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Felice Alfonso Nava,1 Alessandra Mangia,2 Marco Riglietta,3 Lorenzo Somaini,4 Francesco Giuseppe Foschi,5 Ernesto Claar,6 Ivana Maida,7 Claudio Ucciferri,8 Francesca Frigerio,9 Candido Hernandez,10 Melania Dovizio,11 Valentina Perrone,11 Luca Degli Esposti,11 Massimo Puoti12 1U.O. Sanità Penitenziaria e Area Dipendenze, Azienda ULSS 6 Euganea, Padova, Italy; 2UOS Epatologia, Istituto di Ricovero e Cura “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, Italy; 3UOC Dipendenze, ASST Papa Giovanni XXIII, Bergamo, Italy; 4Servizio per le Dipendenze, SERT di Cossato, Biella, Italy; 5UOC Medicina Interna, Ospedale di Faenza, Faenza, Italy; 6UOC Medicina Interna, Ospedale Evangelico “Villa Betania”, Napoli, Italy; 7UOC Malattie Infettive e Parassitarie, Azienda Ospedaliero Universitaria di Sassari, Sassari, Italy; 8Clinica di Malattie Infettive Ospedale “SS Annunziata”, Chieti, Italy; 9Gilead Sciences, Milano, Italy; 10Gilead Sciences, Global Medical Affairs, Stockley Park, London, UB11 1BD, UK; 11CliCon S.R.L. Società Benefit, Health Economics and Outcomes Research, Bologna, Italy; 12SC Malattie Infettive, ASST Grande Ospedale Metropolitano Niguarda, Milano, ItalyCorrespondence: Luca Degli Esposti, CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, Via Murri, 9, Bologna, 40137, Italy, Tel +39 544 38393, Fax +39 544 212699, Email luca.degliesposti@clicon.itPurpose: Hepatitis C virus (HCV) spreads from contact with blood of an infected person. HCV infections are common among people who use drugs (PWUDs), when sharing needles, syringes, or other equipment for injected drugs. The advent of pangenotypic direct-antiviral agents (DAA) in 2017 transformed the treatment landscape for HCV, but PWUDs remain a complex and hard-to-treat population with high risk of HCV reinfection. The aim of this real-world analysis was to characterize the demographic and clinical features of PWUDs in Italy, also focusing on comorbidity profile, treatment with DAAs, resource consumptions for the National Health System (NHS).Patients and Methods: During 01/2011– 06/2020, administrative databases of Italian healthcare entities, covering 3,900,000 individuals, were browsed to identify PWUDs with or without HCV infection. Among HCV+ patients, a further stratification was made into treated and untreated with DAAs. The date of PWUD or HCV first diagnosis or DAA first prescription was considered as index-date. Patients were then followed-up for one year. Alcohol-dependency was also investigated.Results: Total 3690 PWUDs were included, of whom 1141 (30.9%) PWUD-HCV+ and 2549 (69.1%) PWUD-HCV-. HCV-positive were significantly older (43.6 vs 38.5 years, p < 0.001), had a worse comorbidity profile (Charlson-index: 0.8 vs 0.4, p < 0.001), and high rates of psychiatric, respiratory, dermatological, musculoskeletal diseases and genitourinary (sexually transmitted) infections. Moreover, they received more drug prescriptions (other than DAAs, like anti-acids, antiepileptics, psycholeptics) and had undergone more frequent hospitalization, predominantly for hepatobiliary, respiratory system and mental disorders. DDA-untreated had significantly higher Charlson-index than DAA-treated (0.9 vs 0.6, p = 0.003). Alcoholism was found in 436 (11.8%) cases.Conclusion: This Italian real-world analysis suggests that PWUDs with HCV infection, especially those untreated with DAAs, show an elevated drug consumption due to their complex clinical profile. These findings could help to ameliorate the healthcare interventions on PWUDs with HCV infection.Keywords: drug abuse, hepatitis C virus, alcohol dependency, real-world evidence

