Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Use of licit and illicit drugs at the university of Alfenas Uso de drogas lícitas e ilícitas no meio universitário de Alfenas

This paper reports the study of drug consumption carried out within the population of undergraduate students from 2 colleges of Alfenas, in the state of Minas Gerais state. Both licit and illicit drugs were studied, including alcohol, tobacco, marijuana, cocaine, heroin, crack, inhalants, glue, tranquilizers, stimulants, and others. METHODOLOGY: The research included a wide bibliographical search and the application of a questionnaire to approximately 23% of the students (total of 6500 students). RESULTS: A total of 1500 students participated in this investigation. The results demonstrated that there was a significant consumption of both licit and illicit drugs. The pattern of drug consumption in the research sample was similar to other investigations conducted in Brazil and in other countries. DISCUSSION: It was observed that 55% of the university students use drugs. However, the most surprising finding was that most of the students (88%) answered "yes" to the inquiry, "Have you already tried any type of drug, including alcohol and cigarettes?" The students revealed that they had taken drugs even prior to the admission to the university. The results suggest clearly that the university environment does not necessarily represent the starting point for student drug consumption.<br>Este trabalho relata um estudo sobre o consumo de drogas realizado em uma população de estudantes em duas universidades na cidade de Alfenas, no estado de Minas Gerais. Tanto drogas lícitas como ilícitas foram consideradas, incluindo álcool, tabaco, maconha, cocaína, heroína, crack, inalantes, cola, tranquilizantes, estimulantes, entre outras. METODOLOGIA: A pesquisa incluiu uma vasta revisão bibliográfica e a aplicação de um questionário em cerca de 23% dos acadêmicos (total 6.500). RESULTADOS: Um total de 1.500 estudantes participaram desta investigação. Os resultados demonstram que há um consumo significativo de tais drogas. Entretanto, o padrão do consumo de drogas na amostra foi semelhante a outras investigações realizadas no Brasil e em outros países. DISCUSSÃO: Foi verificado que 55% dos universitários realmente utilizam drogas. Entretanto, o achado mais surpreendente foi que a maioria dos estudantes (88%) que responderam "sim" à indagação "Você já experimentou algum tipo de droga, incluindo álcool e cigarros?" espontaneamente eles revelaram que consumiam tais drogas, porém antes da admissão na Universidade. Este resultado sugere claramente que o ambiente universitário não representa necessariamente o ponto de partida para o consumo de drogas