peptides may not be carried over into behenic acid after the twodistillation steps reported in the manufacturing process in amounts beyond 1 mg/kg. The Panel notesthat the maximum amount of mustard protein that could be consumed from emulsifiers manufacturedfrom behenic acid (E 470a, E 471 and E 477) on a single occasion by an adult under the proposedconditions of use would be around 0.00119 mg, which is about 1,000 times lower than the proteindoses repo rted to trigger allergic reactions in mustard-allergic individuals (around 1 mg). On the basisof the data presented, the Panel concludes that oral consumption of emulsifiers manufactured usingbehenic acid from mustard seeds (E 470a, E 471 and E 477) are unli kely to trigger an allergic reactionin susceptible individuals (i.e. mustard-allergic individuals) under the proposed conditions of use.

2016 - Se-human serum albumin (Se-HSA) in human serum and its correlation with other selenium species. [Abstract in Atti di Convegno]
Filippini, Tommaso; Vinceti, Marco; Grill, P; Malagoli, Carlotta; Arcolin, Elisa; Iacuzio, Laura; Storani, Simone; Ferrari, A; Michalke, B.
abstract

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2016 - The epidemiology of selenium and human health. [Capitolo/Saggio]
Vinceti, M; Burlingame, B; Filippini, T; Naska, A; Bargellini, A; Borella, P.
abstract

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2016 - Vitamin E and protection of DNA, proteins and lipids from oxidative damage: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Dominique, Turck; Jean Louis, Bresson; Barbara, Burlingame; Tara, Dean; Susan, Fairweather Tait; Marina, Heinonen; Karen Ildico, Hirsch Ernst; Inge, Mangelsdorf; Harry, Mcardle; Androniki, Naska; Monika, Neuhäuser Berthold; Grażyna, Nowicka; Kristina, Pentieva; Yolanda, Sanz; Anders, Sjödin; Martin, Stern; Daniel, Tomé; Henk, Van Loveren; Vinceti, Marco; Peter, Willatts; Ambroise, Martin; Sean, Strain; Janusz, Ciok; Alfonso, Siani
abstract

Following an application from Specialised Nutrition Europe (formerl y IDACE), submitted forauthorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via theCompetent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) wasasked to deliver an opinion on the scienti fic substa ntiation of a health claim related to vitamin E andprotection of DNA, proteins and lipids from oxid ative dam age. The Panel consider s that vitamin E issufficiently characterised and that protection of DNA, proteins and lipids from oxidative damage is abeneficial physiological effect. The target population proposed by the applicant is infants (from birth)and young children up to 3 years of age. The Panel has pre viously assessed a claim on vitamin E andprotection of DNA, proteins and lipids from oxidative damage with a favourable outcome. The targetpopulation was the general population. The Panel considers that the role of vitamin E in protection ofDNA, proteins and lipids from oxidative damage applies to all ages, including infants and youngchildren up to 3 years of age. The Panel concludes that a cause and effect relationship has beenestablished between the dietary intake of vitamin E and protection of DNA, proteins and lipids fromoxidative damage.

2015 - A review and meta-analysis of outdoor air pollution and risk of childhood leukemia [Articolo su rivista]
Filippini, Tommaso; Heck, J. E.; Malagoli, Carlotta; DEL GIOVANE, Cinzia; Vinceti, Marco
abstract

Leukemia is the most frequent malignant disease affecting children. To date, the etiology of childhood leukemia remains largely unknown. Few risk factors (genetic susceptibility, infections, ionizing radiation, etc.) have been clearly identified, but they appear to explain only a small proportion of cases. Considerably more uncertain is the role of other environmental risk factors, such as indoor and outdoor air pollution.We sought to summarize and quantify the association between traffic-related air pollution and risk of childhood leukemia, and further examined results according to method of exposure assessment, study quality, leukemia subtype, time period, and continent where studies took place. After a literature search yielded 6 ecologic and 20 case-control studies, we scored the studies based on the Newcastle-Ottawa Scale. The studies assessed residential exposure to pollutants from motorized traffic by computing traffic density in the neighboring roads or vicinity to petrol stations, or by using measured or modeled nitrogen dioxide and benzene outdoor air levels. Because heterogeneity across studies was observed, random-effects summary odds ratios (OR) and 95% confidence intervals (CI) were reported. Whenever possible we additionally conducted stratified analyses comparing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Limiting the analysis to high-quality studies (Newcastle-Ottawa Scale ≥ 7), those using traffic density as the exposure assessment metric showed an increase in childhood leukemia risk in the highest exposure category (OR = 1.07, 95% CI 0.93–1.24). However, we observed evidence of publication bias. Results for NO2 exposure and benzene showed an OR of 1.21 (95% CI 0.97–1.52) and 1.64 (95% CI 0.91–2.95) respectively. When stratifying by leukemia type, the results based upon NO2 were 1.21 (95% CI 1.04–1.41) for ALL and 1.06 (95% CI 0.51–2.21) for AML; based upon benzene were 1.09 (95% CI 0.67–1.77) for ALL and 2.28 (95% CI 1.09–4.75) for AML. Estimates were generally higher for exposures in the postnatal period compared to the prenatal period, and for European studies compared to North American studies. Overall, our results support a link between ambient exposure to traffic pollution and childhood leukemia risk, particularly due to benzene.

2015 - Accuratezza della diagnosi di diabete pregestazionale in scheda di dimissione ospedaliera: studio di validazione di una coorte di Modena e Reggio Emilia mediante i registri diabete. [Abstract in Atti di Convegno]
Borsari, Lucia; Malagoli, Carlotta; Violi, Federica; De Girolamo, G; Ballotari, P; Bonora, K; Capelli, O; Solfrini, V; Vinceti, Marco
abstract

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2015 - An approach for manganese biomonitoring using a manganese carrier switch in serum from transferrin to citrate at slightly elevated manganese concentration [Articolo su rivista]
Michalke, B; Aslanoglou, L; Ochsenkühn Petropoulou, M; Bergström, B; Berthele, A; Vinceti, Marco; Lucio, M; Lidén, G.
abstract

After high-dose-short-term exposure (usually from occupational exposure) and even more under low-dose long term exposure (mainly environmental) manganese (Mn) biomonitoring is still problematic since these exposure scenarios are not necessarily reflected by a significant increase of total Mn in blood or serum. Usually, Mn concentrations of exposed and unexposed persons overlap and individual differentiation is often not possible. In this paper Mn speciation on a large sample size (n=180) was used in order to be able to differentiate between highly Mn-exposed or low or unexposed individuals at low total Mn concentration in serum (Mn(S)). The whole sample set consisted of three subsets from Munich, Emilia Romagna region in Italy and from Sweden. It turned out that also at low total Mn(S) concentrations a change in major Mn carriers in serum takes place from Mn-transferrin (Mn-Tf(S)) towards Mn-citrate (Mn-Cit(S)) with high statistical significance (p<0.000002). This carrier switch from Mn-Tf(S) to Mn-Cit(S) was observed between Mn(S) concentrations of 1.5μg/L to ca. 1.7μg/L. Parallel to this carrier change, for sample donors from Munich where serum and cerebrospinal fluid were available, the concentration of Mn beyond neural barriers - analysed as Mn in cerebrospinal fluid (Mn(C)) - positively correlates to Mn-Cit(S) when Mn(S) concentration was above 1.7μg/L. The correlation between Mn-Cit(S) and Mn(C) reflects the facilitated Mn transport through neural barrier by means of Mn-citrate. Regional differences in switch points from Mn-Tf(S) to Mn-Cit(S) were observed for the three sample subsets. It is currently unknown whether these differences are due to differences in location, occupation, health status or other aspects. Based on our results, Mn-Cit(S) determination was considered as a potential means for estimating the Mn load in brain and CSF, i.e., it could be used as a biomarker for Mn beyond neural barrier. For a simpler Mn-Cit(S) determination than size exclusion chromatography inductively coupled plasma mass spectrometry (SEC-ICP-MS), ultrafiltration (UF) of serum samples was tested for suitability, the latter possibly being a preferred choice for routine occupational medicine laboratories. Our results revealed that UF could be an alternative if methodical prerequisites and limitations are carefully considered. These prerequisites were determined to be a thorough cleaning procedure at a minimum Mn(S) concentration >1.5μg/L, as at lower concentrations a wide scattering of the measured concentrations in comparison to the standardized SEC-ICP-MS results were observed.

2015 - Assessment of cadmium levels in serum, toenails and diet: A cross sectional study in Modena, Northern Italy. [Abstract in Atti di Convegno]
Filippini, Tommaso; Bottecchi, Iliaria; Arcolin, Elisa; Iacuzio, Laura; Malagoli, Carlotta; Vescovi, L; Ferrari, Angela; Martino, Antonio; Malavolti, Marcella; Cavazzuti, L; Sieri, S; Krogh, V; Michalke, B; Vinceti, Marco
abstract

Assessment of cadmium levels in serum, toenails and diet: A cross sectional study in Modena, Northern Italy.

2015 - Assessment of selenium and cadmium levels in serum and toenails: A cross-sectional study in Modena, Northern Italy. [Abstract in Atti di Convegno]
Filippini, Tommaso; Malagoli, Carlotta; Arcolin, Elisa; Vinceti, Marco; Michalke, Bernard
abstract

Assessment of selenium and cadmium levels in serum and toenails: A cross-sectional study in Modena, Northern Italy.

2015 - Cadmium dietary intake in a Northern Italy population. [Abstract in Atti di Convegno]
Malavolti, Marcella; Malagoli, Carlotta; Bottecchi, Ilaria; Vescovi, Luciano; Sieri, Sabina; Krogh, Vittorio; Modenesi, M; Vinceti, Marco
abstract

Cadmium dietary intake in a Northern Italy population

2015 - Cadmium exposure and risk of breast cancer: a meta-analysis. [Abstract in Atti di Convegno]
Filippini, Tommaso; Vinceti, Marco
abstract

2015 - Cadmium, lead and mercury levels in cerebrospinal fluid and risk of amyotrophic lateral sclerosis – A case-control study. [Abstract in Atti di Convegno]
Violi, Federica; Filippini, Tommaso; Fini, Nicola; Malagoli, Carlotta; Vinceti, Marco; Bernard, Michalke; Mandrioli, Jessica
abstract

Cadmium, lead and mercury levels in cerebrospinal fluid and risk of amyotrophic lateral sclerosis – A case-control study.

2015 - Correlation between cadmium and selenium blood levels in an Italian population. [Abstract in Atti di Convegno]
Filippini, Tommaso; Storani, Simone; Malagoli, Carlotta; Arcolin, Elisa; Iacuzio, Laura; Castiglia, P; Michalke, B; Vinceti, Marco
abstract

Correlation between cadmium and selenium blood levels in an Italian population.

2015 - Diet Quality and Risk of Melanoma in an Italian Population [Articolo su rivista]
Malagoli, Carlotta; Malavolti, Marcella; Agnoli, Claudia; Crespi, Catherine M; Fiorentini, Chiara; Farnetani, Francesca; Longo, Caterina; Ricci, Cinzia; Albertini, Giuseppe; Lanzoni, Anna; Veneziano, Leonardo; Virgili, Annarosa; Pagliarello, Calogero; Santini, Marcello; Fanti, Pier Alessandro; Dika, Emi; Sieri, Sabina; Krogh, Vittorio; Pellacani, Giovanni; Vinceti, Marco
abstract

Background: Some results from laboratory and epidemiologic studies suggest that diet may influence the risk of melanoma, but convincing evidence for a role of single nutrients or food items is lacking. Diet quality, which considers the combined effect of multiple food items, may be superior for examining this relation. Objective: We sought to assess whether diet quality, evaluated with the use of 4 different dietary indexes, is associated with melanoma risk. Methods: In this population-based case-control study, we analyzed the relation between 4 diet quality indexes, the Healthy Eating Index 2010 (HEI-2010), Dietary Approaches to Stop Hypertension (DASH) index, Greek Mediterranean Index (GMI), and Italian Mediterranean Index (IMI), and melanoma risk in a northern Italian community, with the use of data from 380 cases and 719 matched controls who completed a semiquantitative food frequency questionnaire. Results: In the overall sample, we found an inverse association between disease risk and the HEI-2010 and DASH index, but not the Mediterranean indexes, adjusting for potential confounders (skin phototype, body mass index, energy intake, sunburn history, skin sun reaction, and education). However, in sex stratified analyses, the association appeared only in women (P-trend: 0.10 and 0.04 for the HEI-2010 and DASH index, respectively). The inverse relations were stronger in women younger than age 50 y than in older women, for whom the GMI and IMI scores also showed an inverse association with disease risk (P-trend: 0.05 and 0.02, respectively). Conclusions: These results suggest that diet quality may play a role in cutaneous melanoma etiology among women.

2015 - Dietary cadmium intake and breast cancer risk: a meta-analysis of longitudinal studies and results of the ORDET cohort study. [Abstract in Atti di Convegno]
Vinceti, Marco; Sieri, S; Filippini, Tommaso; Krogh, V.
abstract

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2015 - Dietary cadmium intake in an Italian population. [Abstract in Rivista]
Malavolti, Marcella; Malagoli, Carlotta; Ilaria, Bottecchi; Luciano, Vescovi; Massimo, Modenesi; Paolo, Castiglia; Sabina, Sieri; Vittorio, Krogh; Vinceti, Marco
abstract

Dietary cadmium intake in an Italian population.

2015 - Exploring inconsistencies between observational and experimental studies of selenium and diabetes risk. [Abstract in Rivista]
Vinceti, Marco; Filippini, Tommaso; DEL GIOVANE, Cinzia; Crespi, Cm
abstract

Background: Observational and experimental epidemiologic studies that have addressed the relation between intake of the trace element selenium and cancer risk have yielded strongly conflicting results, as recently reported by a Cochrane review. Most observational studies suggest an inverse association, while randomized controlled trials (RCTs) have indicated a null or direct relation. Little is known about the replication of such inconsistencies when dealing with the risk of other chronic disease. Objectives: We investigated the results of observational and experimental studies linking selenium exposure to the occurrence of type 2 diabetes. Methods: After a literature search we identified 12 observational studies (8 cross-sectional and 4 cohort) and 5 RCTs. Using a random-effects model, we computed the summary relative risk (RR) of type-2 diabetes along with its 95% confidence interval (CI) in subjects with the highest versus the lowest selenium exposure category in observational studies, and in subjects allocated to selenium compared to placebo in the RCTs. Results: Summary RRs were 1.98 (95% CI 1.22-3.23) and 1.13 (0.15-8.45) for cross-sectional studies using serum and toenail selenium for exposure assessment, respectively. Cohort studies based on toenail selenium yielded a summary RR of 0.78 (0.62-0.98), while the only study assessing dietary selenium intake gave a RR of 2.39, (1.32-4.32). For RCTs, summary RR was 1.10 (1.00-1.21) among selenium-supplemented versus placebo. The distinctive feature of the two observational studies (one cross-sectional and one prospective) that failed to find an excess diabetes risk associated with higher selenium exposure was that the subjects were health professionals. Age, gender, study area and other demographic characteristics did not appear to have influenced the results. Conclusions: These results suggest that the ability of observational studies to predict results of RCTs when addressing the health effects of selenium may differ on the basis of the outcome studied (diabetes versus cancer) as well as the indicator used for exposure assessment and the type of population under study.

2015 - FATTORI AMBIENTALI DI RISCHIO DELLA SCLEROSI LATERALE AMIOTROFICA: UNO STUDIO CASO-CONTROLLO DI POPOLAZIONE BASATO SU QUESTIONARI ANAMNESTICI [Abstract in Atti di Convegno]
Violi, F; Fiore, M; Filippini, T; Malagoli, C; Arcolin, E; Iacuzio, L; Ledda, C; Mauceri, C; Dimartino, A; Mandrioli, J; Fini, N; Georgoulopoulou, E; Patti, F; Lo Fermo, S; Sciacca, S; Ferrante, M; Vinceti, M
abstract

Introduzione: La sclerosi laterale amiotrofica (SLA) è una malattia neurodegenerativa progressiva la cui eziologia è ancora sostanzialmente ignota, ad eccezione di alcune rare forme di origine genetica. Numerosi suoi possibili fattori di rischio ambientali sono attualmente oggetto di indagine. Metodi: Abbiamo realizzato uno studio caso-controllo di popolazione nelle province di Modena, Reggio Emilia e Catania, al fine di valutare il ruolo eziologico di alcuni possibili fattori ambientali di rischio. Abbiamo somministrato per via postale un questionario finalizzato alla raccolta di informazioni anamnestiche ai casi di SLA diagnosticati nel periodo 2008-2011 e ad un gruppo di controlli di popolazione appaiati per alcune variabili confondenti. Risultati: Il 35% (n=162, 61 casi e 101 controlli) dei questionari inviati è stato compilato e restituito. In un modello di regressione logistica, i pregressi traumatismi soggetti a valutazione medica sono risultati associati ad un odds ratio (OR) di SLA pari a 1.20 (intervalli di confidenza al 95% (IC 95%) 0.62-2.30), con un valore più elevato (3.04, 1.22-7.55) per traumi alla testa. Gli shock elettrici hanno evidenziato un OR di 2.25 (0.66-7.63). Con riferimento alla storia occupazionale, l’OR associata all’attività lavorativa in ambito agricolo o come saldatore è risultata rispettivamente pari a 2.44 (1.02-5.79) e 1.25 (0.27-5.80). Aver vissuto in zona agricola è stato associato ad un lieve aumento del rischio (OR=1.67, 0.87-3.20), a differenza della pratica sportiva e specificatamente del calcio (OR 0.84 (0.46-1.51) e 1.04 (0.44-2.47). Conclusioni: I risultati ottenuti appaiono di potenziale interesse eziologico e meritevoli di ulteriori approfondimenti, pur tenendo conto del rischio di distorsioni di selezione del campione o di informazione, specie nei pazienti.

2015 - Incidenza della Sclerosi Laterale Amiotrofica nella provincia di Novara: studio di aggregazioni spaziali nel periodo 2002-2012. [Abstract in Atti di Convegno]
Tesauro, M; Filippini, Tommaso; Consonni, M; Mazzini, L; Pisano, F; Chiò, A; Esposito, A; Vinceti, Marco
abstract

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2015 - Increased incidence of childhood leukemia in urban areas: a population-based case-control study [Articolo su rivista]
Malagoli, Carlotta; Malavolti, Marcella; Costanzini, Sofia; Fabbi, Sara; Teggi, Sergio; Palazzi, Giovanni; Arcolin, Elisa; Vinceti, Marco
abstract

Objective. We carried out a population-based case-control study to assess the possibility of an excess risk of childhood leukemia in urban areas, independently from road traffic pollution. Methods. Study subjects were the 111 cases of childhood leukemia diagnosed from 1998 to 2011 among residents of two provinces of the northern Italian Emilia-Romagna region, and 444 controls matched by age and sex. Through mapping of the region carried out by remote sensing, we examined the percentage of urban or rural area in the 100-meter circular buffer around each child's house. We also modeled annual average exposure to benzene and PM10 from vehicular traffic at each residence. Results. In a multivariate model adjusting for benzene and PM10, the odds ratio of leukemia associated with residence in a highly urbanized area and residential area (≥95% land use of this type near the child's home) was 1.4 (95% confidence intervals 0.8-2.4) and 1.3 (0.8-2.2), respectively. An increased risk was also found in association with the proximity to "dumps, scrap yards, and building sites". No association emerged with residence in rural areas or near industrial plants. Conclusions. These results indicate that children living in urban areas experience an excess leukemia risk, independently from exposure to pollutants from vehicles.

2015 - Indice Glicemico e Carico Glicemico e rischio di melanoma in una popolazione della Emilia-Romagna. [Abstract in Atti di Convegno]
Malavolti, Marcella; Malagoli, Carlotta; Brighenti, F; Sieri, S; Krogh, V; Farnetani, Francesca; Longo, Caterina; Pellacani, Giovanni; Vinceti, Marco
abstract

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2015 - Livelli di Cadmio e Manganese e correlazione con caratteristiche individuali e abitudini alimentari - Uno studio di popolazione nel Nord Italia. [Abstract in Atti di Convegno]
Filippini, Tommaso; Malagoli, Carlotta; Storani, Simone; Ferrari, Angela; Cavazzuti, L; De Girolamo, G; Michalke, B; Vinceti, Marco
abstract

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2015 - Long-term mortality in a population exposed to inorganic selenium through drinking water. [Abstract in Atti di Convegno]
Vinceti, Marco; Ballotari, Paola; Malagoli, Carlotta; Luberto, Ferdinando; Malavolti, Marcella; Vicentini, Massimo; Filippini, Tommaso; Giorgi Rossi, Paolo
abstract

Long-term mortality in a population exposed to inorganic selenium through drinking water.

2015 - Long-term mortality in a residential cohort exposed to inorganic hexavalent selenium through drinking water. [Abstract in Atti di Convegno]
Vinceti, Marco; Paola, Ballotari; Malagoli, Carlotta; Ferdinando, Luberto; Malavolti, Marcella; Massimo, Vicentini; Violi, Federica; Paolo, Giorgi Rossi
abstract

Long-term mortality in a residential cohort exposed to inorganic hexavalent selenium through drinking water

2015 - Maternal exposure to benzene and PM10 during pregnancy influences the risk of congenital anomalies in the offspring. A population-based case-control study in a Northern Italy community. [Abstract in Rivista]
Malagoli, Carlotta; Malavolti, Marcella; Cherubini, A; Maffeis, G; Rodolfi, R; Astolfi, G; Calzolari, E; Nicolini, F; Vinceti, Marco
abstract

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2015 - Passive exposure to agricultural pesticides and risk of childhood leukemia in an Italian community. [Abstract in Atti di Convegno]
Malagoli, Carlotta; Malavolti, Marcella; Costanzini, Sofia; Teggi, Sergio; Giovanni, Palazzi; Vinceti, Marco
abstract

Passive exposure to agricultural pesticides and risk of childhood leukemia in an Italian community

2015 - Population density and risk of Amyotrophic Lateral Sclerosis: an Italian population-based study. [Abstract in Rivista]
Filippini, Tommaso; Malagoli, Carlotta; Violi, Federica; Iacuzio, Laura; Arcolin, Elisa; Nicola, Fini; Georgoulopoulou, Eleni; Mandrioli, Jessica; Vinceti, Marco
abstract

Population density and risk of Amyotrophic Lateral Sclerosis: an Italian population-based study.

2015 - Risk of ALS and passive long-term residential exposure to pesticides: a population based study. [Abstract in Rivista]
Violi, Federica; Filippini, Tommaso; Malagoli, Carlotta; Mandrioli, Jessica; Carlo, Signorelli; Aanna, Odone; Margherita, Ferrante; Maria, Fiore; Ledda, C; Cristina, Mauceri; Patti, F; Costanzini, Sofia; Fabbi, Sara; Teggi, Sergio; Vinceti, Marco
abstract

Risk of ALS and passive long-term residential exposure to pesticides: a population based study.

2015 - Risk of ALS and passive residential exposure to pesticides: a population based study. [Abstract in Atti di Convegno]
Violi, Federica; Filippini, Tommaso; Malagoli, Carlotta; Mandrioli, Jessica; Signorelli, C; Odone, A; Ferrante, M; Fiore, M; Ledda, C; Mauceri, C; Patti, F; Costanzini, Sofia; Fabbi, Sara; Teggi, Sergio; Vinceti, Marco
abstract

. Risk of ALS and passive residential exposure to pesticides: a population based study.

2015 - Scientific Opinion on Dietary Reference Values for copper [Articolo su rivista]
Bresson, J. L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K. I.; Mangelsdorf, I.; Mcardle, H.; Naska, A.; Neuhauser-Berthold, M.; Nowicka, G.; Pentieva, K.; Sanz, Y.; Siani, A.; Sjodin, A.; Stern, M.; Tome, D.; Turck, D.; Van Loveren, H.; Vinceti, M.; Willatts, P.
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for copper. Owing to the absence of appropriate biomarkers of copper status and the limitations of available balance studies, the Panel was unable to derive Average Requirements (ARs) and Population Reference Intakes (PRIs). Hence, Adequate Intakes (AIs) were defined based on mean observed intakes in several European Union (EU) countries, given that there is no evidence of overt copper deficiency in the European population. Data from balance studies were used as supportive evidence. For adults, AIs of 1.6 mg/day for men and 1.3 mg/day for women are proposed. For children, AIs are 0.7 mg/day for children aged 1 to &lt; 3 years, 1 mg/day for children aged 3 to &lt; 10 years, and 1.3 and 1.1 mg/day for boys and girls aged 10 to &lt; 18 years, respectively. For infants aged 7–11 months, based on mean observed intakes in four EU countries, an AI of 0.4 mg/day is proposed, which is supported by upwards extrapolation of estimated copper intake in exclusively breast-fed infants. For pregnant women, an increment of 0.2 mg/day is estimated to cover the amount of copper deposited in the fetus and the placenta over the course of pregnancy and in anticipation of the needs for lactation, and for lactating women the same increment is estimated to cover the amount of copper secreted with breast milk. Thus, for pregnant and lactating women, the Panel derived an AI of 1.5 mg/day.

2015 - Scientific Opinion on Dietary Reference Values for iron [Articolo su rivista]
Bresson, J. L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K. I.; Mangelsdorf, I.; Mcardle, H.; Naska, A.; Neuhauser-Berthold, M.; Nowicka, G.; Pentieva, K.; Sanz, Y.; Siani, A.; Sjodin, A.; Stern, M.; Tome, D.; Turck, D.; Van Loveren, H.; Vinceti, M.; Willatts, P.
abstract

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies derived Dietary Reference Values (DRVs) for iron. These include Average Requirement (AR) and Population Reference Intake (PRI). For adults, whole-body iron losses were modelled using data from US adults. Predicted absorption values, at a serum ferritin concentration of 30 µg/L, of 16 % for men and 18 % for women were used to convert physiological requirements to dietary iron intakes. In men, median whole-body iron losses are 0.95 mg/day, and the AR is 6 mg/day. The PRI, calculated as the dietary requirement at the 97.5th percentile, is 11 mg/day. For postmenopausal women, the same DRVs as for men are proposed. In premenopausal women, additional iron is lost through menstruation but, because losses are highly skewed, the Panel set a PRI of 16 mg/day to cover requirements of 95 % of the population. In infants and children, requirements were calculated factorially, taking into consideration the needs for growth, replacement of losses and percentage iron absorption from the diet (10 % up to 11 years and 16 % thereafter). PRIs were estimated using a coefficient of variation of 20 %. They are 11 mg/day in infants (7–11 months), 7 mg/day in children aged 1–6 years and 11 mg/day in children aged 7–11 years and boys aged 12–17 years. For girls aged 12–17 years, the PRI of 13 mg/day is the midpoint of the calculated dietary requirement of 97.5 % of girls and the PRI for premenopausal women; this approach allows for the large uncertainties in the rate and timing of pubertal growth and menarche. For pregnant and lactating women, for whom it was assumed that iron stores and enhanced absorption provide sufficient additional iron, DRVs are the same as for premenopausal women.

2015 - Selenium and human health: witnessing a Copernican revolution? [Articolo su rivista]
Jablonska, Ewa; Vinceti, Marco
abstract

In humans, selenium was hypothesized to lower the risk of several chronic diseases, mainly due to the antioxidant activity of selenium-containing proteins. Recent epidemiologic and laboratory studies, however, are changing our perception of the biological effects of this nutritionally essential trace element. We reviewed the most recent epidemiologic and biochemical literature on selenium, synthesizing the findings from these studies into a unifying view. Randomized trials have shown that selenium did not protect against cancer and other chronic diseases, but even increased the risk of specific neoplasms such as advanced prostate cancer and skin cancer, in addition to type 2 diabetes. Biochemical studies indicate that selenium may exert a broad pattern of toxic effects at unexpectedly low concentrations. Furthermore, its upregulation of antioxidant proteins (selenium-dependent and selenium-independent) may be a manifestation of self-induced oxidative stress. In conclusion, toxic effects of selenium species occur at lower concentrations than previously believed. Those effects may include a large range of proteomic changes and adverse health effects in humans. Since the effects of environmental exposure to this element on human health still remain partially unknown, but are potentially serious, the toxicity of selenium exposure should be further investigated and considered as a public health priority.

2015 - Selenium and its compounds [Capitolo/Saggio]
Fan, Anna M.; Vinceti, Marco
abstract

Selenium exists in various chemical forms (speciation) and oxidation states that can affect its occurrence, properties, use and toxicity. Human exposures occur in the workplace, and via food and drinking water, through dermal, inhalation or ingestion routes involving organic or inorganic forms. Ingestion of the organic form from food, including dietary supplements, is the main source of exposure for the general population. Evaluation of exposure and health effects of selenium has to consider both essentiality and toxicity. The occupational and environmental limits and reference values that are established are associated with the specific route of exposure and the chemical form, where data exist, as shown below (CDC 1996, 2010; ICPS 2001).

2015 - Selenium in humans: which is the safe range of intake? [Abstract in Atti di Convegno]
Vinceti, Marco; Filippini, Tommaso; Violi, Federica; Malavolti, Marcella; Malagoli, Carlotta; Bargellini, Annalisa; Borella, Paola
abstract

Selenium in humans: which is the safe range of intake?

2015 - Selenium speciation in human serum and its implications for epidemiologic research: a cross-sectional study [Articolo su rivista]
Vinceti, Marco; Grill, Peter; Malagoli, Carlotta; Filippini, Tommaso; Storani, Simone; Malavolti, Marcella; Michalke, Bernhard
abstract

Observational studies addressing the relation between selenium and human health, particularly cancer risk, yielded inconsistent results, while most recent randomized trials showed a fairly consistent pattern suggesting null or adverse effects of the metalloid. One of the most plausible explanations for such inconsistencies is inadequate exposure assessment in observational studies, commonly carried out by measuring total Se content without taking into account the specific exposure to the individual chemical forms of the metalloid, whose toxic and nutritional properties may vary greatly. Data on the distribution of these species in human blood and their correlation with overall selenium levels are very limited. The concentrations of organic and inorganic selenium species were analyzed in serum of fifty subjects sampled from the general population of the municipality of Modena, northern Italy, aged from 35 to 70 years. Samples were collected during a 30-month period, and determinations of selenium species were carried out using high pressure liquid chromatography coupled with inductively coupled plasma dynamic reaction cell mass spectrometry. The majority of selenium was found to be present as organic species, but the inorganic forms showed higher levels than expected. These species showed limited correlations with age, sex and body mass index, while the organic forms increased in subjects consuming selenium-containing dietary supplements and decreased in smokers. The length of the sample storage period strongly influenced the distribution of selenium compounds, with a clear tendency towards higher inorganic and lower organic selenium levels over time. In multivariate analysis adjusting for potential confounders, total serum selenium correlated with human serum albumin-bound selenium and, in males, with two organic species of the metalloid (selenocysteine and glutathione peroxidase-bound selenium), while little association existed with the other organic forms and the inorganic ones. These findings highlight the potential for exposure misclassification of observational epidemiologic investigations based on overall selenium content in blood and possibly other tissues, and the critical role of the storage conditions for speciation analysis.

2015 - Skin Cancer Diagnosis With Reflectance Confocal Microscopy: Reproducibility of Feature Recognition and Accuracy of Diagnosis [Articolo su rivista]
Farnetani, Francesca; Scope, Alon; Braun, Ralph P; Gonzalez, Salvador; Guitera, Pascale; Malvehy, Josep; Manfredini, Marco; Marghoob, Ashfaq A; Moscarella, Elvira; Oliviero, Margaret; Puig, Susana; Rabinovitz, Harold S; Stanganelli, Ignazio; Longo, Caterina; Malagoli, Carlotta; Vinceti, Marco; Pellacani, Giovanni
abstract

IMPORTANCE: Reflectance confocal microscopy (RCM) studies have been performed to identify criteria for diagnosis of skin neoplasms. However, RCM-based diagnosis is operator dependent. Hence, reproducibility of RCM criteria needs to be tested. OBJECTIVE: To test interobserver reproducibility of recognition of previously published RCM descriptors and accuracy of RCM-based skin cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Observational retrospectiveweb-based study of a set of RCM images collected at a tertiary academic medical center. Nine dermatologists (6 of whom had ≥3 years of RCM experience) from 6 countries evaluated an RCM study set from 100 biopsy-proven lesions, including 55 melanocytic nevi, 20 melanomas, 15 basal cell carcinomas, 7 solar lentigines or seborrheic keratoses, and 3 actinic keratoses. Between June 15, 2010, and October 21, 2010, participanting dermatologists, blinded to histopathological diagnosis, evaluated 3 RCM mosaic images per lesion for the presence of predefined RCM descriptors. MAIN OUTCOMES AND MEASURES: The main outcomewas identification of RCM descriptors with fair to good interrater agreement (κ statistic ≥0.3) and independent correlation with malignant vs benign diagnosis on discriminant analysis. Additional measures included sensitivity and specificity for diagnosis of malignant vs benign for each evaluator, for majority diagnosis (rendered by ≥5 of 9 evaluators), and for experienced vs recent RCM users. RESULTS: Eight RCM descriptors showed fair to good reproducibility and were independently associated with a specific diagnosis. Of these, the presence of pagetoid cells, atypical cells at the dermal-epidermal junction, and irregular epidermal architecture were associated with melanoma. Aspecific junctional pattern, basaloid cords, and ulceration were associated with basal cell carcinomas. Ringed junctional pattern and dermal nests were associated with nevi. The mean sensitivity for the group of evaluators was 88.9% (range, 82.9%-100%), and the mean specificity was 79.3%(range, 69.2%-90.8%). Majority diagnosis showed sensitivity of 100% and specificity of 80.0%. Sensitivity was higher for experienced vs recent RCM users (91.0% vs 84.8%), but specificity was similar (80.0%vs 77.9%). CONCLUSIONS AND RELEVANCE: The study highlights key RCM diagnostic criteria for melanoma and basal cell carcinoma that are reproducibly recognized among RCM users. Diagnostic accuracy increases with experience. The higher accuracy of majority diagnosis suggests that there is intrinsically more diagnostic information in RCM images than is currently used by individual evaluators.

2015 - Sources of cadmium exposure in an Italian population: a cross-sectional study [Abstract in Atti di Convegno]
Filippini, Tommaso; Cherubini, A; Greco, S; Maffeis, G; Malagoli, Carlotta; Bottecchi, Iliaria; Malavolti, Marcella; Sieri, S; Krogh, V; Vescovi, L; Modenesi, M; Castiglia, P; Michalke, B; Vinceti, Marco
abstract

Sources of cadmium exposure in an Italian population: a cross-sectional study.

2015 - The GIS methodology and its application in exposure assessment – Experience of the University of Modena and Reggio Emilia [Abstract in Rivista]
Filippini, Tommaso; Iacuzio, Laura; Arcolin, Elisa; Violi, Federica; Storani, Simone; Costanzini, Sofia; Fabbi, Sara; Malagoli, Carlotta; Vinceti, Marco
abstract

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2015 - The influence of outdoor air pollution on cadmium exposure assessment: a cross-sectional population-based Italian study. [Abstract in Atti di Convegno]
Filippini, Tommaso; Cherubini, A; Maffeis, G; Greco, S; Malagoli, Carlotta; Malavolti, Marcella; Sieri, S; Krogh, V; Vescovi, L; Modenesi, M; Michalke, B; Vinceti, Marco
abstract

The influence of outdoor air pollution on cadmium exposure assessment: a cross-sectional population-based Italian study.

2015 - Toenail selenium and risk of type 2 diabetes: the ORDET cohort study [Articolo su rivista]
Vinceti, Marco; Grioni, S.; Alber, D.; Consonni, D.; Malagoli, Carlotta; Agnoli, C.; Malavolti, Marcella; Pala, V.; Krogh, V.; Sieri, S.
abstract

Epidemiologic studies, particularly randomized controlled trials, have shown a direct relation between dietary and environmental exposure to the metalloid selenium and risk of type 2 diabetes. We investigated the association between baseline toenail selenium levels and diabetes occurrence in a case-control study nested in ORDET, a population-based female cohort in Northern Italy. After a median follow-up of 16 years, we identified 226 cases of type 2 diabetes cases and 395 age-matched control women with available toenail samples at baseline. The multivariate odds ratios of diabetes in increasing a priori defined categories of toenail selenium exposure were 1.09 (95% confidence interval 0.61, 1.96), 0.71 (0.38, 1.34) and 1.14 (0.46, 2.80) compared with the lowest category. The results were not substantially altered when quartile distribution of toenail selenium in controls was used to define exposure categories. Spline regression analysis did not show homogeneous risk trends. Overall, we did not find an association between toenail selenium and subsequent development of diabetes. Since the diabetogenic activity of selenium is strongly supported by experimental studies and some observational investigations, our null results might be explained by the limitations of overall selenium toenail content to assess environmental exposure to selenium species of etiologic relevance in the study population.

