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TOMMASO FILIPPINI

Professore Associato
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 - 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 - Climate change-related factors and west nile virus spread in italy: a systematic review [Abstract in Atti di Convegno]
Granata, M; Tommasi, L; Verzelloni, P; Lorenzon, A; Paduano, S; Malavolti, M; Bargellini, A; Filippini, T; Righi, E; Vinceti, M
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 - 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 - Fluoride and caries prevention: a scoping review of public health policies [Articolo su rivista]
Veneri, Federica; Vinceti, Silvio Roberto; Filippini, Tommaso
abstract

Background: Dental caries is the most common infectious disease, affecting approximately 60 to 90% of the world population, especially young children, and disadvantaged communities. Due to the extremely high prevalence and the significant negative impact on general health, well-being, and quality of life it is considered a global public health problem. Despite the improvement of policies to promote oral health care in the past decades, dental caries is still a healthcare challenge, characterized by increasing disparities among different social groups between and within countries. Fluoride-based prevention of dental caries is a cost-effective approach, that has been implemented since 1940's. It includes systemic and topical administrations, through community-based or individual programs. Preventive interventions should be tailored to individual and community caries risk assessment and estimate of cumulative fluoride intake, in order to maximize the preventive effect and avoid the risk of potential adverse effects associated with excessive fluoride exposure. Regulation of public health policies plays a major role in this context. Study design: Scoping review. Methods: The aim of this scoping review was to report an overview of current guidelines regarding fluoride-based preventive strategies for dental caries and relevant policies on the matter, as well as to address current issues related to public health aspects of dental caries prevention. We searched for the relevant literature on the matter, focusing on policy documents, such as recommendations, position papers and guidelines, issued from the major scientific and regulatory institutions involved in oral health promotion and on publications concerning relevant aspects of public health law. Results: Prevention of dental caries through fluoride can rely on topical fluorides for home-use (toothpastes and mouthrinses), professionally applied topical fluorides (gels, varnishes, silver diamine fluoride, fluoride-releasing restorative materials and sealants), fluoride supplements (tablets and drops), and community-based strategies (community water fluoridation, fluoridated salt and milk). Current relevant guidelines for all these preventive aids are outlined in the paper. A significantly greater preventive effect of topical fluorides has been widely established in the recent past, as compared to systemic effects. Furthermore, increasing concerns have emerged on potential adverse effects on general health associated with early and excessive systemic exposure to fluoride, especially for children, supported by recent meta-analyses. Also, community water fluoridation has raised significant aspects of relevance for health law and policies. In a public health perspective, healthcare policymakers should tackle social iniquities by promoting information and oral health literacy, through community and school-based programs, ensuring access to early dental visits and basic dental care and improving availability and affordability of fluoride topical products. Conclusions: Fluoride-based prevention can provide a simple and cost-effective approach to reduce the incidence of dental caries and the associated social burden. Among fluoride-based preventive strategies, systemic community-based administration of fluoride should be considered with great caution, due to the unfavorable risk-benefit ratio currently established. Topical fluoridated products are generally preferred, given the optimal risk-benefit ratio. Further efforts must be made to identify and tackle the barriers to dental caries prevention and related social iniquities from a public health perspective. Policies and laws on oral health should promote access to caries prevention with targeted comprehensive strategies.

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 - Greenness and neuropsychiatric symptoms in dementia [Articolo su rivista]
Tondelli, M.; Chiari, A.; Vinceti, G.; Galli, C.; Salemme, S.; Filippini, T.; Carbone, C.; Minafra, C.; De Luca, C.; Prandi, R.; Tondelli, S.; Zamboni, G.
abstract

Objectives: It is acknowledged that living in a green environment may help mental well-being and this may be especially true for vulnerable people. However, the relationship between greenness and neuropsychiatric symptoms in dementia has not been explored yet. Methods: We collected clinical, neuropsychiatric, and residential data from subjects with dementia living in the province of Modena, Northern Italy. Neuropsychiatric symptoms were measured with the Neuropsychiatry Inventory, a questionnaire administered to the caregiver who assesses the presence and severity of neuropsychiatric symptoms, including delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, sleep disturbances, and appetite/eating changes. Normalized Difference Vegetation Index (NDVI) was used as a proxy of greenness. Regression models were constructed to study the association between greenness and neuropsychiatric features. Results: 155 patients with dementia were recruited. We found that greenness is variably associated with the risk of having neuropsychiatric symptoms. The risk of apathy was lower with lower levels of greenness (OR = 0.42, 95% CI 0.19–0.91 for NDVI below the median value). The risk of psychosis was higher with lower levels of greenness but with more imprecise values (OR = 1.77, 95% CI 0.84–3.73 for NDVI below the median value). Conclusion: Our results suggest a possible association between greenness and neuropsychiatric symptoms in people with dementia. If replicated in larger samples, these findings will pave the road for identifying innovative greening strategies and interventions that can improve mental health in dementia.

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 - 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.

2024 - Water fluoridation between public health and public law: an assessment of regulations across countries and their preventive medicine implications [Articolo su rivista]
Vinceti, Silvio Roberto; Veneri, Federica; Filippini, Tommaso
abstract

Background: Among health professionals and health policymakers concern is growing as to the difficulty of balancing the prevention of dental caries through cost-effective interventions and the need to limit unnecessary exposure of the population, and especially children, to environmental chemicals. In this respect, the use of water fluoridation to prevent tooth decay epitomizes the dilemma by raising questions relevant to both public health and public law, ranging from the balance of public health and medical selfdetermination, the division of powers between local or national authorities over water fluoridation, and the need to avoid the adverse effects of socioeconomic inequalities as well as both under- and over-exposure. Study design: We carried out a narrative review by searching the relevant literature about the laws and rules related to drinking water fluoridation at the community level in the US, UK, and Europe, in order to discuss how the issue is handled from both a public health and public law perspective. Methods: Sources of data for this review were the biomedical and legal literature retrieved by searching online databases, and websites of public health and legal institutions. Results and conclusions: We found that water fluoridation is still largely adopted throughout the US, while in the UK and particularly in the European Union only a minor part of the population is subject to it. In addition, the recommended and maximum allowed amounts of fluoride in drinking water are being adapted to the public health recommendations and the new regulations, within an evolving evaluation of the epidemiologic evidence and the risk assessment currently in progress by two major regulatory agencies, the US National Toxicology Program - NTP and the European Food Safety Authority - EFSA. Under a comparative public law perspective, the three investigated legislations are facing a reassessment of their policies and regulations, to allow for effective and safe public health measures in the field of water fluoridation and more generally for a preferred use of topical fluoride for caries.

