AVALIAÇÃO HISTOPATOLÓGICA DO FÍGADO DE Brachyplatystoma rousseauxii (CASTELNAU, 1855) DA BAÍA DO GUAJARÁ, BELÉM, PARÁ

The species Brachyplatystoma rousseauxii is one of the most important economic resources of the Amazon region. The objective of the present work was to analyze the histopathology of the liver of B. rousseauxii and to indicate this species as a biomonitor of the environmental quality of the Guajará Bay. Samples were collected in four areas: a control area and three areas identified as discharge sites of solid and liquid wastes. Sampling was carried out in four season periods: dry/wet season, wet season, wet/dry season and dry season. The number of collected specimens was 36. The fishes were submitted to biometry after catching. They presented mean total length of 33.45 cm (±7.72), total weight of 239.21 g (±135.24), and liver weight of 1.22 g (±0.56). Liver fragments were processed for light microscopy analysis. Histopathologic analysis demonstrated that 70% of the fish presented hepatitis, inflammation, fatty degeneration, and congestion, and that 30% presented well-organized liver structures, and they were considered healthy. The hepatic changes observed and the number of specimens collected suggest that the environmental quality of the Guajará Bay is affected and that the species B. rousseauxii  is probably adapted to the areas where there are waste discharges. KEY WORDS: Amazonian biome, biomonitor, liver, histopathology, fish

GQ-16, a TZD-derived partial PPARγ agonist, induces the expression of thermogenesis- related genes in brown fat and visceral white fat and decreases visceral adiposity in obese and hyperglycemic mice

Background Beige adipocytes comprise a unique thermogenic cell type in the white adipose tissue (WAT) of rodents and humans, and play a critical role in energy homeostasis. In this scenario, recruitment of beige cells has been an important focus of interest for the development of novel therapeutic strategies to treat obesity. PPARγ activation by full agonists (thiazolidinediones, TZDs) drives the appearance of beige cells, a process so-called browning of WAT. However, this does not translate into increased energy expenditure, and TZDs are associated with weight gain. Partial PPARγ agonists, on the other hand, do not induce weight gain, but have not been shown to drive WAT browning. The present study was designed to investigate the effects of GQ-16 on BAT and on browning of WAT in obese mice. Methods Male Swiss mice with obesity and hyperglycemia induced by high fat diet were treated with vehicle, rosiglitazone (4 mg/kg/d) or the TZD-derived partial PPARγ agonist GQ-16 (40 mg/ kg/d) for 14 days. Fasting blood glucose, aspartate aminotransferase, alanine aminotransferase and lipid profile were measured. WAT and brown adipose tissue (BAT) depots were excised for determination of adiposity, relative expression of Ucp-1, Cidea, Prdm16, Cd40 and Tmem26 by RT-qPCR, histological analysis, and UCP-1 protein expression analysis by immunohistochemistry. Liver samples were also removed for histological analysis and determination of hepatic triglyceride content. Results GQ-16 treatment reduced high fat diet-induced weight gain in mice despite increasing energy intake. This was accompanied by reduced epididymal fat mass, reduced liver triglyceride content, morphological signs of increased BAT activity, increased expression of thermogenesis- related genes in interscapular BAT and epididymal WAT, and increased UCP-1 protein expression in interscapular BAT and in epididymal and inguinal WAT. Conclusion This study suggests for the first time that a partial PPARγ agonist may increase BAT activity and induce the expression of thermogenesis-related genes in visceral WAT. General Significance These findings suggest that PPARγ activity might be modulated by partial agonists to induce WAT browning and treat obesity

Type I Interferon Transcriptional Signature in Neutrophils and Low-Density Granulocytes Are Associated with Tissue Damage in Malaria

Neutrophils are the most abundant leukocyte population in the bloodstream, the primary compartment of Plasmodium sp. infection. However, the role of these polymorphonuclear cells in mediating either the resistance or the pathogenesis of malaria is poorly understood. We report that circulating neutrophils from malaria patients are highly activated, as indicated by a strong type I interferon transcriptional signature, increased expression of surface activation markers, enhanced release of reactive oxygen species and myeloperoxidase, and a high frequency of low-density granulocytes. The activation of neutrophils was associated with increased levels of serum alanine and aspartate aminotransferases, indicating liver damage. In a rodent malaria model, we observed intense recruitment of neutrophils to liver sinusoids. Neutrophil migration and IL-1beta and chemokine expression as well as liver damage were all dependent on type I interferon signaling. The data suggest that type I interferon signaling has a central role in neutrophil activation and malaria pathogenesis

Exposure to endocrine-disrupting chemicals and anthropometric measures of obesity : a systematic review and meta-analysis

