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Platelet–leukocyte interactions in the pathogenesis of viral infections
No full textEvolving evidence demonstrates that platelets have major roles in viral syndromes through
previously unrecognized viral sensing and effector functions. Activated platelets and increased
platelet-leukocyte aggregates are observed in clinical and experimental viral infections. The
mechanisms and outcomes of platelet–leukocyte interactions depend on the interacting
leukocyte as well as on the pathogen and pathological conditions. In this review, we discuss
the mechanisms involved in platelet interactions with leukocytes and its functions during viral
infections. We focus on the contributions of human platelet–leukocyte interactions to pathophysiological
and protective responses during viral infections of major global health relevance,
including acquired immunodeficiency syndrome (AIDS), dengue hemorrhagic fever/dengue
shock syndrome (DHF/DSS), influenza pneumonia, and COVID-19
Los profesionales de la Atención Primaria de la Salud ante las demandas de Salud Mental: perspectivas y desafíos
No full textA atenção à Saúde Mental (SM) na Atenção Primária à Saúde (APS) é complexa e demanda integração das ações entre diversos níveis de atenção para maior efetividade. Buscou-se compreender como profissionais da APS de 11 municípios de Minas Gerais que possuíam Núcleo de Atenção à Saúde da Família (Nasf) lidavam com demandas de SM. Trata-se de estudo qualitativo, conduzido por meio de grupos focais que contaram com 134 profissionais de saúde. Os profissionais não possuíam instrumentos ou estratégias para quantificar e organizar a demanda em SM; as ações de capacitação em SM eram insuficientes; relataram dificuldades na implementação das propostas do Nasf; e identificam problemas na organização e articulação da Rede de Atenção Psicossocial (Raps) que prejudicavam a continuidade do cuidado em SM. Apesar das fragilidades apresentadas, existem reflexões em direção às mudanças da lógica tradicional biomédica em cuidados em saúde.Mental Health (MH) in Primary Health Care is complex and requires the integration of actions across various levels of care. This study sought to understand how primary care professionals in 11 municipalities in Minas Gerais with family health centers (FHC) deal with MH demands. We conducted a qualitative study with focus groups made up of 134 health professionals. The professionals were not equipped with tools or strategies to quantify and organize MH demands; MH training was insufficient; the professionals reported difficulties implementing FHC proposals and problems in the organization and coordination of the psychosocial care network, compromising the continuity of MH care. Despite the weaknesses identified by this study, there are signs of a shift in the traditional biomedical logic of health care
Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease
No full textCenter for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador 41253-190, Brazil;
[email protected] (C.K.V.N.); [email protected] (L.d.A.F); [email protected] (K.N.S.);
[email protected] (B.D.P); [email protected] (B.S.d.F.S.)
2 Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil;
[email protected] (G.L.S.); [email protected] (B.R.C);
[email protected] (R.K.); [email protected] (F.G.T); [email protected] (C.S.M);
[email protected] (E.d.S.S); [email protected] (C.T.M.);
[email protected] (V.P.C.R); [email protected] (R.R.d.S.)
3 D’Or Institute for Research and Education (IDOR), Rio de Janeiro 20000-000, Brazil
4 Senai Institute of Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador 41253-190, Brazil
5 Department of Cardiology, São Rafael Hospital, Salvador 41253-190, Brazil
6 Department of Clinical Genetics, University Hospital of Southern Denmark-Vejle, 7100 Vejle, Denmark;
[email protected] State Foundation for Research (FAPESB)
and Instituto Nacional de Ciência e Tecnologia (INCT REGENERA; 465656/2014-5).Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), remains a serious public
health problem for which there is no effective treatment in the chronic stage. Intense cardiac fibrosis
and inflammation are hallmarks of chronic Chagas disease cardiomyopathy (CCC). Previously, we
identified upregulation of circulating and cardiac miR-21, a pro-fibrotic microRNA (miRNA), in
subjects with CCC. Here, we explored the potential role of miR-21 as a therapeutic target in a model
of chronic Chagas disease. PCR array-based 88 microRNA screening was performed in heart samples
obtained from C57Bl/6 mice chronically infected with T. cruzi and serum samples collected from CCC
patients. MiR-21 was found upregulated in both human and mouse samples, which was corroborated
by an in silico analysis of miRNA-mRNA target prediction. In vitro miR-21 functional assays (gainand
loss-of-function) were performed in cardiac fibroblasts, showing upregulation of miR-21 and
collagen expression upon transforming growth factor beta 1 (TGF 1) and T. cruzi stimulation, while
miR-21 blockage reduced collagen expression. Finally, treatment of T. cruzi-infected mice with locked
nucleic acid (LNA)-anti-miR-21 inhibitor promoted a significant reduction in cardiac fibrosis. Our
data suggest that miR-21 is a mediator involved in the pathogenesis of cardiac fibrosis and indicates
the pharmacological silencing of miR-21 as a potential therapeutic approach for CCC