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

2023 - ADHD Follow-Up in Adulthood among Subjects Treated for the Disorder in a Child and Adolescent Mental Health Service from 1995 to 2015 [Articolo su rivista]
Lorenzo Rosaria, Di; Balducci, Jessica; Cutino, Anna; Latella, Emanuela; Venturi, Giulia; Rovesti, Sergio; Filippini, Tommaso; Ferri, Paola
abstract

Background and Objectives: ADHD is a neurodevelopmental disorder characterized by inattention and hyperactivity/impulsivity and can persist in adulthood. The aim of this study is to deepen knowledge about adult ADHD follow-up. Materials and Methods: This observational study consists of one retrospective part aimed at collecting records of children and adolescents treated for ADHD in the Children and Adolescent Mental Health Service (CAMHS) from 1995 to 2015 and, successively, at identifying their adult follow-up in Adult Mental Health Service (AMHS); the second part consists of ADHD scale administration, Diagnostic Interview for ADHD in Adults (DIVA 2-0) and Adult Self Rating Scale (ASRSv1.1), for the subjects currently being treated at AMHS who agreed to participate in the study. Results: We observed that among the 55 patients treated at CAMHS between 1995 and 2015 for ADHD and subsequently at the AMHS, none presented a diagnosis of ADHD; instead, they were treated for Intellectual Dysfunction (33%), Borderline Personality Disorder (15%) and Anxiety Disorders (9%), and two individuals were also diagnosed with comorbid substance/alcohol abuse (4%). Of the 55 patients, only 25 (45%) were treated at AMHS during the study period. Though we asked for their informed consent to administer the questionnaires, we were able to test only seven patients. The ASRS-V1.1 score showed that 43% of patients reported symptoms of ADHD persistence in adulthood. For DIVA 2.0, 57% of individuals reported scores indicating the persistence of the ADHD inattention component, and 43% the persistence of both ADHD dimensions. Conclusions: ADHD cannot be considered a disorder confined to childhood/adolescence but instead is a chronic and complex condition that can persist into adulthood. The very small size of our final sample may account for both the high ADHD dropout rate over the long follow-up period and the difficult transition from child to adult health care in ADHD treatment. Our investigation suggests the need for specific training in the diagnosis and treatment of adult ADHD and the implementation of transition protocols between minor and adult services to improve long-term treatments.

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 - 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 - 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 - Comparison of video-assisted pleurectomy/decortication surgery plus hyperthermic intrathoracic chemotherapy with VATS talc pleurodesis for the treatment of malignant pleural mesothelioma: A pilot study [Articolo su rivista]
Migliore, M.; Fiore, M.; Filippini, T.; Tumino, R.; Sabbioni, M.; Spatola, C.; Polosa, R.; Vigneri, P.; Nardini, M.; Castorina, S.; Basile, F.; Ferrante, M.
abstract

Hyperthermic intrathoracic chemotherapy (HITHOC) adjunct to surgery for Malignant Pleural Mesothelioma (MPM) has no definite role. The primary objective of this pilot-trial was to evaluate the feasibility for future large studies. The study design was a prospective randomized three-centric pilot trial. We recruited patients diagnosed with MPM and prospectively assigned them to two groups: Group A: Video Assisted Thoracic Surgery (VATS) talc pleurodesis or Group B: Video-assisted P/D plus HITHOC. From November-2011 to July-2017 24 males and 3 females, with a median age of 68-years were enrolled (recruitment rate 5 patients/year). Preoperative stage was I-II, and 18 had epithelioid type. 14 patients were in the Group A. Operative mortality was 0. Follow-up ranged 6–80 months. The median overall survival time started to diverge at 20 months, being 19 months (95% CI 12–25) in Group A and 28 months (95% CI 0–56) in Group B. Survival rate for the epithelioid type was 15 months (95% CI 0–34) in Group A and 45 months (95% CI 0–107) in the Group B. These findings suggest that video-assisted P/D plus HITHOC may improve survival time in MPM patients undergoing surgical treatment and support the need for a larger multicenter randomized clinical trial.

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 - Education and Disparities in Cardiac Rehabilitation Effectiveness [Articolo su rivista]
Filippini, Tommaso; Malavolti, Marcella
abstract

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 - Glycemic control predicts SARS-CoV-2 prognosis in diabetic subjects. [Articolo su rivista]
Greco, Carla; Pirotti, Tommaso; Brigante, Giulia; Filippini, Tommaso; Pacchioni, Chiara; Trenti, Tommaso; Simoni, Manuela; Santi, Daniele
abstract

Aim The coronavirus disease (COVID)‐19 incidence was higher in diabetes mellitus (DM), although several differences should be considered on the basis of characteristics of cohorts evaluated. This study was designed to evaluate the prevalence and potential consequences of COVID-19 in a large diabetic population in Northern Italy. Design Observational, longitudinal, retrospective, clinical study. Methods Subjects with both type 1 and type 2 DM living in the Province of Modena and submitted to at least one SARSCoV- 2 swab between March 2020 and March 2021 were included. Data were extracted from the Hospital data warehouse. Results 9553 diabetic subjects were enrolled (age 68.8 ± 14.1 years, diabetes duration 11.0 ± 6.9 years, glycated hemoglobin 57.2 ± 16.2 mmol/mol). COVID-19 was detected in 2302 patients (24.1%) with a death rate of 8.9%. The mean age and diabetes duration were significantly lower in infected versus non-infected patients. SARS-CoV-2 infection was more frequent in youngest people, according to quartile of age and retirement pension age of 65 years. No differences were detected considering sex. Higher HbA1c was detected in infected compared to non-infected patient. Death was predicted by diabetes duration and HbA1c. ROC analyses for death risk showed significant threshold for diabetes duration (10.9 years) and age (74.4 years). Conclusion In our cohort, SARS-CoV-2 infection correlates with age, diabetes duration and disease control. Diabetic patients

2023 - Health surveillance for SARS-CoV-2: infection spread and vaccination coverage in the schools of Modena province, Italy [Articolo su rivista]
Paduano, S.; Facchini, M. C.; Borsari, L.; D’Alterio, A.; Iacuzio, L.; Greco, A.; Fioretti, E.; Creola, G.; Kahfian, Z.; Zona, S.; Bargellini, A.; Filippini, T.
abstract

IntroductionIn Italy, over 4.8 million individuals aged 0-19 years have been infected with SARS-CoV-2. This study aims to evaluate the spread of SARS-CoV-2 within schools in Modena province and the influence of anti-SARS-CoV-2 vaccination coverage.MethodsWe performed a survey in the period 1 September-15 December 2021, involving student population aged 0-19 years and related teachers screened for SARS-CoV-2 infection using nasopharyngeal swab after the detection of an index case within their class. During the study period, vaccination against SARS-CoV-2 was actively offered to all subjects aged >= 12 years.ResultsA total of 13,934 subjects were tested, 12,534 students and 1,400 teachers (594 classes). We identified a total of 594 and 779 index and secondary cases, respectively. We found that 9.8% of students and 10.6% of teachers were positive for SARS-CoV-2. Overall at the test time, 32.5% were vaccinated with at least one dose of anti-SARS-CoV-2 vaccine. Among secondary cases, 7.8% were vaccinated compared to 34.9% among negative tested subjects. A higher secondary attack rate was for non-vaccinated subjects rather than vaccinated ones (8.1% vs. 1.4%). Higher secondary attack rates were reported for subjects attending infant and primary school (5.9 and 9.6%, respectively). Lower secondary attack rates were for those who attended middle school (4.9%) and especially high school (1.7%).ConclusionOur results highlight the differential spread of the infection within various educational settings and that the vaccination, available in the study period for the population aged >= 12, have mitigated SARS-CoV-2 spread in high and middle schools.

