The Role of Social Deprivation and Cannabis Use in Explaining Variation in the Incidence of Psychotic Disorders: Findings From the EU-GEI Study.

BACKGROUND AND HYPOTHESIS: Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings. STUDY DESIGN: We used incidence data in people aged 18-64 years from 14 settings of the EU-GEI study. We estimated the prevalence of daily and high-potency cannabis use in controls as a proxy for usage in the population at-risk; multiple imputations by chained equations and poststratification weighting handled missing data and control representativeness, respectively. We modeled FEP incidence in random intercepts negative binomial regression models to investigate associations with the prevalence of cannabis use in controls, unemployment, and owner-occupancy in each setting, controlling for population density, age, sex, and migrant/ethnic group. STUDY RESULTS: Lower owner-occupancy was independently associated with increased FEP (adjusted incidence rate ratio [aIRR]: 0.76, 95% CI: 0.61-0.95) and non-affective psychosis incidence (aIRR: 0.68, 95% CI: 0.55-0.83), after multivariable adjustment. Prevalence of daily cannabis use in controls was associated with the incidence of affective psychoses (aIRR: 1.53, 95% CI: 1.02-2.31). We found no association between FEP incidence and unemployment or high-potency cannabis use prevalence. Sensitivity analyses supported these findings. CONCLUSIONS: Lower setting-level owner-occupancy and increased prevalence of daily cannabis use in controls independently contributed to setting-level variance in the incidence of different psychotic disorders. Public health interventions that reduce exposure to these harmful environmental factors could lower the population-level burden of psychotic disorders.

Endocrine disruptors and arterial hypertension: A developing story.

Endocrine disrupting Chemicals (EDCs) are substances that interfere with hormones by several mechanisms including receptor activation or antagonism, changes in gene and protein expression, modification of signal transduction, and/or epigenetic modifications in hormone-producing cells. A survey conducted by the European Union in a Northern Italian region led to the discovery of a large environmental contamination of drinking water by perfluoroalkyl substances (PFAS). As the exposed population showed a high prevalence of arterial hypertension and cardiovascular disease, we decided to investigate if PFAS could enhance the biosynthesis of aldosterone. To this aim, we exposed human adrenocortical carcinoma HAC15 cells to PFAS and found that PFAS markedly increased aldosterone synthase (CYP11B2) gene expression and aldosterone secretion. Moreover, we found that they promoted reactive oxygen species (ROS) production in mitochondria, the organelles where aldosterone biosynthesis takes place. PFAS also enhanced the effects of the aldosterone secretagogue angiotensin II (Ang II) on CYP11B2 gene expression and aldosterone secretion. We also found that not only PFAS but also polychlorinated biphenyl 126 (PCB126), a chemical compound belonging to a different category of EDCs, can increase CYP11B2 gene expression and aldosterone secretion in adrenocortical cells. This novel information needs to be considered in the context of a widespread exposure to the most common EDC, that is excess Na+ intake, whose detrimental effects on human health occur in the setting of aldosterone production exceeding the physiological needs and lead to high blood pressure, congestion, and cardiovascular and renal damage.

HUMORAL AND CELLULAR IMMUNOGENICITY and SAFETY UP TO 4 MONTHS AFTER VACCINATION WITH BNT162B2 mRNA COVID-19 VACCINE IN HEART AND LUNG TRANSPLANTED YOUNG ADULTS

BackgroundImmunizations among vulnerable population, including solid organ transplant recipients (SOT), present suboptimal responses at vaccination and over time. We investigated safety and immunogenicity of the BNT162B2 mRNA COVID-19 vaccine in 34 SOT young adults as compared to 36 healthy controls (HC). Methodsimmunogenicity was measured through the analysis of anti SARS-CoV2 IgG Antibodies and antigen specific CD4 T cells (CD40L+), detected by flow cytometry before vaccination, 21 days after priming (T21), 7 days after booster dose (T28) and 2-4 months after priming (T120). Baseline T and B cell immune phenotype was deeply investigated. The safety profile was investigated by close monitoring and self-reported diary. ResultsAnti-S and anti-Trimeric Ab responses were significantly lower in SOT vs HC at T21 (p<0.0001) and at T28 (p<0.0001). Ten out of 34 SOT (29%) at T28 and 3 out of 33 (9%) at T120 had undetectable SARS-CoV-2 IgG. The analysis of SARS-CoV-2 specific CD4 T cells showed lower CD40L expression after in vitro stimulation in SOT compared to HC. Lower frequencies of memory B cells were found in patients not responding to vaccination. Lack of seroconversion was higher in patients treated with mycophenolate (p=0.0005). The vaccination was safe and well tolerated. Only short-term adverse events, were reported and no hospitalization or graft rejection were observed after vaccinations. ConclusionsThese data show that SOT have a suboptimal immune response following mRNA vaccinations as compared to HC. Alternative strategies should be investigated to improve the immunization against SARS-CoV-2 in these patients.