Stefano Fagiuoli,1 Pierluigi Toniutto,2 Nicola Coppola,3 Domenica Daniela Ancona,4 Margherita Andretta,5 Fausto Bartolini,6 Fulvio Ferrante,7 Alessandro Lupi,8 Stefano Palcic,9 Francesca Vittoria Rizzi,10 Davide Re,11 Gema Alvarez Nieto,12 Candido Hernandez,13 Francesca Frigerio,14 Valentina Perrone,14 Luca Degli Esposti,14 Alessandra Mangia15 1Department of Medicine and Surgery, University of Milan Bicocca & Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Bergamo, Italy; 2Hepatology and Liver Transplantation Unit, Azienda Ospedaliero Universitaria, Udine, Italy; 3Infectious Diseases Unit, University of Campania L. Vanvitelli, Naples, Italy; 4Dipartimento Farmaceutico ASL BAT, Trani, Italy; 5UOC Assistenza Farmaceutica Territoriale, Azienda Ulss 8 Berica, Vicenza, Italy; 6Dipartimento Farmaceutico-Usl Umbria 2, Terni, Italy; 7Dipartimento Diagnostica Ed Assistenza Farmaceutica – ASL Frosinone, Frosinone, Italy; 8Struttura Complessa Di Cardiologia – ASL VCO, Omegna, Italy; 9Farmaceutica Territoriale- Azienda Sanitaria Universitaria Integrata Giuliano-Isontina (ASUGI), Trieste, Italy; 10UOS Farmacovigilanza e Monitoraggio Spesa Farmaceutica- ASL BAT, Trani, Italy; 11Servizio Farmaceutico Territoriale ASL Teramo, Teramo, Italy; 12Gilead Sciences, Medical Affairs Italy, Milan, Italy; 13Gilead Sciences, Global Medical Affairs, London, UK; 14Clicon S.r.l., Health Economics and Outcomes Research, Bologna, Italy; 15Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, 24127, ItalyCorrespondence: Luca Degli Esposti, CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, Via Murri, 9, Bologna, 40137, Italy, Tel +390544 38393, Email luca.degliesposti@clicon.itPurpose: The study aims at investigating the impact of polymedication and aging in the prevalence of multiple drug-drug interactions (DDIs) on HCV patients treated with sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB).Patients and Methods: This is a retrospective analysis based on administrative data covering around 6.9 million individuals. Patients treated with SOF/VEL or GLE/PIB over November 2017–March 2020 were included. Index date corresponded to SOF/VEL or GLE/PIB first prescription during such period; patients were followed up for treatment duration. Analyses were then focused on patients with ≥ 2 comedications at risk of multiple DDIs. The severity and the effect of multiple DDI were identified using the Liverpool University tool.Results: A total of 2057 patients with SOF/VEL and 2128 with GLE/PIB were selected. Mean age of SOF/VEL patients was 58.5 years, higher than GLE/PIB ones (52.5 years) (p < 0.001), and patients > 50 years were more present in SOF/VEL vs GLE/PIB cohorts: 72% vs 58%, (p < 0.001). Most prescribed co-medications were cardiovascular, alimentary and nervous system drugs. Proportion of patients with ≥ 2 comedications was higher in SOF/VEL compared to GLE/PIB cohort (56.5% vs 32.3%, p < 0.001). Those at high-risk of multiple DDIs accounted for 11.6% (N = 135) of SOF/VEL and 19.6% (N = 135) of GLE/PIB (p < 0.001) patients with ≥ 2 comedications. Among them, the potential effect of DDI was a decrease of DAA serum levels (11% of SOF/VEL and GLE/PIB patients) and an increased concentration of comedication serum levels (14% of SOF/VEL and 42% of GLE/PIB patients).Conclusion: This real-world analysis provided a thorough characterization on the burden of polymedication regimens in HCV patients treated with SOF/VEL or GLE/PIB that expose such patients to an increased risk of DDIs. In our sample population, SOF/VEL regimen was more frequently detected on elderly patients and on those with ≥ 2 comedications at risk of multi-DDI, ie, among patients characterized by higher rates of comorbidities and polypharmacy.Keywords: administrative database, glecaprevir/pibrentasvir, hepatitis C, sofosbuvir/velpatasvir, polymedication

