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Massimo PELLEGRINI

Ricercatore Universitario
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede ex-Sc. Biomediche


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Pubblicazioni

- Nuovo sostituto dermico e sua applicazione terapeutica [Brevetto]
Giannetti, Alberto; Magnoni, Cristina; Benassi, Luisa; Pellegrini, Massimo
abstract

Il prodotto oggetto del brevetto è costituito da:a)cellule staminali/stromali multipotenti autologhe ottenute da microaspirazione di tessuto adiposo sottocutaneo e in grado di differenziare nelle cellule che costituiscono il derma umano e di produrre matrice connettivale; b) da una matrice biocompatibile tridimensionale.Le cellule stromali autologhe multipotenti sono seminate nello scaffold dopo un periodo di selezione-coltura in vitro. Questo prodotto è destinato alle strutture sanitarie specialistiche con le seguenti indicazioni terapeutiche: lesioni con perdita di tessuti molli di varia eziologia, sia di natura acuta (traumatiche, ustioni, esiti post-chirurgici) sia di natura cronica (ferite da pressione, ulcere vascolari, ulcere del piede diabetico).


2023 - Abdominal Fat Characteristics and Mortality in Rectal Cancer: A Retrospective Study [Articolo su rivista]
Pellegrini, Massimo; Besutti, Giulia; Ottone, Marta; Canovi, Simone; Bonelli, Efrem; Venturelli, Francesco; Farì, Roberto; Damato, Angela; Bonelli, Candida; Pinto, Carmine; Ligabue, Guido; Pattacini, Pierpaolo; Giorgi Rossi, Paolo; El Ghoch, Marwan
abstract

: The aim of this study was to evaluate the association of adipose tissue characteristics with survival in rectal cancer patients. All consecutive patients, diagnosed with stage II-IV rectal cancer between 2010-2016 using baseline unenhanced Computed Tomography (CT), were included. Baseline total, subcutaneous and visceral adipose tissue areas (TAT, SAT, VAT) and densities (TATd, SATd, VATd) at third lumbar vertebra (L3) were retrospectively measured. The association of these tissues with cancer-specific and progression-free survival (CCS, PFS) was assessed by using competitive risk models adjusted by age, sex and stage. Among the 274 included patients (median age 70 years, 41.2% females), the protective effect of increasing adipose tissue area on survival could be due to random fluctuations (e.g., sub-distribution hazard ratio-SHR for one cm2 increase in SAT = 0.997; 95%confidence interval-CI = 0.994-1.000; p = 0.057, for CSS), while increasing density was associated with poorer survival (e.g., SHR for one Hounsfield Unit-HU increase in SATd = 1.03, 95% CI = 1.01-1.05, p = 0.002, for CSS). In models considering each adipose tissue area and respective density, the association with CSS tended to disappear for areas, while it did not change for TATd and SATd. No association was found with PFS. In conclusion, adipose tissue density influenced survival in rectal cancer patients, raising awareness on a routinely measurable variable that requires more research efforts.


2022 - Approaching Sarcopenic Obesity in Young and Middle-Aged Female Adults in Weight Management Settings: A Narrative Review [Articolo su rivista]
Pellegrini, M.; Itani, L.; Rossi, A. P.; Kreidieh, D.; El Masri, D.; Tannir, H.; El Ghoch, M.
abstract

This paper presents a review of the available literature on sarcopenic obesity (SO) in young and middle-aged female adults with obesity in weight management settings. A literature review using the PubMed/Medline and Science Direct databases was conducted, and the data were summarized through a narrative approach. Firstly, some physical performance tests and questionnaires are available for screening young and middle-aged female adults with a high risk of SO. Secondly, these patients can undergo instrumental measurements such as dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) to confirm or reject a diagnosis of SO, applying definitions that account for body mass. Thirdly, SO is a prevalent phenotype in females seeking weight management treatment, as well as being strongly associated (vs. non-SO) with obesity-related comorbidities that need to be promptly managed, initially with nutritional programs or/and in combination with medications. Finally, patients with SO have a reduced baseline resting energy expenditure and more sedentary behaviors, which seem to account for the relationship between SO and poorer weight management outcomes, such as a higher early dropout rate and major later difficulties in weight loss maintenance. Therefore, specific strategies for personalized weight management programs for patients with SO should be incorporated to determine a successful management of this phenotype.


2022 - Do Lifestyle Interventions before Gastric Bypass Prevent Weight Regain after Surgery? A Five-Year Longitudinal Study [Articolo su rivista]
Vaccaro, Salvatore; Itani, Leila; Scazzina, Francesca; Bonilauri, Stefano; Maria Cartelli, Concetto; El Ghoch, Marwan; Pellegrini, Massimo
abstract

It is unclear whether weight loss (WL) achieved by means of lifestyle interventions (LSIs) before bariatric surgery (BS) can improve long-term WL outcomes after surgery. We aimed to assess the impact of a structured LSI on WL% after gastric bypass (GBP). Two groups of patients were selected from a large cohort of participants with obesity who underwent GBP surgery at Santa Maria Nuova Hospital (Reggio Emilia, Italy). The groups were categorized as those who have or have not received LSI prior to GBP. The LSI group included 91 participants (cases) compared to 123 participants (controls) in the non-LSI group. WL% was measured at follow-up times of 1, 3, 6, 12, 24, 36, 48, and 60 months. The LSI group achieved a clinically significant WL% (-7.5%) before BS, and at the time of surgery, the two groups had similar body weights and demographic statuses. At all points, until the 24-month follow-up, the two groups displayed similar WLs%. With regard to the longer follow-ups, the LSI group maintained weight loss until the last timepoint (60 months), whereas the non-LSI group experienced weight regain at 36, 48, and 60 months. In a real-world context, a structured behavioral LSI prior to GBP seems to prevent longer-term weight regain.


2022 - Impact of low skeletal muscle mass and quality on clinical outcomes in patients with head and neck cancer undergoing (chemo)radiation [Articolo su rivista]
Bardoscia, Lilia; Besutti, Giulia; Pellegrini, Massimo; Pagano, Maria; Bonelli, Candida; Bonelli, Efrem; Braglia, Luca; Cozzi, Salvatore; Roncali, Massimo; Iotti, Cinzia; Pinto, Carmine; Pattacini, Pierpaolo; Ciammella, Patrizia
abstract

The study aimed to explore the impact of low skeletal muscle mass and quality on survival outcomes and treatment tolerance in patients undergoing radical chemo-radiation therapy for head and neck cancer (HNC). This is significant given the growing interest in sarcopenia as a possible negative predictive/prognostic factor of disease progression and survival. From 2010 to 2017, 225 patients were included in the study. Pre-treatment computed tomography (CT) scans of HNC patients undergoing (chemo)radiation therapy were retrospectively reviewed. The skeletal muscle area, normalized for height to obtain the skeletal muscle index (SMI), the skeletal muscle density (SMD) and the intramuscular adipose tissue area (IMAT) were measured at the level of the L3 vertebra. Low SMD and low SMI were defined according to previously reported thresholds, while high IMAT was defined using population-specific cut-point analysis. SMI, SMD, and IMAT were also measured at the proximal thigh (PT) level and tested as continuous variables. Clinical morpho-functional parameters, baseline nutritional markers with a known or suspected impact on HNC treatment, clinical outcomes and sarcopenia were also collected. In multivariate analyses, adjusted by age, sex, stage, diabetes, body mass index (BMI), and weight loss, L3-SMI was not significantly associated with survival, while poor muscle quality was negatively associated with overall survival (OS) (HR = 1.88, 95% CI = 1.09–3.23, p = 0.022 and HR = 2.04, 95% CI = 1.27–3.27, p = 0.003, for low L3-SMD and high L3-IMAT, respectively), progression-free survival (PFS) (HR = 2.26, 95% CI = 1.39–3.66, p = 0.001 and HR = 1.97, 95% CI = 1.30–2.97, p = 0.001, for low L3-SMD and high L3-IMAT, respectively) and cancer-specific survival (CSS) (HR = 2.40, 95% CI = 1.28–4.51, p = 0.006 and HR = 1.81, 95% CI = 1.04–3.13, p = 0.034, for low L3-SMD and high L3-IMAT, respectively). Indices at the PT level, tested as continuous variables, showed that increasing PT-SMI and PT-SMD were significant protective factors for all survival outcomes (for OS: HR for one cm2/m2 increase in PT-SMI 0.96; 95% CI = 0.94–0.98; p = 0.001 and HR for one HU increase in PT-SMD 0.90; 95% CI = 0.85–0.94; p < 0.001, respectively). PT-IMAT was a significant risk factor only in the case of CSS (HR for one cm2 increase 1.02; 95% CI = 1.00– 1.03; p = 0.046). In conclusion, pre-treatment low muscle quality is a strong prognostic indicator of death risk in patients affected by HNC and undergoing (chemo)radiotherapy with curative intent.