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 - Involuntary Hospitalizations in an Italian Acute Psychiatric Ward: A 6-Year Retrospective Analysis [Articolo su rivista]
Di Lorenzo, Rosaria; Reami, Matteo; Dragone, Diego; Morgante, Martina; Panini, Giulia; Rovesti, Sergio; Filippini, Tommaso; Ferrari, Silvia; Ferri, Paola
abstract

Purpose: We evaluated the differences between demographic (age, sex, nationality, employment, housing, schooling, support administrator), clinical (hospitalization reason, aggressive behaviour, length of hospitalization, psychiatric diagnosis and comorbidities, psychiatric medications, discharge destination, “revolving door” hospitalizations) and environmental (pre-and pandemic period) variables in voluntary (VHs) and involuntary hospitalizations (IHs) in an acute psychiatric ward during a 6-year period. Patients and Methods: We retrospectively collected the selected variables concerning the hospitalizations of subjects over 18 years of age in the Service for Psychiatric Diagnosis and Care of Mental Health and Drug Abuse Department in Modena from 01/01/2017 to 31/12/2022. Results: We observed a progressive and sharp reduction in the number of VHs (n = 1800; 61.41%) during the pandemic and a stability of IHs (n = 1131; 38.59%), which in 2022 became prevalent. We highlighted the following differences between VHs and IHs: an increase in hospitalization length in IHs (14.25 mean days ± 15.89 SD) in comparison with VHs (8.78 mean days ± 13.88 SD), which increased more during the pandemic; an increase in aggressive behavior in IHs, especially during the pandemic (Pearson Chi2 = 90.80; p = 0.000); a prevalence of schizophrenia and bipolar disorders (Pearson Chi2 = 283.63; p = 0.000) and more frequent maladaptive social conditions among subjects in IHs. Conclusion: During the 6-year observation period, we underscored a trend of increasingly reduced recourse to VHs, whereas IHs increased even in the pandemic. Our results suggest that IHs in Psychiatry represented an extreme measure for treating the most severe psychopathological situations such as schizophrenia and bipolar disorders, characterized by aggressive behaviour and precarious social conditions, which needed longer stay than VHs, especially during the pandemic.

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 - Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium [Articolo su rivista]
Lupo, Philip J; Chambers, Tiffany M; Mueller, Beth A; Clavel, Jacqueline; Dockerty, John D; Doody, David R; Erdmann, Friederike; Ezzat, Sameera; Filippini, Tommaso; Hansen, Johnni; Heck, Julia E; Infante-Rivard, Claire; Kang, Alice Y; Magnani, Corrado; Malagoli, Carlotta; Metayer, Catherine; Bailey, Helen D; Mora, Ana M; Ntzani, Evangelia; Petridou, Eleni Th; Pombo-de-Oliveira, Maria S; Rashed, Wafaa M; Roman, Eve; Schüz, Joachim; Wesseling, Catharina; Spector, Logan G; Scheurer, Michael E
abstract

: Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

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 - 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 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 - 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 - 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 spread of sars-cov-2 and vaccination coverage: Results of health surveillance in schools of modena province, italy [Abstract in Rivista]
Galante, Pasquale; Paduano, Stefania; Borsari, Lucia; D'Alterio, Alessandra; Iacuzio, Laura; Greco, Antonella; Fioretti, Elisabetta; Creola, Giacomo; Casaletti, Giovanni; Bargellini, Annalisa; Filippini, Tommaso
abstract

2023 - Toxicological effects of selenium nanoparticles in laboratory animals: A review [Articolo su rivista]
Ryabova, Yuliya V; Sutunkova, Marina P; Minigalieva, Ilzira A; Shabardina, Lada V; Filippini, Tommaso; Tsatsakis, Aristides
abstract

This paper provides a comprehensive summary of the main toxicological studies conducted on selenium nanoparticles (NPs) using laboratory animals, up until February 28, 2023. A literature search revealed 17 articles describing experimental studies conducted on warm-blooded animals. Despite some uncertainties, in vivo studies have demonstrated that selenium NPs have an adverse effect on laboratory animals, as evidenced by several indicators of general toxic action. These effects include reductions of body mass, changes in hepatotoxicity indices (increased enzyme activity and accumulation of selenium in the liver), and the possibility of impairment of fatty acid, protein, lipid, and carbohydrate metabolisms. However, no specific toxic action attributable solely to selenium has been identified. The LOAEL and NOAEL values are contradictory. The NOAEL was 0.22 mg/kg body weight per day for males and 0.33 mg/kg body weight per day for females, while the LOAEL was assumed to be a dose of 0.05 mg/kg of nanoselenium. This LOAEL value is much higher for rats than for humans. The relationship between the adverse effects of selenium NPs and exposure dose is controversial and presents a wide typological diversity. Further research is needed to clarify the absorption, metabolism, and long-term toxicity of selenium NPs, which is critical to improving the risk assessment of these compounds.

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 - Attention deficit among preschool and school-aged children living near former metal-processing plants in Romania [Articolo su rivista]
Nedelescu, M.; Stan, M.; Ciobanu, A. -M.; Balalau, C.; Filippini, T.; Baconi, D.
abstract

Industrial areas affected by high and long-term heavy metal pollution have a great impact on health of the resident population. Children represent a group at high-risk with an increased susceptibility to chronic heavy metal intoxication. Our work included the assessment of attention particularities through a case-control study in pre-school and school-aged children (4–6 years and 8–11 years) from two study areas, Copşa Mică and Zlatna, compared to a non-polluted locality with no history of heavy metal pollution. Copşa Mică and Zlatna are two of the most polluted heavy metals regions in Romania due to non-ferrous metallurgy for a long period of time. Recruitment of participants was made by a random selection of an entire class for each age within the schools and kindergartens from the study areas (Copşa Mică and Zlatna) and from the non-polluted region. Interpretation of data was performed using statistical analysis (ANOVA and Student's t-test). Preschool children (4–6 years) were tested using Wechsler Preschool and Primary Scale of Intelligence (WPPSI) tests, Animal House and labyrinth samples. The results of the attention tests applied to pre-school children were lower in the study areas compared to the control group, but no statistical differences were found. The results of the attention tests applied to children aged between 8 and 11 years (Toulouse-Pieron test and Traffic light test) indicate lower average scores within the study groups from polluted areas, compared to the control group. Differences with statistically significance were registered for the 8 years age group (p = 0.037). In these areas efficient strategies and precise intervention measures are needed in order to limit or remove the heavy metal exposure and protect the human health, especially the groups exposed to a high level of risk.

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 - 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 - Emergency Planning and Community Right-to-Know Act (EPCRA) [Capitolo/Saggio]
Filippini, Tommaso; Urbano, Teresa
abstract

The US Emergency Planning and Community Right-to-Know Act (EPCRA) established requirements for federal, state and local governments, Indian tribes, and industrial facilities regarding emergency planning and “community right-to-know” reporting on hazardous and toxic chemicals. EPCRA's emergency planning provisions help communities prepare for potential chemical accidents, while EPCRA's right-to-know provisions help increase public knowledge of and access to information on the presence, use, and release of chemicals at individual facilities. The information is provided with the aim to improve chemical safety and protect public health and the environment.