Vehicle dynamics quality is generally evaluated by two approaches: subjective evaluations using driver ratings and objective measurements of vehicle dynamics characteristics. In both approaches it is important to define features of vehicle dynamics in order to cover all aspects, but without redundancy. For this reason, the first part of the paper tries to summarize the principal qualities and to how they might be organized. In the second part, the paper describes those procedures that can be used to obtain objective quality indices. First of all, criteria used in subjective testing (questionnaire design, jury selection, etc.) are described. Then it is determined which manoeuvres can be performed, and which physical quantities should be considered, in order to obtain objective parameters that correlate with subjective evaluation. After this, the paper briefly describes the statistical technique used to identify which measured variables best correlate with vehicle dynamics qualities. In the third part, the paper contains a practical application of the objective index identification procedure regarding handling quality. Some examples are given about how these indices are used in different phases of a new car development, from target setting to target deployment, and in target achievement and verification during final tuning. [ABSTRACT FROM AUTHOR]

Abstract: We studied whether pharmacological blockade of the IL-1β-mediated signaling, rapidly activated in forebrain by epileptogenic injuries, affords neuroprotection in two different rat models of status epilepticus (SE). As secondary outcome, we measured treatment's effect on SE-induced epileptogenesis. IL-1β signaling was blocked by systemic administration of two antiinflammatory drugs, namely human recombinant IL-1 receptor antagonist (anakinra), the naturally occurring and clinically used competitive IL-1 receptor type 1 antagonist, and VX-765 a specific non-peptide inhibitor of IL-1β cleavage and release. Antiinflammatory drugs were given 60min after antiepileptic (AED) drug-controlled SE induced by pilocarpine, or 180min after unrestrained electrical SE, for 7days using a protocol yielding therapeutic drug levels in brain. This drug combination significantly decreased both IL-1β expression in astrocytes and cell loss in rat forebrain. Neuroprotection and the antiinflammatory effect were more pronounced in the electrical SE model. Onset of epilepsy, and frequency and duration of seizures 3months after electrical SE were not significantly modified. Transcriptomic analysis in the hippocampus showed that the combined treatment did not affect the broad inflammatory response induced by SE during epileptogenesis. In particular, the treatment did not prevent the induction of the complement system and Toll-like receptors, both contributing to cell loss and seizure generation. We conclude that the IL-1β signaling represents an important target for reducing cell loss after SE. The data highlight a new class of clinically tested agents affording neuroprotection after a delayed post-injury intervention. Earlier blockade of this rapid onset inflammatory pathway during SE, or concomitant treatment with antiinflammatory drugs targeting additional components of the broad inflammatory response to SE, or co-treatment with AEDs, is likely to be required for optimizing beneficial outcomes. [Copyright &y& Elsevier]

The purpose of this study was to investigate the protective effect of black tea (BT) extract against induced oxidative damage in Jurkat T-cell line. Cells supplemented with 10 or 25 mg/L BT were subjected to oxidation with ferrous ions. Malondialdehyde (MDA) production as marker of lipid peroxidation, DNA single strand breaks as marker of DNA damage, and modification of the antioxidant enzyme activity, glutathione peroxidase (GPX) were measured. Results show the efficacy of BT polyphenols to decrease DNA oxidative damage and to affect GPX activity (P<0.05), while no effect was shown on MDA production. The succeeding investigation of the activity of caffeine and epigallocatechin gallate demonstrated their antioxidant potential with respect to the cellular markers evaluated. In conclusion, this study supports the protective effect of BT against ferrous ions induced oxidative damage to DNA and the ability of BT to affect the enzyme antioxidant system of Jurkat cells. [Copyright &y& Elsevier]