Objective Endocrine-disrupting chemicals (EDCs) are viewed as a major potential link between the environment and obesity development. We did a systematic review and meta-analysis to examine the association between exposure to EDCs and obesity. Data sources, design and eligibility criteria PubMed, Scopus and Web of Science were searched from inception to 6 June 2018 for studies primarily addressing the association between exposure to EDCs after the age of 2 years and anthropometric measures of obesity or body fat. The Newcastle-Ottawa scale was used to assess the risk of bias. Data extraction and synthesis Two independent reviewers screened and conducted data extraction and synthesis. A third reviewer resolved disagreements. Results A total of 73 studies investigating bisphenol A (32 286 individuals), organochlorine compounds (34 567 individuals), phthalates (21 401 individuals), polybrominated biphenyls (2937 individuals), polycyclic aromatic hydrocarbons (5174 individuals), parabens (4097 individuals), benzoic acid (3671 individuals) and polyfluoroalkyl substances (349 individuals) met our inclusion criteria. Most had a cross-sectional design and low or medium risk of bias. In qualitative analysis, bisphenol A and phthalates were consistently associated with general and abdominal obesity, in children and adults, and some studies suggested this association was age-dependent and gender-dependent. Meta-analysis indicated a significant association between exposure to bisphenol A and overweight (OR 1.254, 95%CI 1.005 to 1.564), obesity (OR 1.503, 95%CI 1.273 to 1.774) and increased waist circumference (OR 1.503, 95%CI 1.267 to 1.783) in adults, and between exposure to 2,5-dichlorophenol and obesity in children (OR 1.8, 95%CI 1.1018 to 3.184). Conclusion Most observational studies supported a positive association between obesity and exposure to EDCs. Although causality cannot be determined from these data, they underscore the need to limit human exposure to EDCs in light of the evidence from animal and cellbased studies indicating the effects of these chemicals on adiposity

Integrality in Brazil and Venezuela : similarities and complementarities

O presente estudo tem como objetivo comparar a Atenção Primária à Saúde (APS) no Brasil e na Venezuela, observando suas características quanto à integralidade. Possui abordagem qualitativa, por meio de análise documental, entrevistas semiestruturadas com informantes-chave e anotações em diário de campo. Observou-se as três dimensões de integralidade inseridas no processo de trabalho em saúde: o cuidado integral e holístico, visão do indivíduo como um ser complexo com múltiplas necessidades, exigindo a conexão de diversos saberes em saúde; a continuidade do cuidado na micropolítica institucional com articulação interprofissional, de forma a contemplar o cuidado singular; a continuidade do cuidado na macropolítica, quando é necessário um deslocamento aos demais níveis de atenção; incluiu-se ainda a intersetorialidade, quando as necessidades de um indivíduo e comunidade exigem uma articulação transetorial, com ação sobre os determinantes e condicionantes do processo saúde-doença. Ressalta-se ainda a tendência singular de inclusão de uma formação médica comunitária integral. Conclui-se que estes países, fortalecidos pela democracia, aproximam-se em suas práticas de integralidade, bem como na construção de políticas sociais e de saúde para as populações menos favorecidas, em favor da equidade.This study aims to compare Primary Health Care (PHC) in Brazil and Venezuela, considering its characteristics as to integrality. It has a qualitative approach, using documental analysis, semi-structured interviews with key informants and field diary notes. We observed the three realms of integrality inherent to the health work process: comprehensive and holistic care, the individual viewed as a complex being with multiple needs, requiring the connection of various health knowledge; continuity of care in institutional micro-policy with interprofessional articulation, in order to consider individual care; continuity of care in macro-policy, when a shift to other levels of care is needed; intersectoriality was also included, when the needs of an individual and community require a cross-sectoral coordination, with action on determinants and conditionants of the health-disease process. It is worth highlighting the natural tendency to include a comprehensive community medical training. We conclude that those countries strengthened by democracy draw their integrality practices closer, as well as the construction of social and health policies for underprivileged populations to achieve equity

As alterações celulares e imunológicas e suas implicações no Transtorno de Déficit de Atenção e Hiperatividade (TDAH)

O Transtorno do Déficit de Atenção e Hiperatividade (TDAH) é uma condição neuropsiquiátrica prevalente em crianças, adolescentes e adultos, com impactos significativos em diversos aspectos da vida. Estudos recentes exploram possíveis vínculos entre o sistema imunológico e o TDAH, concentrando-se nas citocinas pró-inflamatórias. O artigo irá abordar as alterações celulares e imunológicas com o TDAH de forma concisa baseada nas interleucinas, no Eixo hipotalâmico-pituitário-adrenal (HPA) e o cortisol, no Eixo intestino-cérebro e a obesidade, finalizando com Neurotrofinas, Estresse oxidativo e Micróglia. Em julho de 2023 foi realizada uma busca na base de dados via PubMed, Lilacs e Scielo, com o uso dos descritores ‘’ADHD’’ and ‘’Inflammatory’’ and “Imunne” e aplicado o filtro dos últimos 8 anos. Foram encontrados 216 artigos e após aplicar os critérios de inclusão e exclusão, 10 foram selecionados para o estudo. Embora as evidências sugiram uma associação potencial entre as interleucinas especialmente a interleucina-6, alguns eixos como o eixo HPA e o eixo intestino-cérebro, além de associar o cortisol, neurotrofinas, estresse oxidativo e células da micróglia com o transtorno abordado, é importante destacar que a problemática em destaque é multifatorial e envolve uma complexa interação de fatores genéticos, ambientais e neurobiológicos