2015 - Valutazione dell’esposizione passiva a pesticidi a lungo termine mediante flussi informativi di popolazione: aspetti metodologici. [Abstract in Atti di Convegno]
Vinceti, Marco; Fiore, M; Odone, A; Malagoli, Carlotta; Filippini, Tommaso; Violi, Federica; Arcolin, Elisa; Iacuzio, Laura; Ledda, C; Mauceri, C; Dimartino, A; D’Agati, Mg; Floridia, A; Rossi, R; Mazzini, F; Nannini, R; Marchi, N; Staffilani, F; Guermandi, M; Fornaciari, M; Costanzini, Sofia; Teggi, Sergio; Sciacca, S; Signorelli, C; Ferrante, M.
abstract

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2015 - Vitamin C and contribution to the normal function of the immune system: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Bresson, J. L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K. I.; Mangelsdorf, I.; Mcardle, H.; Naska, A.; Neuhauser-Berthold, M.; Nowicka, G.; Pentieva, K.; Sanz, Y.; Siani, A.; Sjodin, A.; Stern, M.; Tome, D.; Turck, D.; Loveren, H. V.; Vinceti, M.; Willatts, P.
abstract

Following an application from Specialised Nutrition Europe (formerly IDACE), submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to vitamin C and ‘helps to support a healthy immune system’. The Panel considers that vitamin C is sufficiently characterised, and that contribution to the normal function of the immune system is a beneficial physiological effect. The Panel has previously assessed a claim on vitamin C and its contribution to the normal function of the immune system with a favourable outcome. The target population was the general population. The Panel considers that the role of vitamin C in the functioning of the immune system applies to all ages, including infants and young children (from birth to three years of age). The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin C and contribution to the normal function of the immune system. The following wording reflects the scientific evidence: ‘Vitamin C contributes to the normal function of the immune system.’ The target population is infants and young children up to three years of age.

2014 - Cd, Pb and Hg Biomonitoring in Fish of the Mediterranean Region and Risk Estimations on Fish Consumption [Articolo su rivista]
Elisavet, Renieri; Athanasios, Alegakis; Michalis, Kiriakakis; Vinceti, Marco; Eren, Ozcagli; Martin, Wilks; Aristidis, Tsatsakis
abstract

Cadmium (Cd), lead (Pb) and mercury (Hg) are toxic metals with increasing interest due to their tendency to bioaccumulate in fish tissue which may pose a threat to human health via fish consumption. This review of the recent literature on Cd, Pb, Hg levels summarizes data of fish biomonitoring studies in the Mediterranean Sea in order to determine potential risks due to dietary intake of metals. The analytical methods applied are described, with Atomic Absorption Spectroscopy and Inductively Coupled Plasma Mass Spectroscopy being the most popular. Most of the literature reviewed is focused on the Eastern Mediterranean. Results from the studies indicate that metals mostly accumulate in liver, followed by muscle. Although there are few studies reporting metal levels in fish exceeding the maximum residue levels (MRLs), the bulk of the studies cite levels below the MRLs. The hazard index (HI) of fish consumption, namely the ratio of estimated weekly intake to provisional tolerable weekly intake (EWI/PTWI) was estimated for adult consumers and no risk emerged. The EWI/PTWI ratios of lead and mercury for Italy (0.14 and 0.22 respectively) represent the highest HI levels estimated. In view of maximizing the benefits while minimizing the risks of fish consumption, a more detailed fish-specific database on intakes for consumers is required and extended bimonitoring in as many regions as possible.

2014 - Diabete materno e rischio di macrosomia fetale: uno studio di coorte nella regione Emilia-Romagna. [Abstract in Atti di Convegno]
Malagoli, Carlotta; Filippini, Tommaso; Rodolfi, R; Bertolotti, Marco; Astolfi, G; Calzolari, E; Puccini, A; Martini, M; Nicolini, F; Vinceti, Marco
abstract

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2014 - Do dietary intake and blood level of total selenium predict circulating levels of selenium species? A cross-sectional study. [Abstract in Atti di Convegno]
Vinceti, Marco; Malagoli, Carlotta; Storani, Simone; Grill, P; Michalke, B.
abstract

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2014 - Epidemiology of amyotrophic lateral sclerosis in Emilia Romagna Region (Italy): A population based study. [Articolo su rivista]
Mandrioli, Jessica; Biguzzi, S; Guidi, C; Venturini, E; Sette, E; Terlizzi, E; Ravasio, A; Casmiro, M; Salvi, F; Liguori, R; Rizzi, R; Pietrini, V; Chierici, E; Santangelo, M; Granieri, E; Mussuto, V; Borghi, A; Rinaldi, R; Fini, N; Georgoulopoulou, E; De Pasqua, S; Vinceti, Marco; Bonvicini, Federica; Ferro, S; D'Alessandro, R; Errals, Group
abstract

Our objective was to describe incidence and clinical features of ALS from a prospective population-based study in Emilia Romagna Region (ERR). From 2009 onwards, a prospective registry recorded all incident cases of ALS among residents in the ERR (population, 4.4 million inhabitants), involving 17 neurological departments. For each patient, detailed demographic and clinical information was collected by caring physicians. Results showed that from 1 January 2009 to 31 December 2011, 347 patients received a new diagnosis of ALS with a crude incidence rate of 2.63/100,000/year. There was micro-geographic heterogeneity throughout ERR, with higher incidence rates in the low density population (3.27/100,000) (p < 0.01). ALS patients have been more frequently employed in agriculture than the general ERR population (8.64% vs. 4.6%, p < 0.01). Clinical features were similar to those described in previous population based studies. In conclusion, we report incidence rates similar to those reported by European registries, reflecting good accuracy of our prospective study. We confirmed previous studies reporting higher incidence rates in rural areas and among agricultural workers. Although genetics has been gaining increasing importance in ALS aetiology, some epidemiological data are still unexplained. Identifying geographical areas or populations with high incidence rates can be a starting point for identifying environmental risk factors.

2014 - Fattori predittivi per la cessazione dal fumo nel centro per il trattamento del tabagismo della provincia di Reggio Emilia: analisi di due anni di attivita’. [Abstract in Atti di Convegno]
Storani, Simone; Tamelli, M; Malagoli, Carlotta; Filippini, Tommaso; Vinceti, Marco
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2014 - I pesticidi quali possibili fattori ambientali di rischio nella sclerosi laterale amiotrofica: uno studio caso-controllo di popolazione in Emilia-Romagna. [Abstract in Atti di Convegno]
Arcolin, Elisa; Fiore, M; Mandrioli, Jessica; Iacuzio, Laura; Malagoli, Carlotta; Violi, Federica; Filippini, Tommaso; Georgoulopoulou, E; Ledda, C; Mauceri, C; Floridia, A; Di Martino, A; D’Agati, M. G; Fazio, R; Patti, F; Zappia, M; Sciacca, S; Ferrante, M; Vinceti, Marco
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2014 - Mercury and selenium intake by seafood from the Ionian Sea: A risk evaluation. [Articolo su rivista]
Copat, C; Vinceti, Marco; D’Agata, Mg; Arena, G; Mauceri, V; Grasso, A; Fallico, R; Sciacca, S; Ferrante, M.
abstract

The subject of the present study is the evaluation of the concentrations of mercury (Hg) and selenium (Se) in fish and shellfish from the Gulf of Catania (Ionian Sea) and the assessment of related risk-based consumption limits per single contaminant in adults and children. In contrast to the potential harm from Hg, Se is an essential element that is normally found in high levels in seafood. If the amount of Hg is high enough, it could bind Se and irreversibly inhibit selenium-dependent enzymes. Thus, adequate levels of Se need to be available to replace the amount of Se lost to Hg sequestration, thereby maintaining normal selenoprotein synthesis. Hg analysis was conducted using a flow injection analysis system coupled with an atomic adsorption spectrometer, and Se analysis was conducted using an inductively coupled plasma mass spectrometry (ICP-MS). Of the trace elements investigated, only Hg has a limit set by the European Community for human consumption, and this was never exceeded. Nevertheless, based on Target Hazard Quotient (THQ) over 1, and on the Estimated Daily Intake per meal (EDIm) higher than the Provisional Tolerable Intake (PTI) suggested by the Joint FAO/WHO Expert Committee on Food Additive (JECFA), Hg oral exposure derived from consumption of the benthonic fish and of the bigger pelagic fish species analyzed, could follow the occurrence of systemic effects. Se was found always in molar excess respect to Hg in all pelagic fish and in the shellfish, nearly equimolar in the benthonic fish. Determining the evidence that foods, such as pelagic fish, with high molar excess of Se, could contribute to replace the amount of Se bound to Hg and thereby maintaining normal selenoprotein synthesis, is useful for a better understanding of the seafood safety.

2014 - Modeling of population exposure to airborne pesticides [Relazione in Atti di Convegno]
Costanzini, Sofia; Teggi, Sergio; Fabbi, Sara; Vinceti, Marco; Malagoli, Carlotta
abstract

Air pollution due to pesticides emitted by farming practices is an environmental topical issue nowadays and little it’s known about its effects on human health. Pesticides can contaminate the atmosphere through various pathways, especially by volatilization and by adsorption on particulate matter. Although the use of certain substances (i.e. dichlorodiphenyltrichloroethane, DDT) has been banned over the years, there are still few groups of substances (i.e. phosphorganic insecticides, triazole and phenylenediamine fungicides applied on fruit orchards and vineyards) whose characteristics of toxicity, carcinogenicity, and persistence can lead to severe effects on human health. This paper shows a methodology for the modeling of the population exposure to airborne pesticides based on the AERMOD Gaussian air dispersion model and on geoprocessing and spatial analysis techniques implemented in a GIS (Geographic Information System) environment using the Python programming language. This analysis relies on several spatial data (i.e. hazard sources localization), appropriate processing and on management techniques achievable in a GIS environment. The methodology has been applied to a test site, located in Centre Po Valley near the city of Modena, Italy. In this territory several epidemiological studies have been carried out so far. These activities are framed in the context of a partnership between the DIEF and the CREAGEN of the University of Modena and Reggio Emilia. The main steps followed for the methodology can be summarized in: definition of the computational domain, realization of a GIS input geodatabase (hazard source localization, wind field, demography), realization of a Python procedure to allow the interaction between the GIS input dataset and AERMOD, data processing and visualization in a GIS environment. Fruit orchards and vineyards extracted from the Corine Land Cover have been modeled in AERMOD as areal hazard sources. The designed methodology allows to assess the spatial distribution in the test site of a relative concentration value associated to the use of phosphorganic insecticides, triazole and phenylenediamine fungicides in farming practices. In the future the parameterization of the hazard sources emission (currently only related to the area of the source) will be improved, in order to employ the methodology in epidemiological studies related to the occurrence of potential pathologies.

2014 - Mushroom and dietary selenium intakes in relation to fasting glucose levels in a free-living Italian adult population: The Moli-sani Project. [Articolo su rivista]
Pounis, G; Costanzo, S; Persichillo, M; de Curtis, A; Sieri, S; Vinceti, Marco; Zito, F; Di Castelnuovo, Af; Donati, Mb; de Gaetano, G; Iacoviello, L.
abstract

AIM: Mushrooms are known to be a major food source of selenium, a mineral associated with diabetes prevalence. This study aimed to evaluate the relationship between mushroom and dietary selenium intakes and blood glucose levels in a free-living adult Italian population. METHODS: A total of 6879 men and 6891 women (aged 53.1±11.0years) with neither diabetes nor on special diets were analyzed from the population randomly recruited for the Moli-sani study. The European Prospective Investigation into Cancer and Nutrition (EPIC) food frequency questionnaire was used for dietary assessment. Fasting blood glucose (FBG) levels were measured from fasting serum samples, and diabetes prevalence was determined according to American Diabetes Association diagnostic criteria. RESULTS: In men, an increase of one (30-g) portion/week in mushroom consumption was associated with a 0.43-0.55mmol/L increase in FBG at different levels of adjustment (P<0.05). In both men and women, dietary selenium was positively associated with blood glucose in both unadjusted and fully adjusted models (P<0.05 for all). Both mushroom and dietary selenium intakes were independently associated with blood glucose on multivariate analyses. In addition, high intakes of both were associated with higher diabetes prevalence in men and women (OR>1, P<0.05). CONCLUSION: The association of mushroom and selenium intakes with FBG suggests that mushroom and selenium might each independently increase the risk of diabetes. However, prospective studies are now necessary to confirm this hypothesis.

2014 - Non-invasive and invasive ventilation and enteral nutrition for ALS in Italy. [Articolo su rivista]
Fini, N; Georgoulopoulou, E; Vinceti, Marco; Monelli, M; Pinelli, G; Vacondio, P; Giovannini, M; Dallari, R; Marudi, A; Mandrioli, Jessica
abstract

Introduction: We performed a population-based study to assess amyotrophic lateral sclerosis (ALS) survival after noninvasive ventilation (NIV), invasive ventilation (IV), and enteral nutrition (EN). Methods: We included patients diagnosed from 2000 to 2009 in Modena, where a prospective registry and a Motor Neuron Diseases Centre have been active since 2000. Results: Of the 193 incident cases, 47.7% received NIV, 24.3% received tracheostomy, and 49.2% received EN. A total of 10.4% of the patients refused NIV, 31.6% refused IV, and 8.7% refused EN. The median survival times after NIV, IV, and EN were 15, 19, and 9 months, respectively. Of the tracheostomized patients, 79.7% were discharged from the hospital; 73.0% were discharged to home. The median survival times for tracheostomized patients who were cared for at home and in nursing homes were 43 and 2 months, respectively. The multivariate analysis demonstrated that the place of discharge was the only independent prognostic factor after IV (P<0.01). Conclusions: Service organizations may promote adherence to NIV, IV, EN, and influence postprocedure survival. These data may be useful in defining health plans regarding advanced ALS care and in patient counseling.

2014 - Pattern alimentari e rischio di melanoma cutaneo: studio epidemiologico multicentrico in una popolazione del nord-Italia. [Abstract in Atti di Convegno]
Malavolti, Marcella; Malagoli, Carlotta; Agnoli, C; Fiorentini, Chiara; Longo, Caterina; Farnetani, Francesca; Sieri, S; Krogh, V; Pellacani, Giovanni; Vinceti, Marco
abstract

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2014 - Pesticidi e rischio di sclerosi laterale amiotrofica: il contributo della metodologia gis in uno studio in Emilia-Romagna e in Sicilia. [Abstract in Atti di Convegno]
Filippini, Tommaso; Fiore, M; Mandrioli, Jessica; Odone, A; Malagoli, Carlotta; Iacuzio, Laura; Arcolin, Elisa; Violi, Federica; Mazzini, F; Rossi, R; Nannini, R; Guermandi, M; Staffilani, F; Marchi, N; Fabbi, Sara; Teggi, Sergio; Costanzini, Sofia; Ghermandi, Grazia; Pietrini, V; Fini, N; Ledda, C; Mauceri, C; Di Martino, A; Patti, F; Sentina, E; Signorelli, C; Ferrante, M; Vinceti, Marco
abstract

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2014 - Residence near electrical transformer rooms and risk of childhood leukemia: an Italian population-based case-control study. [Abstract in Atti di Convegno]
Storani, Simone; Malagoli, Carlotta; Fabbi, Sara; Zanichelli, P; Notari, B; Poli, M; Sesti, D; Teggi, Sergio; Vinceti, Marco
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2014 - Risk of birth defects associated with maternal pregestational diabetes. [Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; Rothman, Kj; Rodolfi, R; Astolfi, G; Calzolari, E; Puccini, A; Bertolotti, Marco; Lunt, M; Paterlini, L; Martini, M; Nicolini, F.
abstract

Maternal diabetes preceding pregnancy may increase the risk of birth defects in the offspring, but not all studies confirm this association, which has shown considerable variation over time, and the effect of having type 1 versus type 2 diabetes is unclear. We conducted a population-based cohort study in the Northern Italy Emilia-Romagna region linking administrative databases with a Birth Defects Registry. From hospital discharge records we identified all diabetic pregnancies during 1997-2010, and a population of non-diabetic parturients matched for age, residence, year and delivery hospital. We collected available information on education, smoking and drug prescriptions, from which we inferred the type of diabetes. We found 62 malformed infants out of 2,269 births among diabetic women, and 162 out of 10,648 births among non-diabetic women. The age-standardized prevalence ratio (PR) of malformation associated with maternal pregestational diabetes was 1.79 (95 % confidence interval 1.34-2.39), a value that varied little by age. Type of diabetes strongly influenced the PR, with higher values related to type 2 diabetic women. Most major subgroups of anomalies had PRs above 1, including cardiovascular, genitourinary, musculoskeletal, and chromosomal abnormalities. There was an unusually high PR for the rare defect 'extra-ribs', but it was based on only two cases. This study indicates that maternal pregestational type 2 diabetes is associated with a higher prevalence of specific birth defects in offspring, whereas for type 1 diabetic mothers, particularly in recent years, the association was unremarkable.

2014 - Selenium for preventing cancer. [Articolo su rivista]
Vinceti, Marco; Dennert, G; Crespi, Cm; Zwahlen, M; Brinkman, M; Zeegers, Mp; Horneber, M; D'Amico, Roberto; DEL GIOVANE, Cinzia
abstract

BACKGROUND: This review is an update of the first Cochrane publication on selenium for preventing cancer (Dennert 2011).Selenium is a metalloid with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVES: Two research questions were addressed in this review: What is the evidence for:1. an aetiological relation between selenium exposure and cancer risk in humans? and2. the efficacy of selenium supplementation for cancer prevention in humans? SEARCH METHODS: We conducted electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 1), MEDLINE (Ovid, 1966 to February 2013 week 1), EMBASE (1980 to 2013 week 6), CancerLit (February 2004) and CCMed (February 2011). As MEDLINE now includes the journals indexed in CancerLit, no further searches were conducted in this database after 2004. SELECTION CRITERIA: We included prospective observational studies (cohort studies including sub-cohort controlled studies and nested case-control studies) and randomised controlled trials (RCTs) with healthy adult participants (18 years of age and older). DATA COLLECTION AND ANALYSIS: For observational studies, we conducted random effects meta-analyses when five or more studies were retrieved for a specific outcome. For RCTs, we performed random effects meta-analyses when two or more studies were available. The risk of bias in observational studies was assessed using forms adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies; the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias in RCTs. MAIN RESULTS: We included 55 prospective observational studies (including more than 1,100,000 participants) and eight RCTs (with a total of 44,743 participants). For the observational studies, we found lower cancer incidence (summary odds ratio (OR) 0.69, 95% confidence interval (CI) 0.53 to 0.91, N = 8) and cancer mortality (OR 0.60, 95% CI 0.39 to 0.93, N = 6) associated with higher selenium exposure. Gender-specific subgroup analysis provided no clear evidence of different effects in men and women (P value 0.47), although cancer incidence was lower in men (OR 0.66, 95% CI 0.42 to 1.05, N = 6) than in women (OR 0.90, 95% CI 0.45 to 1.77, N = 2). The most pronounced decreases in risk of site-specific cancers were seen for stomach, bladder and prostate cancers. However, these findings have limitations due to study design, quality and heterogeneity that complicate interpretation of the summary statistics. Some studies suggested that genetic factors may modify the relation between selenium and cancer risk-a hypothesis that deserves further investigation.In RCTs, we found no clear evidence that selenium supplementation reduced the risk of any cancer (risk ratio (RR) 0.90, 95% CI 0.70 to 1.17, two studies, N = 4765) or cancer-related mortality (RR 0.81, 95% CI 0.49 to 1.32, two studies, N = 18,698), and this finding was confirmed when the analysis was restricted to studies with low risk of bias. The effect on prostate cancer was imprecise (RR 0.90, 95% CI 0.71 to 1.14, four studies, N = 19,110), and when the analysis was limited to trials with low risk of bias, the interventions showed no effect (RR 1.02, 95% CI 0.90 to 1.14, three studies, N = 18,183). The risk of non-melanoma skin cancer was increased (RR 1.44, 95% CI 0.95 to 1.17, three studies, N = 1900). Results of two trials-the Nutritional Prevention of Cancer Trial (NPCT) and the Selenium and Vitamin E Cancer Trial (SELECT)-also raised concerns about possible increased risk of type 2 diabetes, alopecia and dermatitis due to selenium supplements. An early hypothesis generated by NPCT that individuals with the lowest blood selenium levels at baseline could reduce their risk of cancer, particularly of prostate cancer, by increasing selenium in

2014 - Selenium neurotoxicity in humans: Bridging laboratory and epidemiologic studies. [Articolo su rivista]
Vinceti, Marco; Mandrioli, Jessica; Borella, Paola; Michalke, B; Tsatsakis, A; Finkelstein, Y.
abstract

Selenium is a metalloid of considerable interest in the human from both a toxicological and a nutritional perspective, with a very narrow safe range of intake. Acute selenium intoxication is followed by adverse effects on the nervous system with special clinical relevance, while the neurotoxicity of long-term overexposure is less characterized and recognized. We aimed to address this issue from a public health perspective, focusing on both laboratory studies and the few epidemiologic human studies available, with emphasis on their methodological strengths and limitations. The frequently overlooked differences in toxicity and biological activity of selenium compounds are also outlined. In addition to lethargy, dizziness, motor weakness and paresthesias, an excess risk of amyotrophic lateral sclerosis is the effect on the nervous system which has been more consistently associated with chronic low-level selenium overexposure, particularly to its inorganic compounds. Additional research efforts are needed to better elucidate the neurotoxic effects exerted by selenium overexposure.

2014 - Traffic-related air pollution and risk of childhood leukemia: a meta-analysis. [Abstract in Atti di Convegno]
Filippini, Tommaso; Malagoli, Carlotta; Vinceti, Marco
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2013 - Association between dietary vitamin C and risk of cutaneous melanoma in a population of Northern Italy [Articolo su rivista]
Malavolti, Marcella; Malagoli, Carlotta; Fiorentini, Chiara; Longo, Caterina; Farnetani, Francesca; Ricci, Cinzia; Albertini, Giuseppe; Lanzoni, Anna; Reggiani, Camilla; Virgili, Annarosa; Pagliarello, Calogero; Santini, Marcello; Fanti, Pier A; Dika, Emi; Sieri, Sabina; Krogh, Vittorio; Pellacani, Giovanni; Vinceti, Marco
abstract

Cutaneous melanoma incidence has been increasing during the last few years, and diet has been suggested as one of the lifestyle factors responsible for this increase. Since antioxidant nutrients such as ascorbic acid might prevent skin carcinogenesis, we investigated the risk of cutaneous melanoma related to vitamin C intake in a population-based case-control study in Northern Italy based on 380 melanoma patients and 719 matched controls, to whom we administered a semiquantitative food-frequency questionnaire. After adjusting for potential confounders, odds ratio of melanoma were 0.86 (95 % confidence interval 0.65 - 1.15) and 0.59 (95 % confidence interval 0.37 - 0.94) in the intermediate and highest categories of vitamin C dietary intake respectively, compared with the bottom one. The association between vitamin C and decreased risk persisted after adjustment for some potential confounders. In age- and gender-stratified analyses, this association was seen in young females (< 60 years old), and was found to be enhanced in subjects with phototypes II and III. These results suggest a possible protective activity of vitamin C intake against cutaneous melanoma in specific subgroups of this population of Northern Italy.

2013 - Associazione tra vitamina C e rischio di melanoma cutaneo: studio epidemiologico multicentrico in una popolazione del nord Italia. [Abstract in Atti di Convegno]
Malavolti, Marcella; Malagoli, Carlotta; Fiorentini, Chiara; Sieri, S; Krogh, V; Pellacani, Giovanni; Vinceti, Marco
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2013 - Cerebrospinal fluid of newly diagnosed amyotrophic lateral sclerosis patients exhibits abnormal levels of selenium species including elevated selenite. [Articolo su rivista]
Vinceti, Marco; Solovyev, N; Mandrioli, Jessica; Crespi, Cm; Bonvicini, Francesca; Arcolin, Elisa; Georgoulopoulou, Eleni; Michalke, B.
abstract

Exposure to selenium, and particularly to its inorganic forms, has been hypothesized as a risk factor for amyotrophic lateral sclerosis (ALS), a fast progressing motor neuron disease with poorly understood etiology. However, no information is known about levels of inorganic and some organic selenium species in the central nervous system of ALS patients, and recent observations suggest that peripheral biomarkers of exposure are unable to predict these levels for several Se species including the inorganic forms. Using a hospital-referred case-control series and advanced selenium speciation methods, we compared the chemical species of selenium in cerebrospinal fluid from 38 ALS patients to those of 38 reference neurological patients matched on age and gender. We found that higher concentrations of inorganic selenium in the form of selenite and of human serum albumin-bound selenium were associated with increased ALS risk (relative risks 3.9 (95% confidence interval 1.2-11.0) and 1.7 (1.0-2.9) for 0.1μg/L increase). Conversely, lower concentrations of selenoprotein P-bound selenium were associated with increased risk (relative risk 0.2 for 1μg/L increase, 95% confidence interval 0.04-0.8). The associations were stronger among cases age 50 years or older, who are postulated to have lower rates of genetic disease origin. These results suggest that excess selenite and human serum albumin bound-selenium and low levels of selenoprotein P-bound selenium in the central nervous system, which may be related, may play a role in ALS etiology.

2013 - Epidemiologia e fattori ambientali di rischio della sclerosi laterale amiotrofica sporadica: metodologia di uno studio realizzato in ambiente gis. [Abstract in Atti di Convegno]
Vinceti, Marco; Fiore, M; Odone, A; Signorelli, C; Mandrioli, Jessica; Fini, N; Fabbi, Sara; Teggi, Sergio; Costanzini, Sofia; Ghermandi, Grazia; Iacuzio, Laura; Malagoli, Carlotta; Arcolin, Elisa; Ferrante, M.
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2013 - Friend or foe? The current epidemiologic evidence on selenium and human cancer risk [Articolo su rivista]
Vinceti, Marco; Crespi, Cm; Malagoli, Carlotta; DEL GIOVANE, Cinzia; Krogh, V.
abstract

Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s-2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders.

2013 - Gestione delle risorse idriche in italia [Monografia/Trattato scientifico]
Aggazzotti, Gabriella; Agodi, A; Carreri, V; Conversano, M; De Donno, A; Fallico, R; Faggioli, A; Ferrante, M; Francia, F; Monarca, S; Petronio, Mg; Sciacca, S; Signorelli, C; Vinceti, Marco; Olivieri Conti, G; Mauceri, C; Dimartino, A; Fiore, M; Ledda, C; Copat, C; Grasso, A; Cafarella, N.
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2013 - Il consumo di legumi riduce il rischio di melanoma cutaneo: studio caso-controllo nella regione Emilia Romagna. [Abstract in Atti di Convegno]
Malagoli, Carlotta; Malavolti, Marcella; Fiorentini, Chiara; Sieri, S; Krogh, V; Pellacani, Giovanni; Vinceti, Marco
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2013 - Inquinamento da traffi co e rischio di malformazioni congenite: considerazioni metodologiche sull’uso di differenti modellistiche espositive [Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; R., Rodolfi; A., Cherubini; G., Maffeis; S., Greco; Fabbi, Sara; C., Signorelli; Storani, Simone; Iacuzio, Laura; A., Fraulini; Teggi, Sergio; Bergomi, Margherita; G., Astolfi; E., Calzolari; F., Nicolini
abstract

The relation between air pollution from road traffi c and teratogenic risk is an issue of considerable interest in epidemiological research. We examined the risk of birth defects associated with exposure to benzene and particulate matter (PM10) emitted by motorized traffi c in an Italian community, using a validated dispersion model (CALINE4) of these contaminants and two different methodological approaches for exposure assessment within a Geographical Information System. The study population included 228 cases of congenital malformation diagnosed at birth and the same number of matched controls. The results showed that estimates of individual exposure to benzene and PM10 and associated relative risks were substantially affected by the different approaches for exposure assessment.

2013 - Relationship between histological and computer based assessment of melanoma diameter and thickness in head & neck vs. trunk melanoma. [Articolo su rivista]
Seidenari, Stefania; A., Fabiano; S., Al Jalbout; S., Bassoli; S., Borsari; Magnoni, Cristina; Tomasi, Aldo; Vinceti, Marco; Ponti, Giovanni
abstract

BackgroundDiameter represents a controversial parameter in the diagnosis of melanoma (MM). The ABCD rule considers it an important diagnostic parameter, while some authors decrease its relevance. Also, its measurement is not always reliable, histological methods being usually used. The current study aims to compare histological and digital measurements and to evaluate the correlation between MM head- and trunk diameter and thickness. Methods The study population was subdivided according to diameter subgroups considering head- and trunk-limbs lesions separately. Digital diameters measured by an automatic software referring to 477 MM images were compared to diameters reported on the pathologist’s records. Clinical and histological information was also considered, and the correlation between diameter and thickness was assessed. Odds ratios (OR) were computed for different diameter subgroups. Results Mean digital diameters of head MMs and trunk limbs MMs exceeded histological measurements by 11% and 20%, respectively. In head MMs, no correlation between diameter and thickness was observable, whereas in the trunk-limbs group a direct relationship between thickness and diameter was noticed. ORs for non in situ vs in situ andfor ≥ 1 mm vs < 1 mm thick were low for small lesions, increasing for larger ones, indicating that the latter are more likely to be thick. ConclusionMM diameter should be assessed digitally to avoid tissue shrinkage after biopsy and imprecise in vivo measurements. Although nearly 10% of MMs might escape an early diagnosis based only on the D of the ABCD rule, MM diameter may be related to its thickness.The evaluation with a computer vision system should be recommended for small pigmented lesions (<6mm) in order to reduce the percentage of misdiagnosed smaller MMs and to better evaluate the parameter E of the ABCDE rule (Evolving lesion).

2013 - Rischio di malformazioni congenite associato all’inquinamento da traffico in una comunità italiana: uno studio di modellistica in ambiente GIS [Relazione in Atti di Convegno]
Vinceti, Marco; Malagoli, Carlotta; Rodolfi, R; Cherubini, A; Maffeis, G; Signorelli, C; Storani, Simone; Martino, Antonio; Astolfi, G; Calzolari, E; Amelio, F; Nicolini, F.
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2013 - Risk Assessment for Metals and PAHs by Mediterranean Seafood [Articolo su rivista]
Chiara, Copat; Gea Oliveri, Conti; Carlo, Signorelli; Marmiroli, Sandra; Salvatore, Sciacca; Vinceti, Marco; Margherita, Ferrante
abstract

Fish is a very important food because of its high nutritional value. Fish consumption is largely recommended in all countries, so quality and safety of seafood are becoming of great concern. Especially in Mediterranean Sea, where many pollutants, as metals and Polycyclic Aromatic Hydrocarbons (PAHs), are often relieved also in high concentrations, seafood safety has to be checked by a methodologically rigorous risk assessment. So we propose in this paper a stages- risk assessment methodology to estimate the seafood potential risk for human health and point-out critical topics in or-der to support fish advisories.

2013 - Risk of birth defects associated with maternal pregestational diabetes: a population-based cohort study in northern Italy [Abstract in Rivista]
Vinceti, Marco; Malagoli, Carlotta; Rodolfi, R; Rothman, K; Puccini, A; Lunt, M; Bertolotti, Marco; Astolfi, G; Calzolari, E; Nicolini, F.
abstract

Maternal diabetes preceding pregnancy, whether type-1 or type-2, appears to increase the risk of birth defects in the offspring, though several aspects of this relation are still unknown or controversial. We conducted a large population-based cohort study in the Northern Italy region of Emilia-Romagna using administrative databases and a Birth Defects Registry. From hospital discharge records we identified all diabetic pregnancies during 1997-2010, and a population of non-diabetic parturients matched for age, province of residence, year and hospital of delivery. We collected where available information on drug prescriptions, from which we inferred the type of diabetes. We found 62 malformed infants out of 2,269 births among diabetic women, and 162 out of 10,648 births among non-diabetic women. The prevalence ratio (PR) of malformation associated with maternal pregestational diabetes was 1.73 (95% confidence interval 1.28-2.33). Period of birth and type of diabetes strongly influenced the PR, with higher values estimates in the earliest periods and in type-2 diabetic women compared with type-1 diabetic mothers. The latter group exhibited no excess risk in the most recent period, 2006-2010, possibly owing to improvements in metabolic control over time. Most subgroups of anomalies had PRs above 1, but relevant and statistically more precise excess risks were seen for cardiovascular, genitourinary, musculoskeletal, and chromosomal abnormalities. The present study indicates that maternal diabetes increases the risk of specific birth defects in offspring, particularly for type-2 diabetes, whereas for type-1 diabetic mothers in the most recent years, this was not the case.

2013 - Selenium (Se) [Capitolo/Saggio]
Vinceti, Marco; Malagoli, Carlotta; Ferrante, M.
abstract

2013 - Selenium and human health: bridging together epidemiological and laboratory evidence. [Abstract in Atti di Convegno]
Vinceti, Marco; Bargellini, Annalisa; Malagoli, Carlotta; Borella, Paola
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2013 - Serum fatty acids and risk of cutaneous melanoma: a population-based case-control study [Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; Iacuzio, Laura; Catherine M., Crespi; Sabina, Sieri; Vittorio, Krogh; Marmiroli, Sandra; Pellacani, Giovanni; Elisabetta, Venturelli
abstract

Background. Some observational studies have suggested that excess dietary intake of polyunsaturated fatty acids such as linoleic acid increases cutaneous melanoma risk. We aimed at examining the association between serum fatty acids and melanoma risk by conducting a population-based case-control study in a northern Italy community. Methods. e percentage composition of 12 fatty acids was determined in 51 newly diagnosed melanoma patients and 51 age- and sex-matched population controls by extracting total lipids from serum samples using thin layer and gas chromatography. Conditional logistic regression was used to estimate the relative risk of melanoma associated with tertiles of percentage composition of each fatty acid as well as groupings including saturated, monounsaturated, and polyunsaturated fatty acids. Results. We found a slightly increased melanoma risk for stearic and arachidic acids proportion, with and without adjustment for potential confounders. For an n-3 polyunsaturated fatty acid, docosapentaenoic acid, we found a male-specic direct association with melanoma risk. o other associations emerged for the other saturated, monounsaturated, and polyunsaturated fatty acids, individually or grouped by type. Conclusions. These fndings do not suggest a major role of fatty acids, including linoleic acid, on risk of cutaneous melanoma, though their evaluation is limited by the small sample size.

2013 - The impact of clinical factors, riluzole and therapeutic interventions on ALS survival: A population based study in Modena, Italy [Articolo su rivista]
Georgoulopoulou, Eleni; Nicola, Fini; Vinceti, Marco; Marco, Monelli; Paolo, Vacondio; Giorgia, Bianconi; Patrizia, Sola; Nichelli, Paolo Frigio; Mandrioli, Jessica
abstract

The prognostic role of riluzole, enteral nutrition (EN), non-invasive ventilation (NIV) and interdisciplinary care in ALS is still debated. A population based study has been performed focusing on ALS survival, with particular attention to prognostic factors and therapeutic intervention. All patients diagnosed with ALS between 2000 and 2009 and residing in Modena, Italy, have been registered. A centre for motor neuron disease (MND) has been active in our province since 2000, in addition to a prospective registry collecting all incident cases. One hundred and ninety-three incident cases have been collected during the 10 years of the study. Results demonstrated that median survival was 41 months (the overall three-year and five-year survival rates being 54.36% and 28.81%, respectively). Based on univariate analysis, factors related to survival were: age at diagnosis, gender, site of onset, phenotype, riluzole treatment and tracheostomy. In the Cox multivariable model, the factors independently related to a longer survival were age (p < 0.01), site of onset (p = 0.02) and riluzole treatment (p < 0.01), with a median gain in survival of 29 months (patients aged < 55 years compared with patients ≥ 55 years), 20 months (spinal versus bulbar onset), and 12 months (riluzole, yes vs. no), respectively. In conclusion, the study has confirmed the prognostic role of clinical features, but has surprisingly demonstrated that riluzole prolonged life significantly longer than NIV and EN. This observational study described the effects of ALS management in a setting that may approximate routine clinical practice more closely than randomized controlled trial (RCT); effects of uncontrolled potential confounders, however, cannot be excluded. The prognostic role of riluzole, enteral nutrition (EN), non-invasive ventilation (NIV) and interdisciplinary care in ALS is still debated. A population based study has been performed focusing on ALS survival, with particular attention to prognostic factors and therapeutic intervention. All patients diagnosed with ALS between 2000 and 2009 and residing in Modena, Italy, have been registered. A centre for motor neuron disease (MND) has been active in our province since 2000, in addition to a prospective registry collecting all incident cases. One hundred and ninety-three incident cases have been collected during the 10 years of the study. Results demonstrated that median survival was 41 months (the overall three-year and five-year survival rates being 54.36% and 28.81%, respectively). Based on univariate analysis, factors related to survival were: age at diagnosis, gender, site of onset, phenotype, riluzole treatment and tracheostomy. In the Cox multivariable model, the factors independently related to a longer survival were age (p < 0.01), site of onset (p = 0.02) and riluzole treatment (p < 0.01), with a median gain in survival of 29 months (patients aged < 55 years compared with patients ≥ 55 years), 20 months (spinal versus bulbar onset), and 12 months (riluzole, yes vs. no), respectively. In conclusion, the study has confirmed the prognostic role of clinical features, but has surprisingly demonstrated that riluzole prolonged life significantly longer than NIV and EN. This observational study described the effects of ALS management in a setting that may approximate routine clinical practice more closely than randomized controlled trial (RCT); effects of uncontrolled potential confounders, however, cannot be excluded.