The disruptive impact of the COVID-19 pandemic has led the scientific community to undertake an unprecedented effort to characterize viral infection mechanisms. Among these, interactions between the viral glycosylated Spike and the human receptors ACE2 and TMPRSS2 are key to allowing virus invasion. Here, we report and test a fully rational methodology to design molecules that are capable of perturbing the interactions between these critical players in SARS-CoV-2 pathogenicity. To this end, we computationally identify substructures on the fully glycosylated Spike protein that are not intramolecularly optimized and are thus prone to being stabilized by forming complexes with ACE2 and TMPRSS2. With the aim of competing with the Spike-mediated cell entry mechanisms, we have engineered the predicted putative interaction regions in the form of peptide mimics that could compete with Spike for interaction with ACE2 and/or TMPRSS2. Experimental models of viral entry demonstrate that the designed molecules are able to interfere with viral entry into ACE2/TMPRSS2 expressing cells, while they have no effects on the entry of control viral particles that do not harbor the Spike protein or on the entry of Spike-presenting viral particles into cells that do not display its receptors on their surface.

Background: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder. Individuals with PWS face a range of cognitive, behavioral, and emotional challenges that require comprehensive and lifelong care, posing significant demands on their caregivers. The study is not only aimed to assess the psychological conditions of caregivers of adult subjects with PWS focusing on psychological distress and coping, but also to shed light on a crucial yet often overlooked aspect of healthcare. This study aims to compare the psychological well-being of individuals with PWS and their caregivers, providing valuable insights that can potentially improve the quality of care for these individuals. The sample recruited at the Division of Auxology, IRCCS Istituto Auxologico Italiano, was composed of 30 adult subjects with PWS (11 men and 19 women; mean age ± SD: 36.4 ± 10.31 years; mean Body Mass Index (BMI): 35.7 ± 8.92: kg/m2) and their caregivers (10 men and 20 women). To assess the psychological condition of caregivers, the Italian-validated versions of the Depression Anxiety and Stress Scale (DASS-21) and the Coping Orientation to the Problems Experiences (COPE) were used, while to assess the psychological well-being of individuals with PWS and their caregivers, the Italian validated version of the Psychological General Well-Being Index (PGWBI) was used., Results: Depression (p < 0.001), Stress (p = 0.050), and Total score (p = 0.009) of DASS 21 were higher in the caregivers of subjects with PWS than in the general population. PGWBI scores of caregivers were significantly lower than in individuals with PWS in Positive Well-being (p < 0.001), General Health (p = 0.006), Vitality (p = 0.004), and the total score (p = 0.006). The depression subscale of PGWBI was higher in caregivers than in subjects with PWS. Correlations between the subscales of COPE and the total score of PGWBI in caregivers revealed that the Avoidance subscale of COPE had a negative significant correlation with the total score of PGWBI (p = 0.003)., Conclusions: Our results highlighted several critical insights into the profound emotional and psychological challenges faced by the caregivers of individuals with PWS., (© 2024. The Author(s).)

The modulation of protein function via designed small molecules is providing new opportunities in chemical biology and medicinal chemistry. While drugs have traditionally been developed to block enzymatic activities through active site occupation, a growing number of strategies now aim to control protein functions in an allosteric fashion, allowing for the tuning of a target's activation or deactivation via the modulation of the populations of conformational ensembles that underlie its function. In the context of the discovery of new active leads, it would be very useful to generate hypotheses for the functional impact of new ligands. Since the discovery and design of allosteric modulators (inhibitors/activators) is still a challenging and often serendipitous target, the development of a rapid and robust approach to predict the functional profile of a new ligand would significantly speed up candidate selection. Herein, we present different machine learning (ML) classifiers to distinguish between potential orthosteric and allosteric binders. Our approach integrates information on the chemical fingerprints of the ligands with descriptors that recapitulate ligand effects on protein functional motions. The latter are derived from molecular dynamics (MD) simulations of the target protein in complex with orthosteric or allosteric ligands. In this framework, we train and test different ML architectures, which are initially probed on the classification of orthosteric versus allosteric ligands for cyclin-dependent kinases (CDKs). The results demonstrate that different ML methods can successfully partition allosteric versus orthosteric effectors (although to different degrees). Next, we further test the models with FDA-approved CDK drugs, not included in the original dataset, as well as ligands that target other kinases, to test the range of applicability of these models outside of the domain on which they were developed. Overall, the results show that enriching the training dataset with chemical physics-based information on the protein-ligand dynamic cross-talk can significantly expand the reach and applicability of approaches for the prediction and classification of the mode of action of small molecules.