2022 - Modifications of Chest CT Body Composition Parameters at Three and Six Months after Severe COVID-19 Pneumonia: A Retrospective Cohort Study [Articolo su rivista]
Besutti, Giulia; Pellegrini, Massimo; Ottone, Marta; Bonelli, Efrem; Monelli, Filippo; Farì, Roberto; Milic, Jovana; Dolci, Giovanni; Fasano, Tommaso; Canovi, Simone; Costi, Stefania; Fugazzaro, Stefania; Massari, Marco; Ligabue, Guido; Croci, Stefania; Salvarani, Carlo; Pattacini, Pierpaolo; Guaraldi, Giovanni; Giorgi Rossi, Paolo
abstract

We aimed to describe body composition changes up to 6-7 months after severe COVID-19 and to evaluate their association with COVID-19 inflammatory burden, described by the integral of the C-reactive protein (CRP) curve. The pectoral muscle area (PMA) and density (PMD), liver-to-spleen (L/S) ratio, and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) were measured at baseline (T0), 2-3 months (T1), and 6-7 months (T2) follow-up CT scans of severe COVID-19 pneumonia survivors. Among the 208 included patients (mean age 65.6 ± 11 years, 31.3% females), decreases in PMA [mean (95%CI) -1.11 (-1.72; -0.51) cm2] and in body fat areas were observed [-3.13 (-10.79; +4.52) cm2 for TAT], larger from T0 to T1 than from T1 to T2. PMD increased only from T1 to T2 [+3.07 (+2.08; +4.06) HU]. Mean decreases were more evident for VAT [-3.55 (-4.94; -2.17) cm2] and steatosis [L/S ratio increase +0.17 (+0.13; +0.20)] than for TAT. In multivariable models adjusted by age, sex, and baseline TAT, increasing the CRP interval was associated with greater PMA reductions, smaller PMD increases, and greater VAT and steatosis decreases, but it was not associated with TAT decreases. In conclusion, muscle loss and fat loss (more apparent in visceral compartments) continue until 6-7 months after COVID-19. The inflammatory burden is associated with skeletal muscle loss and visceral/liver fat loss.


2022 - New BMI Cut-Off Points for Obesity in Middle-Aged and Older Adults in Clinical Nutrition Settings in Italy: A Cross-Sectional Study [Articolo su rivista]
Di Renzo, Laura; Itani, Leila; Gualtieri, Paola; Pellegrini, Massimo; El Ghoch, Marwan; De Lorenzo, Antonino
abstract

Obesity is a major health problem defined as an excess accumulation of body fat (BF). The World Health Organization (WHO) usually relies on a body mass index (BMI) ≥ 30 kg/m2 as an indicator of obesity. Due to changes in body composition that occur across the lifespan, with an increase in BF and a decrease in lean mass, we aimed to test the validity of this BMI cut-off point for adiposity in middle-aged and older adults. This cross-sectional study, composed of 4800 adults of mixed gender aged between 40 and 80 years, included (according to the WHO BMI classification) 1087 normal-weight, 1826 overweight, and 1887 obese individuals who were referred to the Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Italy. The sample was then categorized by adiposity status based on the total BF% as measured by dual-energy X-ray absorptiometry (DXA), and the best sensitivity and specificity were attained for predicting obesity according to the receiver operating characteristic curve (ROC) analysis. In a real-world clinical setting, a new BMI cut-off point (BMI = 27.27 kg/m2) has been identified for predicting obesity in middle-aged and older adults. Obesity guidelines in Italy therefore need to be revised accordingly.


2022 - Prognostic Role of the Pectoralis Musculature in Patients with COVID-19. A Multicenter Study [Articolo su rivista]
Surov, Alexey; Kardas, Hakan; Besutti, Giulia; Pellegrini, Massimo; Ottone, Marta; Onur, Mehmet Ruhi; Atak, Firat; Erdemir, Ahmet Gurkan; Hocaoglu, Elif; Yıldız, Ömer; Inci, Ercan; Cingöz, Eda; Cingöz, Mehmet; Dursun, Memduh; Korkmaz, İnan; Orhan, Çağrı; Strobel, Alexandra; Wienke, Andreas; Pech, Maciej
abstract


2022 - The Risk of Sarcopenia among Adults with Normal-Weight Obesity in a Nutritional Management Setting [Articolo su rivista]
De Lorenzo, Antonino; Pellegrini, Massimo; Gualtieri, Paola; Itani, Leila; El Ghoch, Marwan; Di Renzo, Laura
abstract

Normal-weight obesity (NWO) is a phenotype characterized by excessive body fat (BF) despite normal body weight. We aimed to assess the association between NWO and the risk of sarcopenia. Two groups of patients with a normal body mass index [BMI (20–24.9 kg/m2)] were selected from a large cohort of participants. Body composition was measured using dual-energy X-ray absorptiometry (DXA), and 748 participants were categorized as NWO or normal-weight without obesity (NWNO) and were classed according to whether or not they were at risk of sarcopenia. The “NWO group” included 374 participants (cases), compared to 374 participants (controls) in the “NWNO group”, all of a similar BMI, age and gender. The participants in the “NWO group” displayed a higher prevalence of the risk of sarcopenia than the control group across both genders (0.6% vs. 14.1% in males; 1.4% vs. 36.5% in females). Regression analysis showed that being in the NWO category increased the risk of sarcopenia 22-fold in males (RR = 22.27; 95%CI: 3.35–147.98) and 25-fold in females (RR = 25.22; 95%CI: 8.12–78.36), compared to those in the NWNO category. In a “real-world” nutritional setting, the assessment of body composition to identify NWO syndrome is vital since it is also associated with a higher risk of sarcopenia.


2022 - The Role of Obesity, Body Composition, and Nutrition in COVID-19 Pandemia: A Narrative Review [Articolo su rivista]
Rossi, Andrea P.; Muollo, Valentina; Dalla Valle, Zeno; Urbani, Silvia; Pellegrini, Massimo; El Ghoch, Marwan; Mazzali, Gloria
abstract

The coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, infecting nearly 500 million people, with more than 6 million deaths recorded globally. Obesity leads people to be more vulnerable, developing worse outcomes that can require hospitalization in intensive care units (ICU). This review focused on the available findings that investigated the link between COVID-19, body composition, and nutritional status. Most studies showed that not only body fat quantity but also its distribution seems to play a crucial role in COVID-19 severity. Compared to the body mass index (BMI), visceral adipose tissue and intrathoracic fat are better predictors of COVID-19 severity and indicate the need for hospitalization in ICU and invasive mechanical ventilation. High volumes of epicardial adipose tissue and its thickness can cause an infection located in the myocardial tissue, thereby enhancing severe COVID-related myocardial damage with impairments in coronary flow reserve and thromboembolism. Other important components such as sarcopenia and intermuscular fat augment the vulnerability in contracting COVID-19 and increase mortality, inflammation, and muscle damage. Malnutrition is prevalent in this population, but a lack of knowledge remains regarding the beneficial effects aimed at optimizing nutritional status to limit catabolism and preserve muscle mass. Finally, with the increase in patients recovering from COVID-19, evaluation and treatment in those with Long COVID syndrome may become highly relevant.