Métodos para avaliação da efetividade de vacinas para COVID-19 com ênfase em abordagens quase-experimentais
No full textFundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Universidade Federal da Bahia. Instituto de Saúde Coletiva. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Brasília, DF, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil. Universidade Federal do Ceará. Departamento de Saúde Comunitária, Centro de Ciências da Saúde. Fortaleza, CE, Brasil. Universidade do Estado do Rio de Janeiro. Instituto de Medicina Social. Rio de Janeiro, RJ, Brasil. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil.A avalição da efetividade de vacinas é feita com dados do mundo real e é essencial para monitorar o desempenho dos programas de vacinação ao longo do tempo bem como frente a novas variantes. Até o momento, a avaliação da efetividade das vacinas para COVID-19 tem sido baseada em métodos clássicos como estudos de coorte e caso controle teste-negativo, que muitas vezes podem não permitir o adequado controle dos vieses intrínsecos da alocação das campanhas de vacinação. O objetivo dessa revisão foi discutir os desenhos de estudo disponíveis para avaliação de efetividade das vacinas, enfatizando os estudos quase-experimentais, que buscam mimetizar os estudos aleatorizados ao introduzir um componente exógeno para atribuição ao tratamento, bem como suas vantagens, limitações e aplicabilidade no contexto dos dados brasileiros. O emprego de métodos quase-experimentais, incluindo as séries temporais interrompidas, o método de diferença em diferenças, escore de propensão, variáveis instrumentais e regressão descontínua, são relevantes pela possibilidade de gerar estimativas mais acuradas da efetividade de vacinas para COVID-19 em cenários como o brasileiro, que se caracteriza pelo uso de várias vacinas, com respectivos número e intervalos entre doses, aplicadas em diferentes faixas etárias e em diferentes momentos da pandemia.The evaluation of vaccine effectiveness is conducted with real-world data. They are essential to monitor the performance of vaccination programmes over time, and in the context of the emergence of new variants. Until now, the effectiveness of COVID-19 vaccines has been assessed based on classic methods, such as cohort and test-negative case-control studies, which may often not allow for adequate control of inherent biases in the assignment of vaccination campaigns. The aim of this review was to discuss the study designs available to evaluate vaccine effectiveness, highlighting quasi-experimental studies, which seek to mimic randomized trials, by introducing an exogenous component to allocate to treatment, in addition to the advantages, limitations, and applicability in the context of Brazilian data. The use of quasi-experimental approaches, such as interrupted time series, difference-in-differences, propensity scores, instrumental variables, and regression discontinuity design, are relevant due to the possibility of providing more accurate estimates of COVID-19 vaccine effectiveness. This is especially important in scenarios such as the Brazilian, which characterized by the use of various vaccines, with the respective numbers and intervals between doses, applied to different age groups, and introduced at different times during the pandemic
Evolution of virulence-related phenotypes of Sporothrix brasiliensis isolates from patients with chronic sporotrichosis and acquired immunodeficiency syndrome
No full textSporotrichosis in immunocompromised patients has a high morbidity and may cause deaths. Particularly, patients with acquired immunodeficiency syndrome (AIDS) with low T CD4 counts develop a chronic disease, with severe and widespread forms. Recently, the ability of Sporothrix brasiliensis, the main agent of zoonotic sporotrichosis, to increase its virulence in a diabetic patient without HIV infection was described. Since it was a unique finding, it is not known how often this occurs in patients with chronic and refractory sporotrichosis. The aim of this study is to compare sequential Sporothrix isolates obtained from patients with sporotrichosis and AIDS in order to detect changes in virulence-related phenotypes and acquisition of antifungal resistance during the evolution of the disease. Fungal growth in different substrates, antifungal susceptibility, thermotolerance, resistance to oxidative stress, and production of hydrolytic enzymes were evaluated. Correlations were assessed between clinical and phenotypic variables. Sixteen isolates, all identified as S. brasiliensis, obtained from five patients were studied. They grew well on glucose and N-acetyl-D-glucosamine, but poorly on lactate. Except from isolates collected from two patients, which were non-wild type for terbinafine, they were considered wild type for the antifungal drugs tested. Thermotolerance of the isolates was moderate to high. Except for phytase and phospholipase, isolates were able to produce virulence-related enzymes on different levels. Changes in all studied phenotypes were observed during the course of the disease in some patients. The results show that the HIV-driven immunosuppression is more relevant than fungal phenotypes on the unfavorable outcomes of disseminated sporotrichosis
Cryptococcal meningitis in non-HIV patients in the State of Amazonas, Northern Brazil