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 - 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 - 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 - Innovative In Vitro Strategy for Assessing Aluminum Bioavailability in Oral Care Cosmetics [Articolo su rivista]
Allaria, Giorgia; De Negri Atanasio, Giulia; Filippini, Tommaso; Robino, Federica; Dondero, Lorenzo; Soggia, Francesco; Rispo, Francesca; Tardanico, Francesca; Ferrando, Sara; Aicardi, Stefano; Demori, Ilaria; Markus, Jan; Cortese, Katia; Zanotti-Russo, Matteo; Grasselli, Elena
abstract

Aluminum is an element found in nature and in cosmetic products. It can interfere with the metabolism of other cations, thus inducing gastrointestinal disorder. In cosmetics, aluminum is used in antiperspirants, lipsticks, and toothpastes. The aim of this work is to investigate aluminum bioavailability after accidental oral ingestion derived from the use of a toothpaste containing a greater amount of aluminum hydroxide than advised by the Scientific Committee on Consumer Safety (SCCS). To simulate in vitro toothpaste accidental ingestion, the INFOGEST model was employed, and the amount of aluminum was measured through the ICP-AES analysis. Tissue barrier integrity was analyzed by measuring transepithelial electric resistance, and the tissue architecture was checked through light microscopy. The margin of safety was also calculated. Overall, our results indicate that the acute exposure to aluminum accidentally ingested from toothpastes is safe for the final user, even in amounts higher than SCCS indications.

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

Mercuric chloride (CAS# 7487-94-7) is used in photographical processes, wood preservatives, disinfectants, fungicides, and some pharmaceutical products. Mercury chloride is one of the most toxic salts of mercury, and it is poisonous if absorbed by inhalation, ingestion, and skin contact. In humans, the gastrointestinal absorption of metallic mercury is generally low. However, ingested metallic mercury is oxidized in the gastrointestinal tract to mercury salts such as mercury chloride, thus increasing the uptake in the central circulation. Central nervous system, gastrointestinal tract, and especially the kidneys are most vulnerable to its toxic effects. Mercuric chloride is primarily a skin and mucous membrane irritant. Acute poisoning by ingestion or inhalation may cause respiratory insufficiency, gastrointestinal disturbances (nausea, vomiting), and renal damage. As little as 0.1 g is enough to cause damage to body tissues, and 1–4 g ingestion may be fatal. As regards chronic exposure, the main target of toxicity is the kidney, but other symptoms may include increased salivation, inflammation of the gums and black lines on the teeth. Although mercuric chloride showed carcinogenic effects in some animal models, evidence in humans are scarce, and therefore it is considered a Group 3 carcinogen.

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 - 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 - Retrospective observational study of Italian patients with diabetes mellitus in Covid-19 era: a big data approach [Abstract in Atti di Convegno]
Greco, Carla; Pirotti, Tommaso; Brigante, Giulia; Filippini, Tommaso; Pacchioni, Chiara; Trenti, Tommaso; Simoni, Manuela; Santi, Daniele
abstract

Background: Diabetes mellitus (DM) prevalence in patients with severe acute respiratory coronavirus virus (SARS-CoV-2) infection differs among studies, although pre-existing DM seems to double the risk of critical infection and mortality. Objectives: To evaluate incidence and mortality risk of SARS-CoV-2 infection in a large diabetic population in Northern Italy in pre-vaccine era. Methods: Retrospective, observational, big data study including non-vaccinated subjects with type 1 and type 2 DM in the Province of Modena, submitted to at least 1 swab for SARS-CoV-2 between March 2020 and March 2021. Results: SARS-CoV-2 infection was detected in 2302 of 9553 diabetic patients (24.1%) with death in 8.9% of cases. No difference in SARS-CoV-2 prevalence was detected considering sex, whereas youngest people showed highest SARS-CoV-2 infection rate. DM duration was shorter in infected than uninfected patients (P < 0.001), but HbA1c was higher in infected compared to uninfected patients (P < 0.001). Accordingly, SARS-CoV-2 was less frequent in patients treated with anti-diabetic drugs compared to those not treated (P < 0.001). SARS-CoV-2 infection was predicted by age (OR 1.013, 95%CI:1.008-1.017), DM duration (OR 1.007, 95%CI:1.001-1.013), and HbA1c (OR 1.009, 95%CI:1.002-1.016). COVID-19 mortality was predicted by DM duration (OR 1.010, 95%CI: 1.005-1.015) and HbA1c (OR 1.005, 95%CI:1.002-1.009). At ROC analyses with death as test variable, worse prognosis was predicted by DM duration longer than 10.9 years (AUC=0.639, 95%CI:0.601–0.676) and age older than 74.4 years (AUC=0.797, 95%CI:0.767–0.827). Conclusion: Our study confirms the correlation between SARS-CoV-2 related mortality and DM. Although SARS-CoV-2 infection was more frequent in the younger patients, a poor glycemic control worsens outcomes, especially in older diabetic people with long DM duration. Patients with DM and SARS-CoV-2 should be followed carefully when older than 74 years and with long DM duration.

2022 - Retrospective observational study of italian patients with diabetes mellitus in Covid-19 pre-vaccine ERA: a big data approach [Abstract in Atti di Convegno]
Colzani, M; Greco, C; Pirotti, T; Brigante, G; Filippini, T; Pacchioni, C; Trenti, T; Simoni, M; Santi, D
abstract

2022 - Revising the legislation of Ethics Committees to ease biomedical research in humans across the world: lessons from the COVID-19 emergency [Articolo su rivista]
Vinceti, Silvio Roberto; Filippini, Tommaso
abstract

: As a legislative domain that considerably influences implementation of biomedical research, the need to improve the legal rules surrounding the organization and functioning of Ethics Committees in public health, toxicology, and clinical medicine is widely recognized within and outside the European Union. Given the often-heard complaints by researchers about the complexity and length of both the application and the review process by Ethics Committees in the authorization of new studies, adjustments to their legislation appears to be warranted. Within the European Union this seems also all the timelier, given the upcoming new regulation of clinical trials to become effective in early 2022. For this process, valuable lessons can be gleaned from the COVID-19 pandemic and the changes in the functioning of Ethics Committees that were adopted to cope with the exceptional circumstances imposed by the health emergency. The pandemic experience clearly indicates that a more responsive and practical system of applications' review by the Ethics Committees can be squared with acceptable levels of transparency and reliability in ethical accountability. For this reason, countries like Italy should consider undertaking a significant revision of the public law rules that govern the review processes of Ethics Committees in light of the pandemic experience. (www.actabiomedica.it).