Background: Eating disorders (EDs) pose a significant risk to health, especially when not diagnosed early. For several years EDs and oral health has been extensively studied, and now it is quite clear the existence of a correlation between specific oral manifestations and these disorders. While these oral signs could potentially aid early diagnosis of EDs, their identification and the eventual establishment of a correlation is currently heavily limited to the clinician's experience. The present systematic review critically examines existing literature, offering an updated overview of oro-dental manifestations associated with EDs., Method: MEDLINE (via PubMed), Web of Science, Scopus, and grey literature were searched, and relevant epidemiological comparative studies were screened using the Rayyan software. No limitations have been imposed on the research regarding oro-dental outcomes, encompassing all medically diagnosed EDs. The quality of the studies was valuated using AXIS appraisal tool for cross-sectional studies., Result: Out of 3990 studies, 32 fulfilled the eligibility criteria and were included in the synthesis. The identified eating disorders include Anorexia Nervosa, Bulimia Nervosa and/or Eating Disorders Not Otherwise Specified, predominantly among female subjects, primarily originating from Europe. The evaluated oro-dental outcomes include dental erosion, caries, saliva assessment, hygiene-periodontal parameters, and mucosal tissue appearance. The association with erosion is confirmed while gingival recession, dentinal hypersensitivity, salivary flow thresholds and aspects relating to oral pathology are receiving increasing support from emerging evidence., Discussion: This trend emphasizes the critical role of the complete intraoral examination to detect significant oro-dental signs that may indicate the onset of an ED., (© 2024. The Author(s).)

Background : The current study aims to assess the psychological conditions of Italian adolescents with obesity seeking an in-hospital multidisciplinary body weight reduction program, by exploring their psychological adjustment, emotional states, and co-occurring eating disorder symptoms. Methods : The study involved ninety-two consecutive Italian adolescents with obesity (31 males, 61 females), with a mean age ± SD: 16.4 ± 1.1 years and body mass index (BMI): 38.3 ± 6.04 kg/m 2 ). The Strengths and Difficulties Questionnaire (SDQ), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), and Eating Attitude Test-26 (EAT-26) were used for the evaluations. Differences between genders, degrees of obesity (Group 1 = BMI SDS 2-2.99 and Group 2: BMI SDS > 3), and those with or without eating disorder symptoms (Group 1: EAT-26 ≤ 20 and Group 2: EAT-26 > 20) were explored. Results : The results showed that females reported higher scores on the Emotional Symptoms, Prosocial Behaviors, Total Difficulties, and Total Impact subscales of the SDQ, the BDI, both subscales of the STAI, and the Bulimia subscales of the EAT-26 than males, independently from the degrees of obesity. Participants with eating disorder symptoms (Group 2: EAT-26 > 20) showed higher scores on the Emotional Symptoms and Total Difficulties subscales of the SDQ, the BDI, and both subscales of the STAI than those of Group 1 (EAT-26 ≤ 20). Conclusions : The study explores the psychological conditions of adolescents with obesity. The results can inform appropriate treatment approaches for the management of obesity in developmental age groups, which not only take into account the medical and physical aspects of obesity, but also the behavioral, emotional, and social difficulties expressed by adolescents, in addition to specific eating disorder symptoms.