2022 - Why should sarcopenic obesity be included in a routine assessment during weight-management programmes? [Articolo su rivista]
El Ghoch, Marwan; Pellegrini, Massimo
abstract


2021 - Prognostic Impact of Muscle Quantity and Quality and Fat Distribution in Diffuse Large B-Cell Lymphoma Patients [Articolo su rivista]
Besutti, G.; Massaro, F.; Bonelli, E.; Braglia, L.; Casali, M.; Versari, A.; Ligabue, G.; Pattacini, P.; Cavuto, S.; Merlo, D. F.; Luminari, S.; Merli, F.; Vaccaro, S.; Pellegrini, M.
abstract

Baseline CT scans of 116 patients (48% female, median 64 years) with diffuse large B-cell lymphoma (DLBCL) were retrospectively reviewed to investigate the prognostic role of sarcopenia and fat compartment distributions on overall survival (OS), progression-free survival (PFS), and early therapy termination. Skeletal muscle index (SMI), skeletal muscle density (SMD), and intermuscular adipose tissue (IMAT) were quantified at the level of the third lumbar vertebra (L3) and proximal thigh (PT). Low L3-SMD, but not low L3-SMI, was associated with early therapy termination (p = 0.028), shorter OS (HR = 6.29; 95% CI = 2.17–18.26; p < 0.001), and shorter PFS (HR = 2.42; 95% CI = 1.26–4.65; p = 0.008). After correction for sex, International Prognostic Index (IPI), BMI, and R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), low L3-SMD remained associated with poor OS (HR = 3.54; 95% CI = 1.10–11.40; p = 0.034) but not with PFS. Increased PT-IMAT was prognostic for poor OS and PFS after correction for sex, IPI, BMI, and R-CHOP therapy (HR = 1.35; CI = 1.03–1.7; p = 0.03, and HR = 1.30; CI = 1.04–1.64; p = 0.024, respectively). Reduced muscle quality (SMD) and increased intermuscular fat (IMAT), rather than low muscle quantity (SMI), are associated with poor prognosis in DLBCL, when measured at the L3 level, and particularly at the level of the proximal thigh. The proximal thigh represents a novel radiological landmark to study body composition.


2021 - Strength and Performance Tests for Screening Reduced Muscle Mass in Elderly Lebanese Males with Obesity in Community Dwellings [Articolo su rivista]
Saadeddine, D.; Itani, L.; Rossi, A. P.; Pellegrini, M.; El Ghoch, M.
abstract

The reduction in skeletal muscle mass (SMM) is a common phenomenon in older adults. It is associated with several diseases, a reduction in physical fitness, longer periods of hospitalization and high rates of mortality. We aimed to identify the reliability of simple tools for screening for reduced SMM among older adult males in Lebanon. The Tanita MC-780MA bioimpedance analyzer (BIA) was used to assess body composition in a population of 102 community-dwelling elderly males with overweight or obesity, in order to be then categorized as with or without reduced SMM. Participants also performed the handgrip strength test and the 4 m gait speed test. Of the total sample of 102 participants (mean age 67.4 ± 6.96 years; BMI 30.8 6 ± 4.04 kg/m2), 32 (31.4%) met the criteria for reduced SMM. Partial correlation analysis showed that handgrip strength (ρ = 0.308, p = 0.002) and 4 m gait speed (ρ = 0.284, p = 0.004) were both associated with low SMM. Receiver operating characteristic (ROC) curve analysis identified discriminating cut-off points of 1.1 m/s for the 4 m gait speed test and 32.0 kg for the handgrip strength test. Our study showed that participants displayed a substantial prevalence of reduced SMM. Reduced 4 m gait speed and handgrip strength were associated with low SMM. Clear cut-off points for strength and functional tests for screening for this condition in Lebanese older men were identified.


2021 - The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients [Articolo su rivista]
Besutti, Giulia; Pellegrini, Massimo; Ottone, Marta; Cantini, Michele; Milic, Jovana; Bonelli, Efrem; Dolci, Giovanni; Cassone, Giulia; Ligabue, Guido; Spaggiari, Lucia; Pattacini, Pierpaolo; Fasano, Tommaso; Canovi, Simone; Massari, Marco; Salvarani, Carlo; Guaraldi, Giovanni; Rossi, Paolo Giorgi; Canovi, Simoneg; Massari, Marcoh; Salvarani, Carloi; Guaraldi, Giovannif; Rossi, Paolo Giorgie; Grilli, Roberto; Marino, Massimiliano; Formoso, Giulio; Formisano, Debora; Bedeschi, Emanuela; Perilli, Cinzia; la Rosa, Elisabetta; Bisaccia, Eufemia; Venturi, Ivano; Vicentini, Massimo; Campari, Cinzia; Gioia, Francesco; Broccoli, Serena; Iotti, Valentina; Mancuso, Pamela; Nitrosi, Andrea; Foracchia, Marco; Colla, Rossana; Zerbini, Alessandro; Ferrari, Anna Maria; Pinotti, Mirco; Facciolongo, Nicola; Lattuada, Ivana; Trabucco, Laura; de Pietri, Stefano; Danelli, Giorgio Francesco; Albertazzi, Laura; Bellesia, Enrica; Corradini, Mattia; Mag-Nani, Elena; Pilia, Annalisa; Polese, Alessandra; Incerti, Silvia Storchi; Zaldini, Piera; Bonanno, Orsola; Revelli, Matteo; Pinto, Carmine; Venturelli, Francesco; Teopompi, Elisabetta; Gallina, Annalisa; Bertellini, Annalisa; Costi, Stefania; Fugazzaro, Stefania
abstract

We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.


2020 - Obesity and Higher Risk for Severe Complications of Covid-19: What to do when the two pandemics meet [Articolo su rivista]
Valerio, A.; Nisoli, E.; Rossi, A. P.; Pellegrini, M.; Todesco, T.; Ghoch, M. E.
abstract

The coronavirus disease 2019 (COVID-19) pandemic has spread around the globe, infecting more than ten million individuals, with more than 500,000 dead; about one half of the infected people have recovered. Despite this fact, a subgroup of individuals affected by COVID-19 is at greater risk of developing worse outcomes and experience a high rate of mortality. Data on the association between obesity and COVID-19 are growing; the available studies, have reported a high prevalence of overweight and obesity in patients experiencing a severe COVID-19 course, with serious complications requiring hospitalization and admission to intensive care units. This paper attempts to highlight potential mechanisms behind the greater vulnerability to COVID-19 of individuals with obesity. The presence of uncontrolled chronic obesity-related comorbidities, particularly pulmonary diseases, can present a primary fertile soil for respiratory tract infection. Combined with immune system impairments, such as alteration in the T-cell proliferation and macrophage differentiation, and the high pro-inflammatory cytokine production by the adipose organ, this may worsen the general condition toward a systemic diffusion of infection. Prevention remains the first line of intervention in these patients that can be achieved by adhering to social distancing and adopting hygiene precautions, combined with a healthy lifestyle. Patients with obesity require preferential access dedicated to primary care services to ensure they are regularly taking their medications for the treatment of any concurrent chronic diseases. Finally, their physicians must promptly manage any medical signs or symptoms in the case of suspected severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection to prevent the risk of severe outcomes.


2019 - In vitro Engineering of a Skin Substitute Based on Adipose-Derived Stem Cells [Articolo su rivista]
Paganelli, A.; Benassi, L.; Pastar, I.; Pellegrini, M.; Azzoni, P.; Vaschieri, C.; Pisciotta, A.; Carnevale, G.; Pellacani, G.; Magnoni, C.
abstract

In the field of wound healing, stem cell-based strategies are gaining importance for their regenerative potential. Adipose-derived stem cells (ADSCs) are a particular subset of mesenchymal stem cells present in the stromal-vascular fraction of the adipose tissue, today considered very attractive for their relative abundance and accessibility in the human body. However, ADSCs are still not routinely used in normal clinical practice. Several studies have also reported ADSC transplantation in association with biomaterials in an attempt to enhance the local retention and growth rate of the cells. The aim of our study was to evaluate the ability of ADSCs to build a dermal scaffold to be potentially used as a dermal substitute in the field of wound healing, with optimal biocompatibility and mechanical properties. ADSCs were defined as CD90-, CD73-, and CD105-positive cells. ADSCs turned out to be capable of secreting all the main components of the extracellular matrix (ECM) upon stimulation, thus efficiently producing a collagen and fibronectin-containing dermal matrix. We also checked whether the ADSC-produced dermal scaffold could be seeded with keratinocytes. The scaffolding material directly produced by ADSCs has several advantages when compared to the commercially available ones: it is easily obtained from the patients and it is 100% biocompatible and supports cell-ECM interaction. Moreover, it represents a possible powerful therapeutic tool for patients with chronic ulcers since it appears to be potentially grafted with keratinocytes layers, thus bypassing the classical two-step grafting procedure.


