SAÚDE MENTAL NA UNIVERSIDADE – A COMPREENSÃO DA SÍNDROME DE BURNOUT EM UNIVERSITÁRIOS A PARTIR DA ANÁLISE DO COMPORTAMENTO

Estudos realizados na última década têm demonstrado uma elevação no número de distúrbios psicológicos em estudantes universitários, afetando a qualidade de vida e o desenvolvimento dessa população. Dentre os transtornos apresentados por universitários a Síndrome de Burnout vem sendo relatada com uma incidência considerável. Investigações sobre a Síndrome de Burnout em estudantes universitários têm sido produzidas com o objetivo de entender como o contexto da educação superior afeta o bem-estar desta população. Entre os principais sintomas da Síndrome de Burnout estão exaustão emocional, despersonalização e sentimento de ineficácia nas atividades realizadas, além de fadiga, depressão e diminuição do desempenho acadêmico. Este estudo se propõe a compreender a Síndrome de Burnout em estudantes universitários, os sintomas mais comuns e as variáveis acadêmicas relacionadas a partir de uma revisão de literatura. Propõe-se também a abordar o problema a partir da compreensão Analítico Comportamental, com o objetivo de esclarecer possibilidades de prevenção e intervenção da Síndrome de Burnout no contexto educacional

Risk-Adjusted Cancer Screening and Prevention (RiskAP): Complementing Screening for Early Disease Detection by a Learning Screening Based on Risk Factors

Breast cancer; Evidence-generating care; Risk-adjusted preventionCáncer de mama; Atención generadora de evidencia; Prevención ajustada al riesgoCàncer de mama; Atenció generadora d'evidències; Prevenció ajustada al riscBackground: Risk-adjusted cancer screening and prevention is a promising and continuously emerging option for improving cancer prevention. It is driven by increasing knowledge of risk factors and the ability to determine them for individual risk prediction. However, there is a knowledge gap between evidence of increased risk and evidence of the effectiveness and efficiency of clinical preventive interventions based on increased risk. This gap is, in particular, aggravated by the extensive availability of genetic risk factor diagnostics, since the question of appropriate preventive measures immediately arises when an increased risk is identified. However, collecting proof of effective preventive measures, ideally by prospective randomized preventive studies, typically requires very long periods of time, while the knowledge about an increased risk immediately creates a high demand for action. Summary: Therefore, we propose a risk-adjusted prevention concept that is based on the best current evidence making needed and appropriate preventive measures available, and which is constantly evaluated through outcome evaluation, and continuously improved based on these results. We further discuss the structural and procedural requirements as well as legal and socioeconomical aspects relevant for the implementation of this concept.The project was funded by the German Federal Ministry of Health (grant No. 2515FSB401 to Rita Schmutzler and Christiane Woopen) for supporting the international expert meetings, and a grant of the EU Horizon 2020 program, BRIDGES (grant No. 634935, PI Peter Devilee, WP5-PI Rita Schmutzler), for the compilation of the most recent findings of genetic risk prediction

Catalytic inhibition of topoisomerase II by a novel rationally designed ATP-competitive purine analogue

ABSTRACT: BACKGROUND: Topoisomerase II poisons are in clinical use as anti-cancer therapy for decades and work by stabilizing the enzyme-induced DNA breaks. In contrast, catalytic inhibitors block the enzyme before DNA scission. Although several catalytic inhibitors of topoisomerase II have been described, preclinical concepts for exploiting their anti-proliferative activity based on molecular characteristics of the tumor cell have only recently started to emerge. Topoisomerase II is an ATPase and uses the energy derived from ATP hydrolysis to orchestrate the movement of the DNA double strands along the enzyme. Thus, interfering with ATPase function with low molecular weight inhibitors that target the nucleotide binding pocket should profoundly affect cells that are committed to undergo mitosis. RESULTS: Here we describe the discovery and characterization of a novel purine diamine analogue as a potent ATP-competitive catalytic inhibitor of topoisomerase II. Quinoline aminopurine compound 1 (QAP 1) inhibited topoisomerase II ATPase activity and decatenation reaction at sub-micromolar concentrations, targeted both topoisomerase II alpha and beta in cell free assays and, using a quantitative cell-based assay and a chromosome segregation assay, displayed catalytic enzyme inhibition in cells. In agreement with recent hypothesis, we show that BRCA1 mutant breast cancer cells have increased sensitivity to QAP 1. CONCLUSION: The results obtained with QAP 1 demonstrate that potent and selective catalytic inhibition of human topoisomerase II function with an ATP-competitive inhibitor is feasible. Our data suggest that further drug discovery efforts on ATP-competitive catalytic inhibitors are warranted and that such drugs could potentially be developed as anti-cancer therapy for tumors that bear the appropriate combination of molecular alterations