No full textCryptococcosis is a life-threatening fungal infection caused by the Cryptococcus neoformans/Cryptococcus gattii species complex. Most cases are recorded in patients suffering from HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome). However, this infection also occurs in non-HIV patients with a proportion of 10-30% of all cases. The study aimed at the clinical and molecular characterization of non-HIV patients diagnosed with cryptococcosis at the Tropical Medicine Foundation (FMT-HVD) from July 2016 to June 2019. Medical records of respective patients were analyzed to describe the course of cryptococcosis in non-HIV patients. In addition, multi-locus sequence typing (MLST) was applied to identify the sequence types of the isolated Cryptococcus strains, to perform phylogenetic analysis, and to evaluate the isolates' genetic relationship to global reference strains. Antifungal susceptibility profiles to amphotericin B, fluconazole, and itraconazole were assessed by broth microdilution. From a total of 7 patients, 4 were female, the age range varied between 10 and 53 years (median of 36.3 years). Cryptococcal meningitis was the common clinical manifestation (100%). The period between onset of symptoms and confirmed diagnosis ranged from 15 to 730 days (mean value of 172.9 days), and the observed mortality was 57.1%. Of note, comorbidities of the assessed cryptococcosis patients comprised hypertension, diabetes mellitus, and intestinal tuberculosis. Genotyping applying PCR-RFLP of the URA5 gene identified all clinical isolates as C. gattii genotype VGII. Using MLST, it was possible to discriminate the sequence types ST20 (n = 4), ST5 (n = 3), and the newly identified sequence type ST560 (n = 1). The antifungals amphotericin B, fluconazole, and itraconazole showed satisfactory inhibitory activity (microdilution test) against all C. gattii VGII strains
Transposable elements expression in Rhinella marina (cane toad) specimens submitted to immune and stress challenge
No full textTransposable elements (TEs) are important components of eukaryotic genomes and compose around 30% of the genome of Rhinella marina, an invasive toad species. Considering the possible role of TEs in the adaptation of populations, we have analyzed the expression of TEs in publicly available spleen tissue transcriptomic data generated for this species after immune and stress challenge. By analyzing the transcriptome assembly, we detected a high number of TE segments. Moreover, some distinct TE families were diferentially expressed in some conditions. Our result shows that several TEs are capable of being transcribed in R. marina and they could help to generate a rapid response of specimens to the environment. Also, we can suggest that these TEs could be activated in the germinative cells as well producing variability to be selected and shaped by the evolutionary processes behind the success of this invasive species. Thus, the TEs are important targets for investigation in the context of R. marina adaptation
Relatório de Atividades das Residências em Saúde - Ano 2021
No full textEste relatório compõe o relato descritivo do conjunto de atividades desenvolvidas pela Coordenação Adjunta de Residências vinculada a Coordenação Geral de Educação da Vice-presidência de Educação, Informação e Comunicação (VPEIC) da Fiocruz, que também coordena o Fórum de Coordenadores, Supervisores de Residências em Saúde da Fiocruz, no ano de 2021. O Fórum é composto pela representação dos atuais 33 programas de Residências em Saúde: 18 em área profissional (13 multiprofissionais, 5 uniprofissionais) e 15 médicas, sendo que 2 programas são em cooperação com Secretaria de Saúde de Campo Grande/MS – 542 vagas ofertadas anuais (R1 a R4) que mobilizam mais de 1000 pessoas na gestão, 100% de ocupação das bolsas MS e Fiocruz. A Fiocruz está presente em 10 estados e as residências são ofertadas em 3 estados e no DF.2030-12-3
Boletim BiblioCovid: aspectos históricos das pandemias
No full textApoio: Letícia Ramalho – Estagiária (ICICT/CRBF). Projeto gráfco: Luciana Rocha Mariz Clua – Multimeios|ICICT|FIOCRUZ. Diagramação: Letícia Ramalho – Estagiária – ICICT/CRBF. Luciana Rocha Mariz Clua – Multimeios|ICICT|FIOCRUZ. Ilustração BiblioCovid: Luciana Rocha Mariz Clua - Multimeios|ICICT|FIOCRUZ
Infective Endocarditis in Patients on Chronic Hemodialysis
No full textCristiane Lamas. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.Background: Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD).
Objectives: This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients.
Methods: Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression.
Results: A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p < 0.001). Cardiac surgery was less frequently performed among HD patients (30.6% vs. 46.2%; p < 0.001), whereas relapses were higher (9.4% vs. 2.7%; p < 0.001). Risk factors for 6-month mortality included Charlson score (hazard ratio [HR]: 1.26; 95% confidence interval [CI]: 1.11 to 1.44; p = 0.001), CNS emboli and other emboli (HR: 3.11; 95% CI: 1.84 to 5.27; p < 0.001; and HR: 1.73; 95% CI: 1.02 to 2.93; p = 0.04, respectively), persistent bacteremia (HR: 1.79; 95% CI: 1.11 to 2.88; p = 0.02), and acute onset heart failure (HR: 2.37; 95% CI: 1.49 to 3.78; p < 0.001).
Conclusions: HD-IE is a health care-associated infection chiefly caused by S. aureus, with increasing rates of enterococcal IE. Mortality and relapses are very high and significantly larger than in non-HD-IE patients, whereas cardiac surgery is less frequently performed