2018 - Management Strategy of Obesity in the Public Health System: Proposal of a New Model to Optimize Human Resources and Patient’s Motivation [Articolo su rivista]
Pellegrini, Massimo; Kob, Michael; Trovato, Rita; Schrei, Marion; Corazzini, Valentina; Facchin, Nicoletta; Mazzoldi, Mariantonietta; Lucchin, Lucio
abstract

Introduction: Obesity, a disease characterized by an excess of adipose tissue, is a worldwide issue of growing interest in public health. Methods: The multifactorial etiology and pathogenesis of obesity strongly orient the scientific community in considering it as a chronic disease without an effective therapy that works for all patients affected by this clinical condition. This leads to a proliferation of non-scientific and dangerous treatment proposals and fake news. The Dietetic and Clinical Nutrition Unit at Bolzano Hospital in Italy has adopted a new strategy based on transparency to optimize time for the first visit and particularly to increase patients’ knowledge and motivation. Results: This new strategy provides a preliminary consultation between patients who ask for a nutritional examination and a clinical team composed of a clinician, a dietician and a psychologist. We discuss the preliminary results obtained during the period between February 2010 and March 2016.


2016 - Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial [Articolo su rivista]
Castagnaro, Silvia; Pellegrini, Camilla; Pellegrini, Massimo; Chrisam, Martina; Sabatelli, Patrizia; Toni, Silvia; Grumati, Paolo; Ripamonti, Claudio; Pratelli, Loredana; Maraldi, Nadir M.; Cocchi, Daniela; Righi, Valeria; Faldini, Cesare; Sandri, Marco; Bonaldo, Paolo; Merlini, Luciano
abstract

A pilot clinical trial based on nutritional modulation was designed to assess the efficacy of a one-year low-protein diet in activating autophagy in skeletal muscle of patients affected by COL6/collagen VI-related myopathies. Ullrich congenital muscular dystrophy and Bethlem myopathy are rare inherited muscle disorders caused by mutations of COL6 genes and for which no cure is yet available. Studies in col6 null mice revealed that myofiber degeneration involves autophagy defects and that forced activation of autophagy results in the amelioration of muscle pathology. Seven adult patients affected by COL6 myopathies underwent a controlled low-protein diet for 12 mo and we evaluated the presence of autophagosomes and the mRNA and protein levels for BECN1/Beclin 1 and MAP1LC3B/LC3B in muscle biopsies and blood leukocytes. Safety measures were assessed, including muscle strength, motor and respiratory function, and metabolic parameters. After one y of low-protein diet, autophagic markers were increased in skeletal muscle and blood leukocytes of patients. The treatment was safe as shown by preservation of lean:fat percentage of body composition, muscle strength and function. Moreover, the decreased incidence of myofiber apoptosis indicated benefits in muscle homeostasis, and the metabolic changes pointed at improved mitochondrial function. These data provide evidence that a low-protein diet is able to activate autophagy and is safe and tolerable in patients with COL6 myopathies, pointing at autophagy activation as a potential target for therapeutic applications. In addition, our findings indicate that blood leukocytes are a promising noninvasive tool for monitoring autophagy activation in patients.


2016 - NMR EVALUATION OF MITOCHONDRIAL DYSFUNCTION IN LOW-PROTEIN DIET IN COLLAGEN VI-RELATED MYOPATHIES [Abstract in Atti di Convegno]
Righi, V.; Mucci, Adele; Pellegrini, Massimo; Merlini, L.; Schenetti, Luisa
abstract

A pilot clinical trial based on nutritional modulation was designed to assess the efficacy of one-year low-protein diet (LPD) in activating autophagy in skeletal muscle of patients affected by COL6/collagen VI-related myopathies. Ullrich congenital muscular dystrophy and Bethlem myopathy are rare inherited muscle disorders caused by mutations of COL6 genes and for which no cure is available yet. Studies in COL6 null mice revealed that myofiber degeneration involves autophagy defects and that forced activation of autophagy results in the amelioration of muscle pathology. Seven adult patients affected by COL6 myopathies underwent a controlled low-protein diet for twelve months and the alterated metabolites pathway was evaluated in blood samples. Safety measures were assessed, including muscle strength, motor and respiratory function, and metabolic parameters. The treatment resulted safe as shown by preservation of lean-fat percentage of body composition, muscle strength and function. Patients displayed a reduction in lactate (ranging from 10% to 60%) and a decrease in acetate serum levels after one year, as revealed by NMR analysis. The reduced concentration of lactate and acetate after LPD suggests an improvement in mitochondrial aerobic energy production through the tricarboxylic acid cycle, with a reduced conversion of pyruvate to lactate. These metabolic changes point to an improved mitochondrial function. The data provide evidence that LPD is able to activate autophagy and is safe and tolerable in patients with COL6 myopathies, indicating autophagy activation as a potential target for therapeutic applications.


2016 - Physical activity, body weight, and resumption of menses in anorexia nervosa [Articolo su rivista]
El Ghoch, Marwan Ibrahim; Calugi, Simona; Pellegrini, Massimo; Chignola, Elisa; Dalle Grave, Riccardo
abstract

Few data are available on long-term outcomes and increased physical activity at the end of inpatient treatment in patients with anorexia nervosa. Hence we assessed the association between physical activity, measured objectively by Sense Wear Armband (SWA), and body mass index (BMI; kg/m2) and menses resumption at one-year follow-up in 32 females with anorexia nervosa who had restored normal body weight by the end of a specialist inpatient treatment. Combined logistic regression models used to evaluate the relationship between variables at discharge, BMI and resumption of menses at one-year follow-up revealed no significant association between BMI at one-year follow-up and physical activity patterns at inpatient discharge. However, total daily steps at inpatient discharge were significantly lower in patients who had resumed menstruation, as confirmed by logistic regression analysis. A small reduction in daily steps at inpatient discharge (~1000 steps) was found to increase the probability of menses resumption at one-year follow-up by ~3%. These data provide preliminary indications as to the potential usefulness of assessing daily steps to predict the resumption of menses at one-year follow-up in patients with anorexia nervosa who restore body weight by the end of inpatient treatment, although confirmation on larger samples is urgently required.


2016 - Sleep Patterns Before and After Weight Restoration in Females with Anorexia Nervosa: A Longitudinal Controlled Study [Articolo su rivista]
El Ghoch, M.; Calugi, S.; Bernabe, J.; Pellegrini, M.; Milanese, C.; Chignola, E.; Dalle Grave, R.
abstract

Objective: To assess sleep patterns in female patients with anorexia nervosa before and after weight restoration. Methods: Sleep patterns were measured objectively using a Sense Wear Armband before and after weight restoration in 50 female patients with anorexia nervosa, and in 25 healthy females. Results: At baseline, patients with anorexia nervosa exhibited lower total sleep time and sleep onset latency than controls, the former apparently associated with baseline BMI, duration of illness and age. However, after weight restoration, total sleep time and sleep onset latency were similar to controls, despite the persistence of longer periods of wake after sleep onset. Discussion: In patients with anorexia nervosa, total sleep time and sleep onset latency appears to be reduced. This sleep disturbance seems to be influenced by the duration and severity of malnutrition, and appears to normalize with weight restoration. Even though a discontinuous sleep pattern seems to persist, this finding should be discussed with patients. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.


2015 - Nutritional Status Evaluation: Body Composition and Energy Balance [Capitolo/Saggio]
Pellegrini, Massimo; Battistini, Nino C.
abstract

Nutritional status is the result of our lifestyle over the long term and a major determinant of our health. The balance between energy we ingest as food and energy we expend in the course of physiological processes during our daily activities defines our body composition, a key component of nutritional status. A positive energy balance is at the base of overweight and obesity, where a generalized or a central increase in fat mass is associated with a higher cardio-metabolic risk. In order to plan an effective dietary intervention, we need to know the current body composition in terms of fat mass and fat-free mass and the basal metabolic rate, that is, the energy expenditure at rest in the postabsorptive state. Basal metabolic rate can be assessed by estimate equations or measured by calorimetry. Body composition can be measured or estimated in the field, at the bedside or clinic, or in the laboratory. Anthropometry, body impedance assessment, dual X-ray absorptiometry, and imaging techniques like computed tomography and magnetic resonance imaging are more commonly used in the clinical settings, while densitometry and dilution methods are typical laboratory methods. Information on body composition and energy expenditure represent a powerful tool available to the health-care worker who deals with nutrition for the prevention or treatment of obesity-associated cardio-metabolic diseases.