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 - 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 - 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 Follow-Up of Eating Disorders from Adolescence to Early Adulthood: A Systematic Review [Articolo su rivista]
Filipponi, Caterina; Visentini, Chiara; Filippini, Tommaso; Cutino, Anna; Ferri, Paola; Rovesti, Sergio; Latella, Emanuela; Di Lorenzo, Rosaria
abstract

Eating disorders (EDs) are common among children and adolescents and are characterized by excessive concerns for physical appearance, distorted body image, and fear of gaining weight. The purpose of this review is to evaluate the follow-up of EDs from adolescence to adulthood, analyzing persistence, relapses, and associated comorbidities. We searched scientific articles in PubMed, PsycInfo, Scopus, and Embase through two research strings, one for quantitative outcomes (recovery/persistence, relapse, and remission) and one for the other outcomes (psychiatric and medical comorbidities, substance use, and social-relational complications). From a total of 8043 retrieved articles, we selected 503 papers after exclusion of duplicates and title/abstract screening. After a full-text evaluation, we included 16 studies eligible for this review. We performed a meta-analysis describing the quantitative results, and we created a narrative synthesis for the qualitative outcomes. Results: Our results confirm that EDs can persist in early adulthood in 40.7% of cases with a relapse percentage of 24.5%. Individuals with an ED more frequently present with an empathy deficit and comorbid anxiety and depressive disorders. EDs are chronic and complex disorders, more frequent in females. In most cases, EDs reduce the autonomy of individuals who present many difficulties in affirming their independence from parental family.

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 - The role of statistical significance testing in public law and health risk assessment [Articolo su rivista]
Filippini, Tommaso; Vinceti, Silvio Roberto
abstract

Following a fundamental statement made in 2016 by the American Statistical Associations and broad and consistent changes in data analysis and interpretation methodology in public health and other sciences, statistical significance/null hypothesis testing is being increasingly criticized and abandoned in the reporting and interpretation of the results of biomedical research. This shift in favor of a more comprehensive and non-dichotomous approach in the assessment of causal relationships may have a major impact on human health risk assessment. It is interesting to see, however, that authoritative opinions by the Supreme Court of the United States and European regulatory agencies have somehow anticipated this tide of criticism of statistical significance testing, thus providing additional support to its demise. Current methodological evidence further warrants abandonment of this approach in both the biomedical and public law contexts, in favor of a more comprehensive and flexible method of assessing exposures of toxicological interest to human and environmental health.

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 - 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 - 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 - Children and adolescents with ADHD followed up to adulthood: A systematic review of long-term outcomes [Articolo su rivista]
Di Lorenzo, R.; Balducci, J.; Poppi, C.; Arcolin, E.; Cutino, A.; Ferri, P.; D'Amico, R.; Filippini, T.
abstract

Objective: To highlight the clinical and social outcomes among adults who suffered from ADHD in their childhood/adolescence. Method: PubMed, PsycINFO, Scopus databases were searched for prospective studies published during the last 5 years addressing patients with ADHD in childhood/adolescence followed up to adulthood. We also included studies published before 2015 reported in other reviews with similar outcomes. Results: 1485 studies were identified but only 39 were included for qualitative and 27 for quantitative analysis. Overall, we found that ADHD persisted into adulthood with a mean rate of 43% and was mainly associated with both substance/alcohol use disorders and antisocial behavior and, less frequently, with anxiety and depressive disorders. The prevalence of persistent ADHD in adulthood reported by studies published after 2011 (55%) was higher than that reported by studies published previously from 1985 to 2011 (34%), suggesting a greater focus on ADHD. Conclusion: Our results highlight that ADHD can be considered not only a neurodevelopmental disorder but a persistent and complex condition, with detrimental consequences for quality of life in adulthood.

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 - 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 - 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 - 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 - 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 - 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 - Italian National Recovery and Resilience Plan: a Healthcare Renaissance after the COVID-19 crisis? [Articolo su rivista]
Filippini, Tommaso; Vinceti, Silvio Roberto
abstract

: Proposed for the first time by European Commission in May 2020, the "NextGenerationEU" (NGEU) program is the European Union's most important effort to address key issues relating to public health and healthcare, digital and technological innovation, climate change, sustainable mobility, and key sociocultural aspects. In addition, the NGEU represents a response to the COVID-19 crisis through an extremely powerful financial intervention (over 800 billion euros). Italy is one of the main recipients of the NGEU plan's resources with almost 200 billion euros received in grants and loans. Implementation of the NGEU in Italy will take place through the National Recovery and Resilience Plan (NRRP). The NRRP not only describes how the NGEU resources will be used, but it singles out crucial public law reforms in national legislation and organization. Unsurprisingly, public health intervention represents a major component of the NRRP. Here we summarize and discuss the rules, regulations and perspective envisaged by the NRRP to foster effective healthcare and to reshape the Italian National Health System through the redesigning of primary care, enhanced communication between hospital and community healthcare, and stronger implementation of digital technologies in public health. (www.actabiomedica.it).

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 - 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 - Public health and public law issues for the toxicological risk assessment of chemical mixtures [Articolo su rivista]
Vinceti, Silvio Roberto; Filippini, Tommaso
abstract

Humans are simultaneously exposed to a near-infinite number of substances of both nutritional and toxicological interest. While traditional risk assessment has been based on the evaluation of effects of single substances, real-life exposure is characterized by their combination into chemical mixtures. As consequence, the need to focus on substance interactions is of considerable relevance. From the public health point of view, factors able to modulate the kinetic and toxicity of chemicals need to be included in the assessment of health effects. Several European projects including SOLUTIONS, EuroMix, ECD-MixRisk and HBM4EU have been implemented aiming at the characterization of hazardous properties of chemical mixtures and the development of new approaches and tools for their risk assessment, including advanced statistical methodologies. From the public law point of view, the legislative status of mixtures is outlined in a still general way, with a specific focus on a few substances only, e.g. dietary exposure to pesticide residues. Although some advances have been made with the ongoing revision of CLP Regulation specifically focusing also on chemical mixtures, identification of mixtures and the regulation of their use raise relevant and challenging issues to be timely addressed within a collaboration of specialists from toxicology, public health, and public law. Moreover, given the transnational scope of the problem, risk assessment of chemical mixtures presents a valuable occasion for a comparative law approach.

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 - 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 - 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.

2021 - Towards the dismissal of null hypothesis/statistical significance testing in public health, public law and toxicology [Articolo su rivista]
Vinceti, Silvio Roberto; Filippini, Tommaso
abstract

Null hypothesis significance testing (NHST) text was once widely popular and almost systematically used for the identification of causal relations and for risk assessment in toxicology and medicine. Interestingly, the public law world has been more prudent and more advanced than the biomedical one in the use of this dichotomous approach, based on the conventional p-value cut-points of 0.05/0.001, to assess causality. The recent 2016 statement by the American Statistical Association, the joint action by methodologists in all fields of science, and not least the seminal decisions by the US Supreme Court have highlighted the pitfalls of the dichotomous approach embedded in NHST. Overall, they also indicated the need to entirely dismiss NHST when assessing causal relations, favoring instead a more flexible and adequate approach for data analysis and interpretation. The demise of statistical significance testing would have major beneficial implications for risk assessment in toxicology, public health, and human medicine, alongside important public law implications. It could also lead to a reanalysis and re-interpretation of previous studies and bodies of evidence that may have been inaccurately assessed due to the flaws inherent in NHST.