Diagnóstico genético pré-implantacional (PGD) e a sua aplicação na reprodução humana / Preimplantational genetic diagnosis (PGD) and its application in human reproduction

Um dos grandes avanços da medicina reprodutiva dos últimos anos é o Diagnóstico Genético Pré-Implantacional (PGD), essa é uma técnica que nos permite conhecer aspectos da composição genética do embrião antes da sua implantação, usando tecnologias da reprodução humana assistida. Ela se divide em duas categorias que vão evidenciar objetivos e protocolos diversos: O PGD para doenças monogênicas (PGT-M), e o (PGT-A) para detectar as alterações cromossômicas no cariótipo. Diante da importância da técnica, objetiva-se apresentar os benefícios do PGD para a reprodução humana e seus aspectos éticos. Por meio dos conhecimentos disponíveis, fez-se uma revisão de literatura com intenção de explorar o diagnóstico genético pré-implantacional empregado na reprodução humana. Durante a escolha dos procedimentos de fertilização in vitro, primeiro é descoberto o que impossibilita o casal de gestar um filho, só então é estudado e analisado as melhores técnicas para tentar minimizar as chances de falhas no procedimento. Com o desenvolvimento de novas técnicas envolvidas no PGD, futuramente os avanços dos estudos irão permitir o diagnóstico de uma gama de alterações genéticas ainda na fase embrionária

Immunological signatures unveiled by integrative systems vaccinology characterization of dengue vaccination trials and natural infection

Introduction: Dengue virus infection is a global health problem lacking specific therapy, requiring an improved understanding of DENV immunity and vaccine responses. Considering the recent emerging of new dengue vaccines, here we performed an integrative systems vaccinology characterization of molecular signatures triggered by the natural DENV infection (NDI) and attenuated dengue virus infection models (DVTs). Methods and results: We analyzed 955 samples of transcriptomic datasets of patients with NDI and attenuated dengue virus infection trials (DVT1, DVT2, and DVT3) using a systems vaccinology approach. Differential expression analysis identified 237 common differentially expressed genes (DEGs) between DVTs and NDI. Among them, 28 and 60 DEGs were up or downregulated by dengue vaccination during DVT2 and DVT3, respectively, with 20 DEGs intersecting across all three DVTs. Enriched biological processes of these genes included type I/II interferon signaling, cytokine regulation, apoptosis, and T-cell differentiation. Principal component analysis based on 20 common DEGs (overlapping between DVTs and our NDI validation dataset) distinguished dengue patients by disease severity, particularly in the late acute phase. Machine learning analysis ranked the ten most critical predictors of disease severity in NDI, crucial for the anti-viral immune response. Conclusion: This work provides insights into the NDI and vaccine-induced overlapping immune response and suggests molecular markers (e.g., IFIT5, ISG15, and HERC5) for anti-dengue-specific therapies and effective vaccination development

Tomografia computadorizada em pacientes acometidos por Covid-19: uma revisão integrativa da literatura / Computed tomography in patients affected by Covid-19: an integrative literature review

Objetivo: Descrever por meio de uma revisão integrativa de literatura a importância da utilização da tomografia computadorizada em pacientes acometidos pela covid-19. Métodos: Trata-se de uma revisão integrativa de literatura que possibilita a análise de bibliografias direcionadas a temática ora delimitada. Os critérios de inclusão que foram utilizados na busca bibliográfica contemplaram artigos originais, completos, livres e gratuitos, na língua portuguesa, condizentes com o objetivo proposto e a partir dos descritores em saúde determinados. Resultados e discussão: A opacidade em vidro fosco, pavimentação em mosaico e consolidação são as principais alterações evidenciadas em pacientes acometidos por patologias pulmonares de variadas etiologias. A consolidação é uma característica, geralmente, associada a uma evolução da lesão em vidro fosco e mosaico (crazy paving), que se apresenta quando há um aumento da densidade pulmonar com o apagamento dos vasos e linhas intersticiais em seu interior. Conclusão: O uso da tomografia computadorizada é essencial no rastreio e controle de pacientes acometidos por COVID-19 atuando conjuntamente com o teste de RT-PCR que, por sua vez, é o que irá confirmar ou não a infecção por essa doença