2014 - Body composition, eating disorder psychopathology, and psychological distress in anorexia nervosa: a longitudinal study [Articolo su rivista]
El Ghoch, Marwan; Milanese, Chiara; Calugi, Simona; Pellegrini, Massimo; Battistini, Nino Carlo; Dalle Grave, Riccardo
abstract

BACKGROUND:Although the effect of immediate weight restoration on body composition and body fat distribution has previously been studied in anorexia nervosa (AN), its influence in women with AN on eating disorder psychopathology and psychological distress has not previously been investigated to our knowledge. OBJECTIVES:We assessed body composition and fat mass distribution before and after body weight restoration and investigated any relation between changes in body fat patterns of patients with AN treated in a specialist inpatient unit and their eating disorder and psychological distress features. DESIGN: Body composition was measured by using dual-energy X-ray absorptiometry in 50 female, adult patients with AN before and after complete weight restoration [body mass index (BMI; in kg/m²) ≥18.5] and 100 healthy control subjects matched by age and post-treatment BMI of study group participants. Eating disorder psychopathology and psychological distress were assessed in the AN group before and after weight restoration by using the Eating Disorder Examination interview and the Global Severity Index of the Brief Symptom Inventory (BSI-GSI), respectively. RESULTS:After the achievement of complete weight restoration, patients with AN had higher trunk (P < 0.001), android (P < 0.001), and gynoid (P < 0.001) fat masses and lower arm (P < 0.001) and leg (P = 0.001) fat masses with respect to control subjects. No relation was shown between body-composition variables and eating disorder psychopathology in the AN group, and the only significant predictor of change in BSI-GSI was the baseline BSI-GSI score. CONCLUSION: The normalization of body weight in patients with AN is associated with a preferential distribution of body fat in central regions, which does not, however, seem to influence either eating disorder psychopathology or psychological distress scores.


2014 - Nutritional status evaluation in patients affected by bethlem myopathy and ullrich congenital muscular dystrophy [Articolo su rivista]
Toni, Silvia; Morandi, Riccardo; Busacchi, Marcello; Tardini, Lucia; Merlini, Luciano; Battistini, Nino Carlo; Pellegrini, Massimo
abstract

Collagen VI mutations lead to disabling myopathies like Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). We have investigated the nutritional and metabolic status of one UCMD and seven BM patients (five female, three male, mean age 31 ± 9 years) in order to find a potential metabolic target for nutritional intervention. For this study, we used standard anthropometric tools, such as BMI evaluation and body circumference measurements. All results were compared to dual-energy X-ray absorptiometry (DXA), considered the "gold standard" method. Energy intake of each patient was evaluated through longitudinal methods (7-day food diary) while resting energy expenditure (REE) was predicted using specific equations and measured by indirect calorimetry. Clinical evaluation included general and nutritional blood and urine laboratory analyses and quantitative muscle strength measurement by hand-held dynamometry. BM and UCMD patients showed an altered body composition, characterized by low free fat mass (FFM) and high fat mass (FM), allowing us to classify them as sarcopenic, and all but one as sarcopenic-obese. Another main result was the negative correlation between REE/FFM ratio (basal energy expenditure per kilograms of fat-free mass) and the severity of the disease, as defined by the muscle megascore (correlation coefficient -0.955, P-value <0.001). We postulate that the increase of the REE/FFM ratio in relation to the severity of the disease may be due to an altered and pathophysiological loss of energetic efficiency at the expense of skeletal muscle. We show that a specific metabolic disequilibrium is related to the severity of the disease, which may represent a target for a nutritional intervention in these patients.


2013 - Body composition, muscle strength, and physical function of patients with Bethlem myopathy and Ullrich congenital muscular dystrophy. [Articolo su rivista]
Miscione, Mt; Bruno, F; Ripamonti, C; Nervuti, G; Orsini, R; Faldini, C; Pellegrini, Massimo; Cocchi, D; Merlini, L.
abstract

Objective. To determine the contributions of body mass, adiposity, and muscularity to physical function and muscle strength in adult patients with Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). Materials and Methods. Evaluation involved one UCMD and 7 BM patients. Body composition was determined by body mass index (BMI) and dual-energy-X-ray-absorptiometry (DXA), muscle strength by dynamometry, physical function by the distance walked in 6 minutes (6MWD), forced vital capacity (FVC) by a spirometer. Results. Six participants were of normal weight and 2 overweight based on BMI; all were sarcopenic based on appendicular fat free mass index (AFFMI); and 7 were sarcopenic obese based on AFFMI and % fat mass. Average muscle strength was reduced below 50% of normal. The 6MWD was in BM patients 30% less than normal. FVC was reduced in 4 of the BM patients. Muscle strength had a good correlation with the physical function variables. Correlation between muscle strength and BMI was poor; it was very high with AFFMI. AFFMI was the best single explicator of muscle strength and physical function. Conclusion. Muscle mass determined by DXA explains most of the variability of the measures of muscle strength and physical function in patients with BM and UCMD.


2013 - Body Fat Mass Assessment: A Comparison between an Ultrasound-Based Device and a Discovery A Model of DXA [Articolo su rivista]
Jean Claude, Pineau; Loïc, Lalys; Pellegrini, Massimo; Nino Carlo, Battistini
abstract

Objective. To examine measurement of body composition by ultrasound compared with a reference technique:dual energy X- ray absorptiometry (DXA). We evaluated the accuracy of a portable ultrasound-based device in estimating total body fat mass with those assessed by DXA in adult. Methods. Body fat mass has been estimated using a portable ultrasound-based device in comparison with a contemporary reference DXA apparatus: the Hologic Discovery A. Anthropometric data has been assessed in order to maximize the output of the software associated with the ultrasound-based device. A cross-validation between ultrasound technique (US) and DXA was developed in this study. Total body fat mass estimated by ultrasound was compared with this DXA model in a sample of 83 women and 41 men. Results. Ultrasound technique (US) of body fat (BF) was better correlated with DXA in both women (2 = 0.97, < 0.01) and men (2 = 0.92, < 0.01) with standard errors of estimates (SEE) being 2.1 kg and 2.2 kg, respectively. Conclusion. The use of a portable device based on a US produced a very accurate BF estimate in relation to DXA reference technique. As DXA absorptiometry techniques are not interchangeable, the use of our ultrasound-based device needs to be recalibrated on a more contemporary DXA.


2013 - Measured physical activity in anorexia nervosa: Features and treatment outcome [Articolo su rivista]
El Ghoch, Marwan; Calugi, Simona; Pellegrini, Massimo; Milanese, Chiara; Busacchi, Marcello; Battistini, Nino Carlo; Bernabè, Jasmine; Dalle Grave, Riccardo
abstract

OBJECTIVE: To assess the role of measured physical activity (PA) in anorexia nervosa treatment outcome, and to compare the PA of patients with anorexia nervosa with age-matched controls. METHOD: PA was assessed by means of Sense Wear Armband before and after a cognitive-behavioral inpatient treatment in 53 consecutive females with anorexia nervosa, and in 53 healthy age-matched controls. RESULTS: At baseline, patients with anorexia nervosa exhibited a higher duration of moderate-vigorous PA (MVPA≥3 Metabolic Equivalent Tasks (METs)) than controls (t = 2.91; p = .004). Dropouts had higher duration (sec) and expenditure (kcal·day(-1)) of MVPA than completers. At the end of treatment, completers had a higher number of daily steps, MVPA duration, and expenditure than controls. However, PA was not correlated to eating disorder psychopathology either before or after treatment. DISCUSSION: PA is higher in patients with anorexia nervosa than age-matched controls both before and after treatment, and is associated with treatment dropout.