In order to tackle the global increase in overweight and obesity prevalence, several nutrient profiling systems have been developed; among others, Food Compass Score (FCS) has been designed to encompass multiple domains of food healthfulness. However, environmental sustainability of healthy diets is another crucial dimension which should not be overlooked in the context of human health. The aim of the present study is to assess the association between healthiness and environmental sustainability of food items, using the FCS and Agribalyse databases, respectively. A total of 806 matching food items were identified, grouped in 12 food categories; within each category, differences in median Z-scores between FCS and Single Environmental Footprint (EF) Score were assessed. While Fruits, Legumes and Nuts, Mixed foods, Meat Poultry and Eggs (MPE), Savory and Sweets, and Vegetables showed statistically significant differences (all p < 0.001), Beverages (p = 0.361), Dairy (p = 0.092), Fats and Oils (p = 0.594), Grains (p = 0.436), Sauce and Condiments (p = 0.093), and Seafood (p = 0.241) had similar Food Compass and Single EF Z-scores distributions. These findings underscore a relevant lack of difference between healthfulness and environmental impact of some prominent food categories, such as Grains and Seafood. Therefore, we suggest matching nutrient profiling systems with adequate environmental sustainability indices., (© 2024. The Author(s).)

Molecular chaperones, a family of proteins of which Hsp90 and Hsp70 are integral members, form an essential machinery to maintain healthy proteomes by controlling the folding and activation of a plethora of substrate client proteins. This is achieved through cycles in which Hsp90 and Hsp70, regulated by task-specific co-chaperones, process ATP and become part of a complex network that undergoes extensive compositional and conformational variations. Despite impressive advances in structural knowledge, the mechanisms that regulate the dynamics of functional assemblies, their response to nucleotides, and their relevance for client remodeling are still elusive. Here, we focus on the glucocorticoid receptor (GR):Hsp90:Hsp70:co-chaperone Hop client-loading and the GR:Hsp90:co-chaperone p23 client-maturation complexes, key assemblies in the folding cycle of glucocorticoid receptor (GR), a client strictly dependent upon Hsp90/Hsp70 for activity. Using a combination of molecular dynamics simulation approaches, we unveil with unprecedented detail the mechanisms that underpin function in these chaperone machineries. Specifically, we dissect the processes by which the nucleotide-encoded message is relayed to the client and how the distinct partners of the assemblies cooperate to (pre)organize partially folded GR during Loading and Maturation. We show how different ligand states determine distinct dynamic profiles for the functional interfaces defining the interactions in the complexes and modulate their overall flexibility to facilitate progress along the chaperone cycle. Finally, we also show that the GR regions engaged by the chaperone machinery display peculiar energetic signatures in the folded state, which enhance the probability of partial unfolding fluctuations. From these results, we propose a model where a dynamic cross-talk emerges between the chaperone dynamics states and remodeling of client-interacting regions. This factor, coupled to the highly dynamic nature of the assemblies and the conformational heterogeneity of their interactions, provides the basis for regulating the functions of distinct assemblies during the chaperoning cycle., (© 2023 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

An emerging research niche has focused on the link between social determinants of health and diabetes mellitus, one of the most prevalent non-communicable diseases in modern society. The aim of the present mini-review is to explore and summarize current findings in this field targeting high-income countries. In the presence of disadvantaged neighborhood factors (including socioeconomic status, food environment, walkability and neighborhood aesthetics), diabetes prevention and care are affected at a multidimensional level. The vast majority of the included studies suggest that, besides individual risk factors, aggregated neighborhood inequalities should be tackled to implement effective evidence-based policies for diabetes mellitus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Frigerio, Muzzioli, Pinto, Donini and Poggiogalle.)

Background: Biopsy remains the gold standard for the diagnosis of hepatic steatosis, the leading cause of pediatric chronic liver disease; however, its costs call for less invasive methods., Objective: This study examined the diagnostic accuracy and reliability of quantitative ultrasound (QUS) for the assessment of liver fat content in a pediatric population, using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard., Materials and Methods: We enrolled 36 patients. MRI-PDFF involved a 3-dimensional T2*-weighted with Dixon pulse multiple-echo sequence using iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL IQ). QUS imaging relied on the ultrasound system "RS85 A" (Samsung Medison, Seoul, South Korea) and the following software: Hepato-Renal Index with automated region of interest recommendation (EzHRI), Tissue Attenuation Imaging (TAI), and Tissue Scatter Distribution Imaging (TSI). For each QUS index, receiver operating characteristic (ROC) curve analysis against MRI-PDFF was used to identify the associated cut-off value and the area under the ROC curve (AUROC). Concordance between two radiologists was assessed by intraclass correlation coefficients (ICCs) and Bland-Altman analysis., Results: A total of 61.1% of the sample (n=22) displayed a MRI-PDFF ≥ 5.6%; QUS cut-off values were TAI=0.625 (AUROC 0.90, confidence interval [CI] 0.77-1.00), TSI=91.95 (AUROC 0.99, CI 0.98-1.00) and EzHRI=1.215 (AUROC 0.98, CI 0.94-1.00). Inter-rater reliability was good-to-excellent for EzHRI (ICC 0.91, 95% C.I. 0.82-0.95) and TAI (ICC 0.94, 95% C.I. 0.88-0.97) and moderate to good for TSI (ICC 0.73; 95% C.I. 0.53-0.85)., Conclusion: Our results suggest that QUS can be used to reliably assess the presence and degree of pediatric hepatic steatosis., (© 2023. The Author(s).)

Purpose: The aim of the study was to examine the effects of meal supervision, provided by health professionals, volunteers or family members, on anthropometric, nutritional, psychological, and behavioural outcomes in patients with eating disorders (EDs)., Methods: The present systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The last search was conducted in three databases (PubMed, Scopus, and the Cochrane library). Inclusion criteria considered paediatric and adult patients suffering from EDs, regardless of ethnicity, and treated in different therapeutic settings. The quality of the studies was evaluated using the Newcastle Ottawa Scale (NOS) adapted for cross-sectional studies and Version 2 of the Cochrane risk-of-bias assessment tool for randomised trials., Results: 3282 articles were retrieved, out of which only 6 met the eligibility criteria. A marked heterogeneity in definitions and approaches to supervised mealtime was observed. This variability emerged in the methodologies used in the supervised meal, and in the reference values for the outcome measures that were used, such as the analysis of different parameters. Based on these observations, mealtime assistance provided to patients with EDs shows an overall positive effect on eating behaviour and dysfunctional attitudes. Future research should be prompted to provide a thorough definition of a structured procedure for meal assistance to be potentially and systematically included in the nutritional rehabilitation protocols for patients with EDs., Level of Evidence: Level IV systematic reviews of uncontrolled trials., (© 2023. Springer Nature Switzerland AG.)

Thanks to the considerable research which has been undertaken in the last few years to improve our understanding of the biology and mechanism of action of SARS-CoV-2, we know how the virus uses its surface spike protein to infect host cells. The transmembrane prosthesis, serine 2 (TMPRSS2) protein, located on the surface of human cells, recognizes the cleavage site in the spike protein, leading to the release of the fusion peptide and entry of the virus into the host cells. Because of its role, TMPRSS2 has been proposed as a drug target to prevent infection by the virus. In this study, we aim to increase our understanding of TMPRSS2 using long scale microsecond atomistic molecular dynamics simulations, focusing on the conformational changes over time. The comparison between simulations conducted on the protein in the native (apo) and inhibited form (holo), has shown that in the holo form the inhibitor stabilizes the catalytic site and induces rearrangements in the extracellular domain of the protein. In turn, it leads to the formation of a new cavity in the vicinity of the ligand binding pocket that is stable in the microsecond time scale. Given the low specificity of known protease inhibitors, these findings suggest a new potential drug target site that can be used to improve TMPRSS2 specific recognition by newly designed inhibitors., (© 2023 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)