2013 - The need for a reassessment of the safe upper limit of selenium in drinking water [Articolo su rivista]
Vinceti, Marco; C. M., Crespi; Bonvicini, Francesca; Malagoli, Carlotta; M., Ferrante; Marmiroli, Sandra; S., Stranges
abstract

Results of recent epidemiologic studies suggest the need to reassess the safe upper limit in drinking water of selenium, a metalloid with both toxicological and nutritional properties. Observational and experimental human studies on health effects of organic selenium compounds consumed through diet or supplements, and of inorganic selenium consumed through drinking water, have shown that human toxicity may occur at much lower concentrations than previously surmised. Evidence indicates that the chemical form of selenium strongly influences its toxicity, and that its biological activity may differ in different species, emphasizing the importance of the few human studies on health effects of the specific selenium compounds found in drinking water. Epidemiologic studies that investigated the effects of selenate, an inorganic selenium species commonly found in drinking water, together with evidence of toxicity of inorganic selenium at low levels in vitro and in animal studies, indicate that health risks may occur at exposures below the current European Union and World Health Organization upper limit and guideline of 10 and 40 µg/l, respectively, and suggest reduction to 1 µg/l in order to adequately protect human health. Although few drinking waters are currently known to have selenium levels exceeding this level, the public health importance of this issue should not be overlooked, and further epidemiologic research is critically needed in this area.

2012 - A case-control study of the risk of cutaneous melanoma associated with three selenium exposure indicators [Articolo su rivista]
Vinceti, Marco; C. M., Crespi; Malagoli, Carlotta; Bottecchi, Iliaria; Ferrari, Angela; S., Sieri; V., Krogh; D., Alber; Bergomi, Margherita; Seidenari, Stefania; Pellacani, Giovanni
abstract

Aims and background. A direct association between exposure to the metalloid sele-nium and risk of cutaneous melanoma has been suggested by some observational and experimental cohort studies, whereas other studies have yielded inconsistent re-sults. Since some of the inconsistencies may be due to exposure misclassification arising from the use of exposure indicators that do not adequately reflect body tissue selenium content or the levels of the biologically relevant species of this metalloid, we examined this issue using multiple indicators of exposure. Methods. We analyzed the relation of selenium exposure with risk of cutaneous melanoma using two different biomarkers, plasma and toenail selenium concentra-tion, and estimated dietary selenium intake in a community-based case-control se-ries (54 cases, 56 controls) from an Italian community. Results. In unmatched and matched logistic regression models as well as nonpara-metric generalized additive models, higher plasma selenium levels were strongly as-sociated with excess disease risk. In contrast, toenail and dietary selenium exhibited little relation with melanoma risk. The pattern of correlation among indicators of ex-posure differed by disease status, with dietary intake associated with plasma seleni-um levels in patients but not in controls. Conclusions. Our data showed that different selenium exposure indicators can yield different inferences about melanoma risk. Although the series was small, our results are consistent with a positive association between circulating levels of selenium and melanoma risk. Further investigation of the exposure classification performance of various selenium biomarkers and of metabolic patterns of the metalloid and of its speciation are needed to help elucidate the relation between selenium exposure and human health.

2012 - Are environmental exposures to selenium, heavy metals, and pesticides risk factors for amyotrophic lateral sclerosis ? [Articolo su rivista]
Vinceti, Marco; Ilaria, Bottecchi; Anna, Fan; Yoram, Finkelstein; Mandrioli, Jessica
abstract

The etiology of sporadic amyotrophic lateral sclerosis (ALS), the most common form of this degenerative disease of the motor neurons, is still unknown, despite extensive investigation of several genetic and environmental potential risk factors. We have reviewed laboratory and epidemiological studies assessing the role of exposure to neurotoxic chemicals (metalloid selenium; heavy metals mercury, cadmium, and lead; pesticides) in ALS etiology by summarizing the results of these investigations and examining their strengths and limitations. Despite limitations in the exposure assessment methodologies typically used in human studies, we found suggestive epidemiological evidence and biologic plausibility for an association between ALS and antecedent overexposure to environmental selenium and pesticides. The relation with mercury, cadmium, and lead appears weaker.

2012 - Dietary exposure to cadmium in a northern italy population [Abstract in Atti di Convegno]
Bottecchi, Iliaria; Arcolin, Elisa; L., Vescovi; Malagoli, Carlotta; Vinceti, Marco
abstract

Background and AimsCadmium (Cd) is a heavy metal which can bevery harmful to the human health, mainlyintroduced into the body through diet.Limited data are available on the amount ofCd contained in vegetable and animal foods.MethodsWe selected foods characterizing the diet ofEmilia-Romagna region population using theresults of an EPIC survey, by selecting from alist of 233 foods foodstuffs and drinks havingaverage consumption ≥3 g/day. Cddeterminations of foods were performed atIren Acqua Gas - IREN company, ReggioEmilia, using mass spectrometer inductivelycoupled plasma following mineralization ofthe food samples. From the results of theEPIC semi-quantitative food frequencyquestionnaire administered to 1099 residentsin the Emilia-Romagna region, we assesseddaily foodstuffs consumption and wecalculated dietary Cd intake.ResultsThe highest average Cd concentration (μgCd/100 g food) was found in cereals (1.14),fish and mussels (5.10), chocolate (8,5),vegetables (0.8) and particularly wildmushrooms (268,90).Average daily Cd intake in the studypopulation resulted to be 11.11 μg, mainlydue to intake of vegetables, wild mushrooms,cereals, fish and mussels.Considering that the European Food SafetyAuthority set in 2010 the tolerable Cd weeklyintake as 2.5 μg/kg body weight (25 μg/dayfor a 70-kg individual) daily intake calculatedin our population did not exceed such limit.According the EC Regulation 1881/2006, inour study only wild mushrooms (2,69 mg/kg)exceeded such limits.ConclusionsThe Cd weekly intake characterizing ourstudy population did not exceed the EFSAlimits. However, considering the high toxicityof this heavy metal particularly for chronicexposure and the relatively high intakeswhich may characterize consumers of largeamounts of wild mushrooms, vegetables,cereals and fish, the issue of dietary Cd intakein the Italian population and its relatedhealth effects appears to be an importantpublic health issue.

2012 - Environmental risk factors for amyotrophic lateral sclerosis: methodological issues in epidemiologic studies [Articolo su rivista]
Vinceti, Marco; M., Fiore; C., Signorelli; A., Odone; M., Tesauro; M., Consonni; Arcolin, Elisa; Malagoli, Carlotta; Mandrioli, Jessica; Marmiroli, Sandra; Sciacca, S. v.; M., Ferrante
abstract

The exact role of environmental risk factors in the etiology of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) is still unknown. Their hypothetical contribution ranges from a minimal impact to a major role. Among the environmental factors strictu sensu (i.e., not life-style factors) suspected to play a role in ALS etiology, we consider pesticides, the metalloid selenium, some heavy metals, magnetic fields and cyanobacteria. However, the possibility exists that these factors exert their activity only in genetically susceptible persons and only after long-term exposures, thus further hampering epidemiologic studies. The recent availability of powerful tools such as population-based ALS registries for case ascertainment and clustering detection, and of environmental modeling techniques and of geographical information systems, may yield unique opportunities for offering insight into the etiology of the disease.

2012 - Estimating Exposure-Response Relationships in Case-Control Studies [Abstract in Atti di Convegno]
Mary, Crespi Catherine; Leeka, Kheifets; Vinceti, Marco
abstract

Many epidemiological exposure variables have right-skewed distributions with sparse data at high exposure levels. Visualizing and estimating exposure-response relationships is further challenging for case-control studies, as the dependent variable is binary. We present improved approaches for estimating the exposure-response relation in such settings. Data from case-control studies of childhood cancer are used to illustrate the methods.

2012 - GIS methods for health and environmental monitoring and assessment [Relazione in Atti di Convegno]
Teggi, Sergio; Ghermandi, Grazia; Fabbi, Sara; Bigi, Alessandro; Vinceti, Marco; Malagoli, Carlotta
abstract

Very often, health and environmental studies are based on the identification of correlations between population exposure to environmental agents and their effects on population health. Time and space are among the principal variables for this kind of analysis. The latter generates a significant increase in complexity of the study. Spatial analysis requires very different methods and skills, such as those on Geographic Information Systems (GIS) and on geostatistics. In this work we describe the models of geographic data (GIS data models) implemented in the framework of several health studies done recently. As an example, we describe the GIS data model generated for the city of Modena. We highlight the potentiality of GIS for health and environmental monitoring and assessment, by describing the GIS data models contents, the elaboration levels and the principal studies for which it has been used so far.

2012 - Leukemia risk in children exposed to benzene and PM10 from vehicular traffic: a case-control study in an Italian population. [Articolo su rivista]
Vinceti, Marco; K. J., Rothman; C. M., Crespi; A., Sterni; A., Cherubini; L., Guerra; G., Maffeis; Ferretti, Enrica; Fabbi, Sara; Teggi, Sergio; D., Consonni; G., De Girolamo; A., Meggiato; G., Palazzi; Paolucci, Paolo; Malagoli, Carlotta
abstract

Benzene, a recognized occupational leukemogen in adults, has been implicated by sparse and conflicting epidemiologic evidence in the etiology of childhood leukemia. We carried out a population-based case-control study in a northern Italy population involving 83 cases with childhood leukemia diagnosed in the years 1998-2009 and 332 matched controls. We assessed residential exposure to benzene and to particulate matter ≤10 µm (PM10) from motorized traffic using geocoded residences and detailed emission and dispersion modeling. Exposure to benzene, and to a lesser extent to PM10, appeared to be independently associated with an excess leukemia risk. When we stratified the study population by age, the relative risk associated with benzene exposure was higher among children aged less than five years. Overall, these findings suggest that low levels of benzene exposure released from motorized traffic may increase the risk of childhood leukemia, and do not rule out an independent effect of PM10.

2012 - Maternal exposure to magnetic fields from high-voltage power lines and the risk of birth defects [Articolo su rivista]
Malagoli, Carlotta; C. M., Crespi; R., Rodolfi; C., Signorelli; M., Poli; P., Zanichelli; Fabbi, Sara; Teggi, Sergio; L., Garavelli; G., Astolfi; E., Calzolari; C., Lucenti; Vinceti, Marco
abstract

The issue of adverse human health effects due to exposure to electromagnetic fields is still unclear, and congenital anomalies are among the outcomes that have been inconsistently associated with such exposure. We conducted a population-based, case–control study to examine the risk of congenital anomalies associated with maternal exposure to magnetic fields (MF) from high-voltage power lines during pregnancy in a community in northern Italy. We identified 228 cases of congenital malformations diagnosed in live births, stillbirths, and induced abortions among women living in the municipality of Reggio Emilia during the period 1998–2006, and a reference group of healthy newborns was matched for year of birth, maternal age, and hospital of birth. We identified maternal residence during early pregnancy and used Geographic Information System to determine whether the residences were within geocoded corridors with MF ≥0.1 µT near high-voltage power lines, then calculated the relative risk (RR) of congenital anomalies associated with maternal exposure. One case and 5 control mothers were classified as exposed, and the RR associated with MF ≥0.1 µT was 0.2 (95% CI: 0.0–2.0) after adjusting for maternal education. While small or moderate effects may have gone undetected due to low statistical power, the results of this study overall do not provide support for major effects of a teratogenic risk due to exposure to MF during early pregnancy.

2012 - Selenium for preventing cancer [Abstract in Rivista]
Dennert, G.; Zwahlen, M.; Brinkman, M.; Vinceti, M.; Zeegers, M. P. A.; Horneber, M.
abstract

BACKGROUND: Selenium is a trace element essential to humans. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVE: Two research questions were addressed in this review: What is the evidence for: 1. an aetiological relationship between selenium exposure and cancer risk in women and men?; 2. the efficacy of selenium supplementation for cancer prevention in women and men? SEARCH STRATEGY: We searched electronic databases and bibliographies of reviews and included publications. SELECTION CRITERIA: We included prospective observational studies to answer research question (a) and randomised controlled trials (RCTs) to answer research question (b). DATA COLLECTION AND ANALYSIS: We conducted random effects meta-analyses of epidemiological data when five or more studies were retrieved for a specific outcome. We made a narrative summary of data from RCTs. MAIN RESULTS: We included 49 prospective observational studies and six RCTs. In epidemiologic data, we found a reduced cancer incidence (summary odds ratio, OR, 0.69; 95% confidence interval, CI, 0.53 to 0.91) and mortality (OR 0.55, 95% CI 0.36 to 0.83) with higher selenium exposure. Cancer risk was more pronouncedly reduced in men (incidence: OR 0.66, 95% CI 0.42 to 1.05) than in women (incidence: OR 0.90, 95% CI 0.45 to 1.77). These findings have potential limitations due to study design, quality and heterogeneity of the data, which complicated the interpretation of the summary statistics. The RCTs found no protective efficacy of selenium yeast supplementation against non-melanoma skin cancer or L-selenomethionine supplementation against prostate cancer. Study results for the prevention of liver cancer with selenium supplements were inconsistent and studies had an unclear risk of bias. The results of the Nutritional Prevention of Cancer Trial (NPCT) and SELECT raised concerns about possible harmful effects of selenium supplements. AUTHORS' CONCLUSIONS: No reliable conclusions can be drawn regarding a causal relationship between low selenium exposure and an increased risk of cancer. Despite evidence for an inverse association between selenium exposure and the risk of some types of cancer, these results should be interpreted with care due to the potential limiting factors of heterogeneity and influences of unknown biases, confounding and effect modification. The effect of selenium supplementation from RCTs yielded inconsistent results. To date, there is no convincing evidence that selenium supplements can prevent cancer in men, women or children.

2012 - Selenium species and heavy metals in cerebrospinal fluid and risk of amyotrophic lateral sclerosis: a hospital-based case-control study [Abstract in Rivista]
Vinceti, Marco; Mandrioli, Jessica; Bonvicini, Francesca; Arcolin, Elisa; Georgoulopoulou, Eleni; N., Solovjev; B., Michalke
abstract

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease which has been ascribed to overexposure to selenium and some heavy metals, on the basis of epidemiologic evidence and laboratory observations. However, no data are available on the specific involvement of single selenium species, all of which have distinctive biological activities, and limited evidence has also been provided for lead, mercury and cadmium in the human. Methods In a hospital-admitted case-control series, we determined the Se compounds and the levels of Cd, Hg and Pb in cerebrospinal fluid samples of thirty-six ALS patients and of thirty-six reference neurological patients. Determinations of Se compounds and of the heavy metals was performed using high pressure liquid chromatography coupled with inductively coupled plasma - dynamic reaction cell - mass spectrometry according to methodologies previously established and described by one of the coauthors (B.M.). Results We found an excess concentration of inorganic Se forms, particularly of the hexavalent and tetravalent ones, while organic Se compounds levels were considerably decreased in ALS cases. These differences were more pronounced in older patients and in females. On the converse, no substantial differences in Cd, Hg and Pb concentrations emerged. Conclusions These results suggest the occurrence of overexposure to inorganic Se species and decreased levels of Se-containing enzymes in ALS, while they offer little evidence of an involvement of three heavy metals, Cd, Hg and Pb, in the etiopathogenesis of this disease. However, caution must be used when inferring etiological clues from analytical results in patients affected by a severe disease such as ALS, and in hospital-referred controls. Further research on the involvement of Se in ALS etiology is clearly warranted.

2012 - The environment and amyotrophic lateral sclerosis: converging clues from epidemiologic studies worldwide [Articolo su rivista]
Vinceti, Marco
abstract

The etiology of one of the most severe human neurological diseases, amyotrophic lateral sclerosis (ALS), remains obscure nearly 150 years after its original description by Charcot, despite substantial advancements in the biomedical research on this disease. The possibility that one or more environmental risk factors may trigger or contribute to the degenerative process of motor neurons characterizing this devastating disease remains appealing, and it is supported by a number of epidemiologic studies, though specific causative factors are yet to be confirmed. Among these, pesticides, the metalloid selenium and heavy metals, trauma, electrical shocks, magnetic fields and several other environmental factors, including infectious agents, have been associated with an excess risk of the disease, and geographical analyses appear to add support for an environmental etiology of the disease.Converging indications from different epidemiologic studies and contexts represent an important clue to the validity of etiological hypotheses. Therefore, the results of the study by Das et al. published in this issue of the Journal appear to be particularly interesting as they add further indications of an etiologic role in ALS of some putative environmental risk factors from a setting entirely different from those subject of epidemiologic studies in Western countries, and apparently never previously investigated with regard to the study hypotheses. In particular, this study, carried out in eastern India using a sound methodological approach, provides evidence of an etiologic role of pesticides (not farming per se), smoking, and electrical shock, though these results must be weighed against studies that have reported conflicting results, duly mentioned by the authors. This discrepancy underscores the need to address these etiological hypotheses in large epidemiologic studies in different geographic areas, seeking better concordance. Such effort would greatly help to confirm or refute previously identified risk factors and make them more specific, e.g., to identify the specific toxin in tobacco smoke, or single drinking water chemicals and neurotoxic pesticides to which the neurodegenerative process may be at least in part ascribed. Furthermore, this evidence should be further investigated in light of the results of genetic studies, whose contribution may be to identify factors that make some people more susceptible to environmental factors, in line with the environment-gene interplay that is currently considered to underlie most chronic disease. Although researchers have so far been unable to confirm in an unequivocal manner an environmental etiology of ALS or to identify any of its singular causes, valuable contributions, studies such as the present one by Das et al. are important to elucidate this still elusive and disturbing issue, which should be considered a primary research priority in biomedical research.

2011 - Changing incidence and subtypes of ALS in Modena, Italy: A 10-years prospective study [Articolo su rivista]
Georgoulopoulou, Eleni; Vinceti, Marco; F., Bonvicini; P., Sola; C. A., Goldoni; G. D., Girolamo; Ferraro, Diana; Nichelli, Paolo Frigio; Mandrioli, Jessica
abstract

We performed a prospective population-based study to describe the temporal pattern of the incidence and prevalence and the clinical features and phenotypes of ALS in Modena, Italy, from 2000 to 2009. From 2000 onwards, a prospective registry has been collecting all cases of incident ALS among residents in the province of Modena. This source was implemented by cases resulting from the provincial hospitals, and by death certificates. Based on 193 newly diagnosed cases, the crude average annual incidence rate of ALS was 2.9 cases per 100,000 person years (py); adjusted incidence rate was 2.8/100,000. The age-standardized incidence rates increased from 2.6 per 100,000 py in 2000-2004 to 2.9 per 100,000 py in 2005-2009, representing an annual increase of approximately 2% throughout the 10-year period. There was a constant increase in prevalence rates throughout the years of the study (from 5.8/100,000 on 31 December 2000 to 11.2/100,000 on 31 December 2009). Median life time was 29 months for patients diagnosed before the year 2000 and 36 months for patients diagnosed from 1 January 2000 (p < 0.01). Thus, we report incidence rates similar to those reported by recent European population based studies, but we observed an increasing trend over the 10 years of the study. The increasing incidence is not explained by aging of the population, and our study raises the question as to whether local environmental or genetic factors are driving this temporal trend. Along with an increasing incidence, we found an important increase in prevalence and survival probably related to access to mutidisciplinary clinics and improvements in symptomatic care of ALS.

2011 - Erratum: Pooled analysis of recent studies of magnetic fields and childhood leukaemia (British Journal of Cancer (2010) 103 (1128-1135) DOI: 10.1038/sj.bjc.6605838) [Articolo su rivista]
Kheifets, L.; Ahlbom, A.; Crespi, C. M.; Draper, G.; Hagihara, J.; Lowenthal, R. M.; Mezei, G.; Oksuzyan, S.; Schuz, J.; Swanson, J.; Tittarelli, A.; Vinceti, M.; Wunsch Filho, V.
abstract

2011 - Esposizione a benzene da traffico e leucemia infantile: influenza delle modellistiche di dispersione atmosferica sulla valutazione del rischio. [Abstract in Rivista]
Vinceti, Marco; Malagoli, Carlotta; Sterni, A; Guerra, L; Cherubini, A; Maffeis, G; Ferretti, Enrica; Fabbi, Sara; Teggi, Sergio; De Girolamo, G; Palazzi, G; Paolucci, Paolo
abstract

INTRODUZIONE E OBIETTIVI: Nell’ambito di uno studio di tipo casocontrollo,volto a studiare la relazione tra esposizione al benzene datraffico veicolare nella provincia di Modena e leucemia infantile, abbiamoapplicato in modo indipendente due differenti modelli di dispersione inatmosfera delle emissioni veicolari di tale inquinante, al fine di valutareeventuali differenze indotte dall’uso di queste due metodologie nellavalutazione del rischio di ordine sanitario preso in esame.METODI: Abbiamo identificato e georeferenziato tutti i casi di leucemiainfantile occorsi nel periodo 1998-2009 nella popolazione della provinciadi Modena (n=47) ed un gruppo di controllo costituito da quattro residentiper ciascun paziente aventi medesimo sesso ed età. Abbiamo inoltredefinito una mappa di concentrazione del benzene emesso dal trafficoautoveicolare nel territorio provinciale di Modena utilizzando due modelligaussiani di dispersione in atmosfera, CALINE4 (California Departmentof Transportation line source model) e ADMS (Advanced DispersionModelling System) Urban, associati alla rilevazione dei flussi di trafficonel 2006 e ai relativi fattori di emissione di benzene, utilizzando lo stessoinput meteorologico. Mediante metodologia GIS su cartografia vettoriale,abbiamo attribuito a ciascun bambino il proprio status espositivo a benzenenell’ambito di ciascun modello, calcolando con regressione logisticacondizionata il rischio relativo di leucemia associato alle concentrazioniatmosferiche di benzene.RISULTATI: Il rischio relativo di leucemia nei residenti nelle aree convalori di benzene > 0.5 μg/m3 è risultato essere pari a 1.5 (IC95% 0.8-2.8;P=0.269; P trend=0.670) e 1.2 (IC95% 0.6-2.4; P=0.660; P trend=0.498),utilizzando i dati espositivi rispettivamente generati da CALINE4 ed ADMSUrban.I rischi ottenuti nei residenti nell’area caratterizzata da valori dibenzene superiori alla concentrazione mediana sono stati pari a 1.0 (IC95%0.5-1.8; P=0.895) e 0.9 (IC95% 0.4-1.6; P=0.645), utilizzandorispettivamente il modello CALINE4 e ADMS-Urban.CONCLUSIONI: La nostra indagine suggerisce come aspetti metodologiciassociati alla modellizzazione delle concentrazioni ambientali del benzeneemesso dal traffico veicolare possano influenzare la valutazione deirischi sanitari associati a tale esposizione.

2011 - Exposure to selenium and risk of cutaneous melanoma. [Abstract in Rivista]
Vinceti, Marco; Malagoli, Carlotta; Ferrari, Angela; Storani, Simone; Pellacani, Giovanni; Seidenari, Stefania
abstract

Selenium (Se) is a metalloid of strong toxicological and nutritional interest in human health, and both beneficial and adverse effects on the risk of human cancer have been suggested on the basis of epidemiologic and laboratory studies. A recent trial has shown no beneficial effects of Se on cancer risk, and two prospective studies indicated an excess incidence of melanoma among subjects with the highest Se exposure. We investigated this possible association through a population-based case-control study in an Italian community.Fifty-nine patients with newly-diagnosed cutaneous melanoma and fifty-nine population controls residing in the city of Modena, northern Italy, reported details about their life-style and dietary habits and yielded a blood sample. We assessed serum Se concentrations through atomic absorption spectrometry, and we calculated the relative risk (RR) of melanoma with its 95% confidence interval (CI) associated with serum Se concentrations through conditional and unconditional logistic regression models, adjusting for potential confounders.RR of melanoma was increased in the middle tertile (2.2, 95% CI 0.7-6.9) and in the upper tertile (4.4, 95% CI 1.5-12.6) of serum Se levels, as compared to subjects in the bottom tertile, with P for linear trend of 0.001. These results were substantially confirmed after adjustment for potential confounders such as family history of melanoma, number of atypical nevi, sun exposure, history of sunburns, and education. Serum Se levels were associated to dietary intake of Se, as evaluated through a semi-quantitative food frequency questionnaire, in patients but not in controls.In this population, disease risk was strongly associated with a biological indicator of Se exposure, serum Se concentration, though risk estimates were statistically unstable due to the small sample size. Study findings appear to confirm that exposure to environmental Se increases the risk of cutaneous melanoma.

2011 - Indici antropometrici e rischio di melanoma: uno studio caso-controllo di popolazione. [Abstract in Rivista]
Malagoli, Carlotta; Bergomi, Margherita; Seidenari, Stefania; Pellacani, Giovanni; Vinceti, Marco
abstract

Introduzione e obiettiviLo studio da noi effettuato, con disegno caso-controllo di popolazione, si è proposto di analizzare il ruolo di alcune misure antropometriche quali Body Mass Index (BMI) e Body Surface Area (BSA) nell’eziologia del melanoma cutaneo. MetodiAbbiamo identificato i casi di melanoma diagnosticati nel periodo 1999-2002 presso la Clinica Dermatologica del Policlinico di Modena, individuando quali controlli di popolazione residenti estratti a caso dalla popolazione generale della provincia di Modena, con un rapporto caso-controllo 1:1 ed appaiamento ai pazienti per età e sesso. Ad ogni soggetto partecipante abbiamo somministrato un questionario per la raccolta di informazioni relative alla dieta abituale, e di ciascuno abbiamo raccolto le misure di peso ed altezza. Abbiamo quindi calcolato gli indici BMI e BSA, quest’ultima utilizzando l’equazione di Mosteller (BSA(m2)=[altezza(cm) x peso(kg) / 3600]1/2). Abbiamo infine calcolato il rischio relativo di melanoma cutaneo associato ai quartili di BMI e BSA (sulla base della distribuzione nei controlli) utilizzando modelli di regressione logistica condizionata.RisultatiAbbiamo incluso nello studio 59 casi di melanoma e un pari numero di controlli. Il rischio relativo di melanoma associato a BMI e aggiustato per BSA e introito calorico è risultato essere, per il quartile più elevato verso il minore, pari a 0.5 (IC95% 0.2-2.1; P trend 0.393). Il rischio relativo di melanoma associato invece alla BSA, dopo aggiustamento per BMI e introito calorico, è risultato pari a 10.4 nel quartile più elevato (IC95% 1.1-101.4; P trend 0.042). Nell’analisi disaggregata per sesso, è emersa un’associazione tra BSA e rischio di melanoma pari a 5.1 nel quartile più elevato (IC95% 0.4-69.5; P trend 0.200) negli uomini e 6.3 nel quartile più elevato (IC95% 0.3-128.9; P trend 0.030) nelle donne.ConclusioniI risultati da noi ottenuti, pur tenendo conto dell’instabilità statistica delle stime di rischio dovute alle limitate dimensioni della popolazione esaminata, indicano come i diversi indici antropometrici predicano in modo sensibilmente differente il rischio di melanoma, e come l’area della superficie corporea rappresenti, soprattutto per le donne, un fattore di rischio di questa patologia.

2011 - Inverse association between dietary vitamin D and risk of cutaneous melanoma in a Northern Italy population [Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; Fiorentini, Chiara; Longo, Caterina; Crespi, Cm; Albertini, G; Ricci, C; Lanzoni, A; Reggiani, M; Virgili, A; Osti, F; Lombardi, M; Santini, M; Fanti, Pa; Dika, E; Sieri, S; Krogh, V; Seidenari, Stefania; Pellacani, Giovanni
abstract

The possibility of an inverse association between vitamin D and risk of cancer and, in particular, of cutaneous malignant melanoma has been suggested, but results of epidemiologic studies are still conflicting. We examined the relation between dietary vitamin D intake and melanoma risk through a population-based case-control study (380 cases, 719 controls) in a northern region of Italy, a country with an average vitamin D intake lower than that in northern Europe or the United States. We assessed average daily intake of vitamin D from foodstuffs using the European Prospective Investigation into Cancer and Nutrition (EPIC) semiquantitative food frequency questionnaire. In this population, levels of vitamin D intake were considerably lower than those observed in recent U.S. studies. We found an inverse relation between dietary vitamin D and melanoma risk in the sample as a whole, in both crude and adjusted analyses. In sex- and age-specific analyses, this association appeared to be stronger among males and among older subjects. These findings suggest that, at the relatively low levels of intake observed in this sample, an inverse relation between dietary vitamin D and risk of cutaneous malignant melanoma may exist.

2011 - Journal of Environmental Science and Health - Part C [Direzione o Responsabilità Riviste]
Y., Woo; A., Fan; P., Fu; Vinceti, Marco
abstract

2011 - Low levels of selenium compounds are selectively toxic for a human neuron cell line through ROS/RNS increase and apoptotic process activation [Articolo su rivista]
Maraldi, Tullia; Riccio, Massimo; L., Zambonin; Vinceti, Marco; DE POL, Anto; G., Hakimb
abstract

Organic and inorganic selenium compounds were used to examinewhether low selenium concentrationis able to trigger apoptotic degeneration in a human neuron cell line in vitro and to explore changes inreactive oxygen and nitrogen species and antioxidant protein content during the apoptotic processes.The results indicated that: (1) SKNBE neuroblastoma cells treated with sodium selenite, sodium selenateand seleno-methionine (0.1, 0.5 and 0.5 mM, respectively) for 24 h exhibited a viability decrease, unlikekidney or prostatic cells; (2) the PARP (poly-ADP-ribose-polymerase) degradation and caspase activationdetected by Western blot and flow cytometry fluorimetric examination showed induction of apoptosis;(3) during selenium treatment, a ROS/RNS increase occurred despite the GSH increment, as revealed byfluorimetric analysis; (4) the RNS production could be blocked by a peroxynitrite scavenger; (5) afterexposure to selenium compounds, the concentration of nitric oxide synthase, manganese superoxidedismutase (SOD2), P-NF-kB (phospho nuclear factor kB), glutathione reductase and glutathioneperoxidase increased, whereas that of P-ERK (phospho extracellular signal-regulated kinase) decreased;(6) selenium presence induced copper/zinc superoxide dismutase (SOD1) translocation into mitochondria,in a way similar to what is observed in amyotrophic lateral sclerosis (ALS). This study supportsepidemiologic studies showing the possibility that excess environmental exposure to Se represents a riskfactor for a devastating human neurodegenerative disease.

2011 - Mapping traffic atmospheric emissions for epidemiological studies using atmospheric dispersion models and geostatistical methods: a case study [Relazione in Atti di Convegno]
Teggi, Sergio; Ghermandi, Grazia; Fabbi, Sara; Malagoli, Carlotta; Vinceti, Marco; L., Guerra; A., Sterni; G., Maffeis
abstract

In some cases, epidemiological studies require the air pollutant concentrations at the exposure points. In these cases air dispersion models represent a very important tool. When additional points of exposure are inserted or when some exposure points must be relocated, spatial interpolators can be used in place of new runs of the air dispersion model. In this work the uncertainties and the problematic related to spatial interpolation methods are inspected. The case studied is based on an epidemiological study aimed to study the risk of childhood leukemia associated with benzene exposure due to traffic emissions. The concentration values of benzene computed by the atmospheric dispersion model ADMS are taken as reference and compared with the concentration values computed using several interpolation methods and additional data sets of concentrations computed by ADMS in the same area. The comparison is done following two approaches: the summary statistics of the differences and the correctness of the assignment of the exposure points to the concentration categories used in the epidemiological study. These comparisons show that the values computed by the interpolators are very problematic: important differences and categories assignment and categories uncertainties were found. The main conclusion of this work is that the use of interpolators must be done with extreme caution. Moreover, it is highlighted the importance and the potential pitfalls of exposure modelling methodologies when assessing the health effects of environmental pollutants

2011 - Methods to assess selenium exposure: evaluation of dietary intake and biomarkers in melanoma patients and population controls. [Abstract in Atti di Convegno]
Storani, Simone; Malagoli, Carlotta; Bottecchi, Iliaria; Ferrari, A; Vinceti, Marco
abstract

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2011 - Municipal Solid Waste Incineration and Risk of Soft-tissue Sarcoma: A Case-control Study [Abstract in Rivista]
N., Borciani; R., Rodolfi; G., Carlinfante; Malagoli, Carlotta; Vinceti, Marco; Bergomi, Margherita
abstract

Soft-tissue sarcoma is a rare neoplasia of the connective tissue with unknown etiology. Heavy metals and dioxins, which are also emitted by municipal solid waste incinerators, are among the environmental factors suspected to play a role in its etiology.We assessed the possible relation between long-term exposure to emissions of a municipal solid waste incinerator and risk of soft-tissue sarcoma in the Italian municipality of Reggio Emilia through a population-based case-control study. We identified 50 cases of newly-diagnosed sarcomas from 2001 to 2008, and we randomly selected 4 population controls for each case, matched for sex and age. We identified and geocoded residential history of study subjects, and we identified two areas of intermediate and high exposure to emissions of the city solid waste incinerator. All this information was added to a Geographical Information System database, to assess exposure status of study subjects and to calculate the associated relative risk (RR) of soft-tissue sarcoma with its 95% confidence interval (CI) in a conditional logistic regression model. Three cases of soft tissue sarcoma occurred among previously exposed subjects. Residence in one of the two exposed areas was associated with a RR of 0.52 (CI 0.12-2.37) at disease diagnosis and with a RR of 1.10 (CI 0.28-4.35) 20 years before, after adjusting for educational attainment. When we limited the analysis to highly exposed subjects, we found a RR relative risk of 1.93 (CI 0.32-11.71) at diagnosis and of 3.70 (CI 0.72-18.97) 20 years before. No dose-response relation between exposure status and disease risk emerged.Overall, risk of soft-tissue sarcoma was increased among subjects with high exposure to incinerator emissions, but risk estimates were statistically very unstable and no evidence of dose-response relation emerged. Larger studies are required to confirm a relation between emissions from waste incineration and incidence of soft-tissue sarcoma.

2011 - Risk of congenital anomalies around a municipal solid waste incinerator [Capitolo/Saggio]
Vinceti, M.; Malagoli, C.; Fabbi, S.; Teggi, S.; Rodolfi, R.; Garavelli, L.; Astolfi, G.; Rivieri, F.
abstract

Waste incineration releases into the environment toxic substances having a teratogenic potential, but little epidemiologic evidence is available on this topic. We aimed at examining the relation between exposure to the emissions from a municipal solid waste incinerator (MSWI) and risk of birth defects in a northern Italy community, using geographical information system (GIS) data to estimate exposure and a population-based case-control study design. By modeling the incinerator emissions, we defined in the GIS three areas of increasing exposure according to predicted dioxins concentrations. We mapped the 228 births and induced abortions with diagnosis of congenital anomalies observed during the 1998-2006 period, together with a corresponding series of control births matched for year and hospital of birth/abortion as well as maternal age, using maternal address in the first 3 months of pregnancy to geocode cases and controls.

2011 - Selenium for preventing cancer.Review information [Articolo su rivista]
G., Dennert; M., Zwahlen; M., Brinkman; Vinceti, Marco; M. P. A., Zeegers; M., Horneber
abstract

Selenium is a trace element essential to humans. Higher selenium exposure and selenium supplements havebeen suggested to protect against several types of cancers.Two research questions were addressed in this review: What is the evidence for1. an aetiological relationship between selenium exposure and cancer risk in women and men?2. the efficacy of selenium supplementation for cancer prevention in women and men?We searched electronic databases and bibliographies of reviews and included publications.Prospective observational studies were included to answer research question (a) and randomised controlledtrials (RCTs) to answer research question (b).Random effects meta-analyses of epidemiological data were conducted when five or more studies wereretrieved for a specific outcome. Data from RCTs were summarised as a narrative.We included 49 prospective observational studies and six RCTs. In epidemiologic data, a reduced cancerincidence (summary odds ratio (OR) 0.69 (95% confidence interval (CI) 0.53 to 0.91) and mortality (OR 0.55,95% CI 0.36 to 0.83) was found with higher selenium exposure. Cancer risk was more pronouncedly reducedin men (incidence: OR 0.66, 95% CI 0.42 to 1.05) than in women (incidence: OR 0.90, 95% CI 0.45 to 1.77).These findings have potential limitations due to study design, quality and heterogeneity of the data, whichcomplicated the interpretation of the summary statistics.The RCTs found no protective efficacy of selenium yeast supplementation against non-melanoma skin canceror L-selenomethionine supplementation against prostate cancer. Study results for the prevention of livercancer with selenium supplements were inconsistent and studies had an unclear risk of bias. The results of theNutritional Prevention of Cancer Trial (NPCT) and SELECT raised concerns about possible harmful effects ofselenium supplements.No reliable conclusions can be drawn regarding a causal relationship between low selenium exposure and anincreased risk of cancer. Despite evidence for an inverse association between selenium exposure and the riskof some types of cancer, these results should be interpreted with care due to the potential limiting factors ofheterogeneity and influences of unknown biases, confounding and effect modification.The effect of selenium supplementation from RCTs yielded inconsistent results. To date, there is no convincingevidence that selenium supplements can prevent cancer in men, women or children.

