AimSARS-CoV-2 infection is a world-wide public health problem. Several aspects of its pathogenesis and the related clinical consequences still need elucidation. In Italy, Sardinia has had very low numbers of infections. Taking advantage of the low genetic polymorphism in the Sardinian population, we analyzed clinical, genetic and immunogenetic factors, with particular attention to HLA class I and II molecules, to evaluate their influence on susceptibility to SARS-CoV-2 infection and the clinical outcome.Method and MaterialsWe recruited 619 healthy Sardinian controls and 182 SARS-CoV-2 patients. Thirty-nine patients required hospital care and 143 were without symptoms, pauci-symptomatic or with mild disease. For all participants, we collected demographic and clinical data and analyzed the HLA allele and haplotype frequencies.ResultsMale sex and older age were more frequent in hospitalized patients, none of whom had been vaccinated during the previous seasonal flu vaccination campaignes. Compared to the group of asymptomatic or pauci-symptomatic patients, hospitalized patients also had a higher frequency of autoimmune diseases and glucose-6-phosphate-dehydrogenase (G6PDH) deficiency. None of these patients carried the beta-thalassemia trait, a relatively common finding in the Sardinian population. The extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0–0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [OR 3.8 (95% CI 1.8–8.1), Pc = 0.025] were more frequently represented in patients than controls. In a comparison between in-patients and home care patients, the HLA-DRB1*08:01 allele was exclusively present in the hospitalized patients [OR > 2.5 (95% CI 2.7–220.6), Pc = 0.024].ConclusionThe data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 has a protective effect against SARS-CoV-2 infection in the Sardinian population. Genetic factors that resulted to have a negative influence on the disease course were presence of the HLA-DRB1*08:01 allele and G6PDH deficiency, but not the beta-thalassemic trait. Absence of influenza vaccination could be a predisposing factor for more severe disease.
Different latent class of schizotypal features can be empirically defined in adolescent community samples. The most extreme class is defined not only by a profile of higher positive replies to the items, but also by anhedonia, high psychological distress, and family history of psychosis. These findings can inform prevention research in schizophrenia.
Background The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study’s focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection. Methods KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas. Results Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1–2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3–0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3–0.7), PM = 0.0005, PMC = 0.005]. Conclusions The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection.
The negative attitudes surrounding mental disorders and their treatment are a major obstacle to the correct identification and treatment of emerging psychopathologies. The purpose of this study was to investigate mental health literacy in a large and representative sample of high school students in Italy, via a booklet containing several questionnaires delivered to 1032 teenagers. The items in the questionnaires probed knowledge about mental health and illness, stigmatization, stereotypes, behaviors, opinions, and attitudes. In general, the students had a reasonable knowledge of mental disorders and were able to distinguish these from somatic disorders. However, a large portion of the students nourished some misconceptions about mental disorders and was also rather skeptical about the effectiveness of treatment or the chance of recovery for people with severe mental disorders. Nevertheless, roughly half of the students reported being willing to provide help to someone with a mental disorder when in need. Poor mental health literacy is a major barrier to seeking help and receiving effective treatment. Young people are the ideal target of raising awareness and antistigma campaigns because they are at a higher risk for developing a psychopathology.
Type 2 diabetes mellitus (T2DM), the most common form of diabetes, is a progressive chronic metabolic disease that has increasingly spread worldwide, enhancing the mortality rate, particularly from cardiovascular diseases (CVD). Lifestyle improvement through diet and physical activity is, together with drug treatment, the cornerstone of T2DM management. The Mediterranean diet (MD), which favors a prevalence of unprocessed vegetable foods and a reduction in red meats and industrial foods, without excluding any food category, is usually recommended. Recently, scientific societies have promoted a very low-calorie ketogenic diet (VLCKD), a multiphasic protocol that limits carbohydrates and then gradually re-introduces them, with a favorable outcome on body weight and metabolic parameters. Indeed, gut microbiota (GM) modifications have been linked to overweight/obesity and metabolic alterations typical of T2DM. Diet is known to affect GM largely, but only a few studies have investigated the effects of VLCKD on GM, especially in T2DM. In this study, we have compared anthropometric, biochemical, lifestyle parameters, the quality of life, and the GM of eleven patients with recently diagnosed T2DM and overweight or obesity, randomly assigned to two groups of six and five patients who followed the VLCKD (KETO) or hypocaloric MD (MEDI) respectively; parameters were recorded at baseline (T0) and after two (T2) and three months (T3). The results showed that VLCKD had more significant beneficial effects than MD on anthropometric parameters, while biochemical improvements did not statistically differ. As for the GM, despite the lack of significant results regarding the alpha and beta diversity, and the Firmicutes/Bacteroidota ratio between the two groups, in the KETO group, a significant increase in beneficial microbial taxa such as Verrucomicrobiota phylum with its members Verrucomicrobiae, Verrucomicrobiales, Akkermansiaceae, and Akkermansia, Christensenellaceae family, Eubacterium spp., and a reduction in microbial taxa previously associated with obesity (Firmicutes and Actinobacteriota) or other diseases (Alistipes) was observed both at T2 and T3. With regards to the MEDI group, variations were limited to a significant increase in Actinobacteroidota phylum at T2 and T3 and Firmicutes phylum at T3. Moreover, a metagenomic alteration linked to some metabolic pathways was found exclusively in the KETO group. In conclusion, both dietary approaches allowed patients to improve their state of health, but VLCKD has shown better results on body composition as well as on GM profile.
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