Association between HLA genotypes and COVID-19 susceptibility, severity and progression: a comprehensive review of the literature.

The COVID-19 pandemic has markedly impacted on cultural, political, and economic structures all over the world. Several aspects of its pathogenesis and related clinical consequences have not yet been elucidated. Infection rates, as well morbidity and mortality differed within countries. It is intriguing for scientists to understand how patient genetics may influence the outcome of the condition, to clarify which aspects could be related the clinical variability of SARS-CoV-2 disease. We reviewed the studies exploring the role of human leukocyte antigens (HLA) genotypes on individual responses to SARS-CoV-2 infection and/or progression, discussing also the contribution of the immunological patterns MHC-related. In March 2021, the main online databases were accessed. All the articles that investigated the possible association between the HLA genotypes and related polymorphisms with susceptibility, severity and progression of COVID-19 were considered. Although both genetic and environmental factors are certainly expected to influence the susceptibility to or protection of individuals, the HLA and related polymorphisms can influence susceptibility, progression and severity of SARS-CoV-2 infection. The crucial role played by HLA molecules in the immune response, especially through pathogen-derived peptide presentation, and the huge molecular variability of HLA alleles in the human populations could be responsible for the different rates of infection and the different patients following COVID-19 infection

Sirt1 activity in pbmcs as a biomarker of different heart failure phenotypes

Heart Failure (HF) is a syndrome, which implies the existence of different phenotypes. The new categorization includes patients with preserved ejection fraction (HFpEF), mid-range EF (HFmrEF), and reduced EF (HFrEF) but the molecular mechanisms involved in these HF phenotypes have not yet been exhaustively investigated. Sirt1 plays a crucial role in biological processes strongly related to HF. This study aimed to evaluate whether Sirt1 activity was correlated with EF and other parameters in HFpEF, HFmrEF, and HFrEF. Seventy patients, HFpEF (n = 23), HFmrEF (n = 23) and HFrEF (n = 24), were enrolled at the Cardiology Unit of the University Hospital of Salerno. Sirt1 activity was measured in peripheral blood mononuclear cells (PBMCs). Angiotensin-Converting Enzyme 2 (ACE2) activity, Tumor Necrosis Factor-alpha (TNF-α) and Brain Natriuretic Peptide (BNP) levels were quantified in plasma. HFpEF showed lower Sirt1 and ACE2 activities than both HFmrEF and HFrEF (p < 0.0001), without difference compared to No HF controls. In HFmrEF and HFrEF a very strong correlation was found between Sirt1 activity and EF (r2 = 0.899 and r2 = 0.909, respectively), and between ACE2 activity and Sirt1 (r2 = 0.801 and r2 = 0.802, respectively). HFrEF showed the highest TNF-α levels without reaching statistical significance. Significant differences in BNP were found among the groups, with the highest levels in the HFrEF. Determining Sirt1 activity in PBMCs is useful to distinguish the HF patients’ phenotypes from each other, especially HFmrEF/HFrEF from HFpEF

Large Capacity Missile Carrier (CMX)

A systems engineering approach to the development of a radically different kind of surface combatant ship is presented, followed by a preliminary design of the ship shown by the analysis to be most effective. The requirement for the project was the development of a ship which would provide a major increase in the missile firepower of a battlegroup. The study conducts an analysis of four warfare scenarios and evaluates the effectiveness of replacing some Aegis ships with the missile carrier (CMX) and examines the relative utility of varying missile loads for the CMX. An alternative is chosen for further development and is designed to the preliminary design level. Data and drawings are included.Naval Sea Systems Command, Ship Design & System Engineering Grouphttp://archive.org/details/largecapacitymis00calvNaval Sea Systems Command, Ship Design & System Engineering GroupApproved for public release; distribution is unlimited

Screening for colorectal cancer: awareness and adherence among Italian women

Objective To evaluate women's awareness about and attendance to colorectal cancer (CRC) screening programs in an area of Southern Italy, and to investigate related potential determinants. Methods The survey was conducted among women through a self-administered questionnaire. Results Overall, only 20.3% of respondents knew the three cancer screening tests offered to women and this knowledge, at the multivariate logistic regression analysis, resulted to be significantly higher in women who knew the two most common cancers in females, in those who were graduated, had a personal or family history of cancer, and had been informed about cancer prevention by physicians. Only 29.2% of women had ever undergone FOBT, 25% for screening purposes and, of these, 76.4% in the previous 2 years. Among those who had never undergone FOBT, 28.9% reported they had not been invited to attend, 34.5% that the test had not been prescribed by anyone, and 19.1% had no time to undergo. The results of the multivariate logistic regression model revealed that significant determinants of having undergone FOBT for screening purposes were having undergone mammography, having at least one chronic disease, not reporting alcohol consumption and having been informed about cancer screening by physicians. Conclusion Our findings have revealed a concerning low awareness about and adherence to CRC screening in women and have highlighted the fundamental role of healthcare workers and of enabling factors in the decision process. Interventions should be directed to increasing awareness, and to promote cancer prevention screening pathways more centered on women's health needs and convenience