2013 - Short-term multidisciplinary non-pharmacological intervention is effective in reducing liver fat content assessed non-invasively in patients with nonalcoholic fatty liver disease (NAFLD) [Articolo su rivista]
Scaglioni, Federica; Marino, Mariano; Ciccia, Stefania; Procaccini, Alessia; Busacchi, Marcello; Loria, Paola; Lonardo, Amedeo; Malavolti, Marcella; Battistini, Nino Carlo; Pellegrini, Massimo; Carubbi, Francesca; Bellentani, Stefano
abstract

Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to steatohepatitis, and cirrhosis in patients with alcohol intake less than 20 g/day, and is usually associated with insulin resistance (IR). We tested the efficacy of a non-pharmacological multidisciplinary intervention based on a personalized diet, physical activity and behavior therapy. In this open non-randomized study, personalized diet, physical exercise and behaviour therapy for 3 months were prescribed in 12 consecutive patients with NAFLD. Data show that the multidisciplinary intervention produced a significant reduction of total caloric intake, a 8% reduction in body weight, a modest increase in daily physical activity, a significant (P<0.001) reduction of aminotransferases and a decrease of total hepatic fat content.


2012 - Comparison between dual-energy X-ray absorptiometry and skinfolds thickness in assessing body fat in anorexia nervosa before and after weight restoration. [Articolo su rivista]
El Ghoch, Marwan Ibrahim; Alberti, M.; Milanese, C.; Battistini, Nino Carlo; Pellegrini, Massimo; Capelli, C.; Calugi, S.; Dalle Grave, R.
abstract

The aim of the study was to evaluate the correspondencebetween body fat mass composition (percentage) measured with dual-energy X-rayabsorptiometry (DXA) and estimated by means of skinfold thicknesses (ST)measurement in patients with anorexia nervosa (AN), before and after weight gain.METHODS: Percentage body fat (%BF) was measured with DXA and estimated by STmeasurements using Siri, Brozek, and Heyward equations in 27 adult patients with AN before and after weight gain (pre- and post-treatment) achieved with inpatienttreatment and in 42 healthy age-matched controls. RESULTS: Due to Lohman criteriaand Bland Altman plot there is no correspondence between the %BF measured withDXA and the %BF estimated by predictive equations based on ST measurements inpatients with AN before and after weight gain, with the exception of Brozekequation which showed a mild agreement in pre-treatment AN. However, acorrespondence was observed between the two procedures in healthy controls.CONCLUSIONS: Our data supporting the use of ST measurements do not appear to bean alternative to DXA in estimating body fat percentage, before and after weight gain in patients with AN.


2012 - La composizione corporea: dal laboratorio alla clinica [Capitolo/Saggio]
Pellegrini, Massimo; Malavolti, Marcella; Busacchi, M; Battistini, Nino Carlo
abstract

I nutrienti influenzano lo stato di nutrizione di un soggetto attraverso diverse variabili quali l’introduzione, l’assorbimento e l’utilizzazione degli stessi. Indagare queste variabili, tuttavia, risulta essere poco funzionale mentre possiamo efficacemente concentrarci soltanto su una di queste tre, l’utilizzazione, che risulta direttamente influenzata dalle due precedenti. Illustrando il concetto di utilizzazione possiamo vedere, secondo un modello operativo dinamico, come lo stato di salute sia legato in modo biunivoco allo stato nutrizionale (OMS/WHO, 1998) attraverso due grandi variabili: quella psico-sociale e quella biologica. Di queste due macrocomponenti la variabile biologica risulta costituita da composizione corporea, bilancio energetico e funzioni corporee che sono valutabili dal nutrizionista attraverso metodiche invasive e metodiche non-invasive. Lo studio della composizione corporea è il miglior indicatore a lungo termine dello stato nutrizionale della persona poiché riflette la disponibilità pregressa di nutrienti. Queste caratteristiche risultano particolarmente evidenti in una popolazione altamente specifica e ben caratterizzata.


2012 - Resting energy expenditure assessment in anorexia nervosa: comparison of indirect calorimetry, a multisensor monitor and the Müller equation. [Articolo su rivista]
El Ghoch, M; Alberti, M; Capelli, C; Calugi, S; Battistini, Nino Carlo; Pellegrini, Massimo; Šubašić, S; Lanza, M; Dalle Grave, R.
abstract

The aim of this study was to compare the estimations provided by three different means of measuring the resting energy expenditure (REE) in anorexia nervosa (AN) patients. REE was measured, after 24 h of refeeding, using a portable multisensor body monitor [SenseWear Pro2 Armband (SWA)], FitMate™ method and the Müller equation for individuals with body mass index < 18.5, the latter being based on dual-energy X-ray absorptiometry assessment of body composition. The mean differences between REE values estimated by SWA and those provided by the Müller equation and the FitMate™ method were significantly different from zero in both cases. In contrast, the mean differences between FitMate™ method and Müller equation were weakly significantly different from zero, and a significant correlation was noted between these two methods. In conclusion, the SWA does not appear to be an alternative to FitMate™ and Müller equation methods for assessing REE in AN patients.


2011 - Developmental overfeeding alters hypothalamic neuropeptide mRNA levels and response to a high-fat diet in adult mice [Articolo su rivista]
Ferretti, Silvia; Fornari, Alice; Pedrazzi, Patrizia; Pellegrini, Massimo; Zoli, Michele
abstract

It has been suggested that nutritional manipulations during the first weeks of life can alter the development of the hypothalamic circuits involved in energy homeostasis. We studied the expression of a large number of the hypothalamic neuropeptide mRNAs that control body weight in mice that were overfed during breastfeeding (mice grown in a small litter, SL) and/or during adolescence (adolescent mice fed a high-fat diet, AHF). We also investigated possible alterations in mRNA levels after 50 days of a high-fat diet (high-fat challenge, CHF) at 19 weeks of age. Both SL and AHF conditions caused overweight during the period of developmental overfeeding. During adulthood, all of the mouse groups fed a CHF significantly gained weight in comparison with mice fed a low-fat diet, but the mice that had undergone both breast and adolescent overfeeding (SL-AHF-CHF mice) gained significantly more weight than the control CHF mice. Of the ten neuropeptide mRNAs studied, only neuropeptide Y (NPY) expression was decreased in all of the groups of developmentally overfed adult mice, but CHF during adulthood by itself induced a decrease in NPY, agouti-related protein (AgRP) and orexin (Orx) mRNA levels. Moreover, in the developmentally overfed CHF mice NPY, AgRP, galanin (GAL) and galanin-like peptide (GalP) mRNA levels significantly decreased in comparison with the control CHF mice. These results show that, during adulthood, hypothalamic neuropeptide systems are altered (NPY) and/or abnormally respond to a high-fat diet (NPY, AgRP, GAL and GalP) in mice overfed during critical developmental periods.


2011 - Valutazione dello stress in un campione di conducenti di autobus [Abstract in Rivista]
Bergomi, Margherita; M., Busacchi; Ferrari, Angela; Ferretti, Enrica; Licitra, Giuseppe; Pellegrini, Massimo; R., Vivoli
abstract