2011 - Stima della esposizione a benzene da traffico veicolare nelle Province di Modena e Reggio Emilia [Abstract in Rivista]
Malagoli, Carlotta; Cherubini, A; Maffeis, G; Sterni, A; Guerra, L; Fabbi, Sara; Teggi, Sergio; Ferretti, Enrica; Vinceti, Marco
abstract

controllo,volto a studiare la relazione tra leucemia infantile ed esposizioneal benzene da traffico veicolare nelle province di Modena e Reggio Emilia,abbiamo applicato un modello di simulazione deterministico e la metodologiaGIS (Geographical Information System) per studiare la dispersione delleemissioni veicolari di tale inquinante e costruire una mappa espositiva, alfine di valutarne l’eventuale associazione col rischio di leucemia infantile.METODI: Abbiamo individuato e georeferenziato i casi di leucemia infantile(n=83) diagnosticati nei bambini residenti nella province di Modena e ReggioEmilia dal 1998 ad oggi ed una popolazione di controllo costituita da quattrosoggetti per ciascun paziente, appaiati per sesso, età e provincia di residenza.Abbiamo quindi definito una mappa della dispersione delle emissioniautoveicolari di benzene con l’utilizzazione dei dati relativi ai flussi di trafficonel periodo 2005-06 sulle principali vie di circolazione sui due territoriprovinciali, alle emissioni ad essi associabili ed alla dispersione in atmosfera,utilizzando per quest’ultima stima il modello gaussiano CALINE4 (CaliforniaDepartment of Transportation line source model). Infine, abbiamo attribuitoin ambito GIS a ciascun bambino il proprio status espositivo.RISULTATI: I soggetti inclusi nello studio sono risultati caratterizzati,presso le loro residenze, da concentrazioni annuali di benzene legatealle sole emissioni da traffico comprese aventi una media di 0.41 μg/m3 e una mediana di 0.26 μg/m3, con concentrazioni massime su baseoraria comprese tra 0.79 e 15.16 μg/m3. Restringendo le analisi allasola popolazione di controllo, 241 soggetti sono risultati residenti in unaarea caratterizzata da una concentrazione media annuale di benzeneinferiore a 0.5 μg/m3; 62 soggetti sono risultati residenti in una zonacaratterizzata da concentrazioni comprese tra e”0.5 e <1.0 μg/m3 e 29soggetti sono risultati abitare in aree con concentrazioni e”1.0 μg/m3.Le stime fornite dalla modellistica in riferimento ai punti di localizzazionedelle centraline di rilevazione del benzene sono apparse complessamentesoddisfacenti, suggerendo la sostanziale validità dell’approcciometodologico utilizzato.CONCLUSIONI: L’applicazione di questa modellistica si è dimostrataefficace nello stimarelo status espositivo a benzene nella popolazione presa in esame ed hasuggerito livelli di concentrazioni ambientali relativamente contenuti,sensibilmente inferiori a quelli documentati dalle rilevazioni strumentalie dai dati di letteratura disponibili per gli anni ‘90.

2010 - A prospective study of dietary selenium intake and risk of type 2 diabetes. [Articolo su rivista]
Stranges, S; Sieri, S; Vinceti, Marco; Grioni, S; Guallar, E; Laclaustra, M; Muti, P; Berrino, F; Krogh, V.
abstract

BACKGROUND: Growing evidence raises concern about possible associations of high selenium exposure with diabetes in selenium-replete populations such as the US. In countries with lower selenium status, such as Italy, there is little epidemiological evidence on the association between selenium and diabetes. This study examined the prospective association between dietary selenium intake and risk of type 2 diabetes.METHODS: The ORDET cohort study comprised a large sample of women from Northern Italy (n = 7,182). Incident type 2 diabetes was defined as a self-report of a physician diagnosis, use of antidiabetic medication, or a hospitalization discharge. Dietary selenium intake was measured by a semi-quantitative food-frequency questionnaire at the baseline examination (1987-1992). Participants were divided in quintiles based on their baseline dietary selenium intake.RESULTS: Average selenium intake at baseline was 55.7 μg/day. After a median follow-up of 16 years, 253 women developed diabetes. In multivariate logistic regression analyses, the odds ratio for diabetes comparing the highest to the lowest quintile of selenium intake was 2.39, (95% CI: 1.32, 4.32; P for linear trend = 0.005). The odds ratio for diabetes associated with a 10 μg/d increase in selenium intake was 1.29 (95% CI: 1.10, 1.52).CONCLUSIONS: In this population, increased dietary selenium intake was associated with an increased risk of type 2 diabetes. These findings raise additional concerns about the association of selenium intake above the Recommended Dietary Allowance (55 μg/day) with diabetes risk.

2010 - Atmospheric dispersion modelling for the assessment of population exposure to contaminants emitted by municipal waste incinerators [Relazione in Atti di Convegno]
Teggi, Sergio; Ghermandi, Grazia; Fabbi, Sara; Vinceti, Marco; Malagoli, Carlotta
abstract

In this work two examples of the use of pollutants atmospheric dispersion modelling for the study of the risk of spontaneous abortion and birth of congenital anomalies due to the emissions from municipal waste incineration plants are shown. The main purposes of the work are to show the importance of atmospheric dispersion modelling for epidemiological studies and to discuss advantages and disadvantages of the different models used. For this study the emissions of polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls (PCDD/F) from the municipal waste incinerators of Modena (Italy, Case A) and of Reggio Emilia (Italy, Case B) have been considered. Ground-level (0 – 10 m) concentrations of PCDD/F over the city of Modena were computed using the ARIA Industry dispersion model for the period from 1 October, 2005 to 1 October, 2006. Ground-level concentrations of PCDD/F over the city of Reggio Emilia were computed using the WinDimula 3.0 model for the years 1999, 2000 and 2001, and for the period from 1 July, 2005 to 30 June, 2006. The ground level concentration grids computed by the models were exported in a GIS along with rates of spontaneous abortion and prevalence at birth of congenital anomalies in women residing or working near the incinerators. Successively, the maps of exposure to PCDD/F and of risk of adverse pregnancy outcomes have been computed in the GIS environment. In both the cases the study results provide little evidence of an excess risk of adverse pregnancy outcomes in women exposed to emissions from a modern municipal solid waste incinerator.

2010 - Campi elettromagnetici e suicidio: un protocollo di studio [Abstract in Rivista]
N., Borciani; Malagoli, Carlotta; R., Rodolfi; F., Luberto; Bergomi, Margherita; Vinceti, Marco
abstract

L’esposizione a campi elettromagnetici può provocare effetti sulla salute. In particolare alcuni studi hanno evidenziato una possibile correlazione tra la esposizione a campi elettromagnetici a frequenze estremamente basse generati dalle linee elettriche ad alta tensione ed alcune patologie quali leucemie infantili e tumori cerebrali. Altri studi hanno inoltre proposto la presenza di una associazione tra la residenza in prossimità di elettrodotti e l’occorrenza di sindromi depressive e suicidi.Abbiamo così steso un protocollo per la conduzione di uno studio di tipo caso-controllo da realizzare con l’ausilio di procedure di georeferenziazione GIS (Geographical Information System) nel territorio di Reggio Emilia. Tale studio si pone i seguenti obiettivi: costruire una mappa di patologia che mostri la distribuzione territoriale dei suicidi occorsi fra i residenti del comune di Reggio Emilia nel periodo 1989-2008; studiare la correlazione tra suicidi e l’esposizione a campi elettromagnetici generati dalle linee elettriche ad alta tensione; identificare eventuali aggregati spaziali di tale fenomeno. Saranno identificati tutti i casi di suicidio occorsi dal 1989 al 2008 nei residenti nel comune di Reggio Emilia. Per ciascuno di essi saranno estratti casualmente dalla popolazione residente due controlli dello stesso sesso ed anno di nascita. Di ogni soggetto in studio saranno ricercati la residenza al momento del suicidio, la professione ed il titolo di studio consultando i registri informatizzati e cartacei dell’anagrafe comunale. Con una simulazione modellistica calcoleremo il campo magnetico generato dalle linee elettriche ad alta tensione (>132kV) presenti sul territorio comunale ed identificheremo fasce di esposizione lungo gli elettrodotti caratterizzate da induzione magnetica con cutoff pari a 0.1, 0.2 e 0.4 microtesla (µT).In un progetto GIS inseriremo le localizzazioni delle abitazioni dei casi e dei rispettivi controlli (dopo avere attribuito ad ogni edificio le proprie coordinate cartografiche) e le aree espositive identificate lungo gli elettrodotti al fine di attribuire ad ogni soggetto il proprio status espositivo.Sarà così elaborata una ‘mappa di patologia’ che descriverà la distribuzione dei casi di suicidio nel territorio del comune di Reggio Emilia e che permetterà, con opportune analisi di cluster, di individuare la presenza di possibili aggregati spaziali. Inoltre, utilizzando modelli multivariati di regressione logistica condizionata e tenendo conto dei possibili fattori confondenti, sarà calcolato il rischio relativo di suicidio associato alla residenza nelle aree a crescente esposizione ai campi elettromagnetici generati da linee elettriche ad alta tensione.

2010 - Come imparare a fare ricerca nell’infermieristica: sintesi di un’esperienza applicativa [Articolo su rivista]
Palese, A; Mecugni, Daniela; Barbieri, M; Bonocore, M; Buscaroli, A; Buscaroli, A; Caparnoni, M; Colognese, S; Costi, D; Di Vaio, S; Lapi, L; Lionte, G; Nasi, Am; Pellicciari, C; Quartieri, M; Ricci, R; Saguatti, K; Saragoni, M; Tarantola, S; Torri, E; Vaccari, S; Volpi, P; Vinceti, Marco
abstract

An innovative teaching strategy focused on problem based approach rather than theorical aiming to facilitate the learning of the research methodology in advanced nursing student has been introduced.Through out a qualitative evaluation of the diary kept by the student nurses involved, advantages anddisadvantages of this innovative approach have been evaluated. This paper reports a synthesis of theteaching strategy and its impact on the competences in the research methodology as it has beenperceived by the students participants.

2010 - Epidemiologia ambientale: attualità e prospettive [Capitolo/Saggio]
Vinceti, Marco; Righi, Elena; Malagoli, Carlotta; Fantuzzi, Guglielmina
abstract

Le tematiche prese in esame dall’epidemiologia ambientale appaiono oggi sempre più rilevanti e nello stesso tempo più complesse rispetto al passato, ponendo ai ricercatori sfide particolarmente impegnative. L’attenzione posta dall’opinione pubblica e dalle istituzioni politico-amministrative nei confronti dei determinanti ambientali di rischio è molto elevata, si pensi a tematiche come il rischio sanitario di insediamenti industriali, l’inquinamento da traffico, i rischi legati ai campi elettromagnetici, la pericolosità di pesticidi, contaminanti organici clorurati e metalli pesanti. Quindi sempre maggior impegno dovrebbe essere posto dai ricercatori sia nel condurre studi sulle problematiche dell’epidemiologia ambientale sia nel contribuire ad una definizione più chiara del suo ambito di competenza affinchè si possa anche rafforzarne il ruolo nei suoi aspetti formativi e metodologici all’interno dei curricula di corsi di laurea, scuole di specializzazione, dottorati di ricerca e master.

2010 - Esposizione a benzene e rischio di leucemia infantile: studio caso-controllo realizzato con metodologia GIS. [Abstract in Atti di Convegno]
Malagoli, Carlotta; Ferretti, Enrica; Fabbi, Sara; Teggi, Sergio; Sterni, A; Guerra, L; Palazzi, G; Paolucci, Paolo; Bergomi, Margherita; Vinceti, Marco
abstract

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2010 - Esposizione a benzene e rischio di neoplasie ematologiche infantili: un protocollo di studio. [Abstract in Rivista]
Vinceti, Marco; Malagoli, Carlotta; Fabbi, Sara; Teggi, Sergio; Guerra, L; Sterni, A; Maffeis, G; Ferretti, Enrica; Palazzi, G; Paolucci, Paolo; Bergomi, Margherita
abstract

OBIETTIVILe neoplasie ematologiche sono patologie a probabile eziologia multifattoriale: oltre a fattori di tipo genetico infatti, possono essere indotte o favorite da fattori ambientali quali contaminanti chimici e radiazioni ionizzanti. In particolare, esistono in letteratura alcune indicazioni che suggeriscono un’associazione tra esposizione a benzene e rischio di leucemia sia nell’età adulta che in quella pediatrica, anche se il numero degli studi è ancora molto limitato e i relativi risultati non sono concordi. Abbiamo messo a punto un protocollo finalizzato alla realizzazione di uno studio caso-controllo nei bambini residenti in aree urbane di due province del nord Italia con l’obiettivo di identificare un possibile aumento del rischio di leucemia e più in generale di neoplasie del sistema linfoematopoietico (codici ICD-9 200-208) in relazione a diversi livelli espositivi a benzene da traffico veicolare.MATERIALIIntendiamo individuare tutti i casi di tali patologie diagnosticati in età compresa tra 0 e 13 anni tra i residenti nelle province di Modena e Reggio Emilia a partire dal 1986, utilizzando il Registro nazionale AIEOP. A questi pazienti affiancheremo una popolazione di controllo, costituita da quattro bambini non ammalati per ciascun caso caratterizzati da medesimo sesso, anno di nascita e provincia di residenza; tali controlli saranno estratti casualmente dalla popolazione residente. La valutazione espositiva di ciascun soggetto incluso nello studio verrà effettuata in ambiente GIS (Geographical Information System). Nel progetto GIS verranno inserite una simulazione modellistica della dispersione delle emissioni autoveicolari di benzene sull’intero territorio delle due province e le localizzazioni delle residenze dei bambini al momento della diagnosi. Intendiamo così individuare per ogni bambino la residenza al momento della diagnosi mediante consultazione dei registri anagrafici comunali informatizzati e cartacei, intervista ai medici di famiglia e ricerche dirette. Ad ogni indirizzo attribuiremo quindi le coordinate cartografiche del baricentro dell’edificio presenti nelle cartografie tecniche o rilevate direttamente sul posto tramite un sistema di posizionamento satellitare GPS. Per ogni soggetto raccoglieremo inoltre informazioni relative a titolo di studio, professione e reddito di entrambi i genitori. Calcoleremo infine il rischio di leucemia e di neoplasie linfoematopoietiche associato ai diversi livelli espositivi a benzene utilizzando modelli multivariati di regressione logistica condizionata e di ‘natural spline regression’, tenendo conto dei possibili fattori confondenti e cercando di identificare eventuali modificatori di effetto.

2010 - Evaluation of the drinking water selenium standard: an update. [Abstract in Atti di Convegno]
Vinceti, Marco; Bonvicini, Francesca; Bergomi, Margherita; Malagoli, Carlotta
abstract

Recent studies suggesting a diabetogenic activity of selenium (Se) have raised concern about the human health effects of this metalloid of considerable nutritional and toxicological interest. Uncertainties exist about the adequate environmental levels of this metalloid, in particular, regarding the safe upper standard in drinking water, considering the very few epidemiologic studies carried out on this topic.We summarize results of our epidemiologic studies on long-term effects of consumption of municipal tapwater with naturally-occurring unusually high levels of Se (7-9 µg/l), within a non-seleniferous Italian area. Speciation analyses demonstrated that in that tapwater Se was almost entirely present in its hexavalent inorganic form, selenate. After checking for potential confounders, long-term consumers of the high-Se drinking water experienced no substantial change in overall mortality and in prevalence at birth of congenital anomalies, whilst incidence of amyotrophic lateral sclerosis and of some site-specific cancers exceeded that expected on the basis of reference rates. No beneficial effect on prostate cancer risk emerged, consistently with results of a recently published large trial carried out in the US.Our results are corroborated by laboratory studies, which demonstrated that inorganic (tetravalent) Se is toxic at concentrations as low as 0,8 µg/l, also confirming that toxicity of inorganic Se species far exceeds that of the organic forms.Overall, these findings indicate that current WHO drinking water upper Se standard, 10 µg/l, might be inadequate to protect human health, suggesting the need for additional epidemiologic studies on health effects of exposure to specific Se species through drinking water.

2010 - Exposure to pesticides and risk of amyotrophic lateral sclerosis: a population-based case-control study [Articolo su rivista]
Bonvicini, Francesca; Marcello, N.; Mandrioli, J.; Pietrini, V.; Vinceti, Marco
abstract

A few epidemiologic studies have suggested an association of agricultural work and pesticidesexposure with a severe degenerative disease of the motor neurons, amyotrophic lateral sclerosis(ALS), though conflicting results have also been provided. We investigated through a populationbasedcase-control study the possible relation between overall occupational exposure to pesticidesand ALS risk in the northern Italy municipality of Reggio Emilia. By administering a questionnaire,we investigated occupational history and leisure-time habits of the 41 ALS patients diagnosed in the1995-2006 period, and of 82 age- and sex-matched randomly sampled population controls. Morecases than controls were found to have been exposed to pesticides for at least six months (31.7% vs13.4%, respectively), in all cases within the occupational environment. In a conditional logistic regressionmodel, we found an excess ALS risk associated with exposure to pesticides, with a relativerisk of 3.6 (95% confidence interval 1.2-10.5). Such association persisted after inclusion in the statisticalanalysis of potential confounders. Despite the limited statistical stability of the risk estimates,these results appear to indicate that occupational exposure to pesticides is a risk factor for ALS,suggesting the need to further investigate this issue.

2010 - Igiene epidemiologia e sanità pubblica [Curatela]
S., Capolongo; E., Colzani; Limina, R. M.; C., Pasquarella; M., Riccò; Righi, Elena; L., Veronesi; Vinceti, Marco
abstract

Il volume è indicato per gli studenti di tutti i corsi di laurea dove vengono insegnate le materie igienistiche e per gli operatori sanitari che vi troveranno informazioni aggiornate sulle principali tematiche della sanità pubblica, novità normative e nuovi argomenti di crescente interesse per la comunità scientifica degli igienisti.

2010 - L’interruzione volontaria di gravidanza nel Distretto socio-sanitario di Ostiglia - Mantova, Lombardia nel periodo 1998-2007: aspetti epidemiologici [Articolo su rivista]
M., Molinari; L., Boldrini; S., Raffanini; V., Pironi; P., Ricci; Bonvicini, Francesca; Vinceti, Marco
abstract

L’interruzione volontaria di gravidanza nel Distrettosocio-sanitario di Ostiglia - Mantova, Lombardia nelperiodo 1998-2007: aspetti epidemiologici.Introduzione. In Italia la Legge N. 194/1978 regolamental’interruzione volontaria di gravidanza. Datempo è attivo un Sistema di Sorveglianza nazionaleche registra annualmente il trend del fenomeno. Nonostantequeste Relazioni epidemiologiche annualinon sono disponibili molte indagini, in ambiti più ristretti,che analizzano il modello assistenziale e lacontinuità del percorso tra Distretti sanitari e Ospedali.Obiettivi:• esaminare i casi di interruzione volontaria digravidanza (I.V.G.) assistiti nel decennio1998/2007;• esplorare correlazioni tra: consulenze psicologiche,prassi di accompagnamento e ritornoper la scelta di una metodica contraccettiva;• verificare gli esiti (IVG, parti) dei casi identificati.Disegno. Studio retrospettivo.Metodi. I dati provengono dalle cartelle consultorialidel Distretto socio-sanitario e dall’Archivio delleschede di dimissione ospedaliera (S.D.O).Risultati. Sono stati assistiti 335 casi su 820 registratinella popolazione residente (copertura: 39%). Laprobabilità che la donna ritorni in consultorio, dopol’IVG, aumenta del 66% se prima dell’invio in ospedaleè realizzato anche il counselling complesso (psicologa):Rischio Relativo = 1,66 (I.C.: 1,19 - 2,31,p<0,04) e del 39% se è effettuata la prenotazione inospedale: Rischio Relativo = 1,39 (I.C.; 1,07 – 1,80,p<0,03).Il 6,5% dei casi assistiti ha proseguito la gravidanza.Conclusioni. Lo studio avvalora l’importanza diidentificare strategie più adeguate per la prevenzionedell’abortività volontaria e per l’assistenza alle donneche cercano di compiere tale scelta. I fattori che possonodeterminare la prosecuzione della gravidanza, dopoaver intrapreso un percorso di IVG, necessitano diessere accuratamente approfonditi in ulteriori studi.

2010 - Pooled analysis of recent studies on magnetic fields and childhood leukaemia [Articolo su rivista]
L., Kheifets; A., Ahlbom; C. M., Crespi; G., Draper; J., Hagihara; R. M., Lowenthal; G., Mezei; S., Oksuzyan; J., Schuz; J., Swanson; A., Tittarelli; Vinceti, Marco; V., Wunsch Filho
abstract

Previous pooled analyses have reported an association between magnetic fields and childhood leukaemia. We presenta pooled analysis based on primary data from studies on residential magnetic fields and childhood leukaemia published after 2000.METHODS: Seven studies with a total of 10 865 cases and 12 853 controls were included. The main analysis focused on 24-h magneticfield measurements or calculated fields in residences.RESULTS: In the combined results, risk increased with increase in exposure, but the estimates were imprecise. The odds ratiosfor exposure categories of 0.1–0.2 mT, 0.2–0.3 mT and X0.3 mT, compared with o0.1 mT, were 1.07 (95% CI 0.81–1.41), 1.16(0.69–1.93) and 1.44 (0.88–2.36), respectively. Without the most influential study from Brazil, the odds ratios increased somewhat.An increasing trend was also suggested by a nonparametric analysis conducted using a generalised additive model.CONCLUSIONS: Our results are in line with previous pooled analyses showing an association between magnetic fields and childhoodleukaemia. Overall, the association is weaker in the most recently conducted studies, but these studies are small and lackmethodological improvements needed to resolve the apparent association. We conclude that recent studies on magnetic fieldsand childhood leukaemia do not alter the previous assessment that magnetic fields are possibly carcinogenic.

2010 - Possible involvement of overexposure to environmental selenium in the etiology of amyotrophic lateral sclerosis: A short review [Articolo su rivista]
Vinceti, Marco; Bonvicini, Francesca; Bergomi, Margherita; Malagoli, Carlotta
abstract

Excess exposure to the metalloid selenium (Se), a trace element with both toxicologicaland nutritional properties, has been implicated in the etiology of a human motor neuron diseaseof unknown origin and extremely severe prognosis, sporadic amyotrophic lateral sclerosis (ALS).This relation has been suggested on the basis of two epidemiologic investigations which found anincreased risk of ALS associated with residence in a seleniferous area or with consumption of drinkingwater with unusually high levels of inorganic hexavalent Se, in South Dakota and in northernItaly respectively. Biological plausibility to a Se-ALS relation is provided by veterinary medicineobservations and toxicological studies, showing that Se, particularly the inorganic forms, has a selectivetoxicity to motor neurons in swine and in cattle. Neurotoxic effects of Se species have also beendemonstrated in laboratory studies and, for the inorganic forms, even at very low concentrations.Selenium has also been shown to affect muscle function in experimental animal models. Overall,these findings from the epidemiologic and the toxicological literature indicate that environmental Se,particularly in its inorganic forms and at unexpectedly low levels of exposure, might be a risk factorfor ALS, suggesting the opportunity to further investigate this issue.

2010 - Prospective Association of High Dietary Selenium Intake with Increased Risk of Type 2 Diabetes in Women: The Ordet Cohort Study [Abstract in Atti di Convegno]
Stranges, S; Sieri, S; Vinceti, Marco; Grioni, S; Guallar, E; Laclaustra, M; Muti, P; Berrino, F; Krogh, V.
abstract

Background: Growing evidence raises concern about possible associations of high selenium exposure with diabetes in the US, a population with high selenium status. In populations with lower selenium status, such as Italy, there is little data on the association of selenium with cardio-metabolic risk factors in the general population. We therefore examined the prospective association of dietary selenium intake with diabetes risk in the ORDET (HORmones and Diet in the ETiology of Breast Cancer) cohort study, a large sample of women from Northern Italy (n=7,182). Methods: Incident type 2 diabetes was defined as a self-report of a physician diagnosis, a self-report of use of antidiabetic medication, a prescription of antidiabetic medication by linkage with a regional prescription drug database, or a hospitalization discharge with a diabetes code by linkage with discharge records. Dietary selenium intake was measured by a semi-quantitative food-frequency questionnaire. Participants were divided in quintiles based on their baseline dietary selenium intake. Results: Average selenium intake at baseline was 55.7 /day. After a median follow-up of 16 years, 253 women in the cohort developed diabetes. In multivariate logistic regression analyses, the odds ratio for diabetes comparing the highest to the lowest quintile of dietary selenium intake was 2.66 (95% CI: 1.48-4.75), with a significant linear trend (p = 0.001). The odds ratio for diabetes associated with an increase in selenium intake of 50 g/d was 3.63 (95% CI: 1.61-8.20). Conclusions: Increased dietary selenium intake was associated with a markedly increased risk of type 2 diabetes in a large sample of Italian women. Consistent with recent studies, these findings raise additional concerns about the association of selenium intake above the Recommended Dietary Allowance (55 g/day) with diabetes risk and sub-clinical metabolic toxicity.

2010 - Residence Near High-voltage Power Lines and Risk of Birth Defects [Abstract in Rivista]
Malagoli, Carlotta; Rodolfi, R; Fabbi, Sara; Teggi, Sergio; Garavelli, L; Astolfi, G; Rivieri, F; Vinceti, Marco
abstract

Background and ObjectiveThe adverse effects on human health of electromagnetic fields are still unclear and congenital anomalies are among the outcomes which have been associated to such exposure. We conducted a case-control study to examine the risk of birth defects associated with maternal exposure to electromagnetic fields from high-voltage power lines during pregnancy in a northern Italy community. Methods We identified all cases of congenital malformations diagnosed during the period 1998-2006 in live- and stillbirths and induced abortions to women living in Reggio Emilia. As a control group, we selected at random a healthy newborn for each case, matched for year of birth, maternal age and hospital of birth. We geocoded each mother’s resident address during the first trimester of pregnancy in a GIS (Geographical Information System) project. We also calculated the cutpoints of magnetic field density of 0.1, 0.2 and 0.4 microtesla (μT) around high-voltage power lines (>132kV) crossing the municipal territory, inputting the corresponding polylines into the GIS to define exposure corridors. We eventually calculated the risk of prevalence of birth defects associated with maternal exposure to magnetic fields from power lines using a conditional logistic regression model and adjusting for some confounding factors.ResultsWe identified 228 cases of birth defects and a corresponding number of control births. Two case and five control mothers had been residing during the first trimester of pregnancy in corridors with magnetic field intensity >0.1 μT. The risk of congenital malformations associated with the maternal residence during the first trimester of pregnancy in the corridors with exposure >0.1 μT was 0.4 (95% CI 0.1-2.3, P = 0.338) after adjustment for maternal age and education. Conclusions These observations do not suggest that exposure to electromagnetic fields during early pregnancy is associated with excess teratogenic risk.

2010 - Residenza in prossimità delle linee elettriche ad alta tensione e rischio di malformazioni congenite: uno studio caso-controllo [Abstract in Rivista]
Malagoli, Carlotta; R., Rodolfi; N., Borciani; Fabbi, Sara; Teggi, Sergio; M., Riccò; L., Garavelli; G., Astolfi; F., Rivieri; Vinceti, Marco
abstract

Gli effetti sulla salute riproduttiva dei campi elettromagnetici da radiazioni a frequenza estremamente bassa non sono ancora del tutto chiari. Abbiamo così realizzato uno studio caso-controllo tra le donne residenti nel comune di Reggio Emilia per studiare la relazione tra residenza materna durante il primo trimestre di gravidanza in prossimità delle linee elettriche ad alta tensione (>132kV) e il riscontro di malformazioni congenite nella progenie.Abbiamo identificato tutti i casi di malformazioni congenite verificatisi nel periodo 1998-2006. Per ciascuno abbiamo estratto un controllo appaiato per anno di nascita, struttura ospedaliera ed età materna. Di ogni madre è stata ricercata la residenza. Tramite modellistica abbiamo calcolato il campo magnetico lungo le linee elettriche. Abbiamo calcolato quindi il rischio di malformazioni congenite nella progenie associato alla residenza della madre in aree esposte a un campo magnetico >0.1 μT.Abbiamo identificato 228 casi di malformazioni congenite. Solo le madri di 2 casi e di 5 controlli sono risultate residenti durante i primi tre mesi di gravidanza in aree con campo magnetico di intensità >0.1 μT. Il rischio di malformazioni nella progenie di donne esposte è risultato essere uguale a 0.4, con intervalli di confidenza al 95% pari a 0.1-2.3.Il nostro studio non ha evidenziato un aumento del rischio di anomalie congenite nella progenie di donne che hanno risieduto durante la prima parte della gravidanza in aree caratterizzate da campi magnetici >0.1 μT.

2010 - Rischio di neoplasie ematologiche infantili e status socioeconomico [Abstract in Rivista]
Malagoli, Carlotta; Borciani, N; Bigi, G; Palazzi, G; Paolucci, Paolo; Vinceti, Marco
abstract

OBIETTIVIAlcuni fattori ambientali quali radiazioni ionizzanti, benzene, pesticidi e sostanze alchilanti, nonché alterazioni genetiche, sono già state identificate con certezza come agenti eziologici delle patologie ematologiche maligne in età infantile. Esistono indicazioni anche a favore di un’associazione tra basso status socioeconomico ed incidenza di tali patologie in età pediatrica, la cui esistenza e significato sono tuttavia incerti. Abbiamo preso in esame questa problematica nell’ambito di uno studio caso-controllo in un’area dell’Italia settentrionale.MATERIALIUtilizzando il Registro nazionale AIEOP, abbiamo individuato tutti i casi di patologia linfoematologica maligna (codici ICD-9 200-208) verificatisi negli anni 1986-2006 tra i bambini fino all’età di 13 anni residenti a Modena e Reggio Emilia, due comuni del nord Italia di 180.000 e 160.000 abitanti rispettivamente. Abbiamo estratto casualmente dagli archivi anagrafici dei due comuni quattro controlli per ciascun caso, appaiati per sesso, anno di nascita e comune di residenza. Di ogni soggetto abbiamo raccolto alcuni indicatori caratterizzanti lo stato socioeconomico del nucleo familiare, ovvero il titolo di studio e il reddito di entrambi i genitori. Mediante regressione logistica condizionata per dati appaiati, abbiamo calcolato il rischio relativo di patologia ematologica maligna associato allo status socio-economico.RIASSUNTONel periodo studiato sono stati diagnosticati 64 casi di patologie ematologiche maligne, 30 residenti a Modena e 34 a Reggio Emilia. Di questi, 46 sono leucemie (72%), 8 linfo- e reticolosarcomi (12%), 5 malattie di Hodgkin (8%) e 5 malattie di Letterer-Siwe (8%). 36 leucemie sono del tipo linfoide acuto (56% del totale). Il rischio di sviluppare tali patologie associato al titolo di studio dei genitori è risultato essere pari a 0,9 (IC 95% 0,6-1,4; P=0,556), quello associato al reddito del padre 1,0 (IC 95% 0,8-1,4; P=0,778). I risultati rimangono invariati restringendo le analisi ai soli casi di leucemia oppure alle sole leucemie linfoidi acute. Non è stato possibile prendere in considerazione nelle elaborazioni il reddito materno in quanto tale dato era irrecuperabile per la maggior parte dei soggetti.CONCLUSIONII risultati ottenuti non sembrano suggerire la presenza di associazioni tra status socioeconomico familiare e rischio di patologie ematologiche maligne infantili. Tuttavia riteniamo necessario approfondire la raccolta delle caratteristiche di questi nuclei familiari per poter così prendere in considerazione altri dei molteplici aspetti necessari per una definizione più articolata e completa dello status socioeconomico.

2010 - Risk of hematological malignancies associated with magnetic fields exposure from power lines: a case-control study in two municipalities of northern Italy [Articolo su rivista]
Malagoli, Carlotta; Fabbi, Sara; Teggi, Sergio; M., Calzari; M., Poli; E., Ballotti; B., Notari; M., Bruni; G., Palazzi; Paolucci, Paolo; Vinceti, Marco
abstract

BackgroundSome epidemiologic studies have suggested an association between electromagnetic field exposure induced by high voltage power lines and childhood leukemia, but null results have also been yielded and the possibility of bias due to unmeasured confounders has been suggested.MethodsWe studied this relation in the Modena and Reggio Emilia municipalities of northern Italy, identifying the corridors along high voltage power lines with calculated magnetic field intensity in the 0.1-&lt;0.2, 0.2-&lt;0.4, and ≥ 0.4 microTesla ranges. We identified 64 cases of newly-diagnosed hematological malignancies in children aged &lt;14 within these municipalities from 1986 to 2007, and we sampled four matched controls for each case, collecting information on historical residence and parental socioeconomic status of these subjects.ResultsRelative risk of leukemia associated with antecedent residence in the area with exposure ≥ 0.1 microTesla was 3.2 (6.7 adjusting for socioeconomic status), but this estimate was statistically very unstable, its 95% confidence interval being 0.4-23.4, and no indication of a dose-response relation emerged. Relative risk for acute lymphoblastic leukemia was 5.3 (95% confidence interval 0.7-43.5), while there was no increased risk for the other hematological malignancies.ConclusionsThough the number of exposed children in this study was too low to allow firm conclusions, results were more suggestive of an excess risk of leukemia among exposed children than of a null relation.

2010 - Sclerose laterale amyotrophique: analyse des facteurs de risques professionels [Abstract in Rivista]
T., Halperin Ben Ami; M., Riccò; A., Odone; C., Boccuni; Vinceti, Marco; V., Pietrini; C., Signorelli
abstract

Sclerose laterale amyotrophique: analyse des facteurs de risques professionels

2010 - Selenium in serum, toenails and diet in an italian population [Abstract in Rivista]
Vinceti, Marco; Malagoli, Carlotta; Ferrari, Angela
abstract

Background. Selenium is a trace element of strong toxicological and nutritional interest, and its deficiency and excess have been involved in the etiology of several human diseases. Uncertainties exist about current selenium status in the Italian population and the optimal methodologies to be used to assess intake of this metalloid in epidemiologic studies.Applied techniques. We analyzed in 56 randomly selected residents in Modena, a municipality of northern Italy, the selenium concentrations in serum and in toenails and the dietary intake of the metalloid. We also investigated the correlations between these indicators of selenium exposure. Serum and toenail selenium levels were determined using atomic absorption spectrometry with Zeeman background correction and neutron activation analysis, respectively, and dietary intake was assessed using a semiquantitative food frequency questionnaire and a specifically developed database of selenium content in foods. Correlation analysis was carried out by calculating Spearman correlation coefficient.Important results. Mean serum selenium concentration was 85.9 µg/l, with a median value of 89.2 and a standard deviation of 21.7. Average levels were higher in females (89.7) than in males (81.2). Mean toenail selenium was 0.65 µg/g, with higher values in females (0.68) than in males (0.61). Dietary selenium intake averaged 59.4 µg/day (standard deviation 19.7), with slightly higher figures for males (60.1) than for females (58.8). We found an association of serum selenium concentrations with toenail levels of the metalloid (P=0.045) but not with dietary intake (P=0.285). Despite the limitations of the study due to the small sample size, these observations clearly indicate the complexity of assessing selenium status, suggesting an association between biological indicators of exposure such as serum and toenail selenium content, and little relation between dietary intake and biomarkers.

2010 - Stima della esposizione a benzene da traffico veicolare in provincia di Modena. [Abstract in Atti di Convegno]
Ferretti, Enrica; Malagoli, Carlotta; Sterni, A; Guerra, L; Fabbi, Sara; Teggi, Sergio; Palazzi, G; Paolucci, Paolo; Vinceti, Marco
abstract

.

2010 - The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face [Articolo su rivista]
Guitera, P; Pellacani, Giovanni; Crotty, Ka; Scolyer, Ra; Li, Lx; Bassoli, Sara; Vinceti, Marco; Rabinovitz, H; Longo, Caterina; Menzies, S. W.
abstract

Limited studies have reported the in vivo reflectance confocal microscopy (RCM) features of lentigo maligna (LM). A total of 64 RCM features were scored retrospectively and blinded to diagnosis in a consecutive series of RCM sampled, clinically equivocal, macules of the face (n=81 LM, n=203 benign macules (BMs)). In addition to describing RCM diagnostic features for LM (univariate), an algorithm was developed (LM score) to distinguish LM from BM. This comprised two major features each scoring +2 points (nonedged papillae and round large pagetoid cells >20 mum), and four minor features; three scored +1 point each (three or more atypical cells at the dermoepidermal junction in five 0.5 x 0.5 mm(2) fields, follicular localization of atypical cells, and nucleated cells within the dermal papillae), and one (negative) feature scored -1 point (a broadened honeycomb pattern). A LM score of >/=2 resulted in a sensitivity of 85% and specificity of 76% for the diagnosis of LM (odds ratio (OR) for LM 18.6; 95% confidence interval: 9.3-37.1). The algorithm was equally effective in the diagnosis of amelanotic lesions and showed good interobserver reproducibility (87%). In a test set of 29 LMs and 44 BMs, the OR for LM was 60.7 (confidence interval: 11.9-309) (93% sensitivity, 82% specificity).Journal of Investigative Dermatology advance online publication, 15 April 2010; doi:10.1038/jid.2010.84.

2010 - The relation between amyotrophic lateral sclerosis and inorganic selenium in drinking water: a population-based case-control study. [Articolo su rivista]
Vinceti, Marco; Bonvicini, Francesca; Rothman, Kj; Vescovi, L; Wang, F.
abstract

ABSTRACT: BACKGROUND: A community in northern Italy was previously reported tohave an excess incidence of amyotrophic lateral sclerosis among residents exposedto high levels of inorganic selenium in their drinking water. METHODS: To assess the extent to which such association persisted in the decade following itsinitial observation, we conducted a population-based case-control studyencompassing forty-one newly-diagnosed cases of amyotrophic lateral sclerosis andeighty-two age- and sex-matched controls. We measured long-term intake ofinorganic selenium along with other potentially neurotoxic trace elements.RESULTS: We found that consumption of drinking water containing one or more mcg/lof inorganic selenium was associated with a relative risk for amyotrophic lateralsclerosis of 5.4 (95% confidence interval 1.1-26) after adjustment forconfounding factors. Greater amounts of cumulative inorganic selenium intake wereassociated with progressively increasing effects, with a relative risk of 2.1(95% confidence interval 0.5-9.1) for intermediate levels of cumulative intakeand 6.4 (95% confidence interval 1.3-31) for high intake. CONCLUSION: Based onthese results, coupled with other epidemiologic data and with findings fromanimal studies that show specific toxicity of the trace element on motor neurons,we hypothesize that dietary intake of inorganic selenium through drinking waterincreases the risk for amyotrophic lateral sclerosis.