TRAF6 Phosphorylation Prevents Its Autophagic Degradation and Re-Shapes LPS-Triggered Signaling Networks

The ubiquitin E3 ligase TNF Receptor Associated Factor 6 (TRAF6) participates in a large number of different biological processes including innate immunity, differentiation and cell survival, raising the need to specify and shape the signaling output. Here, we identify a lipopolysaccharide (LPS)-dependent increase in TRAF6 association with the kinase IKKε (inhibitor of NF-κB kinase subunit ε) and IKKε-mediated TRAF6 phosphorylation at five residues. The reconstitution of TRAF6-deficient cells, with TRAF6 mutants representing phosphorylation-defective or phospho-mimetic TRAF6 variants, showed that the phospho-mimetic TRAF6 variant was largely protected from basal ubiquitin/proteasome-mediated degradation, and also from autophagy-mediated decay in autolysosomes induced by metabolic perturbation. In addition, phosphorylation of TRAF6 and its E3 ligase function differentially shape basal and LPS-triggered signaling networks, as revealed by phosphoproteome analysis. Changes in LPS-triggered phosphorylation networks of cells that had experienced autophagy are partially dependent on TRAF6 and its phosphorylation status, suggesting an involvement of this E3 ligase in the interplay between metabolic and inflammatory circuits

Analisar a alimentação de autistas por meio de revisão de literatura / Analyze the feed of autism through the literature review

O autismo possui como características modificações no comportamento, interação social e comunicação, além disso, apresenta padrões restritivos, repetitivos e estereotipados que estão ligados a seletividade alimentar e recusa de novos alimentos, estas atitudes podem levar a possíveis carências nutricionais devido a alimentação com pouca variedade. Esta pesquisa teve como objetivo analisar a alimentação de autistas por meio de revisão de literatura, abordando a prevalência de autismo, seletividade alimentar e os alimentos mais ou menos consumidos por este grupo de indivíduos. Trata-se de uma revisão de literatura, a busca foi realizada em bibliotecas online, a amostra foi composta por artigos e outros documentos publicados no período entre 2008 e 2020. Foram selecionados 14 artigos com base nos objetivos da pesquisa. Os resultados apontam que a maior prevalência de indivíduos autistas está na Ásia, que no Brasil não existem dados oficiais sobre a prevalência de autismo, apenas pesquisas escassas que abrangem alguns estados. Quanto a seletividade alimentar por indivíduo com TEA, os resultados foram significativos, porém verificou-se que se houver uma intervenção e educação adequada por meio do trabalho de um profissional nutricionista, é possível melhorar a variedade dos alimentos ingeridos por essa população. No que se refere aos alimentos mais e menos consumidos por autistas os resultados apontaram que existe tendência de maior consumo de alimentos ricos em carboidratos e gorduras, já as restrições foram por alimentos que contém proteínas, vitaminais e sais minerais. Concluiu-se que a alimentação adequada para o indivíduo com TEA depende da intervenção precoce do nutricionista

Explaining disappearances as a tool of political terror

Despite the widespread use of disappearances as a central tool of terror in recent decades, little is known about the emergence of the phenomenon or its underlying rationale. We argue that growing international accountability norms, coupled with the improved quality of reporting human rights abuses, paradoxically reshaped the repressive strategies of certain regimes and pushed them to deploy more clandestine and extrajudicial forms of repression, predominantly disappearances. We also explore the timing of disappearances: when a state decides to deploy a particular instrument of terror can greatly benefit our understanding of why it was used. We show that repressive regimes tend to use disappearances in the first period after a coup, taking advantage of the general confusion and opacity to secure strategic benefits and protect the regime from external scrutiny and future accountability. Our findings contribute to the growing literature on human rights and political repression by highlighting an ‘unintended consequence’ of international accountability norms: repressive regimes turn to clandestine crimes

Loss of signalling via Gα13 in germinal center B-cell-derived lymphoma

Germinal centre B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined1,2. Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a Gα12 and Gα13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells3,4. Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding Gα13) and S1PR2 (refs 5,6, 7). Here we show, using in vitro and in vivo assays, that GCB-DLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor's Akt and migration inhibitory functions. Gα13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and Gα13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in Gα13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the Gα13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of Gα13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt's lymphoma, also represses germinal centre B-cell growth and promotes confinement via Gα13. These findings identify a Gα13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma