Occupational physical activity, mortality and CHD events in the Italian Longitudinal Study

PURPOSE: Several recent studies have suggested a ‘physical activity paradox’ whereby leisure-time physical activity benefits health, but occupational physical activity is harmful. However, other studies imply that occupational physical activity is beneficial. Using data from a nationally representative Italian sample, we investigate if the context, or domain, of physical activity matters for mortality and coronary heart disease (CHD) events. METHODS: Among 40,220 men and women aged 40–55 at baseline, we used Cox models to compare associations of occupational, domestic and leisure-time physical activity with risk of mortality and CHD events over a follow-up period of up to 14 years. We accounted for sociodemographic factors, smoking, body mass index (BMI), physical and mental health, and educational qualifications. RESULTS: Occupational physical activity was not significantly associated with risk of mortality or CHD events for women, or with CHD events for men. In crude models, risk of mortality was higher for men in the highest occupational activity group, compared to the lowest (HR 1.26, 95% CI 1.01, 1.57). This attenuated with adjustment for health-related behaviours, health, and education (HR 1.03, 95% CI 0.77, 1.38). In crude models, leisure-time physical activity was significantly associated with decreased mortality and CHD risk only for men. Domestic physical activity was not associated with either outcome for either gender. CONCLUSION: In a large sample of middle-aged Italian workers, we found limited evidence of harmful or beneficial effects of occupational physical activity on mortality or CHD events. However, confidence intervals were wide, and results consistent with a range of effects in both directions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00420-021-01765-0

Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype

A "Down Syndrome critical region" (DSCR) sufficient to induce the most constant phenotypes of Down syndrome (DS) had been identified by studying partial (segmental) trisomy 21 (PT21) as an interval of 0.6-8.3 Mb within human chromosome 21 (Hsa21), although its existence was later questioned. We propose an innovative, systematic reanalysis of all described PT21 cases (from 1973 to 2015). In particular, we built an integrated, comparative map from 125 cases with or without DS fulfilling stringent cytogenetic and clinical criteria. The map allowed to define or exclude as candidates for DS fine Hsa21 sequence intervals, also integrating duplication copy number variants (CNVs) data. A highly restricted DSCR (HR-DSCR) of only 34 kb on distal 21q22.13 has been identified as the minimal region whose duplication is shared by all DS subjects and is absent in all non-DS subjects. Also being spared by any duplication CNV in healthy subjects, HR-DSCR is proposed as a candidate for the typical DS features, the intellectual disability and some facial phenotypes. HR-DSCR contains no known gene and has relevant homology only to the chimpanzee genome. Searching for HR-DSCR functional loci might become a priority for understanding the fundamental genotype-phenotype relationships in DS

Multimorbidity and SARS-CoV-2–Related Outcomes: Analysis of a Cohort of Italian Patients

Background: Since the outbreak of the COVID-19 pandemic, identifying the main risk factors has been imperative to properly manage the public health challenges that the pandemic exposes, such as organizing effective vaccination campaigns. In addition to gender and age, multimorbidity seems to be one of the predisposing factors coming out of many studies investigating the possible causes of increased susceptibility to SARS-CoV-2 infection and adverse outcomes. However, only a few studies conducted have used large samples. Objective: The objective is to evaluate the association between multimorbidity, probability to be tested, susceptibility, and severity of SARS-CoV-2 infection in the Piedmont population (Northern Italy, about 4 million inhabitants). For this purpose, we considered five main outcomes: access to swab, positivity to SARS-CoV-2, hospitalization, ICU admission, and death within 30 days from the first positive swab. Methods: Data were obtained from different Piedmont health-administrative databases. Subjects aged between 45 and 74 years and infections diagnosed between February and May 2020 were considered. Multimorbidity was defined both with the Charlson Comorbidity Index (CCI) and by identifying patients with previous comorbidities such as diabetes, and oncological, cardiovascular, and respiratory diseases. Multivariable logistic regression models (adjusted for age and month of infection and stratified by gender) were performed for each outcome. Analyses were also conducted by separating two age groups (45-59 and 60-74 years). Results: Out of 1,918,549 subjects, 85,348 performed at least one swab, 12,793 tested positive for SARS-CoV-2, 4,644 were hospitalized, 1,508 were admitted to the ICU, and 749 died within 30 days from the first positive swab. Individuals with a higher CCI had a higher probability of being swabbed but a lower probability of testing positive. We observed the same results when analyzing subjects with previous oncological and cardiovascular diseases. Moreover, especially in the youngest group, we identified a greater risk of being hospitalized and dying. Among comorbidities considered in the study, respiratory diseases seem to be the most likely to increase the risk of having a positive swab and worse disease outcomes. Conclusions: Our study shows that patients with multimorbidity, although swabbed more frequently, are less likely to result infected with SARS-CoV-2, probably due to greater attention on protective methods. Moreover, a history of respiratory diseases is a risk factor for a worse prognosis of COVID-19. Nonetheless, whatever comorbidities affect the patients, a strong dose-response effect was observed between an increased score of CCI and COVID-19 hospitalization, ICU admission, and death. These results are important in terms of public health because they help in identifying a group of subjects that are more prone to worse SARS-CoV-2 outcomes. This information is important for promoting targeted prevention and developing policies for the prioritization of public health interventions

Membrane dynamics in cell migration

Migration of cells is required in multiple tissue-level processes, such as in inflammation or cancer metastasis. Endocytosis is an extremely regulated cellular process by which cells uptake extracellular molecules or internalise cell surface receptors. While the role of endocytosis of focal adhesions (FA) and plasma membrane (PM) turnover at the leading edge of migratory cells is wide known, the contribution of endocytic proteins per se in migration has been frequently disregarded. In this review, we describe the novel functions of the most well-known endocytic proteins in cancer cell migration, focusing on clathrin, caveolin, flotillins and GRAF1. In addition, we highlight the relevance of the macropinocytic pathway in amoeboid-like cell migration

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Inequalities in the Health Impact of the First Wave of the COVID-19 Pandemic in Piedmont Region, Italy

(1) Introduction: Several studies observe a social gradient in the incidence and health consequences of SARS-CoV-2 infection, but they rely mainly on spatial associations because individual-level data are lacking. (2) Objectives: To assess the impact of social inequalities in the health outcomes of COVID-19 during the first epidemic wave in Piedmont Region, Italy, evaluating the role of the unequal social distribution of comorbidities and the capacity of the healthcare system to promote equity. (3) Methods: Subjects aged over 35, resident in Piedmont on 22 February 2020, were followed up until 30 May 2020 for access to swabs, infection, hospitalization, admission to intensive care unit, in-hospital death, COVID-19, and all-cause death. Inequalities were assessed through an Index of Socioeconomic Disadvantage composed of information on education, overcrowding, housing conditions, and neighborhood deprivation. Relative incidence measures and Relative Index of Inequality were estimated through Poisson regression models, stratifying by gender and age groups (35–64 years; ≥65 years), adjusting for comorbidity. (4) Results: Social inequalities were found in the various outcomes, in the female population, and among elderly males. Inequalities in ICU were lower, but analyses only on in-patients discount the hypothesis of preferential access by the most advantaged. Comorbidities contribute to no more than 30% of inequalities. (5) Conclusions: Despite the presence of significant inequities, the pandemic does not appear to have further exacerbated health inequalities, partly due to the fairness of the healthcare system. It is necessary to reduce inequalities in the occurrence of comorbidities that confer susceptibility to COVID-19 and promote prevention policies that limit inequalities in the mechanisms of contagion and improve out-of-hospital timely treatment