OBIETTIVI: Lo studio si prefigge di stimare in conducenti di autobus l’entità dello stress generato dalla guida e l’influenza di fattori individuali quali età, profilo psicologico e stile di vita. Metodi-Sono stati reclutati su base volontaria, previo consenso informato, METODI 40 conducenti di mezzi adibiti al trasporto di persone, di sesso maschile ed età compresa tra 28 e 58anni. I partecipanti allo studio sono stati sottoposti ad una accurata anamnesi per acquisire valutazioni antropometriche e dati circa stile di vita, durata e qualità del sonno notturno e profilo di personalità. Le caratteristiche personologiche sono state valutate con l’Eysenck Personality Questionnaire – Forma ridotta (EPQ-R) e il questionario per l’impulsività (IVE). Per la valutazione soggettiva dello stress lavorativo ai conducenti sono stati somministrati il Perceived Stress Scale (PSS) e il Driver Stress Inventory (DSI). Riguardo alla misura oggettiva dello stress, in un giorno lavorativo - prima, durante e al termine del turno diguida - e nello stesso arco orario di un giorno di riposo, i conducenti hanno provveduto a raccogliere campioni salivari, sui quali sono stati determinati cortisolo e á-amilasi, quali indicatori biochimici dei due principali sistemi coinvolti nella reazione da stress.RISULTATI: I punteggi ottenuti dai questionari (PSS, DSI, EPQ-R, IVE) somministrati nel campione finora analizzato sono collocabili per la maggior parte nel range di normalità in rapporto alla fascia di età. Relativamente agli indicatori biochimici misurati nei campioni di saliva, si è rilevato, durante il turno lavorativo rispetto al giorno di riposo assunto come controllo, un incremento dei livelli sia di á-amilasi che di cortisolo, più marcato rispettivamente all’inizio e a metà del turno di guida. L’analisipreliminare delle correlazioni ha evidenziato un’associazione positiva tra lo stress percepito (PSS) con le sottoscale thrill seeking (DSI), estroversione (EPQ-R), nevroticismo (EPQ-R) e impulsività (IVE). I livelli salivari di á-amilasi infine sono risultati positivamente correlati con le sottoscale del thrill seeking (DSI) e dello psicoticismo (EPQ-R).CONCLUSIONI: Nel campione di autisti esaminato i risultati preliminari depongono per un’associazione tra ricerca del brivido (tratto di vulnerabilità allo stress da guida) e valutazione sia soggettiva (stress percepito) che oggettiva di stress (livelli salivari di á-amilasi, marcatore biochimico della reazione di stress acuto). Se i dati preliminari verranno confermati da uno studio più esteso, potranno fornire utili strumenti per una valutazione integrata dello stress lavoro correlato.


2010 - Scapula development is governed by genetic interactions of Pbx1 with its family members and with Emx2 via their cooperative control of Alx1 [Articolo su rivista]
T. D., Capellini; G., Vaccari; E., Ferretti; Fantini, Sebastian; M., He; Pellegrini, Massimo; L., Quintana; G., Di Giacomo; J., Sharpe; L., Selleri; Zappavigna, Vincenzo
abstract

The genetic pathways underlying shoulder blade development are largely unknown, as gene networks controlling limb morphogenesis have limited influence on scapula formation. Analysis of mouse mutants for Pbx and Emx2 genes has suggested their potential roles in girdle development. In this study, by generating compound mutant mice, we examined the genetic control of scapula development by Pbx genes and their functional relationship with Emx2. Analyses of Pbx and Pbx1;Emx2 compound mutants revealed that Pbx genes share overlapping functions in shoulder development and that Pbx1 genetically interacts with Emx2 in this process. Here, we provide a biochemical basis for Pbx1;Emx2 genetic interaction by showing that Pbx1 and Emx2 can bind specific DNA sequences as heterodimers. Moreover, the expression of genes crucial for scapula development is altered in these mutants, indicating that Pbx genes act upstream of essential pathways for scapula formation. In particular, expression of Alx1, an effector of scapula blade patterning, is absent in all compound mutants. We demonstrate that Pbx1 and Emx2 bind in vivo to a conserved sequence upstream of Alx1 and cooperatively activate its transcription via this potential regulatory element. Our results establish an essential role for Pbx1 in genetic interactions with its family members and with Emx2 and delineate novel regulatory networks in shoulder girdle development.


2010 - Skin Squared [Spin Off]
Pellegrini, Massimo; Giannetti, Alberto; Magnoni, Cristina; Benassi, Luisa; Areta International, s. r. l.; Università di Modena e., Reggio Emilia
abstract


2005 - Mouse ovary developmental RNA and protein markers from gene expression profiling. [Articolo su rivista]
L., Herrera; C., Ottolenghi; J. E., Garcia Ortiz; Pellegrini, Massimo; F., Manini; M. S., Ko; R., Nagaraja; Forabosco, Antonino; D., Schlessinger
abstract

To identify genes involved in morphogenetic events during mouse ovary development, we started with microarray analyses of whole organ RNA. Transcripts for 60% of the 15,000 gene NIA panel were detected, and about 2000 were differentially expressed in nascent newborn compared to adult ovary. Highly differentially expressed transcripts included noncoding RNAs and newly detected genes involved in transcription regulation and signal transduction. The phased pattern of newborn mouse ovary differentiation allowed us to (1) extend information on activity and stage specificity of cell type-specific genes; and (2) generate a list of candidate genes involved in primordial follicle formation, including podocalyxin (Podxl), PDGFR-β, and a follistatin-domain-encoding gene Flst1. Oocyte-specific transcripts included many (e.g., Deltex2, Bicd2, and Zfp37) enriched in growing oocytes, as well as a novel family of untranslated RNA's (RLTR10) that is selectively expressed in early stage follicles. The results indicate that global expression profiling of whole organ RNA provides sensitive first-line information about ovarian histogenesis for which no in vitro cell models are currently available.


2003 - Genotype/phenotype correlations of males affected by Simpson-Golabi-Behmel syndrome with GPC3 gene mutations: Patient report and review of the literature [Articolo su rivista]
Mariani, S; Iughetti, Lorenzo; Bertorelli, R; Coviello, D; Pellegrini, Massimo; Forabosco, Antonino; Bernasconi, Sergio
abstract

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth syndrome with associated visceral and skeletal anomalies. Deletions or point mutations involving the glypican-3 (GPC3) gene at Xq26 are associated with a relatively milder form of this disorder (SGBS1). GPC3 encodes a putative extracellular proteoglycan, glypican-3, that is inferred to play an important role in growth control in embryonic mesodermal tissues in which it is selectively expressed. It appears to form a complex with insulin-like growth factor-II (IGF-II), and might thereby modulate IGF-II action. We reviewed the clinical findings of all published patients with SGBS1 with GPC3 mutations to confirm the clinical specificity for the SGBS1 phenotype. Moreover, we report on a new patient with a GPC3 deletion and IGF-II evaluation.


2002 - Emx2 regulates the proliferation of stem cells of the adult mammalian central nervous system [Articolo su rivista]
Galli, R.; Fiocco, R.; De Filippis, L.; Muzio, L.; Gritti, A.; Mercurio, S.; Broccoli, V.; Pellegrini, Massimo; Mallamaci, A.; Vescovi, A. L.
abstract

The appropriate control of proliferation of neural precursors has fundamental implications for the development of the central nervous system and for cell homeostasis/replacement within specific brain regions throughout adulthood. The role of genetic determinants in this process is largely unknown. We report the expression of the homeobox transcription factor Emx2 within the periventricular region of the adult telencephalon. This neurogenetic area displays a large number of multipotent stem cells. Adult neural stem cells isolated from this region do express Emx2 and down-regulate it significantly upon differentiation into neurons and glia. Abolishing or, increasing Emx2 expression in adult neural stem cells greatly enhances or reduces their rate of proliferation, respectively. We determined that altering the expression of Emx2 affects neither the cell cycle length of adult neural stem cells nor their ability to generate neurons and glia. Rather, when Emx2 expression is abolished, the frequency of symmetric divisions that generate two stem cells increases, whereas it decreases when Emx2 expression is enhanced.


2002 - Genes and translocations involved in POF [Articolo su rivista]
D., Schlessinger; L., Herrera; L., Crisponi; S., Mumm; Percesepe, Antonio; Pellegrini, Massimo; G., Pilia; Forabosco, Antonino
abstract

Changes at a single autosomal locus and many X-linked loci have been implicated in women with gonadal dysgenesis [premature ovarian failure (POF) with deficits in ovarian follicles]. For the chromosome 3 locus, a forkhead transcription factor gene (FOXL2) has been identified, in which lesions result in decreased follicles by haploinsufficiency. In contrast, sporadic X; autosomal translocations are distributed at many points on the X, but concentrate in a critical region on Xq. The association of the breakpoints with genes involved in ovarian function is thus far weak (in four analyzed cases) and has not been related to pathology in other POF patients. While many more translocations can be analyzed in detail as the human genome sequence is refined, it remains possible that translocations like X monosomy (Turner syndrome) lead to POF not by interrupting specific genes important in ovarian development, but by causing aberrations in pairing or X-inactivation during folliculogenesis. It is noted that the critical region has unusual features, neighboring the X-inactivation center and including an 18 Mb region of very low recombination. These suggest that chromosome dynamics in the region may be sensitive to structural changes, and when modified by translocations might provoke apoptosis at meiotic checkpoints. Choices among models for the etiology of POF should be feasible based on studies of ovarian follicle development and attrition in mouse models. Studies would prominently include gene expression profiling of developmental-specific pathways in nascent ovaries with controlled levels of Fox12 and interacting proteins, or with defined changes in the X chromosome. Published 2002 Wiley-Liss, Inc.