Waist circumference and healthy lifestyle preferences/Knowledge monitoring in a preschool obesity prevention program

Weight and body mass index (BMI) changes appear to be poor measures for assessing the success of most pediatric obesity prevention programs (POPP). The aim of this study is to evaluate the effectiveness of the preschool-age prevention program (3P) in improving and maintaining overtime preschoolers’ knowledge/preferences about healthy nutrition and physical activity (PA), and the relationship between acquired healthy behaviors and anthropometrics including waist circumference (WC). Twenty-five preschoolers underwent a 24-month healthy lifestyle multi-component pilot intervention followed by a one-year wash-out period; 25 age-matched served as controls. Anthropometric/behavioral data were monitored. After the 2-year study and wash-out, the rates of children overweight and with obesity decreased only in the intervention group, where, also, normal-weight children with visceral obesity attained WC normal values (p = 0.048). While mean values of BMI Z-scores remained unchanged in both the intervention and control groups, WC (values and percentiles) showed a significant reduction only in the intervention group. Children’s adherence to the Mediterranean diet remained acceptable among the entire sample. Although daily sweet beverage consumption remained unchanged in both groups, knowledge/preferences improved significantly more in the intervention group. In conclusion, WC may be more sensitive than BMI for monitoring preschoolers in POPP and reflects healthy behavioral changes acquired during the intervention

Identification of Drug Interaction Adverse Events in Patients with COVID-19: A Systematic Review

Importance: During the COVID-19 pandemic, urgent clinical management of patients has mainly included drugs currently administered for other diseases, referred to as repositioned drugs. As a result, some of these drugs have proved to be not only ineffective but also harmful because of adverse events associated with drug-drug interactions (DDIs). Objective: To identify DDIs that led to adverse clinical outcomes and/or adverse drug reactions in patients with COVID-19 by systematically reviewing the literature and assessing the value of drug interaction checkers in identifying such events. Evidence Review: After identification of the drugs used during the COVID-19 pandemic, the drug interaction checkers Drugs.com, COVID-19 Drug Interactions, LexiComp, Medscape, and WebMD were consulted to analyze theoretical DDI-associated adverse events in patients with COVID-19 from March 1, 2020, through February 28, 2022. A systematic literature review was performed by searching the databases PubMed, Scopus, and Cochrane for articles published from March 1, 2020, through February 28, 2022, to retrieve articles describing actual adverse events associated with DDIs. The drug interaction checkers were consulted again to evaluate their potential to assess such events. Findings: The DDIs identified in the reviewed articles involved 46 different drugs. In total, 575 DDIs for 58 drug pairs (305 associated with at least 1 adverse drug reaction) were reported. The drugs most involved in DDIs were lopinavir and ritonavir. Of the 6917 identified studies, 20 met the inclusion criteria. These studies, which enrolled 1297 patients overall, reported 115 DDI-related adverse events: 15 (26%) were identifiable by all tools analyzed, 29 (50%) were identifiable by at least 1 of them, and 14 (24%) remained nonidentifiable. Conclusions and Relevance: The main finding of this systematic review is that the use of drug interaction checkers could have identified several DDI-associated adverse drug reactions, including severe and life-threatening events. Both the interactions between the drugs used to treat COVID-19 and between the COVID-19 drugs and those already used by the patients should be evaluated.

Sirt1 activity in pbmcs as a biomarker of different heart failure phenotypes

Heart Failure (HF) is a syndrome, which implies the existence of different phenotypes. The new categorization includes patients with preserved ejection fraction (HFpEF), mid-range EF (HFmrEF), and reduced EF (HFrEF) but the molecular mechanisms involved in these HF phenotypes have not yet been exhaustively investigated. Sirt1 plays a crucial role in biological processes strongly related to HF. This study aimed to evaluate whether Sirt1 activity was correlated with EF and other parameters in HFpEF, HFmrEF, and HFrEF. Seventy patients, HFpEF (n = 23), HFmrEF (n = 23) and HFrEF (n = 24), were enrolled at the Cardiology Unit of the University Hospital of Salerno. Sirt1 activity was measured in peripheral blood mononuclear cells (PBMCs). Angiotensin-Converting Enzyme 2 (ACE2) activity, Tumor Necrosis Factor-alpha (TNF-α) and Brain Natriuretic Peptide (BNP) levels were quantified in plasma. HFpEF showed lower Sirt1 and ACE2 activities than both HFmrEF and HFrEF (p < 0.0001), without difference compared to No HF controls. In HFmrEF and HFrEF a very strong correlation was found between Sirt1 activity and EF (r2 = 0.899 and r2 = 0.909, respectively), and between ACE2 activity and Sirt1 (r2 = 0.801 and r2 = 0.802, respectively). HFrEF showed the highest TNF-α levels without reaching statistical significance. Significant differences in BNP were found among the groups, with the highest levels in the HFrEF. Determining Sirt1 activity in PBMCs is useful to distinguish the HF patients’ phenotypes from each other, especially HFmrEF/HFrEF from HFpEF