2010 - Valutazione dell’assunzione di selenio: aspetti metodologici [Abstract in Rivista]
Vinceti, Marco; Malagoli, Carlotta; Ferrari, Angela; Storani, Simone; Bonvicini, Francesca; Bergomi, Margherita
abstract

Il selenio è un oligoelemento di notevole interesse tossicologico e nutrizionale e la sua carenza o il suo eccesso possono avere gravi effetti sulla salute umana. Tuttavia esistono incertezze in merito all’assunzione attuale di selenio nella popolazione italiana e alle metodologie ottimali da utilizzare per valutare l'assunzione di questo metalloide nell’ambito degli studi epidemiologici. In un campione di 56 residenti di una provincia dell’Italia settentrionale, abbiamo analizzato le concentrazioni di selenio nel siero e nelle unghie dei piedi e l'assunzione mediante la dieta, analizzando la correlazione tra questi indicatori di esposizione. I livelli di selenio nel siero e nelle unghie sono stati determinati mediante spettrometria ad assorbimento atomico e attivazione neutronica, rispettivamente, mentre l’assunzione dietetica è stata stimata con il questionario EPIC. La concentrazione sierica media di selenio è risultata 85,9µg/l, con deviazione standard (DS) 21,7, e livelli più elevati nelle femmine. Le concentrazioni nelle unghie sono risultate pari a 0,65µg/g, con valori più elevati nelle donne. L’apporto dietetico di selenio è stato pari a 59,4 µg/die (DS 19,7), con valori leggermente superiori nei maschi. Le concentrazioni di selenio nel siero sono risultate associate ai livelli nelle unghie (P=0,045) ma non all'assunzione alimentare (P=0,285). Nonostante i limiti dello studio soprattutto a causa delle ridotte dimensioni del campione, queste osservazioni indicano chiaramente la complessità della valutazione dello stato del selenio nell’uomo, suggerendo una stretta relazione tra indicatori biologici di esposizione ed un limitato rapporto tra essi e la stima dell’assunzione del metalloide attraverso la dieta.

2009 - Association Between High Selenium Intake and Subsequent Increased Risk of Type 2 Diabetes in an Italian Population [Abstract in Rivista]
Vinceti, Marco; Stranges, S; Sieri, S; Grioni, S; Malagoli, Carlotta; Muti, P; Berrino, F; Krogh, V.
abstract

abstract

2009 - Exposure to pesticides and risk of amyotrophic lateral sclerosis: a population-based case-control study [Abstract in Rivista]
Bonvicini, Francesca; Vinceti, Marco
abstract

Backgroud: A few epidemiologic studies suggested an association of agricultural work and pesticides exposure with a severe degenerative disease of the motor neurons, amyotrophic lateral sclerosis (ALS), though conflicting results have also been provided. Some laboratory investigations have also provided biological plausibility for this hypothesis, indicating that pesticides might adversely affect the motor neurons.Objective: We investigated through a population-based case-control study the possible relation between pesticides and ALS in the northern Italy municipality of Reggio Emilia. Methods: By administering a questionnaire, we investigated occupational history and leisure time habits of the 41 ALS patients diagnosed in the 1995-2006 period, and of 82 age- and sex-matched randomly sampled population controls, to ascertain the regular use of pesticides. All cases of ALS appeared to be of the sporadic form of the disease and were classified as ‘certain’ or ‘probable’ forms of the disease, according to the so-called ‘El Escorial criteria’.Results: More cases than controls were found to have been exposed to pesticides for at least six months (31.7% versus 13.4%, respectively), in all cases within the occupational environment. In a conditional logistic regression model, we found an excess ALS risk associated with exposure to pesticides, with an odds ratio of 3.6 and a 95% confidence interval of 1.2-10.5. Inclusion in the statistical analysis of potential confounders, such as electromagnetic fields exposure and drinking water chemical composition, did not modify such association and it even enhanced it.

2009 - Possible involvement of environmental selenium in the etiology of amyotrophic lateral sclerosis [Abstract in Rivista]
Vinceti, Marco; Bonvicini, Francesca; Bergomi, Margherita; Malagoli, Carlotta
abstract

The metalloid selenium (Se) is of considerable interest in environmental health, since it has both toxicological and nutritional properties, though these potential effects are still debated and not entirely elucidated. The safe range of Se intake in the human has not been clearly defined, but it appears to be very narrow, as also confirmed by recent epidemiologic and laboratory studies. Moreover, it is well recognized that the different Se compounds have distinctive biological activities, and the inorganic species appear to be the most toxic ones, despite being retained in the body to a much lesser extent than the organic forms.Two epidemiologic investigations carried out in South Dakota and in northern Italy have suggested that environmental Se species, particularly the inorganic ones, might be involved in the etiology of a severe motor neuron disease of unknown origin, sporadic amyotrophic lateral sclerosis (ALS). Veterinary medicine observations and toxicological studies have shown that some Se compounds have, in swine and in cattle, a selective toxicity to motor neurons, thus strengthening the still limited epidemiologic evidence. Furthermore, neurotoxic effects of Se species have been shown in several laboratory studies and even at very low concentrations, particularly for the inorganic species. Following Se treatment, a decrease in locomotor activity in rats, hind limb paralysis and cardiorespiratory effects in mice, and paralysis in an experimental worm model have been observed. In laboratory studies carried out using inorganic and less frequently organic Se forms in different animal species, the metalloid has been shown to interfere with several pathogenetic mechanisms potentially related to neurotoxicity, such as inhibition of prostaglandin D synthase in the brain, inhibition of squalene monooxigenase with potential cholesterol synthesis abnormalities, peripheral segmental demelination, and paralysis, increase in dopamine and its metabolies, inhibition of succinic dehydrogenase, acetylcholine esterase and Na+/K+ ATPase, and induction of seizures. Se has also been shown to induce toxic effects in rabbit vascular muscle, in rat heart muscle and in chick muscle, and in addition to inhibit axonal conduction and excitatory postsynaptic potentials, indicating the capacity of this metalloid to alter both nervous and muscle functions.Overall, these findings from the epidemiologic and the toxicological literature indicate that environmental Se, particularly when occurring in its inorganic forms in drinking waters or occupational settings, might be a risk factor for ALS, suggesting the opportunity to further investigate this issue.

2009 - Reflectance confocal microscopy and features of melanocytic lesions: An internet-based study of the reproducibility of terminology [Articolo su rivista]
Pellacani, Giovanni; Vinceti, Marco; Bassoli, Sara; R., Braun; S., Gonzalez; P., Guitera; Longo, Caterina; A. A., Marghoob; S. W., Menzies; S., Puig; A., Scope; Seidenari, Stefania; J., Malvehy
abstract

Objective: To test the interobserver and intraobserver reproducibility of the standard terminology for description and diagnosis of melanocytic lesions in in vivo confocal microscopy. Design: A dedicated Web platform was developed to train the participants and to allow independent distant evaluations of confocal images via the Internet. Setting: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy. Participants: The study population was composed of 15 melanomas, 30 nevi, and 5 Spitz/Reed nevi. Six expert centers were invited to participate at the study. Intervention: Evaluation of 36 features in 345 confocal microscopic images from melanocytic lesions. Main Outcome Measure: Interobserved and intraobserved agreement, by calculating the Cohen κ statistics measure for each descriptor. Results: High overall levels of reproducibility were shown for most of the evaluated features. In both the training and test sets there was a parallel trend of decreasing κ values as deeper anatomic skin levels were evaluated. All of the features, except 1, used for melanoma diagnosis, including roundish pagetoid cells, nonedged papillae, atypical cells in basal layer, cerebriform clusters, and nucleated cells infiltrating dermal papillae, showed high overall levels of reproducibility. However, less-than-ideal reproducibility was obtained for some descriptors, such as grainy appearance of the epidermis, junctional thickening, mild atypia in basal layer, plump bright cells, small bright cells, and reticulated fibers in the dermis. Conclusion: The standard consensus confocal terminology useful for the evaluation of melanocytic lesions was reproducibly recognized by independent observers. ©2009 American Medical Association. All rights reserved.

2009 - Residence near power lines and risk of childhood leukemia in two northern Italy municipalities [Abstract in Rivista]
Malagoli, Carlotta; Vinceti, Marco; M., Calzari; Fabbi, Sara; Teggi, Sergio; G., Palazzi; Paolucci, Paolo; M., Poli; E., Ballotti; B., Notari; M., Bruni
abstract

Background and ObjectiveSome epidemiologic studies suggested an association between electromagnetic fields exposure, such as that induced by residence near high-voltage power lines, and childhood leukemia, but null results have also been yielded and the possibility of bias induced by unmeasured confounders has been suggested.Methods We identified the corridors along the high-voltage power lines in the municipalities of Modena and Reggio Emilia, northern Italy, with estimated magnetic fields exposure cutoffs of 0.1, 0.2 and 0.4 µT. We identified all cases of leukemia diagnosed in children (age 0-13) residing in these two municipalities during the 1986-2006 period through a nation-wide hospital-based registry. As a control group, we randomly selected four residents for each case, matched for year of birth, sex and municipality of residence. We collected information about historical residence and about parental educational attainment of all study subjects. We included this information in a GIS database and we calculated the risk of childhood leukemia associated with residence for at least 6 months in the exposed area.Results Among the 47 cases and 188 controls included in the study, only 1 case and 2 controls had an historical residence in the exposed areas. The risk of leukemia associated with antecedent residence in the area with exposure exceeding 0.1 µT was 2.0 (4.16 in the analysis adjusted for parental education), but this estimate was statistically very unstable, its 95% confidence interval being 0.2-22.1.ConclusionThe number of exposed children in this study was too low to allow firm conclusions, suggesting the need to substantially increase the study population. Though on the basis of these results an excess risk of leukemia among children exposed to electromagnetic fields from high-voltage power lines cannot be ruled out, the possibility of no association must also be considered.

2009 - Residential exposure to electromagnetic fields and risk of amyotrophic lateral sclerosis in Reggio Emilia, Italy. [Abstract in Rivista]
Bonvicini, Francesca; Vinceti, Marco; Fabbi, Sara; Teggi, Sergio; M., Poli; P., Zanichelli
abstract

Background and Objective: The etiology of amyotrophic lateral sclerosis (ALS) is still unknown. Some epidemiologic studies suggest a relation between occupational exposure to electromagnetic fields (EMF) and increased ASL risk, while very little data is available about the possible role of EMF residential exposure. We investigated this issue in an Italian communitythrough a population-based case-control study.Methods: We calculated the area around the high-voltage power lines in the Reggio Emilia municipality, northern Italy, with estimated magnetic field exposure above 0.1 μT, adding 20 mto the distance from the power lines predicted by the model to account for geocoding inaccuracy. We retrieved new cases of ALS diagnosed among residents in Reggio Emilia municipality between 1995 and 2006, using several data sources such as death certificates, clinical records, hospital discharge registers and drug prescriptions. We randomly selected four controls for each case, matched for year of birth and sex, and we collected information about their residence in the 35 years prior to ALS diagnosis. All this information was included in a Geographical Information System to calculate disease risk associated with EMF exposure.Results: The final study population included 42 cases and 168 controls. ALS risk associated with antecedent residence in the exposed area was 1.8, 1.9, 1.8 and 1.6 at 35, 20, 10 and 0years before diagnosis, respectively. However, all estimates were statistically very unstable due to the low number of exposed subjects (6 controls and 3 cases 20 years before disease onset).Conclusion: Though these results might indicate an excess risk of ALS among residents exposed to EMF from high-voltage power lines, limitations of the study, particularly the small number of exposed subjects, suggest the need to further investigate this issue in larger populations.

2009 - Rischio di leucemia linfoide acuta nei bambini esposti ai campi elettromagnetici generati dagli elettrodotti in due comuni del Nord Italia [Abstract in Rivista]
Malagoli, Carlotta; Fabbi, Sara; Teggi, Sergio; Palazzi, G; Paolucci, Paolo; Calzari, Mg; Poli, M; Ballotti, E; Zanichelli, P; Sesti, D; Notari, B; Bruni, M; Vinceti, Marco
abstract

1.ObiettiviL’eziologia delle leucemie è stata attribuita a fattori di tipo ambientale quali radiazioni ionizzanti e non ionizzanti, benzene, pesticidi e sostanze alchilanti, nonché ad alterazioni genetiche. Esistono numerose indicazioni, anche se non del tutto concordanti, a favore di un’associazione tra elevate esposizioni a campi elettromagnetici a bassa frequenza e rischio di leucemia linfoide acuta (LLA) in età pediatrica. Abbiamo condotto uno studio caso-controllo per identificare un possibile aumento del rischio di LLA nei bambini residenti in prossimità delle linee elettriche ad alta tensione in due comuni del nord Italia. 2.Metodi Abbiamo individuato tutti i casi di LLA infantile (0-13 anni) diagnosticati nel periodo 1986-2006 tra i residenti nei comuni di Modena e Reggio Emilia ed appaiato a ciascuno di essi quattro controlli dello stesso sesso, anno di nascita e comune di residenza, estratti casualmente dagli archivi anagrafici. Di ogni soggetto è stata poi scrupolosamente ricostruita la storia residenziale. Il calcolo della induzione magnetica (stimata tramite modellistica) nelle aree limitrofe alle linee elettriche ad alta tensione che attraversano i due comuni, ha permesso di individuare delle fasce territoriali caratterizzate da livelli di campo elettromagnetico con cut offs di 0,1, 0,2 e 0,4 microtesla (µT). L’identificazione dello status espositivo dei soggetti è stato effettuato mediante posizionamento geografico territoriale su cartografia vettoriale con metodologia GIS (Geographical Information System) e attribuzione della fascia di appartenenza.Abbiamo quindi calcolato il rischio relativo di LLA associato alla residenza in prossimità delle linee elettriche ad alta tensione mediante regressione logistica condizionata per dati appaiati e aggiustata per alcuni fattori confondenti.3.Risultati Abbiamo identificato 36 casi di LLA ed appaiato ad essi 144 controlli. Il rischio di leucemia associato alla residenza per almeno sei mesi in un’area con esposizione maggiore di 0,1 µT è risultato pari a 1,4 (IC 95% 0,2-8,0; P=0.707) nell’analisi grezza ed a 2,7 (IC 95% 0,3-20,6; P=0,347) dopo aggiustamento per titolo di studio paterno.4.ConclusioniIl rischio stimato con le nostre analisi risulta particolarmente instabile sotto il profilo statistico. Tuttavia i risultati sembrano suggerire un eccesso di rischio di LLA nella popolazione infantile esposta ai campi elettromagnetici generate dai conduttori di alta tensione, di entità pari a quello riscontrato in altre recenti indagini epidemiologiche.

2009 - Risk of chronic low-dose selenium overexposure in humans: insights from epidemiology and biochemistry. [Articolo su rivista]
Vinceti, Marco; Maraldi, Tullia; Bergomi, Margherita; Malagoli, Carlotta
abstract

The latest developments of epidemiologic and biochemical research suggest that current upper limits of intake for dietary selenium and for overall selenium exposure may be inadequate to protect human health. In particular, recent experimental and observational prospective studies indicate a diabetogenic effect of selenium at unexpectedly low levels of intake. Experimental evidence from laboratory studies and veterinary medicine appears to confirm previous epidemiologic observations that selenium overexposure is associated with an increased risk of amyotrophic lateral sclerosis, and a recent large trial indicated no beneficial effect in preventing prostate cancer. Moreover, the pro-oxidant properties of selenium species and the observation that the selenium-containing enzymes glutathione peroxidases are induced by oxidative stress imply that the increase in enzymatic activity induced by this metalloid may represent at least in part a compensatory response. Taken together, the data indicate that the upper safe limit of organic and inorganic selenium intake in humans may be lower than has been thought and that low-dose chronic overexposure to selenium may be considerably more widespread than supposed.

2009 - Risk of congenital anomalies around a municipal solid waste incinerator: a GIS-based case-control study. [Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; Fabbi, Sara; Teggi, Sergio; Rodolfi, R.; Garavelli, L.; Astolfi, G.; Rivieri, F.
abstract

BACKGROUND: Waste incineration releases into the environment toxic substances having a teratogenic potential, but little epidemiologic evidence is available on this topic. We aimed at examining the relation between exposure to the emissions from a municipal solid waste incinerator and risk of birth defects in a northern Italy community, using Geographical Information System (GIS) data to estimate exposure and a population-based case-control study design. By modelling the incinerator emissions, we defined in the GIS three areas of increasing exposure according to predicted dioxins concentrations. We mapped the 228 births and induced abortions with diagnosis of congenital anomalies observed during the 1998-2006 period, together with a corresponding series of control births matched for year and hospital of birth/abortion as well as maternal age, using maternal address in the first three months of pregnancy to geocode cases and controls. RESULTS: Among women residing in the areas with medium and high exposure, prevalence of anomalies in the offspring was substantially comparable to that observed in the control population, nor dose-response relations for any of the major categories of birth defects emerged. Furthermore, odds ratio for congenital anomalies did not decrease during a prolonged shut-down period of the plant. CONCLUSION: Overall, these findings do not lend support to the hypothesis that the environmental contamination occurring around an incineration plant such as that examined in this study may induce major teratogenic effects.

2009 - Sclerosi laterale amiotrofica: risultati di uno studio caso-controllo relativo ai fattori di rischio. [Abstract in Atti di Convegno]
Riccò, M; Ben Amin Halperin, T; Vinceti, Marco; Pietrini, V; Veronesi, L; Pasquarella, C; Signorelli, C.
abstract

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2009 - Selenium deficiency [Voce in Dizionario o Enciclopedia]
Bergomi, Margherita; Malagoli, Carlotta; Vinceti, Marco
abstract

2009 - Selenium excess [Voce in Dizionario o Enciclopedia]
Bergomi, Margherita; Malagoli, Carlotta; Vinceti, Marco
abstract

2009 - Vitamina D e melanoma cutaneo: studio epidemiologico multicentrico nella regione Emilia-Romagna [Abstract in Rivista]
Vinceti, Marco; Pellacani, Giovanni; Seidenari, Stefania; V., Krogh; S., Sieri; A., Lanzoni; M., Reggiani; G., Albertini; C., Ricci; A., Virgili; F., Osti; Fiorentini, Chiara; Longo, Caterina; P., Fanti; G., De Panfilis; M., Santini; Malagoli, Carlotta
abstract

1.OBIETTIVIAlcuni studi epidemiologici hanno suggerito un ruolo della vitamina D nella riduzione dell’incidenza di alcuni tumori (colon-retto, mammella, melanoma). Essendo la dieta una importante fonte di questa vitamina, abbiamo realizzato uno studio caso-controllo di popolazione multicentrico in alcune province della regione Emilia-Romagna per approfondire la relazione tra il rischio di melanoma cutaneo e la quantità di vitamina D assunta tramite la dieta abituale, ed in generale, con le abitudini alimentari.2.METODIPresso Unità di Dermatologia del territorio emiliano-romagnolo abbiamo reclutato i pazienti con diagnosi di melanoma cutaneo effettuata nel periodo 2005/06. Abbiamo poi tratto dalla popolazione generale quattro controlli per ogni caso (di medesimo sesso, età e provincia di residenza) mediante estrazione casuale dall’anagrafe regionale del Servizio Sanitario Nazionale. Ad ogni soggetto incluso nello studio è stato consegnato un questionario, il Food Frequency Questionnaire di derivazione “EPIC”, composto da 248 items, atto ad analizzare in modo estremamente accurato la dieta abituale. Abbiamo inoltre raccolto informazioni anagrafiche, fisico-costituzionali ed alcuni dati di interesse dermatologico.3.RISULTATILa lettura dei 1099 questionari alimentari autocompilati dai 380 pazienti e dai 719 controlli che hanno aderito allo studio ci ha fornito informazioni sulla quantità e la frequenza di assunzione di numerosi nutrienti ed alimenti presenti nella dieta dei singoli individui.Le analisi multivariate aggiustate per i principali fattori confondenti (introito calorico, body mass index e fototipo) hanno rilevato un effetto protettivo della vitamina D nei confronti del melanoma cutaneo (odds ratio del quintile superiore vs. quintile inferiore 0,55; intervalli di confidenza al 95% 0,33-0,93; P trend: 0,019). L’analisi disaggregata nei due sessi ha evidenziato come questo apparente effetto protettivo della vitamina D sia presente soprattutto nel sesso maschile (odds ratio del quintile superiore vs. quintile inferiore 0,34; intervalli di confidenza al 95% 0,15-0,78; P trend 0,008). 4.CONCLUSIONIPur con la cautela dovuta alle limitazioni degli studi osservazionali ed al possibile effetto confondente dell’esposizione solare, questi risultati sembrano suggerire che la vitamina D assunta con la dieta influenzi in modo significativo il rischio di melanoma cutaneo.

2008 - Adverse pregnancy outcomes in a population exposed to the emissions of a municipal waste incinerator [Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; Teggi, Sergio; Fabbi, Sara; Goldoni, C.; De Girolamo, G.; Ferrari, Paola; Astolfi, G.; Rivieri, F.; Bergomi, Margherita
abstract

Some contaminants emitted by municipal waste incinerators are believed to adversely affect reproductive health in the exposed populations; yet only limited and conflicting epidemiologic evidence on this issue has been provided so far. In this study we analyzed rates of spontaneous abortion and prevalence at birth of congenital anomalies in women residing or working near the municipal solid waste incinerator of Modena, northern Italy, during the 2003--2006 period and who experienced higher levels of exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans, compared to the remaining municipal population. In women residing in two areas close to the incinerator plant with increasing exposure to dioxins, we did not detect an excess risk of miscarriage (relative risk [RR] 1.00, 95% confidence interval [CI] 0.65-1.48) and of birth defects (RR 0.64, 95% CI 0.20-1.55), nor did any indication of dose-response relation emerge. Among female workers employed in the factories located in the exposed areas, we did not observe a higher risk of spontaneous abortion (RR 1.04, 95% CI 0.38-2.30); however, an increase in prevalence of birth defects was noted (RR 2.26), although this risk estimate was statistically very unstable (95% CI 0.57-6.14). Overall, the study results provide little evidence of an excess risk of adverse pregnancy outcomes in women exposed to emissions from a modern municipal solid waste incinerator.

2008 - Diet and melanoma risk: effects of choice of hospital versus population controls [Articolo su rivista]
Malagoli, Carlotta; Vinceti, Marco; Pellacani, Giovanni; S., Sieri; V., Krogh; Seidenari, Stefania; Bergomi, Margherita
abstract

Aims and background. Hospital-referred subjects are widely used as controls in studies oil the relation between diet and cancer risk. However, concern has been raised about the potential for bias of such type of referents, and few studies seem to have examined their reliability in estimating dietary habits of the underlying general population. Methods. In a northern Italian setting, the differences in dietary patterns between 41 individuals referred for non-neoplastic lesions to hospital surgical outpatient units and age- and sex-matched subjects drawn from the general population were examined. The effects of such differences when carrying out a case-control study oil a neoplastic disease, cutaneous melanoma, were also analyzed. Dietary intake was assessed using the EPIC food frequency questionnaire. Results. Population controls showed higher intakes of energy, animal proteins and animal fats compared with sex- and age-matched hospital controls, whereas intake of carbohydrates and fiber was comparable. An excess melanoma risk associated with intake of animal proteins and fats emerged when hospital controls were used as the referent group, whereas no such relation was detected when cases were compared to population controls. Conclusions. The results suggest that hospital-referred subjects may not reflect dietary habits of the underlying general population and may be unsuitable for case-control studies concerning the relation between diet and cancer risk.

2008 - Esposizione alle emissioni di un inceneritore per rifiuti solidi urbani e rischio di malformazioni congenite. [Abstract in Rivista]
Malagoli, Carlotta; Fabbi, Sara; Teggi, Sergio; Rodolfi, R; Rivieri, F; Astolfi, G; Garavelli, L; Vinceti, Marco
abstract

Abbiamo preso in esame nella città di Reggio Emilia la possibile relazione tra rischio di malformazioni congenite ed emissioni dell’inceneritore per rifiuti solidi urbani, dotato di sistemi avanzati di abbattimento delle emissioni ed in funzione nel 1968 (ad eccezione di un periodo di interruzione da aprile 2002 a giugno 2005). Abbiamo individuato tutti i casi di malformazioni congenite diagnosticati nei nati e negli aborti di donne residenti nel Comune di Reggio Emilia nel periodo 1998-2006, associando a ciascuno di essi un nato sano ‘di controllo’ utilizzando come variabili di appaiamento l’anno ed il centro di nascita unitamente all’età materna. Il territorio municipale è stato suddiviso in tre aree in base alle concentrazioni ambientali di diossine/furani e metalli pesanti emessi dall’inceneritore, assegnando lo status espositivo in base alla residenza materna nel primo trimestre di gravidanza con l’ausilio di metodiche GIS. Abbiamo quindi calcolato i rischi relativi nei diversi gruppi espositivi, anche in relazione al periodo di funzionamento, utilizzando procedure di regressione logistica condizionale ed aggiustando per titolo di studio materno.I risultati, riferiti ad un numero complessivo di 228 casi e 228 controlli, non hanno evidenziato modificazioni significative del rischio nei diversi gruppi espositivi nell’intero periodo considerato, né sono stati in grado di mostrare variazioni nel tempo dei rischi associate al regime di funzionamento dell’impianto di incenerimento. In particolare, il rischio relativo di malformazione congenita nelle residenti nell’area a maggiore esposizione e in quelle con esposizione intermedia, nei confronti della rimanente popolazione municipale, è risultato rispettivamente pari a 0,67 (I.C. al 95% 0,25-1,77) e 1,55 (0,67-3,58) con un P-trend pari a 0,883, senza indicazioni di un decremento del rischio nel periodo di inattività dell’impianto. Queste osservazioni non sembrano nel complesso indicare il verificarsi di effetti teratogeni a seguito dell’esposizione alle emissioni di un inceneritore per rifiuti solidi urbani tecnologicamente avanzato.

2008 - Food intake and risk of cutaneous melanoma in an Italian population [Articolo su rivista]
Vinceti, Marco; Bonvicini, Francesca; Pellacani, Giovanni; S., Sieri; Malagoli, Carlotta; Giusti, Francesca; V., Krogh; Bergomi, Margherita; Seidenari, Stefania
abstract

We investigated the association of melanoma risk with food consumption in a northern Italian population in which disease risk was shown to correlate with linoleic acid and soluble carbohydrates intake. We collected information regarding the habitual consumption of 188 food items in 59 patients with newly diagnosed cutaneous melanoma and 59 sex- and age-matched population controls. In the unadjusted analyses, the intake of several foodstuffs directly or inversely correlated with melanoma risk. In multivariate analysis adjusting for several potential confounders, risk correrlated directly with vegetable oil intake and inversely with consumption of crispbreads and rusk. Overall, most of the food items rich in linoleic acid and soluble carbohydrated were unrelated to disease risk. Despite the limited statistical precision of the point estimates, these findings seem to indicate that consumption of specific foods may influence melanoma risk.

2008 - How global is our knowledge? Population diversity in observational studies on selenium and cancer risk. [Abstract in Atti di Convegno]
Dennert, G; Brinkman, M; Vinceti, Marco; Zeegers, Mp; Zwahlen, M; Horneber, Ma
abstract

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2008 - Identificazione dell’infezione tubercolare latente in una popolazione di immigrati ‘irregolari’: studio sulla compliance deisoggetti e valutazione della prevalenza. [Abstract in Atti di Convegno]
Bonvicini, Francesca; Fornaciari, R.; Greci, M.; Manghi, M.; Vinceti, Marco; Algeri, A.
abstract

Identificazione dell’infezione tubercolare latente in una popolazione di immigrati ‘irregolari’: studio sulla compliance deisoggetti e valutazione della prevalenza.

2008 - Melanoma epidemic across the millennium: time trends of cutaneous melanoma in Emilia-Romagna (Italy) from 1997 to 2004 [Articolo su rivista]
Pellacani, Giovanni; G., Lo Scocco; Vinceti, Marco; G., Albertini; A. A., Raccagni; L., Baldassari; S., Catrani; S., Donelli; P., Ghetti; A., Lanzoni; M., Leardini; M., Reggiani; M., Santini; I., Stanganelli; A., Virgili; Seidenari, Stefania
abstract

Background After a rapid increase in malignant melanoma (MM) incidence trends of the melanoma epidemic in the recent years seemed in-the last decades, not homogeneous. Objective This study aimed at the monitoring of some epidemiological data referring to melanoma in a region of the Northern Italy during the past 8-year period. Methods All cases of melanoma, including also in situ lesions, diagnosed in Emilia-Romagna and San Marino State, with the exclusion of Cesena province, from 1997 to 2004 were recorded and the incidence of melanoma, adjusted for the European standard population by the direct method, was calculated. Results Mean standardized incidence was 9.7 for invasive MMs and 11.9 considering also in situ ones, showing an ascending trend with an increment of 3.3 new incident cases in 2004. compared with 1997. No differences in age distribution, gender and site were reported. Concerning tumour thickness, although a general ascending trend in all subtypes, only thin melanoma incidence significantly increased over the study period. Conclusions Contrary to data from Northern European countries, melanoma incidence still showed an ascending trend in the Italian population of Emilia Romagna.

2008 - Metodologie per la sorveglianza sanitaria della popolazione residente in prossimita’ di discariche ed inceneritori per rifiuti solidi urbani. [Abstract in Rivista]
Vinceti, Marco; Malagoli, Carlotta; Bergomi, Margherita; Aggazzotti, Gabriella; Fantuzzi, Guglielmina; C., Signorelli; Vivoli, Gianfranco
abstract

Le due principali modalità di gestione e smaltimento dei rifiuti solidi urbani nel nostro Paese e più in generale nei paesi industrializzati sono rappresentate dal conferimento in discarica controllata e dall’incenerimento con impianti tecnologicamente avanzati. Tenendo conto dell’inevitabile rilascio di quantità seppure limitate di contaminanti nelle matrici ambientali da parte di queste due modalità di smaltimento e delle preoccupazioni generalmente manifestate dalle popolazioni residenti in prossimità dei siti interessati, è opportuno che le istituzioni operanti nel campo della sanità pubblica esercitino in modo continuativo un’attenta sorveglianza dell’impatto sanitario di tali processi di gestione dei rifiuti solidi urbani e dei relativi impianti, anche in considerazione di eventuali specificità dei diversi contesti locali e delle incertezze scientifiche ancora esistenti su queste tematiche. In particolare, appare appropriato da parte di tali programmi di sorveglianza sanitaria privilegiare l’utilizzazione di indicatori di rischio sanitario a breve termine, con riferimento sia alle popolazioni limitrofe ai siti interessati sia ai lavoratori professionalmente esposti. Due approcci metodologici sono particolarmente idonei per la realizzazione di questi programmi di sorveglianza: lo studio epidemiologico degli effetti sanitari a breve termine legati a contaminanti ad azione teratogena, quali il rischio di malformazioni congenite e di aborto spontaneo, e la valutazione del rischio tossicologico utilizzando indicatori biologici di esposizione a contaminanti quali diossine, furani e metalli pesanti. Entrambe tali metodologie sono caratterizzate da rilevanti limitazioni quali l’interferenza da parte di fattori confondenti, nonché dall’inadeguatezza dei flussi informativi per quanto riguarda l’analisi del rischio teratogeno ed dal rilevante impegno organizzativo ed economico riferibile all’uso dei bioindicatori. La prima tipologia di analisi, tuttavia, può attualmente avvalersi di significative innovazioni nel campo della modellistica teorica della dispersione dei contaminanti atmosferici e delle metodologie GIS (Geographical Information System) per l’analisi dei dati espositivi, demografici e sanitari.

2008 - Prevalence of birth defects in a population living nearby a municipal solid waste incinerator with intermittent operativity. [Abstract in Rivista]
Vinceti, Marco; Malagoli, Carlotta; Teggi, Sergio; Fabbi, Sara; Rodolfi, R; Garavelli, L; Astolfi, G; Calzolari, E.
abstract

Municipal waste incineration induces environmental contamination with toxic substances such as dioxins,furans and heavy metals, which have a teratogenic potential, but little epidemiologic evidence is available onthis topic. We examined the risk of congenital anomalies associated with maternal exposure to emissions of amodern municipal solid waste incinerator in a northern Italy community (Reggio Emilia, population about150,000) during the period 1998-2006 , through a population-based case-control study. In the analysis weincluded the livebirths and stillbirths as well as the induced abortions with diagnosis of congenital anomalies,and a corresponding series of control births, using maternal age as an additional matching variable and limitingthe analysis to women residing in the municipality. Sources of data were the Hospital Discharge Registry andthe population-based Registry of Birth Defects ‘IMER’ of the Emilia-Romagna Region, yielding an overallnumber of 352 congenital anomalies diagnoses and 352 control births during the study period. We calculatedthe risk of prevalence of birth defects in the offspring associated with maternal residence near the incinerator byusing a conditional logistic regression model. In the two periods (1998-2002 and 2006) of normal operation ofthe incinerator, among women residing <1 km and 1-2 km from the plant the prevalence of birth defects in theoffspring was not higher than that observed in the remaining municipal population. Furthermore, there was noreduction in the risk of congenital anomalies in the offspring of women residing up to 2 km from the incineratorin the shut-down period, from 2003 to 2005. Further adjustment for educational attainment level did notappreciably change these results. Findings of the study do not appear to support the hypothesis that theenvironmental contamination occurring around an incineration plant as examined in this study inducesteratogenic effects in the exposed population.

2008 - Risk of Birth Defects in a Population Living Near a Municipal Solid Waste Incinerator During Different Operating Periods [Abstract in Rivista]
Vinceti, Marco; Malagoli, Carlotta; Rodolfi, R.; Fabbi, Sara; Teggi, Sergio; Garavelli, L; Astolfi, G; Calzolari, E.
abstract

abstract

2008 - The effect of a strategy to improve adherence of irregular non UE citizens to tuberculosis screening in a clinic of Reggio Emilia [Articolo su rivista]
Leone, N; Bonvicini, Francesca; Fornaciari, R; Greci, M; Manghi, M; Vinceti, Marco; Mecugni, Daniela
abstract

Latent tubercolar infection in irregular non EU-citizens in Italy is an important issue of public health. Aim of this paper is to describe the effects of a new organization of the Centre for the health of foreign families of Reggio Emilia. METHOD: A dedicated nurse, responsible of patients' screening and follow-up, in strict collaboration with a cultural interpreter were made available. Patients adherence to the screening was measured. RESULTS: On 177 eligible patients, 12 (6.7%) refused the Mantoux text. Over the 165 screened patients, 147 (89%) returned to the clinic after 3-4 days. Only 16 (10.8%) needed a phone reminder. Adherence to the screening improved remarkably compared to the previous year (89% vs 68%). CONCLUSIONS: A dedicated nurse and the improvement of communication may contribute to improve patients compliance.

2008 - The epidemiology of amyotrophic lateral sclerosis in Reggio Emilia, Italy [Articolo su rivista]
Bonvicini, Francesca; Vinceti, Marco; Marcello, N.; Rodolfi, R.; Rinaldi, M.
abstract

Incidence and mortality rates of amyotrophic lateral sclerosis (ALS) vary between countries, and in some studies appear to increase over time. We performed a study to assess ALS incidence in a northern Italy area over a 10-year period. We identified the new cases of probable or definite ALS diagnosed among residents in Reggio Emilia province between 1996 and 2005 using several sources of data, such as death certificates, clinical records, hospital discharge registers and drug prescriptions. A total of 94 newly-diagnosed patients were identified. The average standardized incidence in the period was 2.0 and 1.0 cases/100,000/year, using the Italian and the world population, respectively, as reference. There was no variation in rates over time. Incidence was 1.3 in males and 0.8 in females. No cases were observed in patients under 35 years of age. Incidence increased after the age of 55 years, reaching a peak in the group aged 70-74 years and declining thereafter. We concluded that ALS incidence in this population was similar to that observed in other Italian regions and European countries, and no variation was identified during the study period.

2008 - Valutazione di impatto sanitario (VIS) dei termovalorizzatori. [Relazione in Atti di Convegno]
C., Signorelli; Vinceti, Marco; M., Riccò; P., Manotti
abstract

I termovalorizzatori rientrano tra gli impianti per i quali è prevista una specififa Valutazione di ImpattoSanitario (VIS), inserita nella più generale Valutazione di impatto ambientale (VIA) del nuovo impianto. LaVIA impone alle professionalità coinvolte la raccolta di informazioni preliminari (interventi previsti; effettoambientale, stato di salute della popolazione potenzialmente esposta) allo scopo di documentare il decisorerelativamente ad una stima degli effetti sanitari futuri. La VIS richiede di conseguenza l'analisi criticadella letteratura scientifica aggiornata relativa all'argomento; ciò, nell'ambito specifico dei termovalorizzatori,è spesso associato ad un ampio grado di incertezza circa l'effettiva qualità ed attendibilità dei datidisponibili in proiezione futura. Il testo qui presentato illustra le attuali disposizioni legislative relative allaconduzione della VIS, proponendo a suo completamento una messa a punto circa le attuale evidenzescientifiche degli effetti sanitari dell'esposizione alle emissioni degli impianti.