2021 - Updating the European Union's regulation on classification, labelling and packaging of substances and mixtures (CLP): A key opportunity for consumers, workers and stakeholders with interests in the legislation and toxicology of hazardous chemicals [Articolo su rivista]
Vinceti, S. R.; Docea, A. O.; Tsitsimpikou, C.; Filippini, T.
abstract

Recent advancements in toxicology and the European Union's Green Deal, with its Chemicals Strategy for Sustainability, have paved the way for major changes in EU legislation on the control of environmental chemicals for a cleaner and safer environment. Another substantial legislative advancement underway is the update of the “Regulation on Classification, Labelling and Packaging of Substances and Mixtures (CLP),” an ambitious piece of EU legislation with exceptional scientific toxicological background in identifying a hazard, aiming at better protecting its citizens and the environment from the risk of chemical substances and products, the occupational settings included. Update of CLP legislation additionally aims at facilitating the free exchange of chemicals in the European Internal Market, provided that proper labelling and packaging processes are implemented. Participation in the ongoing online public consultation on these issues, ending on November 15, 2021, is of key relevance to ensure a transparent and effective definition of such an important piece of legislation, fully compliant with current EU priorities in terms of human and environmental protection and animal welfare.

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 - Chemical characterization and quantification of titanium dioxide nanoparticles (Tio2-nps) in seafood by single-particle icp-ms: Assessment of dietary exposure [Articolo su rivista]
Grasso, A.; Ferrante, M.; Zuccarello, P.; Filippini, T.; Arena, G.; Fiore, M.; Cristaldi, A.; Conti, G. O.; Copat, C.
abstract

The significant increase in the production and variety of nanoparticles (NPs) has led to their release into the environment, especially into the marine environment. Titanium dioxide nanoparticles (TiO2-NPs) are used in different industrial sectors, from the food industry to several consumer and household products. Since the aquatic environment is highly sensitive to contamination by TiO2-NPs, this work aimed to give a preliminary assessment of the contamination of packaged seafood, where the food additive TiO2 (E171) is not to be intentionally added. This allowed providing a chemical characterization and quantification of TiO2-NPs in processed canned fish products belonging to different trophic positions of the pelagic compartment and in canned clam. The new emerging technique called single-particle inductively coupled plasma mass spectrometry (spICP-MS) was applied, which allows the determination of nanoparticle number-based concentration, as well as the dissolved titanium. This study highlights how processed food, where the pigment E171 was not intentionally added, contains TiO2 in its nanoparticle form, as well as dissolved titanium. Processed clam represented the seafood with the highest content of TiO2-NPs. In pelagic fish species, we found progressively higher levels and smaller sizes of TiO2-NPs from smaller to larger fish. Our results highlight the importance of planning the characterization and quantification of TiO2-NPs in food both processed and not, as well as where the pigment E171 is intentionally added and not, as it is not the only source of TiO2-NPs. This result represents a solid step toward being able to estimate the real level of dietary exposure to TiO2-NPs for the general population and the related health risks.

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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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.

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 - 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 - 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 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 - 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 - 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 - 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 - 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 - Prevalenza ed impatto sociale delle demenze ad esordio precoce (Early onset dementia-EOD) nella provincia di Modena [Abstract in Rivista]
Chiari, A; Galli, C; Tondelli, M; Vinceti, G; Fiondella, L; Molinari, M; Costa, M; Garuti, C; Adani, G; Filippini, T; Zamboni, G
abstract

Introduzione. Le demenze in cui l’esordio dei sintomi si verifica prima dei 65 anni (Early Onset Dementia-EOD), hanno caratteristiche cliniche ed impatto socio-sanitario diversi rispetto alle demenze ad esordio tardivo. I dati epidemiologici disponibili sono scarsi, con stime di prevalenza variabili tra 15 e 150/100.000 soggetti appartenenti alla fascia di età 45-64 anni. Non sono attualmente disponibili dati di prevalenza in Italia. Metodi. Abbiamo ricercato i casi di EOD in pazienti residenti in Provincia di Modena, esaminando i pazienti valutati presso i Centri per i Disturbi Cognitive e Demenze (CDCD) della provincia (2 neurologici, 8 geriatrici dislocati in tutto il territorio provinciale) tra il 1/1/2006 e il 31/12/2018. I casi con esordio antecedente al 1/1/2017 sono stati identificati retrospettivamente, mentre i casi con esordio successivo sono stati accertati prospetticamente, mediante invio da parte dei Medici di Medicina Generale e dai Geriatri ai due CDCD neurologici della provincia. La diagnosi di EOD è stata posta da un Neurologo esperto in disturbi cognitivi. Abbiamo incluso nello studio i pazienti con diagnosi di EOD al 31/12/2018. Abbiamo esaminato diagnosi, età di insorgenza, età e gravità dei disturbi cognitivi alla diagnosi. Per un sottogruppo di pazienti abbiamo inoltre raccolto variabili socio-demografiche quali la composizione del nucleo familiare e la condizione occupazionale del paziente e del caregiver principale. Risultati. Abbiamo identificato 248 pazienti con EOD al 31/12/2018, con una prevalenza di 116,5/100.000 soggetti a rischio nella fascia di età 45-64 anni e 71,8/100.000 nella fascia di età 30-64 anni. Il 41% dei pazienti ha ricevuto una diagnosi di malattia di Alzheimer (31% non amnesici), il 26% di demenza fronto-temporale, il 10% di demenza vascolare, il 7% demenza in parkinsonismo. L’età media all’esordio è stata di 58,9 anni (range 39-64), l’età media alla diagnosi è stata di 61,9 (range 40-72) con un significativo ritardo diagnostico. Il MMSE medio alla diagnosi è risultato pari a 22,2/30 (range 10-28). Il 22% dei pazienti svolgeva attività lavorativa alla diagnosi, mentre il 24% è stato costretto a lasciare il lavoro a causa della malattia. Il 3,4% dei pazienti aveva figli minori al momento della diagnosi. I caregivers, aventi età media di 59 anni, per il 70% svolgevano attività lavorativa, sperimentando una perdita media di 2 giornate lavorative al mese a causa della malattia del familiare. Il 7,4% e 20,5% dei pazienti ha usufruito rispettivamente di un centro diurno o struttura protetta, che tuttavia in nessun caso era specificamente dedicata a pazienti con EOD. Conclusioni. I dati raccolti permettono per la prima volta di valutare il numero e le caratteristiche dei pazienti con EOD nella Provincia di Modena. I risultati ottenuti saranno essenziali per organizzare servizi appropriati, dal punto di vista sanitario e socioassistenziale, per pazienti con EOD ed i loro familiari.