2001 - Agenesis of the scapula in Emx2 homozygous mutants [Articolo su rivista]
Pellegrini, Massimo; Pantano, S.; Fumi, Mp; Lucchini, F.; Forabosco, Antonino
abstract

The shoulder and pelvic girdles represent the proximal bones of the appendicular skeleton that connect the anterior and posterior limbs to the body trunk. Although the limb is a well-known model in developmental biology, the genetic mechanisms controlling the development of the more proximal elements of the appendicular skeleton are still unknown. The knock-out of Pax1 has shown that this gene is involved in patterning the acromion, while the expression pattern candidates Hoxc6 as a gene involved in scapula development. Surprisingly, we have found that scapula and ilium do not develop in Emx2 knock-out mice. In the homozygous mutants, developmental abnormalities of the brain cortex, the most anterior structure of the primary axis of the body, are associated with important defects of the girdles, the more proximal elements of the secondary axis. These abnormalities suggest that the molecular mechanisms patterning the more proximal elements of the limb axis are different from those patterning the rest of appendicular skeleton. While Hox genes specify the different segments of the more distal part of the appendicular skeleton forming the limb, Emx2 is concerned with the more proximal elements constituting the girdles,


1998 - Gpc3 expression correlates with the phenotype of the Simpson-Golabi-Behmel syndrome [Articolo su rivista]
Pellegrini, Massimo; G., Pilia; S., Pantano; F., Lucchini; M., Uda; M., Fumi; A., Cao; D., Schlessinger; Forabosco, Antonino
abstract

Interest in glypican-3 (GPC3), a member of the glypican-related integral membrane heparan sulfate proteoglycans (GRIPS) family, has increased with the finding that it is mutated in the Simpson-Golabi-Behmel overgrowth syndrome (Pilia et al. [1996] Nat. Genet. 12:241-247). The working model suggested that the membrane-bound protein acts locally to limit tissue and organ growth and that it may function by interacting with insulin-like growth factor 2 (IGFS) to limit its local effective level. Here we have tested two predictions of the model. In situ hybridization with the mouse gene cDNA was used to study the expression pattern during embryonic and fetal development. In agreement with predictions, the gene is expressed in precisely the organs that overgrow in its absence; and the patterns of expression of Gpc3 and those reported for Igf2 are strictly correlated. Dev. Dyn. 1998;213:431-439.


1997 - Emx2 developmental expression in the primordia of the reproductive and excretory systems [Articolo su rivista]
Pellegrini, Massimo; S., Pantano; F., Lucchini; M., Fumi; Forabosco, Antonino
abstract

The development of the urogenital system hasalways attracted many investigators owing to the peculiaraspects of the embryology of the reproductive and excretoryorgans and to the high number of congenital anomaliesrelated to these structures. It is remarkable becauseof the common origin of the kidneys, gonads, and genitaltracts from the intermediate mesoderm and because differentiation of these organs involves extensive mesenchymeto epithelium transition. Our knowledge about themolecular mechanisms controlling the differentiation ofthese diverse structures from the same precursor has takenadvantage of gene expression data and gene-targetingexperiments using genes with a specific expression patternin the urogenital system. A more detailed functionin kidney development has been postulated for transcriptionfactors such as WT-1, Pax-2 or other molecules suchas glial cell line-derived neurotrophic factor (GDNF),Wnt-4, c-ret. In the present work we have described theexpression pattern of the homeobox-containing geneEmx2 during the development of the urogenital system inmouse embryos. We have found that Emx2 is expressedin the early primordia of the organs that will form the excretoryand reproductive systems. In particular we havefound that Emx2 is expressed in the epithelial componentsof pronephros and mesonephros, in Wolffian andMüllerian ducts, in the ureteric buds with their branchesand in the early epithelial structures derived from metanephrogenic mesenchyme. Emx2 is also intensely expressedin the “bipotential” or “indifferent” gonads andovaries. These data and the recent finding that Emx2 homozygousmutant mice die soon after birth because ofthe absence of kidneys indicate an essential role of Emx2in the morphogenesis of the urogenital system.


1996 - Dentate gyrus formation requires Emx2 [Articolo su rivista]
Pellegrini, Massimo; A., Mansouri; A., Simeone; E., Boncinelli; P., Gruss
abstract

Emx 1 and 2 are the murine homologues of the Drosophilaempty spiracles gene and based on their expression patternmay be involved in the regional specification of themammalian forebrain. During early embryogenesis, Emx2is expressed in the presumptive cerebral cortex andolfactory bulbs and later, in the hippocampus proper anddentate gyrus. The latter are involved in memory processes.To understand the role of Emx2 in vivo, we have mutatedthe gene in mice. Homozygous embryos die postnatallybecause of severe urogenital alterations. These micepresent cerebral hemispheres with a reduced size andexhibit specific morphological alterations in allocorticalstructures of the medial wall of the brain. The dentategyrus is missing and the hippocampus proper is reduced.The medial limbic cortex is also severely shortened. Thedevelopment of the dentate gyrus is affected at the onset ofits formation with defects in the neuroepithelium fromwhich it originates. These findings demonstrate that Emx2is required for the development of several forebrain structures.


1995 - Cryptorchidism and homeotic transformations of spinal nerves and vertebrae in Hoxa-10 mutant mice [Articolo su rivista]
F. M., Rijli; R., Matyas; Pellegrini, Massimo; P., Gruss; P., Chambon
abstract

Homozygous mice mutated by homologous recombination for the AbdB-related Hoxa-10 gene are viable but display homeotic transformations of vertebrae and lumbar spinal nerves. Mutant males exhibit unilateral or bilateral criptorchidism due to developmental abnormalities of the gubernaculum, resulting in abnormal spermatogenesis and sterility. These results reveal an important role of Hoxa-10 in patterning posterior body regions and suggest that Hox genes are involved in specifying regional identity of both segmented and nonovertly segmented structures of the developing body.


1992 - Isolation of a zinc finger motif (ZNF75) mapping on chromosome Xq26 [Articolo su rivista]
Villa, A.; Patrosso, C.; Biunno, I.; Frattini, A.; Repetto, M.; Mostardini, M.; Evans, G.; Susani, L.; Strina, D.; Redolfi, E.; Lazzari, B.; Pellegrini, M.; Vezzoni, P.
abstract

We report here the partial characterization of a new human zinc finger (ZNF75) gene of the Kruppel type mapping to the long arm of the X chromosome. A cosmid clone was isolated from a library specific to the Xq24-qter region by hybridization to a degenerate oligonucleotide representing the link between two contigous fingers of the C2H2 type. The sequence of the pertinent cosmid fragments demonstrated five consecutive zinc finger motifs, all pertaining to the Kruppel family. A reading frame starting at least 75 amino acids before the first zinc finger and ending 11 amino acids after the last one was identified; comparison with other ZF genes suggests that this genomic fragment represents the carboxy-terminal exon of the gene. Homology of approximately 55% in the zinc finger region was detected with many zinc finger genes including mouse Zfp-35 and human ZFN7 cDNA clones. Mapping using a panel of sematic cell hybrids and chromosomal in situ hybridization localized the gene to Xq26, in a region not previously known to contain zinc finger genes. © 1992.


1991 - The nucleotide sequence of a CpG island demonstrates the presence of the first exon of the gene encoding the human lysosomal membrane protein lamp2 and assigns the gene to Xq24 [Articolo su rivista]
Manoni, M.; Tribioli, C.; Lazzari, B.; Debellis, G.; Patrosso, C.; Pergolizzi, R.; Pellegrini, M.; Maestrini, E.; Rivella, S.; Vezzoni, P.; Toniolo, D.
abstract

An EagI-EcoRI clone of human genomic DNA, p2-7, mapped to Xq24 has been sequenced. This analysis has confirmed the presence of a CpG island and has identified the first exon of the human LAMP2 gene, encoding a glycoprotein of the lysosomal membrane. Since the p2-7 clone corresponds to single-copy DNA, we can assign the human LAMP2 gene to Xq24. © 1991.