2008 - Waste incinerator and human health: a state-of-the-art review [Articolo su rivista]
Signorelli, C.; Riccò, M.; Vinceti, Marco
abstract

Emissions of municipal solid waste incinerator plants consist as a suspected risk factor for the human health. Scientific literature about this theme appears contradictory: main sanitary outcomes actually evaluated, stating on geographic- or occupational-based epidemiologic approaches, produced inconsistent results. Research procedures applied, and effective quality of analyzed data, are the likely causes of such dissimilarities. Up to date, respiratory, cardiovascular renal, and hormonal pathologies, and also neoplasia, and developmental/reproductive disorders have been related to this kind of exposures: otherwise, an objective review of available data suggests a consistent relation only between residential or occupational exposure and the latter outcomes, always as a topic of multifactorial models. Finally, rigorous public health surveillance programs on exposed subjects appear mandatory steps to be established by Institutional Authorities. Also more accurate epidemiologic studies should be designed, eventually associating the retrieval of data relative to biomarkers of exposure or early health effect.

2007 - Case-control study of toenail cadmium and prostate cancer risk in Italy [Articolo su rivista]
Vinceti, Marco; M., Venturelli; C., Sighinolfi; P., Trerotoli; F., Bonvicini; A., Ferrari; Bianchi, Giampaolo; G., Serio; Bergomi, Margherita; Vivoli, Gianfranco
abstract

A role of cadmium exposure in prostate cancer etiology has been suggested by epidemiologic and laboratory studies, but conclusive evidence on this topic is still lacking. We investigated the relation between cadmium exposure, estimated by determining toenails cadmium levels, and prostate cancer risk in forty patients newly diagnosed with prostate cancer and fifty-eight hospital controls recruited in two provinces from southern and northern Italy. We found an excess cancer risk in subjects in the third and fourth (highest) quartiles of toenail cadmium concentration (odds ratio 1.3 and 4.7, respectively) compared with subjects in the bottom quartile. Results were basically unchanged when limiting the analysis to each province or entering toenail cadmium concentrations as continuous values in the regression model (P=0.004). Despite the limited statistical stability of the point estimates, these findings appear to support the hypothesis that cadmium exposure increases prostate cancer risk. (c) 2006 Elsevier B.V All rights reserved.

2007 - Health effects of environmental exposure to electromagnetic fields in Reggio Emilia, northern Italy [Abstract in Rivista]
Vinceti, Marco; Calzari, M.; Bonvicini, Francesca; Malagoli, Carlotta
abstract

Objective: Environmental exposure to electromagnetic fields has been suggested to increase the risk of acute lymphoblastic leukemia, particularly in children, amyotrophiclateral sclerosis and birth defects. We aimed at analyzing the risk of these diseases in a population residing near highvoltagepower lines.Material and methods: We identified all cases of acute lymphoblastic leukemia, amyotrophic lateral sclerosis and birth defects diagnosed between 1986 and 2005, from 1996 to 2005 and from 1998 to 2005, respectively, in the population of Reggio Emilia, northern Italy (around 140,000 inhabitants).We then examined the life-time residential history of thesepatients (or their mothers for congenital anomalies), as well as of age- and sex-matched population controls, to analyze whether prior residence near 4 power lines in the western part of the municipal territory, where electromagnetic fields exposure renged from 0.1 to over 0.5 μT. Results: Residence in the exposed area did notassociated with excess risk of acute lymphoblastic leukemia and amyotrophic lateral sclerosis, and of birth defects in the offspring.Conclusions: We were unable to identify adverse health effects ofelectromagnetic fields exposure in this population. Further research in a larger population exposed to electromagnetic fields is currently in progress.

2007 - Identificazione dei casi di malformazione congenita attraverso l'uso di tre fonti informative [Abstract in Rivista]
G., De Girolamo; Malagoli, Carlotta; C. A., Goldoni; Vinceti, Marco
abstract

Introduzione. Nell'ambito del programma di sorveglianza sanitaria della popolazione residente in prossimità dell'inceneritore per rifiuti solidi urbani di Modena, abbiamoselezionato i due principali indicatori di rischio teratogeno legato ad esposizioni ambientali: le malformazioni congenite e l'abortività spontanea. Presentiamo i risultati dei primi dueanni (2003-2004) relativamente alle malformazioni congenite. Metodi. Per l'individuazione degli eventi di interesse (parti e malformazioni congenite) abbiamo utilizzato i seguentiflussi informativi: - la Banca dati delle Schede di Dimissione Ospedaliere (SDO) della Regione Emilia-Romagna. Abbiamo considerato come SDO di parto quelle con DRG(Diagnosis-Related Group) dal 370 al 375 e come possibili SDO di parto quelle contenenti almeno un codice di patologia del settore ICD9-CM-97 "Complicazioni della Gravidanza del Parto e del Puerperio". Tali schede sono state verificate utilizzando gli altri flussi informativi (SDO dei nati, Certificato di Assistenza al Parto (CEDAP), dati anagrafici comunali). Abbiamo considerato indicative di malformazione congenita le SDO contenentialmeno un codice ICD9 compreso nell'intervallo 740,0-759,9 in qualsiasi campo diagnosi; - tutti i CEDAP relativi a parti di residenti nel Comune di Modena verificatisi presso ospedali della Regione. I CEDAP vengono compilati immediatamente dopo il parto (anchenel caso di bambino nato morto) da parte di personale sanitario e contengono informazioni anche in relazione alla presenza di malformazioni congenite; - il Registro delleMalformazioni Congenite della Regione Emilia-Romagna (IMER). Tale Registro, istituito su base volontaria presso la Università di Ferrara, raccoglie dalla quasi totalità dei punti nascita dettagliate informazioni riguardo la tipologia delle malformazioni. I dati sonorelativi sia ai nati sia alle interruzioni volontarie di gravidanza: vista la scarsa completezza di quest'ultimo flusso abbiamo ritenuto di non includerne i dati. La procedura utilizzata èstata la seguente: identificate tutte le madri del biennio 2003-2004 residenti nel Comune di Modena (da Anagrafe comunale, SDO di parto), vi abbiamo legato le SDO neonatali, tra le quali abbiamo infine individuato quelle con diagnosi di malformazione. Risultati. Abbiamo identificato 181 nati malformati su un totale di 3.229 parti. Delle tre fonti, il CEDAP hafornito pochissimi casi, mai in maniera esclusiva; invece il 71,2% della casistica è stato identificato dalle SDO ed il 51,9% da IMER. Solo il 23,7% dei casi era presente in entrambe le fonti. Conclusioni. L'esperienza illustrata dimostra come l'uso di una sola fonte informativa, per quanto riguarda le malformazioni congenite, sia da considerarsi largamente insufficiente per una accettabile completezza della casistica. D'altra parteulteriori approfondimenti sono necessari per valutare i motivi per i quali, partendo dalla stessa origine ospedaliera, due fonti informative diverse conducano ad esiti così pocosovrapponibili, mentre per la terza (CEDAP) oltre alla recente istituzione del flusso, nuoce probabilmente la compilazione a brevissima distanza dalla nascita.

2007 - Identificazione dell’infezione tubercolare latente in una popolazione di immigrati ‘irregolari’: influenza del modello di assistenza infermieristica sulla compliance dei soggetti. [Abstract in Atti di Convegno]
Fornaciari, R; Bonvicini, Francesca; Leone, N; Greci, M; Manghi, M; Vinceti, Marco; Mecugni, Daniela
abstract

Identificazione dell’infezione tubercolare latente in una popolazione di immigrati ‘irregolari’: influenza del modello di assistenza infermieristica sulla compliance dei soggetti.

2007 - Incidenza della sclerosi laterale amiotrofica nella Provincia di Reggio Emilia. [Abstract in Rivista]
Bonvicini, Francesca; Vinceti, Marco; Marcello, N; Rodolfi, R; Giovanardi, G; Martini, M.
abstract

Obiettivi. Valutare l’incidenza della sclerosi laterale amiotrofica (SLA) a Reggio Emilia (RE), una provincia dell’Italia settentrionale.Materiali e metodi. Al fine di individuare i nuovi casi di SLA diagnosticati tra i residenti nella provincia di RE nel periodo 1996-2005 abbiamo utilizzato le schede di dimissione ospedaliera ed i certificati di decesso aventi un codice di patologia corrispondente a 335.2, nonché la documentazione clinica della Divisione di Neurologia dell’Arcispedale Santa Maria Nuova di RE ed il registro delle prescrizioni farmacologiche di Riluzolo, farmaco impiegato esclusivamente nella SLA. Abbiamo poi contattato telefonicamente i medici di medicina generale ai fini di confermare la diagnosi di SLA e l’anno della diagnosi quando non è stato possibile accedere direttamente alle cartelle cliniche, limitando l’analisi ai casi di SLA ‘probabile’ o ‘accertata’ secondo i criteri diagnostici di ‘El Escorial’.Conclusioni. L’incidenza della SLA nella popolazione residente nella provincia di RE nel periodo 1996-2005 è risultata comparabile a quella recentemente riscontrata in altre regioni italiane e paesi europei e non ha evidenziato modificazioni di rilievo nel corso del tempo. L’incidenza della patologia si modifica sensibilmente in relazione al sesso ed all’età.

2007 - Personality traits as predictors of risky driving [Abstract in Rivista]
Vinceti, Marco; Bergomi, Margherita; Vivoli, R.; Rovesti, Sergio; Bussetti, Pamela; Vivoli, Gianfranco
abstract

Objective:The purpose of the study was to evaluate, in young subjects, the relationships between risky driver behavior and personality factors. Another aim was to assess the neuroendocrine correlates of personality and behavioral factors.Materials and Methods:We recruited 68 students (32 men and 36 women), after having obtained their informed consent. The subjects completed the following self-report questionnaires: the Big five Questionnaire, designed to evaluate the Big Five personality traits, the Sensation Seeking Scale, and the Driver Behaviour Questionnaire that evaluates driving behavior by frequency of lapses, errors, and violations. In urine samples collected from 8 am to 11 am we measured adrenaline, noradrenaline, dopamine, and serotonin levels using a HPLC system with an ESA detector.Results:Both lapses and errors were negatively related with emotional stability. The number of violations of highway code resulted positively related with extroversion and sensation seeking scores. Negative associations of violations with conscientiousness and cooperativity were observed. Regarding the relationship between driving behavior, personality traits, and neuroendocrine parameters, positive relations between violations and dopamine levels, and between driving errors and serotonine levels were observed. The stepwise regression analyses performed using psychological and biochemical measures as predictors and behavioral measures as dependent variables showed conscientiousness and dopamine levels as the main predictors of highway code violations. Only emotional stability remained significant in the final model, including lapses as dependent variable, whereas emotional stability and serotonin levels resulted predictors of errors.Conclusions:Our results, in agreement with previous researches, give further support to the role played by personality dimensions on unsafe driving, and improve the knowledge of the different risky driving behaviors. The interesting findings concerning the neuroendocrine correlates of driving behavior contribute to a better understanding of the biological bases of risky behaviors, including unsafe driving.

2007 - Programma di sorveglianza sanitaria della popolazione limitrofa all’inceneritore per rifiuti solidi urbani di Modena: risultati relativi alle malformazioni congenite. [Abstract in Rivista]
Vinceti, Marco; Malagoli, Carlotta; Teggi, Sergio; De Girolamo, G; Goldoni, C; Ferrari, Paola; Rivieri, F; Astolfi, G; Bergomi, Margherita; Vivoli, Gianfranco
abstract

Obiettivi: Nell’ambito del programma denominato “Sorveglianza sanitaria della popolazione modenese esposta alle emissioni dell’inceneritore per rifiuti solidi urbani”, condotto dal Dipartimento di Scienze di Sanità Pubblica dell’Università di Modena e Reggio Emilia in ottemperanza ad una direttiva della Conferenza dei Servizi della Provincia di Modena, abbiamo preso in esame il rischio di prevalenza alla nascita di malformazioni congenite nella progenie delle donne residenti o svolgenti attività professionale in prossimità dell’impianto di incenerimento.Metodi: Abbiamo analizzato nel periodo 2003-05 la prevalenza di malformazioni congenite nei nati da donne esposte alle emissioni dell’inceneritore per rifiuti solidi urbani di Modena. Abbiano a tal fine suddiviso il territorio comunale in tre aree, in base alla stima di concentrazione in atmosfera e ricaduta al suolo dei maggiori contaminanti emessi dall’inceneritore. Abbiamo quindi individuato le malformazioni congenite verificatesi nei nati dalle donne residenti all’interno di tali aree o in esse aventi la propria sede lavorativa, calcolando i rischi relativi nelle diverse coorti espositive ed esaminando la distribuzione dei casi osservati mediante analisi GIS (Geographical Information System).Risultati: Abbiamo osservato quattro casi di malformazione tra i nati da madre residente in prossimità dell’inceneritore (tutte appartenenti alla coorte ad esposizione ‘intermedia’). Il rischio relativo di malformazione, utilizzando la prevalenza nella rimanente popolazione comunale quale riferimento, è risultato essere nell’intera coorte di residenti esposte 0,79 (intervallo di confidenza al 95% 0,25-1,91), nella coorte più prossima all’inceneritore 0,00 (0,00-6,37) e nella coorte ad esposizione intermedia 0,88 (0,28-2,11). I corrispondenti valori nelle coorti delle lavoratrici, dove si sono verificati due parti di bambini malformati per i quali non abbiamo ancora indagato eventuali rischi specifici, sono risultati pari a 1,92 (0,32-6,35), 1,37 (0,07-6,76) e 3,13 (0,16-15,41).Conclusioni: Questi risultati non suggeriscono che l’esposizione all’inceneritore per rifiuti solidi urbani di Modena abbia indotto nel triennio considerato incrementi di rilievo del rischio teratogeno.

2007 - Programma di sorveglianza sanitaria della popolazione limitrofa all’inceneritore per rifiuti solidi urbani di Modena: risultati relativi all’abortività spontanea. [Abstract in Rivista]
Malagoli, Carlotta; Vinceti, Marco; De Girolamo, G; Goldoni, C; Bergomi, Margherita; Vivoli, Gianfranco
abstract

Obiettivi: Nell’ambito del programma di “Sorveglianza sanitaria della popolazione modenese esposta alle emissioni dell’inceneritore per rifiuti solidi urbani” promosso dalla Conferenza dei Servizi della Provincia di Modena, ci siamo proposti di individuare il rischio relativo di abortività spontanea nella popolazione esposta alle emissioni dell’inceneritore per rifiuti solidi urbani del Comune di Modena.Metodi: Abbiamo realizzato uno studio di coorte nei confronti delle donne aventi il proprio luogo di vita o di lavoro nell’area interessata dalle emissioni di diossine e metalli pesanti provenienti dall’impianto di incenerimento. Abbiamo suddiviso il territorio comunale in tre aree utilizzando una modellistica cartografica sulla base dei valori massimi di emissione autorizzati (area a maggior esposizione, area a minore esposizione ed il restante territorio modenese, non esposto), definendo di conseguenza tre coorti espositive sia di tipo residenziale che professionale. Abbiamo infine calcolato il rischio relativo di aborto spontaneo nelle due coorti a maggiore esposizione negli anni 2003-05, utilizzando quale sorgente informativa il flusso regionale delle schede di dimissione ospedaliera.Risultati: Nel triennio preso in considerazione il rischio relativo di abortività spontanea è risultato essere nell’intera coorte residenziale pari a 1,08 (intervallo di confidenza al 95% 0,67-1,66), ed in particolare 1,03 (0,26-2,82) nella coorte a maggiore esposizione e 1,10 (0,65-1,74) nella coorte a minor esposizione. Nelle lavoratrici i rischi relativi sono risultati pari a 0,40 (0,02-1,99), 0,00 (0,00-2,22) e 0,88 (0,04-4,36) rispettivamente nell’intera coorte e nelle corti a maggior e a minor esposizione. Conclusioni: I risultati ottenuti non indicano il verificarsi di scostamenti di rilievo nel numero di aborti spontanei nelle donne esposte nei confronti del numero di casi attesi sulla base dei tassi di riferimento, suggerendo così come l’esposizione alle emissioni dell’inceneritore per rifiuti solidi urbani di Modena non abbia rappresentato un fattore abortigeno di rilievo.

2006 - Cadmio e rischio di tumore alla prostata [Abstract in Rivista]
Venturelli, Marianna; Vinceti, Marco; Ferrari, Angela; Bonvicini, Francesca; Bussetti, Pamela; Bianchi, Giampaolo; Sighinolfi, Maria Chiara; Farinetti, Alberto; Trerotoli, P; Serio, G; Bergomi, Margherita; Vinceti, M.
abstract

Obiettivi: In questo studio abbiamo esaminato il possibile ruolo del cadmio nell'eziologia della neoplasia prostatica attraverso l'uso di un indicatore di esposizione a lungo termine come la matrice ungueale, in due differenti regioni italiane.Metodi: Abbiamo reclutato 40 casi e 58 controlli rispettivamente presso le cliniche urologiche e quelle chirurgiche dei policlinici universitari di Modena e Bari. L'età dei soggetti reclutati varia dai 43 a 83 anni. Ogni partecipante ha fornito un campione di unghie dei piedi sul quale effet¬tuare la determinazione quantitativa degli elementi, previo lavaggio e mineralizzazione in forno a microonde, mediante spettrofotometria di assorbimento atomico con atomizzazione in fornetto di grafite. I dati sono stati elaborati statisticamente attraverso il software Stata 9.1 al fine di calcolare il rischio relativo di neoplasia prostatica mediante il calcolo del rischio relativo (RR) nei differenti intervalli di esposizione dati dai terzili utilizzati come cutoff.Risultati:1I rischio di neoplasia prostatica è risultato maggiore nel terzile internedio (RR=1.7 -IC95% 0.5/6.4) e più elevato (RR=4.3- IC95% 1.3/ 13.8) (p-trend 0.029)di esposizione a cadmio, sia nell'intera casistica che considerando i dati disaggregati per provincia. L'introduzione delle variabili confondenti quali bmi, abitudini tabagiche e dieta ha modificato sensibil¬mente le stime del rischio relativo.Conclusioni: I risultati prodotti dallo studio che abbiamo condotto, pur con la bassa stabilità statistica dovuta alle ridotte dimensioni della casistica, ci conducono a sostenere l'ipotesi, già suggerita da studi epidemiologici e di laboratorio, che l'esposizione a cadmio possa incrementare il rischio di tu¬more prostatico.

2006 - Epidemiologia dei sarcomi nel Comune di Reggio Emilia nel periodo 2001-2006. [Abstract in Atti di Convegno]
Borciani, N; Rodolfi, R; Carlifante, G; Malagoli, Carlotta; Vinceti, Marco; Bergomi, Margherita
abstract

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2006 - Esposizione a cadmio,selenio,rame e zinco nella popolazione emiliana e pugliese [Abstract in Atti di Convegno]
Venturelli, Marianna; Malavolti, Marcella; Trerotoli, P; Ferrari, Angela; Luisi, Mariateresa; Bussetti, Pamela; Bonvicini, Francesca; Vinceti, Marco; Battistini, Nino Carlo; Bergomi, Margherita; Serio, G; Vivoli, Gianfranco; Dugoni, Manfredo; Farinetti, Alberto
abstract

Introduzione Poche informazioni sono attualmente disponibili sulla esposizione cronica ad elementi in traccia di interesse nutrizionale e tossicologico nella popolazione italiana e sui fattori che influenzano tale esposizione. Abbiamo condotto uno studio su tale problematica in soggetti residenti in due diverse province italiane.Metodologia Abbiamo reclutato 126 soggetti su base volontaria, scelti tra i residenti nelle province di Bari e di Modena che si sono recati ai Policlinici locali nel primo semestre del 2004, per sottoporsi a visite ambulatoriali od interventi di piccola chirurgia (asportazione di cisti, medicazione post-intervento, visite proctologiche). Tra questi, 104 residenti nella provincia di Modena (65 maschi e 39 femmine) e 22 della provincia di Bari tutti di sesso maschile. Abbiamo raccolto da tali soggetti i dati relativi a peso, altezza, abitudine tabagica ed un campione di unghie dei piedi al fine di determinare le concentrazioni di Cd, Se, Cu e Zn. Le determinazioni sono state effettuate, previa digestione acida del campione, mediante spettrofotometria di assorbimento atomico a fornetto di grafite (Cd, Se, Cu) ed a fiamma (Zn). Per ottimizzare le procedure analitiche abbiamo utilizzato i campioni di riferimento della matrice biologica più simili alle unghie, owero campioni certificati di capelli umani CRM 397 e GBW 09101. L'analisi dei dati è stata condotta utilizzando il software statistico Stata (versione 9.1), mediante procedure parametri che e non-parametriche per la comparazione delle medie e l'analisi delle associazioni.Risultati Confrontando le concentrazioni osservate nei maschi modenesi e in quelli baresi, i livelli di Se sono risultati lievemente più elevati nella popolazione pugliese (0.582 ug/g vs. i 0.490 ug/g dei soggetti emiliani; p=0.02) mentre non abbiamo osservato differenze per quanto riguarda le concentrazioni degli altri elementi in traccia. Paragonando le concentrazioni degli oligoelementi tra i due sessi nella popolazione modenese, abbiamo riscontrato, nei soggetti di sesso femminile, livelli più elevati di Zn (112.20 ug/g vs 121.5 ug/g; p=0.06) e di Cd (0.023 ug/g vs 0.064 ug/g; p=0.13), mentre le concentrazioni di Se e Cu non hanno evidenziato differenze di rilievo. In riferimento alle abitudini tabagiche, nel sesso maschile i fumatori hanno evidenziato minori livelli di Cd e maggior livelli di Zn e Cu rispetto ai non fumatori, mentre le concentrazioni di Se sono risultate simili. Sempre per quanto riguarda il Se, tuttavia, le concentrazioni determinate nei non-fumatori del campione barese sono risultate più elevate (0.608 vs 0.473 ug/g dei fumatori), come atteso, di quelle riscontrate nei fumatori della medesima popolazione. Il BMI e l'età non sono risultati associati alle concentrazioni di oligoelementi sia nella popolazione complessiva presa in esame sia nei due sottogruppi identificati su base geografica, con l'unica eccezione dei livelli di Se, i quali sono risultati correlati inversamente all'età nella casistica modenese e nel totale della casistica.Conclusioni La nostra indagine è caratterizzata dall'utilizzazione di un indicatore di esposizione particolarmente adeguato a riflettere l'esposizione a medio termine ad oligoelementi, le unghie, e nel contempo da una significativa limitazione sotto il profilo metodologico, la ridotta potenza statistica. La casistica da noi esaminata è infatti numericamente assai limitata, rendendo di conseguenza difficile l'evidenziazione di associazioni di limitata entità ed un controllo adeguato dei fattori confondenti. Nelcomplesso, l'unico oligoelemento le cui concentrazioni sono risultate associate alla regione di residenza è risultato essere il Se, suggerendo livelli espositivi più elevati nelje regioni meridionali, con ogni probabilità a causa di un maggiore apporto dietetico. Il consumo di tabacco è risultato associato, come atteso, a differenze nell'esposizione a Se, Cu e Zn, mentre più d

2006 - Fattori di rischio ambientali e comportamentali del tumore alla prostata in due popolazioni italiane. [Abstract in Atti di Convegno]
Venturelli, Marianna; Vinceti, Marco; Bergomi, Margherita; Sighinolfi, Maria Chiara; Bianchi, Giampaolo; Malavolti, Marcella; Battistini, Nino Carlo; Farinetti, Alberto; Trerotoli, P; Serio, A; Vivoli, Gianfranco
abstract

Obiettivi: Ci siamo proposti di valutare il ruolo della dieta e di alcuni elementi in traccia di interesse tossicologico e nutrizionale (cadmio, selenio, rame e zinco) nell'eziologia della neoplasia prostatica in due popolazioni italiane, quella emiliana e quella pugliese.Metodi: Abbiamo reclutato un campione di 45 pazienti affetti da neoplasia prostatica di diagnosi recente e di 68 controlli di popolazione presso i Policlinici universitari di Bari e di Modena, limitando la selezione ai soggetti di età superiore a 45 anni e residenti da almeno 10 anni nelle due province. I controlli sono stati selezionati con metodo casuale tra i soggetti afferenti alle Divisioni chirurgiche dei due ospedali per sottoporsi ad interventi di piccola chirurgia, appaiandoli per età ai pazienti (±5anni). Per la determinazione quantitativa degli oligoelementi, previo lavaggio e mineralizzazione delle unghie con HN03 in forno a microonde, abbiamo utilizzato la tecnica AAS con atomizzazione in fometto di grafite (Cd,Se,Cu) e in fiamma (Zn), utilizzando quale materiale di riferimento campioni certificati di capelli umani CRM 397 e GBW 09101. La valutazione della dieta è stata effettuata mediante la somministrazione dei questionari semiquantitativi di frequenza alimentare dello studio europeo 'EPIC'.Risultati: Abbiamo osservato nei casi, rispetto ai controlli, livelli più elevati di cadmio (0.108 vs. 0.034 ug/g) e di rame (5.07 vs. 3.78 ug/lg), mentre non abbiamo riscontrato differenze particolari per selenio e zinco. Il rischio di neoplasia prostatica non è tuttavia risultato associato a nessuno degli elementi studiati. L'analisi dei dati disaggregati sotto il profilo geografico ci ha mostrato rilevanti differenze soprattutto per quanto riguardo il cadmio. I pazienti di Bari hanno infatti evidenziato concentrazioni medie pari a 0.168 ug/g contro i 0.044 ug/g dei controlli, mentre per i soggetti modenesi abbiamo osservato rispettivamente 0.042 e 0.027 ug/g. Per quanto riguarda la dieta, il rischio di tumore pro statico è apparso direttamente associato all'apporto di alcune variabili alimentari, in particolare proteine animali, lipidi animali, acidi grassi saturi totali, alcool, calcio e vitamina D, mentre l'introduzione di proteine vegetali, carboidrati e amido è risultata inversamente corre lata col rischio di patologia.Conclusioni: I risultati di questo studio debbono essere valutati con una certa cautela a causa delle dimensioni limitate della casistica, anche se l'utilizzazione di un bioindicatore particolarmente adatto a stimare l'esposizione a medio termine, le unghie, e di un questionario alimentare completo e validato sotto il profilo epidemiologico ne favoriscono l'attendibilità. I risultati delle determinazioni effettuate sulle unghie non suggeriscono che cadmio, selenio, rame e zinco esercitino un ruolo nelI'eziopatogenesi della neoplasia prostatica. Per quanto riguarda la dieta, abbiamo individuato incrementi del rischio in associazione a variabili alimentari già corre late in studi condotti in altri Paesi a questo tipo di neoplasia, che sembrano confermare come anche in queste due popolazioni italiane, caratterizzate da sensibili differenze sul piano della dieta abituale e presumibilmente delle esposizioni ambientali, la dieta eserciti un ruolo non marginale nel determinismo di questa patologia.

2006 - Flussi Informativi. [Capitolo/Saggio]
Lopalco, Pl; Vinceti, Marco; Fabiani, L.
abstract

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2006 - High risk of cutaneous melanoma amongst carriers of the intercellular adhesion molecule-1 R241 allele [Articolo su rivista]
Vinceti, Marco; Pellacani, Giovanni; B., Casali; Malagoli, Carlotta; D., Nicoli; E., Farnetti; S., Bassissi; Bergomi, Margherita; Seidenari, Stefania
abstract

We examined the relation between cutaneous melanoma risk and the intercellular adhesion molecule-1 (ICAM-1) gene single nucleotide polymorphisms G241R and K469E, as well as the circulating soluble form of ICAM-1 determined in plasma, in the population of Modena Province, northern Italy. Individuals carrying at least one R241 allele, versus those carrying the wild-type GG genotype, had a relative risk of melanoma of 4.3 (P = 0.022), whereas the K469E polymorphism was unrelated to disease risk. Soluble ICAM-1 levels above 10 ng/ml directly and strongly correlated with melanoma risk. In this population, individuals carrying the R241 allele of the ICAM-1 gene appeared to show an enhanced susceptibility to cutaneous melanoma, possibly because of increased ICAM-1 expression.

2006 - Il ruolo dei fattori di distrazione sulla incidentalità stradale [Abstract in Rivista]
Vivoli, R.; Bergomi, Margherita; Vinceti, Marco
abstract

Nell’ambito dei fattori di rischio degli incidenti stradali, un ruolo importante sembra essere svolto dai livelli di attenzione del conducente che possono essere inadeguati per la guida di un autoveicolo, compito particolarmente complesso, basato sull’interazione uomo, ambiente, veicolo, in cui è richiesta una vasta gamma di abilità sia cognitive che fisiche. In relazione allo stato attentivo, i conducenti di un autoveicolo possono essere classificati come: attenti, distratti, sonnolenti, svegli o in uno stato definito come “looked but didn’t see” .Si stima che oltre il 25% degli incidenti stradali sia da attribuire ad una alterazione dei processi attentivi del conducente che può essere riconducibile a stanchezza, sonnolenza, stati psicologici, assunzione farmaci, alcol e/o droghe o all’azione di fattori di distrazione, che distolgono l’attenzione del conducente dal compito principale che sta svolgendo, la guida di un autoveicolo. Le principali fonti di distrazione per un conducente sono rappresentate da persone e/o oggetti esterni al veicolo (pedoni, biciclette, altri veicoli, cartelloni stradali, lavori stradali…) o interni al veicolo stesso e legati principalmente alla presenza di altri passeggeri, all’uso del telefono cellulare, o ad altri dispositivi tecnologici (condizionatore, autoradio o lettore CD, navigatore satellitare …).In alcuni casi il conducente si impegna in compiti secondari che possono essere di diversa complessità manuale o visiva (regolazione della radio, del climatizzatore, del navigatore, sistemazione di oggetti .. assunzione di cibo o bevande…) e/o comportano un impegno mentale in grado di distogliere la sua attenzione dalla guida, con evidenti ripercussioni sulla sicurezza. Considerata la crescente attenzione al ruolo svolto dai fattori di distrazione sul rischio di incorrere in incidenti stradali, vengono illustrate le più recenti acquisizioni in merito al diverso peso dei fattori di distrazione in relazione alle caratteristiche socio demografiche e al profilo cognitivo e comportamentale del guidatore.

2006 - Influenza di fattori psicofisiologici sul comportamento alla guida. Abstract book del Convegno “La ricerca scientifica per la sanità pubblica” della Società Italiana di Igiene, Medicina Preventiva e Sanità Pubblica - Sezione Emilia-Romagna, Modena 22 maggio 2006. [Abstract in Atti di Convegno]
Bussetti, Pamela; Rovesti, Sergio; Vivoli, Roberto; Cacciari, Cristina; Vinceti, Marco; Bergomi, Margherita
abstract

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2006 - Possibili sviluppi per la ricerca nel campo della tubercolosi in Uganda e nei Paesi dell’Africa sub-sahariana. [Abstract in Atti di Convegno]
Bonvicini, Francesca; Cicciò, L; Tagliaferri, E; Vinceti, Marco; Bergomi, Margherita
abstract

Introduzione: Nel 1993 l'OMS ha defrnito la tubercolosi (TB) come una emergenza mondiale di sanità pubblica, in risposta al costante aumento dell'incidenza ed alla diffusione di multi-resistenze farmacologiche. Attualmente il 95% dei casi ed il 98% delle morti attribuibili alla TB si verificano nei paesi in via di sviluppo; l'Uganda è stata inclusa dall'OMS tra i 22 paesi che assieme contribuiscono a1l'80% dei casi di TB nel mondo. La Direct Observed Treatment Short Course, in particolare la variante Community Based (CB-DOTS), è la strategia raccomandata a livello mondiale per il controllo della TB nei paesi in via di sviluppo. Sebbene in Uganda la CB-DOTS abbia raggiunto una copertura del 100% già da alcuni anni, i targets di performances diagnostiche e terapeutiche fissati dall'OMS non sono stati raggiunti..Obiettivo: Partendo dall'analisi delle performances del programma nel Distretto di Arua (Regione West-Nile, Uganda), abbiamo cercato di individuare i punti critici e le possibili strategie per il futuro finalizzate al miglioramento del programma di controllo della TB in Uganda e nei paesi dell' Africa Sub-Sahariana.Metodi: Dai registri TB di Distretto e delle Strutture Sanitarie abbiamo ricavato le informazioni riguardanti le caratteristiche dei pazienti notificati nel triennio 2003-2005, il tipo di patologia tubercolare (con espettorato positivo, con espettorato negativo ed extra-polmonare) e l'esito del trattamento. Dai registri TB di laboratorio delle 4 principali strutture sanitarie del Distretto abbiamo estratto i dati circa le attività di diagnosi microscopica diretta dell'espettorato per il periodo Gennaio-Ottobre 2005. Presso l'ospedale di Arua abbiamo raccolto le informazioni riguardanti l'attività di collaborazione TB-HIV/AIDS per il periodo Gennaio 2005¬Marzo 2006.Risultati: Per quanto riguarda gli aspetti diagnostici, nel 26% dei pazienti con sospetta TB polmonare è disponibile solo l'accertamento relativo ad un campione, il quale consente di identificare il 90% dei soggetti che risulteranno positivi; nel 40% dei casi vengono analizzati due campioni di espettorato, in grado di identificare il 99% dei pazienti positivi. I soggetti con meno di 15 anni di età rappresentano una quota molto importante dei nuovi casi di TB notificati ogni anno: il 12% in media dei pazienti ha età compresa tra 0 e 14 anni e di questi il 60% ha meno di 5 anni. La quota di forme polmonari espettorato-negative nella popolazione 0-4 anni raggiunge una percentuale del 76%. La percentuale di pazienti con nuova diagnosi di TB sottoposti al test dell'HIV è del 45%; di questi, 1'86% è risultato sieropositivo.Discussione: L'aspetto della diagnosi microscopica dell'espettorato basato, in accordo con le linee guida internazionali, su tre campioni risulta un punto particolarmente critico, essendo gravato da lunghi tempi di attesa, livelli di qualità spesso dubbi e bassa compliance dei pazienti. I risultati del nostro studio suggeriscono pertanto l'opportunità, come già espresso da alcuni autori in letteratura, di diminuire a due il numero dei campioni da esaminare. La percentuale di forme espettorato-negative nei bambini è risultata molto più elevata rispetto al 20-25% atteso in base alla letteratura. Il dato merita di essere approfondito, in quanto fa sorgere il sospetto di una sovrastima dei casi, soprattutto nelle età più precoci: gli algoritmi diagnostici attualmente raccomandati a livello internazionale per l'identificazione delle forme espettorato-negative nei paesi a risorse limitate sono basati essenzialmente su indicazioni clinico-ananrnestiche, che potrebbero essere migliorate ed adattate al contesto locale. La percentuale di pazienti con TB sottoposti al test dell'HIV è bassa; la quota di siero-positivi è risultata molto più elevata rispetto al 50% atteso in base alle stime dell'OMS, suggerendo una sottostima della prevalenza della coinfezione o una distorsione di selezione del campione

2006 - Prevalence at birth of congenital anomalies in a population living around a modern municipal solid waste incinerator. [Abstract in Rivista]
Vinceti, Marco; Malagoli, Carlotta; Rodolfi, R; Astolfi, G; Rivieri, F; Fiorini, S; Muzii, M; Campagna, A; Bergomi, Margherita; Vivoli, Gianfranco
abstract

Introduction. Chemicals emitted by the municipal waste incinerators are suspected to increase risk of birth defects in exposed populations. We examined the prevalence at birth of congenital anomalies in offspring of women potentially exposed to the emissions of a municipal solid waste incinerator.Methods. Within a health surveillance program monitoring reproductive health in the population (around 180,000) of an Italian city where a modern incinerator has been operating for thelast few years, we identified all pregnancies occurring in 2003-04 in two cohorts of women aged 16-49, residing in two exposure areas close to the incinerator plant: area A, with the highestexposure, and area B, with intermediate exposure. We also identified the pregnancies occurring in two cohorts of women aged 16-49 who were working in the A and B areas in 2003. Weretrieved birth defects from livebirths and stillbirths through the Emilia-Romagna region hospital discharge records and the regional registry of congenital malformations named IMER. Wecalculated the age-adjusted relative risk (RR) of prevalence at birth of congenital anomalies in newborns to women belonging to the A and B cohorts, using prevalence in the remainingmunicipal population as reference rate. We also retrieved individual data about socioeconomic status from the General Registry Office for the two exposure cohorts and for the remainingmunicipal female population.Results. In the offspring of women having the highest exposure (cohort A) we did not observe any case of birth defects whilst 0.41 cases were expected in 2003-04. In the same period, wedetected two cases of congenital anomalies among newborns to women having intermediate exposure (cohort B), whilst the number of expected cases was 3.42, yielding a RR of 0.6 (95%confidence limits 0.1-1.9, P-value 0.480). We detected one case in offspring of employees working in the A area (RR 2.1, 95% confidence limits 0.1-10.3, mid-P-value 0.464) and no cases innewborns to employees working in the B area vs. 0.26 expected cases. Socioeconomic status of exposed cohorts did not appear to be higher than in the remaining municipal population.Discussion and conclusions. Results of this study seem to suggest that residence in the proximity of a modern municipal waste incinerator does not exert major teratogenic effects, al leastwith reference to the risk of birth defects in offspring. The low statistical stability of the point estimates, however, warrants further follow-up of the study cohorts.