SARS-CoV-2 has evolved rapidly in the first 3 years of pandemic diffusion. The initial evolution of the virus appeared to proceed through big jumps in sequence changes rather than through the stepwise accumulation of point mutations on already established variants. Here, we examine whether this nonlinear mutational process reverberates in variations of the conformational dynamics of the SARS-CoV-2 Spike protein (S-protein), the first point of contact between the virus and the human host. We run extensive microsecond-scale molecular dynamics simulations of seven distinct variants of the protein in their fully glycosylated state and set out to elucidate possible links between the mutational spectrum of the S-protein and the structural dynamics of the respective variant, at global and local levels. The results reveal that mutation-dependent structural and dynamic modulations mostly consist of increased coordinated motions in variants that acquire stability and in an increased internal flexibility in variants that are less stable. Importantly, a limited number of functionally important substructures (the receptor binding domain, in particular) share the same time of movements in all variants, indicating efficient preorganization for functional regions dedicated to host interactions. Our results support a model in which the internal dynamics of the S-proteins from different strains varies in a way that reflects the observed random and non-stepwise jumps in sequence evolution, while conserving the functionally oriented traits of conformational dynamics necessary to support productive interactions with host receptors.

Nutrient profiling and front-of-pack labeling (FOPL) have been developed to categorize food products as more or less healthy based on their nutrient content and to easily communicate this information to consumers. The goal is to change individual food choices toward a healthier diet. Since global climate change has recently become an urgent matter, this paper also aims to investigate the correlations between different food health scales, including some FOPLs currently adopted by one or more countries, and several sustainability indicators. For this purpose, a food sustainability composite index has been developed to summarize environmental indicators and compare food scales. Results indicate, as expected, that well-known healthy and sustainable diets are strongly correlated with both environmental indicators and the composite index, while FOPLs based on portions or on 100 g show moderate and weak correlation values, respectively. Within-category analysis has not found any associations that explain these results. Hence, 100 g standard, on which FOPLs are usually developed, seems not to be the ideal basis for developing a label that aspires to communicate healthiness and sustainability in a unique format, as required by the need for simple messaging. On the contrary, FOPLs based on portions appear to be more likely to achieve this goal.

Accumulating evidence supports a connection between sarcopenic obesity (SO) and NAFLD. The extent to which fatty liver contributes to impaired muscle contractility is not yet well established. The aim of our study was to investigate the effect of NAFLD on dynapenia in patients with SO. In this study, 71 non-diabetic subjects (age 55 (7.8) years, BMI 35.2 kg/m 2 (32.6-38.8)) were classified as having SO and non-sarcopenic obesity (NSO). SO patients displayed worse serum lipid profiles, higher body fat, and lower skeletal muscle mass (both total and appendicular) than NSO patients, despite the absence of any significant differences in body weight, glycometabolic parameters, and hepatic steatosis prevalence. A positive correlation between disposition index and muscle quality index (MQI) ( r = 0.393, p = 0.013) emerged after controlling for menopause and body fat percentage. Based on multiple linear regression analysis, MQI was significantly positively associated with the disposition index (β: 0.059, SE: 0.002, p = 0.006) after adjustment for menopause, body fat percentage, and the presence of hepatic steatosis according to the hepatorenal index (HRI). Similar findings emerged when including liver enzyme levels in place of hepatic steatosis. Muscle quality was positively associated with β-cell function corrected for insulin resistance among patients with obesity and sarcopenic obesity, irrespective of the presence of fatty liver disease.

The definition of metabolic syndrome (MetS) has undergone several changes over the years due to the difficulty in establishing universal criteria for it. Underlying the disorders related to MetS is almost invariably a pro-inflammatory state related to altered glucose metabolism, which could lead to elevated cardiovascular risk. Indeed, the complications closely related to MetS are cardiovascular diseases (CVDs) and type 2 diabetes (T2D). It has been observed that the predisposition to metabolic syndrome is modulated by complex interactions between human microbiota, genetic factors, and diet. This review provides a summary of the last decade of literature related to three principal aspects of MetS: (i) the syndrome's definition and classification, pathophysiology, and treatment approaches; (ii) prediction and diagnosis underlying the biomarkers identified by means of advanced methodologies (NMR, LC/GC-MS, and LC, LC-MS); and (iii) the role of foods and food components in prevention and/or treatment of MetS, demonstrating a possible role of specific foods intake in the development of MetS., Competing Interests: The authors declare no conflict of interest.