Prioritizing the first doses of SARS-CoV-2 vaccine to save the elderly: the case study of Italy

Many countries are currently facing high mortality caused by the circulation of SARS-CoV-2 among the elderly not yet vaccinated. Vaccine shortage poses relevant challenges to health authorities, called to act in a timely manner, and with scarcity of vaccine, and data. We have developed a model for estimating of the impact of vaccination on the mortality of the elderly following a schedule of mRNA SARS-CoV-2 vaccine that prioritize first dose administration, as alternative to the standard schedule of two doses administered 3 to 4 weeks apart. We studied the Italian scenario, considering it representative of other Countries facing similar conditions in terms of virus circulation, mortality, and vaccine shortage, in the period from February 10 to April 14 2021. Under different conditions of quantity of vaccine administration, the schedule prioritizing first doses showed always significant increase of protected individuals, and a decrease of deaths, up to 19.8% less than the standard schedule. These findings support the vaccination option of prioritizing first dose in the elderly until vaccine supplies are adequate.

The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19

SARS-CoV-2 infection is typically very mild and often asymptomatic in children. A complication is the rare Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2 and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T-cell subsets, IL-17A and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C. HIGHLIGHTSHyperinflammation in MIS-C differs from that of acute COVID-19 T-cell subsets discriminate Kawasaki disease patients from MIS-C IL-17A drives Kawasaki, but not MIS-C hyperinflammation. Global autoantibodies profiling indicate possibly pathogenic autoantibodies

SIRT1, heme oxygenase-1 and NO-mediated vasodilation in a human model of endogenous angiotensin II type 1 receptor antagonism: implications for hypertension.

Reduced NO availability is associated with endothelial dysfunction, hypertension, insulin resistance and cardiovascular remodeling. SIRT1 upregulates eNOS activity and inhibits endothelial cell senescence, and reduced SIRT1 is related to oxidative stress and reduced NO-dependent dilation. Bartter's/Gitelman's syndromes (BS/GS) are rare diseases that feature a picture opposite to that of hypertension in that they present with normo/hypotension, reduced oxidative stress and a lack of cardiovascular remodeling, notwithstanding high levels of angiotensin II and other vasopressors, upregulation of NO system, and increased NO-dependent vasodilation (FMD), as well as increase in both endothelial progenitor cells and insulin sensitivity. To our knowledge, in BS/GS patients SIRT1 has never been evaluated. BS/GS patients' mononuclear cell SIRT1 (western blot), FMD (B-mode scan of the right brachial artery) and heme oxygenase (HO)-1 (sandwich immunoassay), a potent antioxidant protein, were compared with the levels in untreated stage 1 essential hypertensive patients (HPs) and in healthy subjects (C). SIRT1 (1.86 ± 0.29 vs. 1.18 ± 0.18 (HP) vs. 1.45 ± 0.18 (C) densitometric units, P<0.0001) and HO-1 protein (9.44 ± 3.09 vs. 3.70 ± 1.19 (HP) vs. 5.49 ± 1.04 (C) ng ml⁻¹, P<0.0001) levels were higher in BS/GS patients than in the other groups. FMD was also higher in BS/GS patients: 10.52 ± 2.22% vs. 5.99 ± 1 .68% (HP) vs. 7.99 ± 1.13% (C) (ANOVA: P<0.0001). A strong and significant correlation between SIRT1 and FMD was found only in BS/GS patients (r(2)=0.63, P=0.0026). Increased SIRT1 and its direct relationship with increased FMD in BS/GS patients, while strengthening the relationship among SIRT1, NO and vascular function in humans, point toward a role for reduced SIRT1 in the endothelial dysfunction of hypertension.

Estudo comparativo entre o método pilates® e exercícios terapêuticos sobre a força muscular e flexibilidade de tronco em atletas de futebol / Comparative study of the method pilates® and therapeutic exercises on muscle strength and flexibility in trunk of soccer players

Introdução: O treinamento intenso e repetitivo de um esporte provoca a hipertrofia muscular e a diminuição da flexibilidade. Objetivo: Analisar o comportamento da força muscular e da flexibilidade dos músculos extensores de tronco.Métodos: Foram utilizados dois protocolos (exercícios terapêuticos e método Pilates® no solo) em 26 atletas de futebol. A força muscular foi avaliada com o dinamômetro isométrico de tronco e a flexibilidade com o banco de Wells e o flexímetro. Realizaram-se três avaliações: pré, pós-imediata e pós-tardia. Resultados: O protocolo de exercícios terapêuticos incrementou a flexibilidade nas avaliações pré e pós-imediata e pré e pós-tardia, no banco de Wells (p<0,05) e no flexímetro (p<0,05), não se obtendo diferenças com relação à força muscular. Já no GP não houve significância estatística no aumento da flexibilidade e força (p>0,05). Conclusão: Sugere-se que mais estudos sejam realizados, confrontando essas duas modalidades terapêuticas a fim de esclarecer todas as possibilidades de aplicação desses métodos.

Introduction: The intense and repetitive training of a sport causes muscle hypertrophy and decreased flexibility. Objective: To analyze the behavior of muscle strength and flexibility of the extensor muscles tronco.Métodos: We used two protocols (therapeutic exercises and Pilates ® in the soil) in 26 soccer players. Muscle strength was assessed with the dynamometer isometric trunk and flexibility with the bank by Wells and fleximeter. There were three assessments: pre-, post-immediate and delayed post. Results: The therapeutic exercise protocol increased flexibility in the pre and immediate post-and pre-and post late in the bank by Wells (p <0.05) and in Fleximeter (p <0.05), no differences were obtained with respect to muscle strength. In the GP, no statistically significant increase flexibility and strength (p> 0.05). Conclusion: It is suggested that more studies be conducted, comparing these two treatment modalities in order to clarify all the possibilities of applying these methods.