2006 - Risk of miscarriage in women exposed to the emissions of a modern municipal solid waste incinerator [Abstract in Rivista]
Malagoli, Carlotta; Vinceti, Marco; Rodolfi, R.; Bigi, G.; Campagna, A.; Muzii, M.; Bergomi, Margherita; Vivoli, Gianfranco
abstract

Introduction. There is an increasing trend towards using incineration to solve the problem of waste management, raising concern about its potential health impact. We implemented asurveillance program on reproductive health of the population of an Italian city (population around 180,000) where a modern incinerator has been operating for the past few years. This currentstudy focuses on miscarriage risk in women living in proximity to this plant.Methods. We conducted a prospective study among two dynamic cohorts of women aged 16-49 residing in three distinct areas according to predicted fall-out of the incinerator pollutants(area A, with the highest exposure; area B, with intermediate exposure; area C, corresponding to the remaining municipal territory, considered as ‘unexposed’). We also followed two cohorts of female employees aged 16-49, working in the A and B areas, though occupational information for these women was available only for 2003. During the 2003-04 period, we identified all cases of spontaneous abortion occurring in these cohorts through the regional hospital discharge database, and we calculated the age-standardized morbidity ratio (SMR) of miscarriage in the ‘exposed’ cohorts, using rates in the whole municipal population as reference incidence.Results. In the residential cohorts, we detected 14 spontaneous abortions (7 in 2003 and 7 in 2004) among 1979.3 person-years of follow-up. In the occupational cohorts encompassing atotal of 189.4 person-years, we did not observe any cases of miscarriage. We did not detect an excess risk of spontaneousabortion in women residing or working in proximity to the waste incinerator in either of the exposure areas. SMR of miscarriage were lower in the area with the highest exposure compared with the intermediate exposure area.Data about socioeconomic status abstracted from the General Registry Office were substantially similar for the three residential cohorts.Discussion and conclusions. These results do not suggest that exposure to the emissions of a modern municipal waste incinerator is associated with increased risk of miscarriage, though the limited statistical stability of the point estimates suggests caution in the evaluation of the study findings.

2006 - Sensibilità ed accuratezza diagnostica dei flussi informativi del Servizio Sanitario Nazionale nella rilevazione dell’incidenza delle patologie linfoproliferative in una popolazione italiana. [Articolo su rivista]
M., Calzari; Vinceti, Marco; P., Avanzini; R., Rodolfi; L., Serra; F., Luberto; A., Tieghi
abstract

We examined the sensitivity and the accuracy of three health databases (hospital discharge data, death certificates and pathologic records) between 1997 and 2001 in an Italian community, to evaluate their accuracy for the diagnosis of lymphoid malignancies and their ability to detect newly diagnosed patients affected by these diseases. Hospital discharge data showed the best sensitivity among the examined databases, though they exhibited an unexpectedly high number of diagnostic errors, even when limiting the analysis to patients with repeated hospital admissions over time. Overall, the pathologic registry and the death certificate file showed a higher diagnostic accuracy, though their sensitivity was considerably lower than hospital discharge data.

2005 - A critical evaluation of the role of trace elements in human cancer [Articolo su rivista]
Borella, Paola; Bargellini, Annalisa; Piccinini, Lino; Vinceti, Marco; R., Masironi; Vivoli, Gianfranco
abstract

The interest in the role of trace elements in cancer is increasing, particularly for those with a possible protective action, such as Se and Zn. Despite the vast amount of investigations already conducted, there is a need for further epidemiological studies to better understand what compounds, at what levels, and with which mechanism trace elements are involved in protection against a specific cancer type or groups of cancer. Critical aspects remain the search for the most appropriate biological indicators of body burden, the variability in biological activity according to chemical form and the current state of knowledge of the mechanisms of action which could be mediated by interference of the neuroendocrine and/or immune system. On the basis of our experience on the relationship between trace elements and cancer disease, we discuss the critical aspects of the problem and try to define guidelines for future research.

2005 - A population-based case-control study of diet and melanoma risk in northern Italy [Articolo su rivista]
Vinceti, Marco; Pellacani, Giovanni; Malagoli, Carlotta; S., Bassissi; S., Sieri; Bonvicini, Francesca; V., Krogh; Seidenari, Stefania
abstract

Objective: We aimed at examining the association between dietary constituents and risk of cutaneous melanoma. Design: In an area of northern Italy we recruited 59 newly diagnosed melanoma patients and 59 age- and sex-matched population controls, to whom we administered a validated semi-quantitative food-frequency questionnaire. Results: We found an excess risk of melanoma in subjects with a higher energy-adjusted intake of total polyunsaturated fatty acids and, in particular, of linoleic acid (relative risk=2.16 for intake in the highest tertile compared with the lowest tertile, P for linear trend=0.061). Conversely, disease risk was inversely associated with the consumption of soluble carbohydrates (relative risk=0.34 for intake in the upper vs. the lowest tertile adjusting for total energy intake, P for linear trend=0.046). No other dietary factors, including alcohol, vitamins and trace elements, correlated with melanoma risk. The association of melanoma risk with linoleic acid and soluble carbohydrates intakes was further strengthened in multivariate analysis, and when analysis was limited to females. Conclusions: Overall, these results indicate that an excess energy-adjusted intake of linoleic acid and a lower consumption of soluble carbohydrates may increase melanoma risk.

2005 - Acute-phase reactants and the risk of relapse/recurrence in polymyalgia rheumatica: a prospective followup study [Articolo su rivista]
Salvarani, Carlo; Cantini, Fabrizio; Niccoli, Laura; Macchioni, Pierluigi; Consonni, Dario; Bajocchi, Gianluigi; Vinceti, Marco; Catanoso, Maria Grazia; Pulsatelli, Lia; Meliconi, Riccardo; Boiardi, Luigi
abstract

Objective. To determine laboratory parameters that may be useful in identifying polymyalgia rheumatica (PMR) patients who require long-term corticosteroid therapy. Methods. A prospective followup study of 94 consecutive untreated patients with PMR were assessed for relapse/recurrence for a mean of 39 months. This cohort represented all the patients diagnosed over a 4-year period in 2 Italian secondary referral centers. Patients were monitored for clinical signs and symptoms, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum interleukin-6 (IL-6). IL-6 levels were also measured in 43 controls matched to the patients for age and sex. Results The ESR was elevated in 91.5% of the patients prior to therapy initiation, as were CRP in 98.9% and serum IL-6 in 92.6%. Forty-seven (50.0%) patients had at least 1 relapse/recurrence during the followup period and 24 (25.5%) had at lease 2. After 4 weeks of prednisone therapy, ESR was elevated in 13.2% patients, CRP in 41.9%, and serum IL-6 in 37.2%. IL-6 levels remained persistently elevated in 9.9% and CRP in 8.7% of patients during the first year of followup, whereas no patient had persistently elevated ESR. Persistently elevated CRP and IL-6 levels were significantly associated with an increased risk of relapse/recurrence. In particular, patients with persistently elevated levels of IL-6 during the first year of therapy had the highest relative risk. Conclusion. Despite the control of clinical symptoms, corticosteroids do not adequately control the inflammatory process in a subset of patients with PMR who have persistently elevated levels of CRP and IL-6 and who have a higher risk of relapsing.

2005 - Environmental exposure to trace elements and risk of cutaneous melanoma [Articolo su rivista]
Vinceti, Marco; Bassissi, Stefania; Malagoli, Carlotta; Pellacani, Giovanni; D., Alber; Bergomi, Margherita; Seidenari, Stefania
abstract

Purpose: Our aim was to examine the risk of melanoma in association with exposure to trace elements of toxicological and nutritional interest. Methods: We analyzed the concentrations of cadmium, lead, chromium, selenium, copper and zinc in toenails of 58 patients with newly diagnosed cutaneous melanoma as well as in 58 age- and sex-matched control subjects, randomly selected from the population of Modena province in northern Italy. Results: Melanoma risk was substantially unrelated to toenail levels of cadmium, chromium, lead and selenium. Subjects with higher toenail copper levels showed an excess risk, both in the crude analysis and after adjusting for sun exposure and level of education, while in both analyses high iron concentrations were associated with a decreased risk of the disease. A weak direct association between zinc levels and melanoma risk also emerged in the multivariate analysis. Conclusions: Overall, these results do not suggest an involvement of heavy metals in melanoma etiology, while they do give some support to a possible role of zinc and, in particular, copper and iron exposure in influencing disease risk. However, these findings must be evaluated with caution due to the limited statistical stability of the point estimates.

2005 - Health risk assessment of municipal solid waste inceneration [Capitolo/Saggio]
Vinceti, Marco; R., Vivoli; Malagoli, Carlotta; Bergomi, Margherita; Teggi, Sergio; Ghermandi, Grazia
abstract

The incineration of municipal solid waste leads to the environmemal release of some toxic substances, albeit of low atmospheric concentration in the proximity of the most recently built incinerators thanks to the substantial advancements in air pollution control equipment. An excess risk of some adverse health outcomes (cancer, birth defects, and respiratory diseases in particular) has been linked to the environmental release of these toxic substances on the basis or epidemiologic and laboratory studies. The methodologies most frequently adopted by environmental scientists and regulatory agencies to evaluate these potential risk are the potential risk are the modelling of carcinogenic and non-carcinogenic health risks, and the implementation of epidemiologic studies in the populations residing near the incincrators. Geographic lnfornation System (GlS) software to map specific diseases in the areas around the incinerators can also be used in support of data management and data representation. We describe a health surveillance program concerning the popubtion of a northen Italian town where capacity of a municipal solid waste incinerator is planned to substantially increase in the near future. The program wilI analyse the risk of birth defects and spontaneous abortions in the population potentially exposed to the incinerator emissions.

2005 - Health risk assessment of municipal solid waste incineration [Relazione in Atti di Convegno]
Vinceti, M.; Vivoli, R.; Malagoli, C.; Bergomi, M.; Teggi, S.; Ghermandi, G.
abstract

The incineration of municipal solid waste leads to the environmental release of some toxic substances, albeit of low atmospheric concentration in the proximity of the most recently built incinerators thanks to the substantial advancements in air pollution control equipment. An excess risk of some adverse health outcomes (cancer, birth defects, and respiratory diseases in particular) has been linked to the environmental release of these toxic substances on the basis of epidemiologic and laboratory studies. The methodologies most frequently adopted by environmental scientists and regulatory agencies to evaluate these potential risk are the modelling of carcinogenic and non-carcinogenic health risks, and the implementation of epidemiologic studies in the populations residing near the incinerators. Geographic Information System (GIS) software to map specific diseases in the areas around the incinerators can also be used in support of data management and data representation. We describe a health surveillance program concerning the population of a northern Italian town where the capacity of a municipal solid waste incinerator is planned to substantially increase in the near future. The program will analyse the risk of birth defects and spontaneous abortions in the population potentially exposed to the incinerator emissions. © 2005 WIT Press.

2005 - I tumoti in provincia di Modena nel 2003 [Monografia/Trattato scientifico]
Federico, Massimo; Rashid, I.; Artioli, M. E.; Cirilli, C.; Fracca, A.; Vinceti, Marco; Maiorana, Antonino; De Girolamo, G.
abstract

Monografia sui dati di incidenza e sopravvivenza delle neoplasie nella provincia di Modena

2005 - Progetto di sorveglianza sanitaria della popolazione residente in prossimità dell’inceneritore per rifiuti urbani di Modena [Abstract in Rivista]
Malagoli, Carlotta; Vinceti, Marco; Vivoli, R; Bergomi, Margherita; Teggi, Sergio; Ghermandi, Grazia
abstract

Poichè l’incenerimento è ormai divenuto una delle risposte più diffuse nei paesi industrializzati per affrontare il problema dello smaltimento dei rifiuti urbani, gli eventuali effetti sulla salute legati al rilascio di inquinanti da tali impianti meritano particolare attenzione da parte delle istituzioni preposte alla tutela della salute pubblica e della comunità scientifica. In tal senso, ed in relazione all’imminente ampliamento dell’inceneritore per rifiuti solidi urbani sito nel Comune di Modena, è stato predisposto da parte dell’Università degli Studi di Modena e Reggio Emilia un programma di sorveglianza sanitaria della popolazione potenzialmente esposta alle emissioni di tale impianto. Tale programma prenderà in esame l’abortività spontanea e la prevalenza nei nuovi nati di malformazioni congenite, in quanto la salute riproduttiva appare essere un indicatore particolarmente sensibile e tempestivo degli eventuali rischi sanitari associati all’esposizione a diossine e metalli pesanti. Il programma disorveglianza verrà a applicato a due coorti di residenti in prossimità dell’inceneritore ed ai lavoratori la cui sede di lavoro è sita nelle vicinanze dell’impianto stesso. In particolare, verranno calcolati in tali coorti i rischi di aborto spontaneo e di nati con malformazioni, utilizzando come riferimento i rischi rilevati nella rimanente popolazione del comune di Modena. Quali fonti informative verranno utilizzati i flussi SDO e CEDAP delServizio Sanitario Nazionale ed il Registro Malformazioni della regione Emilia Romagna (IMER-EUROCAT).Sarà inoltre realizzato un report cartografico utilizzando il Geographical Information System (GIS), in grado di fornire un’analisi di tipo spaziale georeferenziata dei risultati. L’elaborazione verrà effettuata per ciascun anno compreso nel periodo 2003-2011, ed i dati ottenuti verranno presentati alla Conferenza dei Servizi della Provincia di Modena ed alla popolazione locale.

2005 - Risultati preliminari dello studio multicentrico “Apporto alimentare di policlorobifenili e di metalli in traccia in relazione col rischio di tumore mammario”. Unità operativa di Parma [Abstract in Rivista]
Zoni, R; Veronesi, L; Riveda, Am; Ribaldi, E; Dichiara, M; Di Mauro, D; Pastiglia, P; Serio, G; Vinceti, Marco; Bergomi, Margherita; Sieri, S; Sansebastiano, G.
abstract

Si è voluto indagare l'eventuale associazione tra alcuni tossici ambientali (policlorobifenili) assunti con la dieta e la patologia neoplastica mammaria attraverso uno studio caso-controllo multicentrico.I dati raccolti non hanno permesso di mettere in evidenza differenze statistiche significative tra le concentrazioni dei PCBs nei sieri dei casi e dei controlli.

2005 - Ruolo di selenio, rame e zinco nell’eziologia del melanoma: uno studio caso-controllo nella provincia di Modena [Abstract in Rivista]
Vinceti, Marco; Venturelli, Marianna; Pellacani, Giovanni; Seidenari, Stefania; Bonvicini, Francesca; Dugoni, Manfredo; Bussetti, Pamela; Ferrari, Angela; Castiglia, P; Serio, G; Trerotoli, P; Sansebastiano, G; Bergomi, Margherita; Vivoli, Gianfranco
abstract

OBIETTIVI: Abbiamo condotto uno studio caso-controllo sul ruolo di tre elementi di interesse nutrizionale e tossicologico, selenio, rame e zinco, nell’eziologia del melanoma, nel contesto di un progetto di ricerca PRIN comprendente le università di Bari, Modena, Parma e Sassari. Quale indicatore di esposizione abbiamo utilizzato la concentrazione di tali elementi a livello ungueale.METODI: Abbiamo reclutato 26 pazienti affetti da melanoma presso la Clinica Dermatologica dell’Università di Modena e Reggio Emilia e 52 controlli, appaiati per sesso ed età, selezionaticasualmente tra i pazienti sottoposti ad interventi di cosiddetta ‘piccola chirurgia’ presso ilPoliclinico di Modena. Abbiamo quindi effettuato la determinazione dei livelli di selenio, rame e zinco nelle unghie dei piedi raccolte dai soggetti inclusi nello studio, previo lavaggio e digestioneacida in forno a microonde, mediante spettrofotometria di assorbimento atomico con fornetto di grafite per selenio e rame ed atomizzazione a fiamma per lo zinco. Abbiamo infine calcolato il rischio relativo di melanoma in associazione ai livelli espositivi agli elementi presi in esame utilizzando un modello di regressione logistica condizionale.RISULTATI: Non abbiamo osservato particolari differenze tra casi e controlli per quanto riguarda le concentrazioni di selenio, mentre in riferimento ai livelli di rame ed in particolare di zinco abbiamo riscontrato livelli lievemente inferiori nei controlli. Infatti, le concentrazioni medie di rame sono risultate pari a 4.30μg/g nei casi e 3.87μg/g nei controlli, mentre i corrispondenti valori per lo zinco sono risultati rispettivamente pari a 130μg/g e 114.1μg/g, confermando precedenti osservazioni.Abbiamo calcolato i rischi relativi di melanoma associati ad incrementi dei parametri espositivi considerati come valori continui (p-trend) o dicotomici (con cutoff pari alla mediana calcolata nei controlli). L’esposizione ai tre elementi in traccia presi in esame non è risultata associata al rischio di melanoma, ad eccezione dello zinco, per il quale il valore di p-trend è risultato pari a 0.032.CONCLUSIONI: I risultati ottenuti, pur tenendo conto delle limitate dimensioni del campione in esame, non indicano un coinvolgimento dell’assunzione di selenio e rame nell’eziologia di questa patologia, mentre per quanto riguarda l’esposizione a zinco il dato necessita di ulteriori approfondimenti che rafforzino tali osservazioni.

2005 - Selenium for preventing cancer (Protocol). Cochrane Database Syst Rev [Articolo su rivista]
Dennert, G; Zwahlen, M; Brinkman, M; Vinceti, Marco; Zeegers, Mp; Horneber, Ma
abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:(1) To assess the association between selenium and cancer incidence/mortality.(2) To draw conclusions and give recommendations for future research.

2005 - Studio caso-controllo sui rapporti tra neoplasia prostatica e elementi in traccia [Abstract in Rivista]
Bergomi, Margherita; Venturelli, Marianna; Serio, G; Bianchi, Giampaolo; Trerotoli, G; Sighinolfi, Maria Chiara; Malavolti, Marcella; Bonvicini, Francesca; Ferrari, Angela; Farinetti, Alberto; Vinceti, Marco; Castiglia, P; Sansebastiano, G; Vivoli, Gianfranco
abstract

OBIETTIVI: Abbiamo condotto uno studio multicentrico caso-controllo al fine di valutare il ruolo di alcuni elementi in traccia di interesse tossicologico e nutrizionale (cadmio, selenio, rame e zinco) ed altri fattori ambientali e comportamentali nell’eziopatogenesi della neoplasia prostatica. La valutazionedell’esposizione a tali elementi è stata effettuata misurandone le concentrazioni nelle unghie quali bioindicatori di esposizione a medio-lungo termine.METODI: Sia i casi che i controlli, appaiati per età, sono stati reclutati dalle unità operative di Bari e Modena presso le cliniche urologiche e quelle chirurgiche dei rispettivi policlinici universitari. La determinazione degli oligoelementi è stata effettuata, previo lavaggio e mineralizzazione delle unghie con HNO3 in forno amicroonde, mediante spettrofotometria di assorbimento atomico con atomizzazione in fornetto di grafite per cadmio, selenio e rame, e in fiamma per lo zinco. RISULTATI:Nella popolazione complessiva presa in esame, abbiamo osservato livelli medi più elevati sia di cadmio che di rame nei 45 casi rispetto ai 68 controlli, mentre non abbiamo riscontrato particolari differenze per selenio e zinco. Le concentrazionimedie nelle unghie dei casi e dei controlli sono risultate rispettivamente per il cadmio pari a 0,108 e 0,068μg/g e per il rame pari a 5,07 e 3,78μg/g, mentre per lo zinco abbiamo riscontrato una media di 119.06μg/g per i casi e 111.04μg/g neicontrolli. Abbiamo successivamente effettuato il calcolo dell’OR quale stima del rischio relativo, utilizzando le concentrazioni quali variabili continue (ptrend) nonché dicotomiche (con cut-off pari alla mediana nei controlli). Nella popolazione complessiva presa in esame, l’OR è risultato pari a 2.57 (p=0.026) per il cadmio, OR=1.31 (0.548) per il selenio, OR=1.3 (p=0.529) per ilrame ed infine OR=1.81 (p=0.161) per lo zinco. L’analisi sui valori continui ha inoltre suggerito una possibile relazione tra esposizione a rame e rischio di neoplasia prostatica.L’analisi dei dati disaggregati sotto il profilo geografico ha fattoemergere rilevanti differenze soprattutto per quanto riguardo il cadmio. I pazienti di Bari hanno infatti evidenziato concentrazioni medie pari a 0.168 μg/g contro i 0.045 μg/g dei controlli, mentre per i soggetti dell’unità modenese abbiamo osservato rispettivamente 0.042 e 0.08μg/g. Il selenio ha invece evidenziatoconcentrazioni medie pari a 0.466μg/g nei casi e 0.468μg/g nei controlli a Modena, mentre i corrispondenti valori per la popolazione barese sono risultati pari a 0.627μg/g e 0.583μg/g. Le concentrazioni di rame nella popolazione baresesono risultate, rispettivamente nei casi e nei controlli, pari a 4.72 e 4.08μg/g, mentre per i soggetti modenesi abbiamo riscontrato 5.43 e 3.66μg/g. Infine le concentrazioni di zinco riscontrate nei pazienti affetti da neoplasia prostatica sono risultate pari a 116.98μg/g nei pazienti di Bari e 115.67μg/g nei relativi controlli,con corrispondenti valori nella casistica modenese pari a 121.14μg/g e108.83μg/g. Per quanto riguarda i rischi relativi di neoplasia, gli unici incrementi di un certo rilievo sono relativi alla casistica di Bari in associazione all’esposizione a cadmio (p-trend 0.054) e nella popolazione di Modena in associazione all’esposizione a rame (p-trend 0.096) e zinco (p-trend 0.092).CONCLUSIONI:I nostri risultati, considerando le limitate dimensioni del campione, sembrano supportare l’ipotesi, già avanzata da altri Autori, che l’ esposizione a cadmio può esercitare un ruolo nell’eziopatogenesi della neoplasia prostatica, mentre non sonoemerse indicazioni che suggeriscano un coinvolgimento del selenio. Per quello che riguarda il rame e lo zinco è necessario approfondire i dati attraverso un ampliamento del campione.

2005 - Studio pilota sui correlati biochimici e psicologici dei comportamenti alla guida. [Abstract in Atti di Convegno]
Bergomi, Margherita; Bussetti, Pamela; Rovesti, Sergio; Cacciari, Cristina; Vivoli, Roberto; Ferrari, A; Vinceti, Marco; Vivoli, Gianfranco
abstract

Studio pilota sui correlati biochimici e psicologici dei comportamenti alla guida.

2005 - Trace elements and melanoma [Articolo su rivista]
Bergomi, Margherita; Pellacani, Giovanni; Vinceti, Marco; S., Bassissi; Malagoli, Carlotta; D., Alber; S., Sieri; L., Vescovi; Seidenari, Stefania; R., Vivoli
abstract

Melanoma incidence has been steadily increasing in recent years in most western countries, thus suggesting a role of environmental risk factors. Among these determinants, it has been hypothesized that some trace elements of nutritional and toxicological interest may be implicated in the etiology of the disease. We examined patients with newly diagnosed melanoma of the skin and population controls from the Modena province northern Italy. Clinical and dietary data were collected through questionnaires, and toenails were sampled for trace element determination. Levels of cadmium, chromium, lead, selenium, zinc, copper and iron in toenails were measured by inductively coupled plasma optical emission spectrometry and by neutron activation analysis. Data obtained from 58 cases and 58 controls indicated higher levels of copper and lower concentrations of iron in melanoma patients, whilst no other differences were seen for the remaining elements. Patterns of correlations of zinc and copper with the estimated intake of some dietary factors were different between cases and controls. Results of the present study suggest that abnormal intake or metabolism of copper and of iron might be implicated in the etiology of melanoma, whilst they do not indicate an involvement of exposure to cadmium, chromium, lead, selenium and zinc in this disease.

2004 - A retrospective cohort study of trihalomethane exposure through drinking water and cancer mortality in northern Italy [Articolo su rivista]
Vinceti, Marco; Fantuzzi, Guglielmina; L., Monici; M., Cassinadri; Predieri, Guerrino; Aggazzotti, Gabriella
abstract

A few epidemiologic studies have suggested that consumption of drinking water with high trihalomethane content increases the risk of cancer. We investigated the mortality of a cohort of 5144 residents in Guastalla, northern Italy, who were supplied tap water with high chloroform and trihalomethane content between 1965 and 1987. Using death rates of a nearby community as reference rates, the standardized mortality ratio from all cancers between 1987 and 1999 was slightly increased for both males (1.2, 95% confidence interval 1.1-1.4) and females (1.1, 95% confidence interval 1.0-1.3). This was mainly due to a higher mortality from stomach, liver, lung, prostate and bladder cancer in males and from stomach, pancreas, breast and ovarian cancer and lymphocytic leukaemia in females. We also noted excess mortality from melanoma in both males and females. Overall, our findings were consistent with an association between trihalomethane exposure and increased cancer risk at some sites. However, the point estimates were statistically imprecise, due to the limited number of deaths for some site-specific cancers. In addition, we were unable to rule out the possibility of confounding due to smoking and other life-style factors with regard to some of the excess rates.

2004 - Epidemiologia e metodologia epidemiologica - Epidemiologia: definizione e ambiti della disciplina. [Capitolo/Saggio]
Bergomi, Margherita; Vinceti, Marco
abstract

Principali misure utilizzate in epidemiologia, le misure di associazione e di impatto sulla popolazione, fonti di dati, tipi di studi epidemiologici, distorsioni negli studi, criteri di valutazione delle relazioni causali negli studi epidemiologici, principali software per la gestione dei dati.

2004 - Low back pain risk in nurses and its prevention [Articolo su rivista]
Martinelli, S.; Artioli, G.; Vinceti, Marco; Bergomi, Margherita; Bussolanti, N.; Camellini, R.; Celotti, P.; Capelli, P.; Roccato, L.; Gobba, Fabriziomaria
abstract

We present the results of a study on the prevalence of low back pain (LBP) in a group of hospital nursing personnel. In 180 subjects (89% women) a questionnaire on LBP was collected. The prevalence of LBP episodes during the last 12 months was 63,9%; no difference was observed according to the working area (medicine, surgery, emergency). The proportion of subjects with LBP tended to increase according to the previous duration of work, but not with age. The prevalence of LBP was significantly lower in nursing personnel working according the team nursing model, that is less repetitive, and involves less work load, compared to the functional nursing model. Furthermore, LBP prevalence was lower among nurses that received an adequate formation on the prevention of occupational LBP. The results of the study confirm the relevance of LBP in nursing personnel, but suggest also that an adequate preventive programme can significantly reduce the risk.

2004 - Protocollo di uno studio sulla associazione tra esposizione a policlorobifenili con l’alimentazione e insorgenza di tumore mammario. [Abstract in Rivista]
Sansebastiano, G; Zoni, R; Bigliardi, L; Veronesi, L; Castiglia, P; Bergomi, Margherita; Vinceti, Marco
abstract

Abbiamo disegnato il protocollo per la realizzazione di uno studio caso-controllo multicentrico per valutare l'associazione tra insorgenza di alcune patologie neoplastiche ed esposizione attraverso gli alimenti ai PCB.

2004 - Trace elements and melanoma. [Abstract in Atti di Convegno]
Bergomi, Margherita; Malagoli, Carlotta; Pellicani, G; Bassissi, S; Vinceti, Marco; Alder, D; Seidenari, Stefania; Vivoli, Gianfranco
abstract

Trace elements and melanoma.

2003 - Correspondence re: Duffield-Lillico et al., Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial. 11: 630-639, 2002. [Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; Bergomi, Margherita; Vivoli, Gianfranco
abstract

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2003 - Italian family with two independent mutations:3358T/A in BRCA1 and 8756delA in BRCA2 genes. [Articolo su rivista]
Cortesi, L.; Turchetti, D.; Bertoni, Carlo Maria; ZANOCCO MARANI, Tommaso; Silvestri, C.; Vinceti, Marco; Federico, Massimo; Silingardi, Vittorio; Ferrari, Sergio
abstract

Hereditary breast/ovarian cancer is a well-characterized clinical entity, largely attributed to the inheritance of BRCA1 or BRCA2 mutations. Among general population, the mutation's frequency of these genes is very low; therefore, the identification of two independent mutations in the same family is a rare event. This study reports the presence of two mutations, one in the BRCA1 and the second in the BRCA2 gene in an Italian Caucasian kindred. This family is composed of more than 250 individuals, spanning through five generations, among which endogamy was a common phenomenon. Considering the tumor spectrum, this family is characterized by a high incidence of different types of cancer. In our study, we considered only three out of seven family units for BRCA1 and BRCA2 analysis. In one of the family units, we found independent mutations of both BRCA genes. The BRCA1 mutation on exon 11 (3358TA) was identified originally in the index case and subsequently in 18 members of this family, whereas the same mutation was not detected in a related family member with male breast cancer. The male breast cancer patient led to the identification, through mutational analysis, of a new BRCA2 mutation (8756delA). This BRCA2 mutation was also found in the male breast cancer patient's daughter. The discovery of the BRCA2 mutation allowed us to alert the patient's daughter who, otherwise, could be falsely reassured since she had a negative BRCA1 test.

2003 - Risk of sporadic amyotrophic lateral sclerosis associated with seropositivity for herpesviruses and echovirus-7. [Articolo su rivista]
Cermelli, Claudio; Vinceti, Marco; Beretti, Francesca; Pietrini, V.; Nacci, G.; Pietrosemoli, P.; Bartoletti, A.; Guidetti, D.; Sola, P.; Bergomi, Margherita; Vivoli, Gianfranco; Portolani, Marinella
abstract

We examined the association between risk of sporadic amyotrophic lateral sclerosis (ALS) and seroprevalence of antibodies to echovirus-7 (echo-7) and herpesviruses 6, 7, and 8 through a population-based case-control study. We enrolled in a northern Italy area 20 newly diagnosed ALS cases and 20 referents. Risk of ALS was higher in subjects seropositive for echo-7 when we used the immunofluorescent assay, while little increase was noted with the neutralization test. Considering the different characteristics of these two serological assays, these results suggest an association between disease risk and infection with enterovirus (EV) family members (not specifically echo-7). ALS risk was slightly associated with seropositivity of human herpesvirus-6 (odds ratio: 3.2; p = 0.102) and more strongly with human herpesvirus-8 seropositivity (odds ratio: 8.4; p = 0.064), though these point estimates were statistically unstable due to the limited number of observed cases. The findings of this study warrant further investigation in larger studies of the possible etiologic role of EV or herpesvirus infection in sporadic ALS.

2003 - Toenail selenium as biomarker: reproducibility over a one-year period and factors influencing reproducibility [Relazione in Atti di Convegno]
V., Krogh; V., Pala; Vinceti, Marco; F., Berrino; A., Ganzi; A., Micheli; P., Muti; L., Vescovi; Ferrari, Angela; Fortini, Katia; S., Sieri; Vivoli, Gianfranco
abstract

We assessed the reproducibility of selenium levels in toenails, comparing concentrations in two sets of specimens collected about a year apart, from 80 women (40 pre-menopausal and 40 post-menopausal) in the period October 1990 to February 1992. The women were participants in a prospective study on hormones and diet in relation to prediagnostic breast cancer (the ORDET study) conducted in northern Italy. Toenail selenium was determined by electrothermal atomic absorption spectrometry. The data were log-transformed as they were not normally distributed. To assess reproducibility Pearson correlation coefficients (r) for the two selenium determinations were calculated in pre- and post-menopausal women, according to smoking status and acetone treatment. A weighted kappa statistic (k) assessed inter-quintile agreement between the two sets of measures. Toenail selenium levels were highly reproducible (r = 0.57, p < 0.001), especially in pre-menopausal women (r = 0.66, p <0.001). Smoking lowered selenium levels (mean difference of 0.24 microg/g, p < 0.05 between smokers and non smokers) but did not significantly influence reproducibility. Acetone treatment to remove nail polish did not modify selenium levels but affected inter-quintile agreement, with moderate agreement (k = 0.58, p < 0.001) when acetone was used at both or neither samplings; and fair non significant agreement (k = 0.39, p = 0.06) when acetone was used at one sampling but not the other. As selenium levels in toenails are highly reproducible, notwithstanding variation in selenium levels in food and long-term changes in individuals' food choices, toenail selenium may be a useful biomarker of selenium exposure, particularly since toenail samples provide a measure of long-term exposure. However age, smoking status and acetone treatment are possible causes of misclassification.

2002 - Changes in breast cancer incidence and stage distribution in Modena, Italy: the effect of mammographic screening program. [Articolo su rivista]
D., Turchetti; L., Mangone; R., Negri; G., Rossi; L., Cortesi; Vinceti, Marco; Maiorana, Antonino; E., Gallo; Federico, Massimo
abstract

Objective: Assessing changes in breast cancer (BC) incidence and stage distribution in the District of Modena, Italy, during the period 1992-1998, and their relationship to a mammographic screening program launched in 1995. Methods: Demographic, clinical, and pathological data of all BC cases reported to the population-based Modena Cancer Registry between 1992 and 1998 were collected and linked to the screening database. Results: A total of 3429 women were diagnosed with BC in the District of Modena between 1992 and 1998. In this period the incidence rate increased by 15.7% (from 134.3 in 1992 to 155.4 per 100,000 in 1998). The increase began in 1995 and exclusively included women aged 50-69; the incidence rose by 30.4%. Moreover, the rise was confined to early tumors, with more than half (54%) of all cases reported in 1998 diagnosed as stage 0 or I disease, compared with 42% in 1992. Screen-detected tumors were significantly smaller (13.2 mm) than other tumors diagnosed in women aged 50-69 (18.5 mm), with 46% of screen-detected tumors smaller than 10 mm. Overall, a decline in the average tumor diameter was shown (from 20.2 mm in 1992-1994 to 18 mm in 1996-1998). Conclusions: Our data confirm that mammographic screening leads to an increase in the incidence of early-stage BC cancers.

2002 - Environmental exposure to trace elements and risk of amyotrophic lateral sclerosis: A population-based case-control study [Articolo su rivista]
Bergomi, Margherita; Vinceti, Marco; Nacci, G.; Pietrini, V.; Bratter, P.; Alber, D.; Ferrari, Adriano; Vescovi, L.; Guidetti, D.; Sola, P.; Malagù, S.; Aramini, C.; Vivoli, Gianfranco
abstract

We analyzed the association between the environmental exposure to trace elements and the risk of sporadic amyotrophic lateral sclerosis (ALS) in a population-based case-control study in the Emilia-Romagna region in northern Italy. We evaluated exposure to selected trace elements by measuring toenail concentrations of the same by means of inductively coupled plasma optical spectrometry and instrumental neutron activation analysis. The final number enrolled in the study was 22 patients and 40 controls. Disease progression, assessed through a clinical score, was generally unassociated with toenail trace element levels, with the exception of an inverse relation with zinc and selenium content and a direct correlation with copper concentration. In logistic regression analysis, we found no evidence of an association between ALS risk and toenail content of cadmium, lead, copper, zinc, manganese, selenium, chromium, cobalt, iron, and aluminum. This investigation does not suggest a major role in sporadic ALS etiology of environmental exposure to these trace elements, though results for zinc, selenium, and copper should be evaluated with caution due to the potentiallimitations of toenails as biomarkers of chronic exposure in patients.

2002 - Erythrocyte zinc, copper, and copper/zinc superoxide dismutase and risk of sporadic amyotrophic lateral sclerosis: a population-based case-control study. [Articolo su rivista]
Vinceti, Marco; Bergomi, Margherita; Nacci, G.; Pietrini, V.; Ferrari, Adriano; Fortini, K; Guidetti, D.; Sola, P.; Rocchi, Emilio; Mancia, D.; Vivoli, Gianfranco
abstract

We investigated through a population-based case-control study the hypothesis that disturbances in the chemistry of copper and zinc and in activity of the antioxidant enzyme copper/zinc superoxide-dismutase (SOD1) are involved in the etiopathogenesis of sporadic amyotrophic lateral sclerosis (ALS). We recruited 20 patients with sporadic ALS and 22 population controls from three northern Italian provinces, and we analyzed zinc and copper content and SOD1 activity in erythrocytes. These variables were unrelated to disease progression as evaluated through a disability score; zinc concentrations inversely correlated with copper in referents but not in patients. SOD1 activity was lower and erythrocyte zinc and copper levels were slightly higher in patients than in referents. Comparing the second to the bottom tertile of erythrocyte SOD1 activity, relative risk of ALS was 0.4 (95% confidence interval 0.1-2.0); the risk further decreased to 0.1 (95% confidence interval 0-0.9) for comparison of highest to lowest tertile (P for trend 0.027). Copper and zinc levels were not associated with disease risk. Our findings indicate that a lower SOD1 activity is associated with ALS, but we cannot be sure whether this association is a marker of causal action or is secondary to a confounder, or to disease onset itself.