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 - 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 - 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 - 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 - 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
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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.
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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.
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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.
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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.
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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 - 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 - 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 - 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 - 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 - 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 - 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 - 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
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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 - 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.
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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
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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
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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 - 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 - 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 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 - 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 - 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.
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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]
Violi, F; Filippini, T; Malagoli, C; Fiore, M; Ledda, C; Mauceri, Mc; Dimartino, A; Mandrioli, J; Fini, N; Patti, F; Ferrante, M; Vinceti, M.
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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 - 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.
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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.
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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.
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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 - Selenium in human neurodegenerative diseases: friend or foe? [Abstract in Atti di Convegno]
Vinceti, M; Filippini, T; Malagoli, C.
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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.
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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 - 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 - Strategies for Disease Prevention and Health Promotion in Urban Areas: The Erice 50 Charter [Articolo su rivista]
D'Alessandro, D; Arletti, S; Azara, A; Buffoli, M; Capasso, L; Cappuccitti, A; Casuccio, A; Cecchini, A; Costa, G; De Martino, A M; Dettori, M; Di Rosa, E; Fara, G M; Ferrante, M; Giammanco, G; Lauria, A; Melis, G; Moscato, U; Oberti, I; Patrizio, C; Petronio, M G; Rebecchi, A; ROMANO SPICA, Vincenzo; Settimo, G; Signorelli, C; Capolongo, S; Attendees of the 50th Course Urban, Health; Alessi, V; Apollonio, F; Barbagallo, E; Bassot, Am; Bernini, D; Borghini, A; Borri, M; Brandimarte, A; Copat, C; Cracchiolo, M; Cribellati, S; Cristaldi, A; D'Agati, P; D'Amico, A; De Marchis, A; Dell'Ovo, M; Donia, Am; Filippini, T; Giannetti, G; Giorgi, S; Gola, M; Grasso, A; Graziano, G; Lanzilotti, C; Laudani, N; Lopuzzo, M; Malfer, M; Marchese, V; Marzella, A; Mascarello, A; Milicia, Gm; Nurchis, P; Ogana, S; Oliveri Conti, Cg; Pacifico, C; Paduano, S; Paglione, L; Palmeri, S; Pieve, G; Raffo, M; Raguzzoni, G; Raia, Dd; Righi, A; Rochira, Andrea; Rondinelli, L; Salvia, C; Sciaraffa, R; Trogu, F; Ubiali, A; Valt, R; Vantaggiato, V; Ventura, G; Zuccarello, P
abstract

The Erice 50 Charter titled "Strategies for Diseases Prevention and Health Promotion in Urban Areas" was unanimously approved at the conclusion of the 50th Residential Course "Urban Health. Instruments for promoting health and for assessing hygienic and sanitary conditions in urban areas", held from 29th March to 2nd April 2017 in Erice, at the "Ettore Majorana" Foundation and Centre for Scientific Culture and promoted by the International School of Epidemiology and Preventive Medicine "G. D'Alessandro" and the Study Group "Building Hygiene" of the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI). At the conclusion of the intense learning experience during the Course, with more than 20 lectures, workshops and long-lasting discussions between Professors and Students, the participants identified the major points connecting urban features and Public Health, claiming the pivotal role of urban planning strategies for the management of Diseases Prevention and Health Promotion activities. The Erice 50 Charter is configured as a Decalogue for Healthy Cities and as a Think Tank for designing effective strategic actions and best practices to develop urban regeneration interventions and improve the urban quality of contemporary cities. The Decalogue is structured into the following key strategic objectives: 1. Promoting urban planning interventions that address citizens towards healthy behaviours; 2. Improving living conditions in the urban context; 3. Building an accessible and inclusive city, with a special focus on the frail population; 4. Encouraging the foundation of resilient urban areas; 5. Supporting the development of new economies and employment through urban renewal interventions; 6. Tackling social inequalities; 7. Improving stakeholders' awareness of the factors affecting Public Health in the cities; 8. Ensuring a participated urban governance; 9. Introducing qualitative and quantitative performance tools, capable of measuring the city's attitude to promote healthy lifestyles and to monitor the population's health status; 10. Encouraging sharing of knowledge and accessibility to informations. Finally, all the participants underlined that a multidisciplinary team, composed of Physicians specialized in Hygiene, Preventive Medicine, Public Health and Technicians as Architects, Urban planners and Engineers, is needed to deepen the research topic of Urban Health.

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 (<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.

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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Team Reading (Peer Review) of Suspicious/Positive Slides for Continuous Quality Improvement in Cervical-Vaginal Cytology: A Comparison between Methods and Indicators [Articolo su rivista]
Placidi, Antonio; Capparucci, Paola; Di Luzio, Antonella; Manca, Gabriella; Mania, Eloisa; Filippini, Tommaso; Giorgi Rossi, Paolo
abstract

In 2013, the Local Health Unit Roma 2 ex C screening laboratory introduced a new set of indicators for quality assurance. We compare 2 sets of indicators based on routine multiple readings (peer review) for their ability to identify problems in single-reader accuracy. Methods: All suspect slides were blindly reviewed by all the cytologists of the laboratory. The standard set of indicators includes interreader Cohen's kappa, positivity rate and atypical squamous cell of undetermined significance/squamous intraepithelial lesion (ASC-US/SIL) ratio. The new set included sensitivity for cervical intraepithelial neoplasia of grade 2 or worse (CIN2+), positive predictive value (PPV) and percentage of positive high-risk (HR)-HPV cases among ASC-US. In order to estimate sensitivity and PPV, we considered all women for whom there was a consensus of negative cytology, negative HR-HPV test, negative colposcopy or negative histology true negative. Results: Kappa values ranged from 0.521 to 0.753, with narrow 95% confidence intervals (CIs). Positivity rate ranged from 73.9 to 85.7 and the ASC-US/SIL ratio from 0.61 to 0.81. Sensitivity for CIN2+ at the low-grade SIL threshold ranged from 85.8 to 94.2, PPV ranged from 14.8 to 19.4, and both had a broad 95% CI. Readers with low sensitivity did not show low kappa values. The percentage proportion of HR-HPV-positives (HR-HPV+) among ASC-US ranged from 39.9 to 43.8% with a narrow 95% CI. Conclusion: The proportion of HR-HPV+ among ASC-US cases is a powerful indicator to address in training.

2016 - The epidemiology of selenium and human health. [Capitolo/Saggio]
Vinceti, M; Burlingame, B; Filippini, T; Naska, A; Bargellini, A; Borella, P.
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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 - Assessing multiple sources of cadmium exposure in an Italian population. [Abstract in Atti di Convegno]
Filippini, Tommaso; Cherubini, Alessandro; Maffeis, Giuseppe; Malagoli, Carlotta; Malavolti, Marcella; Sieri, Sabina; Krogh, Vittorio; Vescovi, Luciano; Modenesi, Marina; Michalke, Bernhard
abstract

Assessing multiple sources of cadmium exposure in an Italian population.

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 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 - 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.
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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
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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
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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 - 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 - 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 - 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
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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 - 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.
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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
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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 fattori comportamentali tra i lavoratori in Emilia-Romagna secondo la sorveglianza PASSI [Abstract in Atti di Convegno]
Venturelli, F; Carrozzi, G; Balestra, F; Sampaolo, L; Bolognesi, L; Bertozzi, N; Filippini, T; Ferrari, D; Bernardini, M; Giannini, A; Bargellini, A; Finarelli, C
abstract

INTRODUZIONE: In Italia, la promozione della salute sui luoghi di lavoro sta evolvendo, orientata dal D.lgs. 81/2008 e in linea con iniziative internazionali come il Workplace Health Promotion (WHP). Accanto a scuole e luoghi di cura, anche il posto di lavoro è ormai identificato come setting opportunistico per svolgere attività di prevenzione, non solo mirata a fattori di rischio occupazionali o alla cultura della sicurezza, ma anche come educazione a stili di vita salutari. L’obiettivo è descrivere i differenziali dei principali fattori di rischio comportamentali in relazione alla condizione lavorativa, alla mansione e al settore d’impiego per indirizzare la promozione della salute nei luoghi di lavoro. MATERIALI E METODI: Sono state analizzate 9977 interviste PASSI di persone di 18-69 anni, raccolte nel triennio 2010-12 in Emilia-Romagna, regione aderente al modulo opzionale sulla sicurezza sul lavoro. PASSI è una sorveglianza nazionale sui fattori comportamentali di salute realizzata mediante interviste telefoniche effettuate da operatori dei Dipartimenti di prevenzione delle ASL italiane. L’analisi mette in relazione alcuni comportamenti con le principali variabili socio-demografiche (classe d’età, sesso, livello d’istruzione, difficoltà economiche, cittadinanza) e quelle riguardanti mansione svolta e settore d’impiego. I fattori indagati sono: abitudine tabagica, consumo di alcol, indice di massa corporea e attività fisica svolta. RISULTATI: Il 29.3% degli intervistati ha dichiarato di essere fumatore. L’abitudine tabagica è maggiore negli uomini (32.9%), nella fascia d’età 18-34 anni (34.0%), nelle persone con bassa scolarità (32.9%) e con molte difficoltà economiche percepite (42.2%). Emergono differenze per condizione lavorativa: fuma il 31.3% (IC95% 30.1-32.5) di chi lavora in modo continuativo, il 37.2% (IC95% 32.7-42.0) di chi lavora in modo non continuativo e il 23.6% (IC95% 22.0-25.3) di chi non lavora. Il dato è disomogeneo anche per settori d’impiego, dal 18.5% del settore scolastico al 39.5% dell’industria del legno e della carta, e per mansione svolta, dal 14.6% nelle forze dell’ordine al 39.8% negli operai. Il fumo è più frequente tra chi svolge una mansione manuale (38.4% IC95% 36.2-40.7). Secondo i criteri PASSI, il 21.4% degli intervistati è definito consumatore di alcol a maggior rischio per la salute. Tale dato è maggiore negli uomini (27.9%), tra 18-34 anni (34.2%) e in persone con alto grado d’istruzione (23.1%). La prevalenza per condizione lavorativa è del 21,3% (IC95% 20.3-22.4) tra chi lavora in modo continuativo, 27.3% (IC95% 23.3-31.8) tra chi in modo discontinuo e del 20.7% (IC95% 19.1-22.3) in chi non lavora. Tra i lavoratori è più diffuso il consumo definito binge drinking (12.0% IC95% 11.2-12.8). I settori meno interessati sono la pubblica amministrazione e la sanità (14.8%), mentre nei trasporti si raggiunge il 28%. Il 42.9% degli intervistati risulta in eccesso ponderale: il 31.7% in sovrappeso e l’11.2% obeso. Gli uomini (53.1%), la fascia d’età 50-69 anni (58.1%), le persone a bassa scolarità (53.1%) e coloro che percepiscono difficoltà economiche (46.5%) sono le categorie più coinvolte. Tra chi lavora in modo continuativo la prevalenza è del 41.4% (IC95% 40.1-42.7), tra chi lavora saltuariamente è del 39.0% (IC95% 34.5-43.7) e 46.7% (IC95% 44.8-48.6) tra chi non lavora. Tra settori, l’eccesso ponderale è meno rappresentato in quello scolastico (30.2%) e molto diffuso nell’agricolo (55.1%). Tra le mansioni, è più frequente in chi lavora manualmente (47.4%) e le percentuali vanno dal 28.0% degli insegnanti al 55.9% delle forze dell’ordine. Secondo i criteri PASSI, il 21.5% degli intervistati è sedentario, il 41,7% parzialmente attivo e il 36,8% attivo. La sedentarietà è più diffusa tra le donne (22.4%), nella fascia d’età 50-69 anni (25.5%), in persone con basso livello d’istruzione (

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 - 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
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2014 - Ruolo dell’igienista nella sorveglianza e nel controllo dei casi sospetti di Ebola: un esempio di integrazione ospedale-territorio nella Provincia di Modena [Relazione in Atti di Convegno]
Bellucci, C; Bottosso, E; Filippini, T; Santangelo, M; Soncini, F; Venturelli, F; Borella, P
abstract

Il Virus Ebola è un Filovirus responsabile di una grave forma di Febbre Emorragica con un tasso di letalità compreso tra il 50 e il 90%. Non esistono attualmente terapie approvate per uso umano al di fuori del trattamento di supporto: sono in fase di sviluppo differenti strategie terapeutiche fra cui vaccini, molecole interferenti con la produzione di proteine virali e anticorpi monoclonali. Da 9 mesi è in corso in Africa Occidentale nei territori di Nigeria, Sierra Leone, Guinea e Liberia la più grave ed estesa epidemia di Ebola registrata dalla scoperta del virus con più di 3000 casi fra confermati e sospetti ed oltre 1500 decessi. In ragione di ciò l’OMS ha dichiarato tale epidemia “un’emergenza di Sanità Pubblica di rilevanza internazionale” ed ha emanato specifiche raccomandazioni per i paesi direttamente colpiti e per gli Stati membri. La Regione Emilia Romagna, in accordo con le indicazioni del Ministero della Salute, ha emanato una specifica circolare sulla base della quale l’Ausl di Modena ha predisposto un piano condiviso con l’AOU Policlinico allo scopo di individuare e gestire prontamente i casi sospetti. L’agente infettivo viene trasmesso per contatto diretto di mucose o cute non integra coi fluidi corporei e secrezioni di persone e animali infetti. Dopo un periodo di incubazione variabile tra 2 e 21 giorni, i primi sintomi di malattia sono aspecifici (febbre, malessere generale, cefalea, mialgie) mentre col progredire dell’infezione si può assistere ad un’evoluzione verso l’insufficienza multi-organo o forme francamente emorragiche. Sono state formalizzate istruzioni operative per la gestione protetta del caso sospetto, dall’accettazione, alla diagnosi, fino al trasferimento presso i centri di riferimento nazionali (Spallanzani-Roma, Sacco-Milano), resi fruibili dispositivi di protezione individuali per gli operatori e informato il personale sanitario dei percorsi strutturati mediante adeguati corsi di formazione. A livello locale, le Direzioni Sanitarie dovranno promuovere l’integrazione delle attività di comunicazione tra le diverse strutture coinvolte (ospedali, distretti, Dipartimenti di Sanità Pubblica, Dipartimenti delle Cure Primarie, Servizi di Continuità Assistenziale) con i medici di medicina generale e i pediatri di libera scelta, per garantire un’informazione corretta sulla malattia, sui rischi e sulle misure di prevenzione e per contribuire ad evitare immotivati allarmismi, facendo riferimento a quanto pubblicato e costantemente aggiornato sul sito del Ministero della Salute.

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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