2002 - Is duplex ultrasonography useful for the diagnosis of giant-cell arteritis? [Articolo su rivista]
Salvarani, Carlo; M., Silingardi; A., Ghirarduzzi; G., Lo Scocco; P., Macchioni; G., Bajocchi; Vinceti, Marco; F., Cantini; I., Iori; L., Boiardi
abstract

Background: Evidence of a dark halo on ultrasonography has been considered a specific sign of giant-cell arteritis and may replace temporal artery biopsy for the diagnosis of giant-cell arteritis in patients with typical clinical manifestations. Objective: To assess the usefulness of temporal artery duplex Ultrasonography and to compare this mode of ultrasonography with physical examination of temporal arteries for the diagnosis of giant-cell arteritis in patients with suspected giant-cell arteritis or polymyalgia rheumatica. Design: Diagnostic test study. Setting: Several divisions of Reggio Emilia Hospital, Reggio Emilia, Italy. Patients: 86 consecutive patients with a suspected diagnosis of giant-cell arteritis or polymyalgia rheumatica identified over a 22-month period. Measurements: The temporal arteries were examined in all 86 patients. Duplex ultrasonography of the temporal arteries was then performed by two ultrasonographers who were unaware of the clinical diagnosis. Before corticosteroid therapy was started; temporal artery biopsies were performed in all patients at the site targeted by the ultrasonographer. Results: A hypoechoic halo around the lumen of the temporal arteries had a sensitivity of only 40% (95% Cl, 16% to 68%) and a specificity of 79% (Cl, 68% to 88%) for the diagnosis of biopsy-proven giant-cell arteritis. The negative likelihood ratio was 0.8 (Cl, 0.5 to 1.2), and the positive likelihood ratio was 1.9 (Cl, 0.9 to 4.1). When the thickness of the halo was at least 1 mm, specificity increased to 93% (Cl, 84% to 98%) and the positive likelihood ratio increased to 5.7 (Cl, 2.0 to 16.2); however, sensitivity remained low at 40% (Cl, 16% to 68%). On physical examination, temporal artery abnormalities had a higher sensitivity of 67% (Cl, 38% to 88%), a higher specificity of 99% (Cl, 92% to 100%), and a higher positive likelihood ratio of 47.3 (Cl, 6.5 to 342.4) than did ultrasonographic findings. None of the patients with giant-cell arteritis had a normal temporal artery inspection and a hypoechoic halo on ultrasonography. Conclusion: Evidence on ultrasonography of a halo around temporal arteries, either any halo or a halo 1 mm or greater in thickness, only modestly increased the probability of biopsy-proven giant-cell arteritis but did not improve the diagnostic accuracy of a careful physical examination.

2002 - Risk of second cancer in patients with hairy cell leukemia: Long-term follow-up [Articolo su rivista]
Federico, Massimo; Pl, Zinzani; A., Frassoldati; Vinceti, Marco; A., Mode; L., Annino; T., Chisesi; G., Pagnucco; R., Invernizzi; M., Spriano; L., Resegotti; M., Bendandi; Ee, Damasio
abstract

Purpose : The purpose of the present study was to assess the risk of second cancers in patients with hairy cell leukemia (HCL). Patients and Methods: We investigated the incidence of additional cancers in those patients registered in the nationwide registry of the Italian Cooperative Group for the Study of HCL, asking the cooperating centers for additional information on initial and subsequent therapies and on time and type of second malignancies, if they developed. Here we report the final results of this survey, consisting of 54 cases of second malignancies (excluding nine cases of epithelial skin cancer) which developed in 54 patients of 1,022 with adequate follow-up. Results: The cumulative risk of development of a second cancer was 5%, 10%, and 14% at 5, 10, and 15 years, respectively. The incidence of second malignancies was not significantly higher than the expected rate (standardized incidence ratio [SIR], 1.01; 95% confidence interval [CI], 0.74 to 1.33; P = 1.0). However, the SIR of non-Hodgkin´s lymphoma in the entire cohort was 5.3 (95% Cl, 1.9 to 11.5). Second malignancies occurred in eight (4.7%) of 386 patients who never received interferon (IFN), nine (5.9%) of 495 patients treated with IFN at the time of diagnosis, and seven (6.9%) of 102 patients who received IFN as second-line therapy. These differences were not statistically significant. Analysis of the separate calendar periods did not reveal any particular trends with respect to variations in SIR. Conclusion: The present study does not support the suspicion that patients with HCL are at increased risk of additional second malignancies, although the incidence of lymphoid neoplasms was significantly higher than expected. In addition, our data indicate that IFN therapy did not exert an oncogenic effect in such patients.

2002 - Selenite inhibition of Coxsackie virus B5 replication: implications on the etiology of Keshan disease. [Articolo su rivista]
Cermelli, Claudio; Vinceti, Marco; Scaltriti, E.; Bazzani, E.; Beretti, Francesca; Vivoli, Gianfranco; Portolani, Marinella
abstract

Keshan disease is a cardiomyopathy of unknown origin reported in some areas of China. Because of epidemiologic features, this disease was ascribed to an infectious agent, likely a Coxsackie virus, but it has also been thought to depend on selenium deficiency, mainly because selenite is effective in its prophylaxis. We examined the hypothesis that pharmacological activity of selenite on Coxsackie virus growth was associated with prevention of Keshan disease. We studied the antiviral effects of three selenium compounds on Coxsackie virus B5 replication: five μM selenite reduced viral replication, whilst 10 μM selenate and selenomethionine did not exhibit any antiviral activity. The inhibitory activity of selenite on viral replication was due to its toxicity following its interaction with thiols, as that activity could be blocked by dithiothreitol, a sulfhydryl-protecting agent known to reverse several toxic effect of selenite. Zinc, another inhibitor of selenite toxicity, also counteracted the antiviral effect of selenite. The selenium compounds showed only limited activity against herpes simplex 1 virus and IHD strain of vaccinia virus. A direct inhibitory effect of selenite on Coxsackie virus replication might explain the efficacy demonstrated by this compound in the prophylaxis of Keshan disease.

2001 - Adverse health effects of selenium in humans [Articolo su rivista]
Vinceti, Marco; Et, Wei; Malagoli, Carlotta; Bergomi, Margherita; Vivoli, Gianfranco
abstract

Epidemiologic studies and case reports have shown that chronic exposure to selenium compounds is associated with several adverse health effects in humans. An early toxic effect of selenium is on endocrine function, particularly on the synthesis of thyroid hormones following dietary exposure of around 300 micrograms Se/d, and on the metabolism of growth hormone and insulin-like growth factor-1. Other adverse effects of selenium exposure can be the impairment of natural killer cells activity and at higher levels, hepatotoxicity and gastrointestinal disturbances. Dermatologic effects, such as nail and hair loss and dermatitis, occur after exposure to high levels of environmental selenium. Assessing the toxicity and morbidity after long-term exposure to environmental selenium is difficult: neurotoxicity, particularly the degeneration of motor neurons leading to increased risk of amyotrophic lateral sclerosis, might occur after chronic exposure to both organic and inorganic selenium compounds. The results of laboratory investigations and cohort studies suggest that selenium species exhibit a bivalent effect in cancer, either increasing or decreasing risk. Current environmental selenium exposure limits appear to be inadequate for averting adverse health effects.PMID: 12041880 [PubMed - indexed for MEDLINE]

2001 - Effetti teratogeni dell'esposizione ambientale a piombo: uno studio caso-controllo di popolazione. [Articolo su rivista]
Vinceti, Marco; Rovesti, Sergio; Calzolari, E.; Vivoli, R.; Astolfi, G.; Bergomi, Margherita
abstract

Al fine di valutare l'associazione tra rischio di malforma¬zioni congenite ed esposizione materna a piombo, abbiamo calcolato il rischio relativo (RR) di malformazioni del siste¬ma cardiovascolare e di labiopalatoschisi associato alla resi¬denza matema nel Distretto Ceramico, un'area delle provin¬ce di Modena e Reggio Emilia. Tale area è stata caratterizza¬ta sino al termine degli anni '80 da una severa contaminazio¬ne ambientale da piombo, dovuta all'elevato numero di sta¬bilimenti ceramici in essa localizzato. Il rischio di malfor¬mazioni cardiovascolari associato alla residenza materna nel Distretto Ceramico è risultato pari a 2,7 nel periodo 1982-88 (intervallo di confidenza (IC) al 95% 1,6-4,5), mentre nel periodo successivo 1989-96, caratterizzato da livelli di con¬taminazione ambientale da piombo sensibilmente minori, il RR si è ridotto a 0,9 (IC 95% 0,5-1,5). L'eccesso di rischio associato alla residenza matema nel Distretto Ceramico è risultato evidente anche limitando l'analisi ai nati da madre casalinga e da padre non professionalmente esposto a piom¬bo. Abbiamo inoltre riscontrato un moderato eccesso di ri¬schio di labiopalatoschisi nei figli di madri residenti nel Di¬stretto Ceramica, ma le stime ad esso relative sono risultate caratterizzate da un notevole instabilità statistica e non han¬no evidenziato una chiara tendenza al decremento nel tem¬po. I figli di madri residenti nel Distretto Ceramico occupate quali operaie nel settore industriale hanno evidenziato un incremento del rischio di malformazioni del sistema cardiovascolare (RR 2,9, IC 95% 1,3-6,8) e, con minore evi¬denza, di labiopalatoschisi (RR 1,6, rc 95% 0,4-5,6).

2001 - Risk of birth defects in a population exposed to environmental lead pollution [Articolo su rivista]
Vinceti, Marco; Rovesti, Sergio; Bergomi, Margherita; E., Calzolari; S., Candela; A., Campagna; M., Milan; Vivoli, Gianfranco
abstract

To investigate the relation between environmental lead and risk of birth defects in humans, we examined the prevalence at birth of congenital anomalies in an industrial area of northern Italy heavily polluted with lead. Through a population-based registry of birth defects, we identified anomalies diagnosed during three consecutive periods characterized by decreasing environmental lead exposure, 1982-1986, 1987-1990 and 1991-1995. In the lead-polluted area, we observed an excess risk of cardiovascular defects which decreased from 2.59 [95% confidence interval (CI) 1.68-3.82] in the first period to 1.18 (95% CI 0.62-2.06) and 0.97 (95% CI 0.57-1.54) in the subsequent periods. We also found an excess risk of oral clefts and musculoskeletal anomalies, with decreasing trends over time. We could not identify homogeneous patterns of temporal variation for other congenital anomalies, neither did we detect cases of neural tube defects. These results appear to support an association between severe parental lead exposure and specific birth defects.

2000 - Comparison between genotype and phenotype identifies a high-risk population carryingBRCA1 mutations [Articolo su rivista]
Laura, Cortesi; Daniela, Turchetti; Chiara, Bertoni; Roberta, Bellei; Lucia, Mangone; Vinceti, Marco; Federico, Massimo; Vittorio, Silingardi; Ferrari, Sergio
abstract

Hereditary breast carcinomas constitute about 10% of all malignant mammary tumors, but the selection criteria to identify a high-risk population carrying BRCAI mutations are not yet well-defined. We have collected $1 pedigrees of familial breast cancer, 16 pedigrees of familial breast and ovarian cancer, and 30 cases of early-onset breast cancer (<35 years of age) without any family history of breast cancer. The index cases of the 97 selected families were further subdivided into three groups based on histopathological parameters: group A (n = 19) was characterized by tumor grade III, negative estrogen and progesterone receptors, and high proliferative rate; group B (n = 20) was characterized by grade I-II tumors, positive hormonal receptors, and low proliferative rate; and group C (n = 58) was not homogeneous for the histopathological criteria. The aim of our study was to evaluate, in patients with a family history of breast cancer or with early diagnosis of breast cancer, the incidence of BRCAI mutation on the basis of tumor phenotype. We found the highest rate of BRCAI mutations in group A (53%), and low frequencies in groups B (5%) and C (0%). Our data strongly indicate that an aggressive tumor phenotype in patients with a positive family history or early diagnosis identifies a population with high probability of carrying BRCAI mutations.

2000 - I flussi informativi del servizio sanitario nello studio dell’incidenza delle malattie linfoproliferative in una popolazione italiana [Articolo su rivista]
N., Borciani; Vinceti, Marco; P., Avanzini; F., Ilariucci; L., Mangone; M., Martini; M., Merlin; A., Ferretti; M., Frassineti; R., Rodolfi; Bergomi, Margherita
abstract

We tested the usefulness of the National Health Service Databases for investigating the incidence of lymphoid malignancies in an Italian community. We analyzed hospital discharge data, drug prescription, pathologic records and death certificates to identify the new cases of Hodgkin's disease, non Hodgkin's lymphoma, multiple myeloma, and acute and chronic lymphocytic leukemia diagnosed in the municipal population of Reggio Emilia, northern Italy, 1991 through 1996. The completeness of Hospital discharge data was very high, and several incident cases could be identified only through this source. Completeness of the pathologic registry was satisfactory for Hodgkin's disease and non-Hodgkin's lymphoma, and this source independently yielded a few incident cases of lymphoid neoplasms. Analysis of death certificates and drug prescriptions appears to be of limited value in the epidemiology of lymphoproliferative diseases.

2000 - Mortality in a population with long-term exposure to inorganic selenium via drinking water [Articolo su rivista]
Vinceti, Marco; G., Nacci; Rocchi, Emilio; T., Cassinadri; R., Vivoli; C., Marchesi; Bergomi, Margherita
abstract

We analyzed the 1986-1997 mortality in a cohort of 2065 residents of an Italian municipality which had been exposed to drinking water with a high content of inorganic selenium over a long period of time, and compared it with mortality in the remainder of the municipal population. Mortality from malignant neoplasms increased [standardized mortality ratio (SMR) 1.17, 95% confidence interval (CI) 0.96-1.42], mainly due to an excess mortality from melanoma and colorectal cancer in both sexes, kidney cancer in men, and lymphoid malignancies in women. Overall cardiovascular mortality changed little (SMR 1.05, 95% CI 0.89-1.23), despite the higher cerebrovascular mortality (SMR 1.43, 95% CI 1.03-1.93). Coronary disease mortality slightly decreased (SMR 0.87,95% CI 0.63-1.16), due to a low mortality among women. We also noted an excess mortality from Parkinson's disease in men and from motor neuron disease in women. Evaluation of these findings is, however, hampered by the lack of information about potential lifestyle confounders, the fact that the exposure could only be characterized by a simple dichotomization, and the inconsistencies of most estimates between the two sexes. (C) 2000 Elsevier Science Inc. All rights reserved.

2000 - Reproductive outcomes in a population exposed long-term to inorganic selenium via drinking water [Articolo su rivista]
Vinceti, Marco; Ci, Cann; E., Calzolari; R., Vivoli; L., Garavelli; Bergomi, Margherita
abstract

Despite being an essential element in mammals and lower animals at very low doses, selenium is recognized as a teratogen and a growth-inhibiting substance in several animal species. Some inorganic selenium compounds have also been shown to be mutagenic and pro-oxidant: however, very little is known about their effects on human reproduction. Between 1972 and 1988, a few thousand residents in the municipality of Reggio Emilia, northern Italy, were accidentally exposed to drinking water with unusually high levels of inorganic selenium (selenate), range 7-9 mu g/l, through a local public water supply system. We found no deleterious effect on overall body weight and length of newborns and stillborns delivered by 18 women previously exposed to high-selenium tapwater, Rates of spontaneous abortions, however, were increased slightly (RR = 1.73; 95% CI = 0.62-4.80), compared with rates among unexposed women from the same municipality. From 1980 through 1988 the prevalence of congenital malformations at birth among the exposed population was similar to that expected, but estimates were imprecise owing to small numbers. Results do not suggest marked effects on human reproduction from chronic exposure to selenate in drinking water at < 10 mu g/l. (C) 2000 Elsevier Science B.V. All rights reserved.

2000 - The epidemiology of selenium and human cancer [Articolo su rivista]
Vinceti, Marco; Rovesti, Sergio; Bergomi, Margherita; Vivoli, Gianfranco
abstract

The relation between the trace element selenium and the etiology of cancer in humans remains elusive and intriguing, despite the number of epidemiologic studies published on the topic. We address some methodologic issues, such as misclassification of exposure, particularly to single selenium compounds, effect modification, confounding, and other sources of bias, which may explain the inconsistencies in the literature. We also review the results of cohort studies, which have yielded either inverse or null or direct associations between selenium exposure and subsequent cancer risk. To date, no beneficial effect on cancer incidence at major sites, including prostate cancer, has emerged from the Finnish program begun in 1984 to increase the average selenium intake in its population. Populations exposed to unusually high or low levels of environmental selenium might offer unique opportunities to investigate if selenium exposure is related to the etiology of human cancer.

1999 - Rising melanoma incidence in an Italian community from 1986 to 1997 [Articolo su rivista]
Vinceti, Marco; Bergomi, Margherita; N., Borciani; L., Serra; Vivoli, Gianfranco
abstract

We examined the incidence of primary invasive melanoma in the municipality of Reggio Emilia, northern Italy, in the period from 1986 to 1997. We identified 169 cases, five of which were intraocular. After adjustment for confounders, the risk of having a thick melanoma (Breslow greater than or equal to 1 mm) did not decrease over time, except in older females. The age-standardized incidence of cutaneous melanoma during the entire study period was 7.57 in males and 11 in females; from 1986-1991 to 1992-1997, it rose from 5.04 to 10.04 cases/100,000 person-years in males and from 8.96 to 13.09 cases/100,000 person-years in females. In males, the increase in incidence was almost entirely confined to subjects aged 30 or more, suggesting a possible cohort effect. We noted rising age-standardized incidences over time both in males with thin tumours (Breslow < 1 mm) (from 2.05 to 4.38 cases/100,000 person-years) and thick tumours (from 2.73 to 5.51 cases/100,000 person-years), while in females the increase was limited to thin melanomas (from 3.14 to 6.93 cases/100,000 person-years), mainly due to an increase in the older age groups (50-69 years and greater than or equal to 70 years). The increase in thick melanomas among males and the expected cohort effects suggests antecedent exposure to environmental risk factors.

1998 - Commentary re: M. Vinceti et al., Excess melanoma incidence in a cohort exposed to high levels of environmental selenium. Cancer Epidemiol. Biomark. Prev., 7 : 853-856, 1998 [Articolo su rivista]
Vinceti, Marco; Kj, Rothman; Bergomi, Margherita; N., Borciani; L., Serra; Vivoli, Gianfranco
abstract

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1998 - Excess melanoma incidence in a cohort exposed to high levels of environmental selenium [Articolo su rivista]
Vinceti, Marco; Kj, Rothman; Bergomi, Margherita; N., Borciani; L., Serra; Vivoli, Gianfranco
abstract

Epidemiological studies on the relation between selenium and human cancer have yielded strongly conflicting results. Prompted by the observation of a positive association between selenium intake and site-specific cancers, including melanoma, in a large cohort of nurses, we studied the 11-year melanoma incidence in an Italian cohort that consumed unusually high levels of inorganic selenium in tap water from 1975 to 1985, The setting was Reggio Emilia, an Italian municipality that provided a natural experiment relating to intake of high levels of inorganic selenium, We identified 2,065 individuals with high selenium exposure, who contributed a total of 20,179 person-years of follow-up, and we compared their experience with the 1,384,386 person-years of follow-up in the remaining population of Reggio Emilia, We included all cases of pathologically confirmed malignant melanoma, including intraocular melanoma, identified from the Reggio Emilia Hospital, the Bologna regional registry of hospital discharges, and the Milan National Cancer Institute. Eight cases of malignant melanoma occurred in the exposed cohort during the follow-up. Melanoma incidence was 3.9 times greater in the exposed than in the unexposed cohort (95% exact confidence limits, 1.8-7.4).

1998 - Fattori di rischio occupazionali di sclerosi laterale amiotrofica in una comunità italiana [Articolo su rivista]
Bergomi, Margherita; Vinceti, Marco; Vivoli, R; Guidetti, D; Vivoli, Gianfranco
abstract

Alcuni studi epidemiologici hanno suggerito come il rischio di contrarre la sclerosi laterale amiotrofica (SLA) sia più elevato nei lavoratori nel settore agricolo, nell'industria ed a seguito di esposizioni prolungate a campi elettromagnetici, anche se non mancano risultati contrastanti. Nell'ambito di uno studio caso-controllo che ha preso in esame 16 pazienti affetti da SLA sporadica e 39 controlli di popolazione residenti nella provincia di Reggio Emilia, abbiamo osservato un maggiore rischio di SLA associato all'occupazione a lungo termine in agricoltura (odds ratio 4,2, intervallo di confidenza al 95% 1,3-16,3), mentre meno convincente è il rischio collegabile all'esposizione pregressa a tossici industriali ed a campi elettromagnetici. Pur tenendo conto della ridotta precisione dei rischi relativi, dovuta alle dimensioni limitate del campione esaminato, questi risultati sembrano confermare una associazione tra esposizioni occupazionali e SLA.

1997 - Epidemiology of amyotrophic lateral sclerosis in Italy, 1988-1993. [Abstract in Rivista]
Bergomi, Margherita; Vinceti, Marco; Rovesti, Sergio; R., Vivoli; N., Borciani; Vivoli, Gianfranco
abstract

Epidemiology of amyotrophic lateral sclerosis in Italy, 1988-1993.

1997 - Lead, cadmium, and selenium in blood of patients with sporadic amyotrophic lateral sclerosis. [Articolo su rivista]
Vinceti, Marco; D., Guidetti; Bergomi, Margherita; E., Caselgrandi; R., Vivoli; M., Olmi; L., Rinaldi; Rovesti, Sergio; F., Solime
abstract

We determined whole blood lead and cadmium levels, and serum selenium levels in patients with sporadic amyotrophic lateral sclerosis and age- and sex-matched controls. Disability due to the disease directly correlated with lead levels, and there was a strong inverse correlation with selenium concentrations. Lead and selenium concentrations tended to be similar in the cases and controls, bath in the study population as a whole and after the removal from the analysis of the patients with the highest degree of disability. In the patients with limited disability, cadmium concentrations were higher than in the controls. Our findings lend limited support to a possible involvement of cadmium, but not lead, in the etiology of sporadic amyotrophic lateral sclerosis, and strongly suggest that short-term indicators of exposure are inadequate to investigate the relationship between selenium and the disease.

1997 - Selenium and lymphoid malignancies (Reply) [Articolo su rivista]
Avanzini, P; Vinceti, M; Ilariucci, F
abstract

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1997 - Zinc and copper status and blood pressure [Articolo su rivista]
Bergomi, Margherita; Rovesti, Sergio; Vinceti, Marco; E., Caselgrandi; Vivoli, Gianfranco
abstract

In order to elucidate the relationships between Zn and Cu and blood pressure, the present case-control study was carried out. Zn and Cu status was evaluated in 60 subjects, pharmacologically untreated, affected by mild stable hypertension and in 60 normotensives matched for sex, age and smoking habits. Different markers of Zn and Cu status, including serum, erythrocyte and urine levels of the two trace elements and activities of some Znor Cu-dependent enzymes (alkaline phosphatase, lactic dehydrogenase, superoxide dismutase and Iysyl oxidase) were evaluated. No significant difference between hypertensives and normotensives was observed in the mean levels of Zn and Cu as well as in Zn- or Cu-dependent enzymes, though higher levels of serum copper were associated with increased risk of hypertension. Interesting relationships between the biological parameters investigated were observed in the hypertensive subjects. Inverse correlations between blood pressures and serum Zn were observed. Furthermore, blood pressure was inversely related to lysyl oxidase activity. These findings give further support to the hypothesis that an imbalance of Zn and Cu bioavailability may be associated to hypertensive condition.

1996 - Amyotrophic lateral sclerosis after long-term exposure to drinking water with high selenium content [Articolo su rivista]
Vinceti, Marco; D., Guidetti; M., Pinotti; Rovesti, Sergio; M., Merlin; L., Vescovi; Bergomi, Margherita; Vivoli, Gianfranco
abstract

We examined 9 years' incidence of amyotrophic lateral sclerosis, a disease previously associated with a high-selenium environment, in a cohort of 5,182 residents of Reggio Emilia, Italy. This cohort had accidentally been exposed to drinking water with high selenium content. Four cases were diagnosed during the follow up. Using the remainder of the municipal population as the reference group, the standardized incidence ratio was 4.22 (95% confidence interval=1.15-10.80). The standardized incidence ratio was higher after limiting the analysis to the subcohort with the longest ascertainable exposure period. The findings appear to confirm a causal association between overexposure to environmental selenium and amyotrophic lateral sclerosis.

1996 - Epidemiological survey of amyotrophic lateral sclerosis in the province of Reggio Emilia, Italy: Influence of environmental exposure to lead [Articolo su rivista]
D., Guidetti; M., Bondavalli; R., Sabadini; N., Marcello; Vinceti, Marco; S., Cavalletti; A., Marbini; F., Gemignani; A., Colombo; Ferrari, Adriano; Vivoli, Gianfranco; F., Solime
abstract

We carried out a retrospective incidence, prevalence and mortality survey of amyotrophic lateral sclerosis (ALS) in the province of Reggio Emilia, northern Italy. Based on 79 patients, the mean incidence per year for the period 1980 through 1992 was 1.5 cases per 100,000, On December 31st, 1992, the prevalence rate was 5.4 per 100,000, In the 10-year period of 1983-1992 the average mortality rate was 1.3 per 100,000 per year. The average age at onset was 61.3 +/- 10.2, the average survival period thereafter was 26.3 months +/- 17.7; 27.3 +/- 17.6 for classic ALS, 19.5 +/- 8.4 for progressive bulbar palsy and 36.3 +/- 41.4 for pseudopolyneuritic ALS. The incidence rate, recorded in public health district No. 12, an area with documented lead pollution since the 1970s, was standardized to the sex and age of the population of the province. Its incidence and prevalence rate were comparable to the rates found in the remaining area of the province.

1995 - Cancer mortality in a residential cohort exposed to environmental selenium through drinking water. [Articolo su rivista]
Vinceti, Marco; Rovesti, Sergio; C., Gabrielli; C., Marchesi; Bergomi, Margherita; M., Martini; Vivoli, Gianfranco
abstract

Cancer mortality from 1986 to 1992 was examined in a cohort of 4419 individuals who had been residing in an area of the municipality of Reggio Emilia, northern Italy, where tap water with unusually high selenium content was accidentally supplied. Mortality for all cancers was not significantly different, both in males and in females, from that expected using death rates in the remaining municipal population as standard rates. No significant difference in mortality for site-specific cancers was observed in males, while in females a higher mortality for malignancies of the lymphatic-hematopoietic tissue overall considered and for non-Hodgkin's lymphoma was detected. Even if evaluation of the results is hampered by the low number of cancer deaths on which the analysis is based, findings of the study do not support the hypothesis of a strong inverse independent relationship between dietary intake of selenium and cancer mortality in humans.

1995 - Considerazioni sulle procedure per il calcolo degli anni-persona e del rapporto standardizzato di mortalità negli studi di coorte. [Articolo su rivista]
Vinceti, Marco; Vivoli, R; Tartoni, Pl; Tampieri, Auro
abstract

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1995 - Serum selenium concentrations in patients with newly diagnosed lymphoid malignancies [Articolo su rivista]
P., Avanzini; Vinceti, Marco; F., Ilariucci; L., Masini; M., Dinca; Vivoli, Gianfranco
abstract

Background. Increased mortality from lymphoid malignancies following exposure to environmental selenium has recently been reported, Moreover, conflicting results have been found in investigations examining the relationship between serum concentrations of selenium and some clinical features of malignant lymphoproliferative diseases. Methods, Serum concentrations of selenium were analyzed by atomic absorption spectrometry in fifty-nine patients with newly diagnosed chronic lymphoid malignancies and in forty control subjects. Results. Selenium concentrations were significantly lower in patients than in control subjects, However, when only patients with localized disease were compared to controls, no significant difference in serum selenium concentrations was observed. Clinical stage was inversely associated with selenium levels. High-grade non-Hodgkin's lymphoma was characterized by lower selenium levels than low-grade and intermediate-grade disease. Selenium levels were positively associated with albumin and hemoglobin, and inversely correlated with serum concentrations of beta 2-microglobulin and with erythrocyte sedimentation rate. Conclusions. The findings of this study do not suggest that a high selenium intake represents a risk factor for malignant lymphoproliferative diseases, but limitations of the investigation hamper evaluation of the results. The possible utility of determining serum concentrations of selenium in the clinical evaluation ofpatients with lymphoid malignancies merits examination in larger studies.

1994 - Changes in drinking water selenium and mortality for coronary disease in a residential cohort [Articolo su rivista]
Vinceti, Marco; Rovesti, Sergio; C., Marchesi; Bergomi, Margherita; Vivoli, Gianfranco
abstract

In a part of the municipal territory of Reggio Emilia, northern Italy, selenium in drinking water decreased from 7 mu g/L to less than 1 mu g/L. In a cohort of 4419 individuals, previously exposed for at least 5 yr to the drinking water with higher selenium content, the 7-yr temporal distribution of deaths for coronary disease and for stroke was analyzed to examine a possible relationship with changes in drinking water selenium. From January 1986 until August 1988, when tap water selenium was 7 mu g/L, deaths for coronary disease were one in males and two in females. After the decrease in drinking water selenium, 21 and 10 coronary deaths were observed, respectively, in males and in females from September 1988 to December 1992. No significant difference in the temporal distribution of stroke deaths was observed both in males and in females. Even if an effect of chance and aging in the temporal distribution of coronary deaths may not be excluded, findings of the study seem to be consistent with the hypothesis of a beneficial effect of selenium on coronary disease mortality.

1994 - Diet as a risk factor for abnormal glucose tolerance in subjects with and without family history of diabetes mellitus [Articolo su rivista]
Vinceti, Marco; Rovesti, Sergio; C., Pacchioni; G., Ropa; R., Roncaia; P., Benedetti; Bergomi, Margherita; Vivoli, Gianfranco
abstract

The relationship between diet and glucose tolerance was examined in 118 middle-aged subjects with normal glucose tolerance, impaired glucose tolerance and Type II diabetes mellitus. A significant relationship between body mass index and intake of protein and fat from animal source was observed in the whole study population and in subjects without family history of diabetes, but not in individuals with family history of the disease. An association between worsening of glucose tolerance and higher caloric intake was shown in males, but this appeared to be linked to the increased intake of animal fat and animal protein of these subjects. Adjusting for obesity and total intake of energy, no significant difference in intake of nutrients was detected in males, while in females a lower intake of refined carbohydrate, fibre and potassium was observed in diabetic subjects after adjustment for body mass index. In males without family history of diabetes, after adjustment for obesity and total energy intake a significant association between abnormal glucose tolerance and lower intake of plant protein as well as higher intake of protein from animal source was detected, while total and complex carbohydrate intake was lower in subjects with impaired glucose tolerance than in the two other diagnostic groups. In females without heredity of diabetes, a significantly lower intake of energy, carbohydrates, fibre, plant protein, calcium and potassium was detected in the diabetic group after adjustment for obesity. No significant difference in nutrient intake was observed in subjects with family history of diabetes. Even if evaluation of results is hampered by the limited number of subjects examined, findings of the study support in middle aged subjects an association between vegetarian diet and normal glucose tolerance, suggesting that this relationship might be enhanced in individuals without family history of diabetes.

1992 - Hypertension in newly diagnosed non-insulin-dependent diabetic subjects [Articolo su rivista]
Bergomi, Margherita; Vinceti, Marco; Rovesti, Sergio; P., Benedetti; C., Pacchioni; M., Beneduce; Vivoli, Gianfranco
abstract

Medical records of newly diagnosed non-insulin-dependent diabetic patients attending a Diabetic Centre in Modena, northern Italy, during the period 1985-88 were reviewed to analyze the prevalence of hypertension at age of diagnosis of diabetes and its association with selected risk factors. The prevalence of hypertension was also determined in a representative sample of control subjects. In the multivariate analysis, greater body mass index and older age, but not smoking, were strongly associated with increased rates of hypertension both in control and in diabetic subjects. In diabetic patients, family history of diabetes, defined as presence of diabetes in close relatives, was not significantly associated with hypertension, while rates of hypertension were significantly lower in patients who reported at least one parent affected by diabetes. After adjustment for age and body mass index, newly diagnosed non-insulin-dependent diabetes was not an independent risk factor for hypertension. These findings seem to be consistent with the hypothesis that diabetes and hypertension are not linked by a common genetic background.

1992 - Indagine epidemiologica sul ruolo di alcuni fattori di rischio del diabete non-insulino-dipendente [Articolo su rivista]
Bergomi, Margherita; Vinceti, Marco; Rovesti, Sergio; Lodi, G; Beneduce, M; Roncaia, R; Benedetti, P.
abstract

Il ruolo di alcuni fattori di rischio del diabete non-insulino-dipendente è stato indagato mediante l’analisi dei dati ricavati dalle cartelle cliniche dei pazienti affetti da diabete non-insulino-dipendente di nuova diagnosi e l’esame di una popolazione di controllo. L’obesità e l’età sono risultati significativi fattori di rischio di tale patologia. La familiarità diabetica, significativamente associata al diabete nell’indagine multivariata, sembra interagire in modo sinergico con il grado di sovrappeso nel favorire l’insorgenza della malattia. L’appartenenza al sesso maschile rappresenta un fattore di rischio per il diabete, ma tale incremento di rischio non è documentabile nei gruppi caratterizzati da un livello più elevato di obesità. Le abitudini tabagiche e, limitatamente al sesso maschile, l’ipertensione non sono risultate associate in modo indipendente all’insorgenza del diabete non-insulino-dipendente.

1992 - Relazioni tra acido urico e alcuni fattori di rischio cardiovascolare. [Articolo su rivista]
Bergomi, Margherita; Rovesti, Sergio; Vinceti, Marco; Vivoli, Gianfranco
abstract

Il metabolismo dell’acido urico è influenzato da numerosi fattori via via identificati con il sesso, l’età, il peso corporeo, l’assunzione di alcol e di farmaci. Accertata la presenza di iperuricemia in associazione ad alcuni stati di malattia, rimanevano da indagare le possibili relazioni tra i livelli ematici di acido urico e quelli di altri parametri le cui modificazioni sono state documentate in patologie metaboliche e cardiovascolari di rilevante interesse sociale. Vengono qui presentati i risultati di una ricerca multicentrica italiana, che grazie a nove laboratori di analisi chimico-cliniche ha potuto raccogliere i dati relativi a 1596 soggetti di uricemia, creatininemia, glicemia, trigliceridemia, colesterolemia totale e frazionata, azotemia e insulinemia. Dall’analisi statistica è emersa una significativa correlazione tra l’uricemia e la trigliceridemia, parametro che funge anche da rinforzo dell’associazione tra l’uricemia e la colesterolemia. E’ stata confermata la relazione tra sesso maschile ed elevati livelli uricemici, che peraltro sono risultati parzialmente indipendenti dall’età dei soggetti in esame. Azotemia e creatininemia, espressione del ruolo della funzionalità renale, hanno presentato un andamento correlabile a quello dell’uricemia, a causa dell’escrezione prevalentemente renale dell’acido urico. L’associazione dell’acido urico con diversi fattori di rischio per affezioni metaboliche e cardiovascolari fa sospettare per il parametro in esame una probabile funzione predittiva nei confronti di tali patologie.

1991 - Effetti sulla salute dell'inquinamento degli ambienti confinati [Articolo su rivista]
Bergomi, Margherita; Vinceti, Marco; Rovesti, Sergio; Vivoli, Gianfranco
abstract

L’inquinamento dell’aria degli ambienti confinati e i suoi effetti sfavorevoli sulla salute sono oggetto di una crescente attenzione scientifica. Nella presente rassegna sono presi in esame i principali quadri morbosi attribuibili a tale fenomeno. Un ampio numero di osservazioni sembra confermare la relazione tra inquinamento degli ambienti confinati e patologie di tipo irritativo, immunologico ed infettivo, mentre più controversa è la possibile associazione con alcune patologie neoplastiche. Misure più incisive di sanità pubblica sembrano necessarie per ridurre i rischi per la salute potenzialmente attribuibili alla contaminazione dell’aria negli ambienti confinati.

1991 - La familiarità diabetica quale fattore di rischio del diabete non-insulino-dipendente [Articolo su rivista]
Vinceti, Marco; Rovesti, Sergio; Benedetti, P. G.; Pacchioni, C; Bergomi, Margherita
abstract

Nel corso di una indagine epidemiologica, condotta mediante l’esame delle cartelle cliniche di pazienti diabetici di nuova diagnosi e di un gruppo di soggetti controllo, è stato esaminato il ruolo della familiarità diabetica quale fattore di rischio del diabete non-insulino-dipendente. Dopo aggiustamento per età, indice di massa corporea, sesso, abitudini tabagiche e condizione ipertensiva, l’odds ratio per il diabete non-insulino-dipendente associato alla familiarità diabetica è risultata pari a 4.99 (p<0.001). I dati ottenuti suggeriscono inoltre un effetto sinergico tra la familiarità diabetica e il grado di obesità nel favorire l’insorgenza del diabete non-insulino-dipendente.

1990 - Diabete non-insulino-dipendente e ipertensione essenziale: basi razionali per una strategia integrata di prevenzione [Articolo su rivista]
Bergomi, Margherita; Vinceti, Marco; Rovesti, Sergio; Vivoli, Gianfranco
abstract

Il diabete non-insulino-dipendente e l’ipertensione essenziale sembrano condividere gli stessi meccanismi patogenetici e i medesimi fattori di rischio. Ciò confermerebbe la validità di un intervento integrato di prevenzione, comprendente adeguate misure dietetiche e comportamentali. La determinazione dell’insulinemia potrebbe rivelarsi una metodica efficace per l’identificazione, sin dalla giovane età, dei soggetti ad alto rischio nei confronti di tali patologie.