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    Assessment of Liaison XL Murex Chagas diagnostic performance in blood screening for Chagas disease using a reference array of chimeric antigens

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    Conselho Nacional de Desenvolvimento Científico e Tecnologico, Grant/Award Numbers: 309263/2020-4, 312195/2015-0, 590032/2011-9Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Grant/Award Number: 001Fundação de Amparo à Pesquisa do Estado da Bahia, Grant/Award Numbers: BOL0543/2020, BOL0932/2020Inova Fiocruz/VPPCB, Grant/Award Number: VPPCB-008-FIO-18-2-20Background: Chagas disease (CD) serological screening at blood banks is usually performed by a single highly sensitive serological assay, with chemiluminescent immunoassays (CLIAs) being the method of choice. CLIAs employ recombinant, fusion peptides and/or chimeric antigens that selectively capture anti-Trypanosoma cruzi antibodies. However, despite high sensitivity, the ability of these tests to identify CD-positive cases should be evaluated against T. cruzi strains circulating in specific locales. Herein, we used a latent class analysis (LCA) approach employing an array of four chimeric antigens to assess the diagnostic performance of the Liaison XL Murex Chagas CLIA for the detection of anti-T. cruzi IgG in serum samples. Study Design and Methods: The study included a panel of 5014 serum samples collected from volunteer blood donors at the Hematology and Hemotherapy Foundation of the State of Bahia, submitted to anti-T. cruzi antibody detection using Liaison Chagas CLIA and LCA as a reference test in the absence of a gold standard. Results: LCA classified 4993 samples as negative, while positivity for T. cruzi antibodies was predicted in 21 samples. Compared with LCA, CLIA demonstrated sensitivity and specificity of 76.2% and 99.5%, respectively, providing an overall accuracy of 99.4%. Discussion: In blood banks lacking a de facto highly sensitive screening immunoassay, the low sensitivity offered by Liaison Chagas CLIA renders it unsuitable for standalone use in serological screening procedures for CD. Moreover, blood banks are encouraged to carefully assess the ability of diagnostic methods to identify local T. cruzi strains in circulation

    Perspectives From Systems Biology to Improve Knowledge of Leishmania Drug Resistance

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    Neglected Tropical Diseases include a broad range of pathogens, hosts, and vectors, which represent evolving complex systems. Leishmaniasis, caused by different Leishmania species and transmitted to humans by sandflies, are among such diseases. Leishmania and other Trypanosomatidae display some peculiar features, which make them a complex system to study. Leishmaniasis chemotherapy is limited due to high toxicity of available drugs, long-term treatment protocols, and occurrence of drug resistant parasite strains. Systems biology studies the interactions and behavior of complex biological processes and may improve knowledge of Leishmania drug resistance. System-level studies to understand Leishmania biology have been challenging mainly because of its unusual molecular features. Networks integrating the biochemical and biological pathways involved in drug resistance have been reported in literature. Antioxidant defense enzymes have been identified as potential drug targets against leishmaniasis. These and other biomarkers might be studied from the perspective of systems biology and systems parasitology opening new frontiers for drug development and treatment of leishmaniasis and other diseases. Our main goals include: 1) Summarize current advances in Leishmania research focused on chemotherapy and drug resistance. 2) Share our viewpoint on the application of systems biology to Leishmania studies. 3) Provide insights and directions for future investigation

    Ferramentas e estratégias para qualificação do gerenciamento local na atenção primária à saúde: uma revisão integrativa da literatura

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    Profissionais que atuam como gerentes de Unidades Básicas de Saúde (UBS) do Sistema Único de Saúde (SUS) são atores chave para uma Atenção Primária à Saúde (APS) de qualidade, e possuem inúmeras atribuições que devem ser colocadas em prática da melhor maneira, em cada contexto singular. Este estudo teve como principal objetivo discutir ferramentas e estratégias para qualificação do trabalho gerencial em nível local da APS a fim de apoiar o desenvolvimento de competências profissionais. A pesquisa foi desenvolvida por meio de uma revisão integrativa da literatura com coleta de dados realizada no período de agosto a novembro de 2020, através de busca avançada nas bases de dados PubMed, Lilacs, SciELO, Health Systems Evidence e Biblioteca Digital Brasileira de Teses e Dissertações. O corpus da pesquisa foi composto por 18 estudos publicados entre 2011 e 2020, sendo 3 de origem internacional e 15 de periódicos nacionais. A literatura evidenciou como ferramentas e estratégias para apoiar o público alvo do estudo: a educação permanente em saúde, o gerenciamento de relacionamentos e aprendizagem, o uso de tecnologias da informação em saúde, o apoio matricial e institucional, práticas democráticas e participativas, gestão horizontal, entre outras. O referencial teórico de Mario Testa sobre o pensamento estratégico foi utilizado para discussão dos achados com base nas relações de poder no trabalho em saúde. Considerando a necessidade de mudanças de práticas para consolidação do modelo assistencial da APS, conclui-se que o conhecimento, aprofundamento e uso dos achados podem contribuir para enfrentamento das dificuldades e desafios vivenciados por gerentes locais das UBS e auxiliá-los na condução dos serviços do SUS de maneira mais eficaz.Professionals who work as managers of Basic Health Units (BHU) of the Unified Health System (UHS) are key actors for quality Primary Health Care (PHC), and have numerous attributions that must be put into practice in the best way, in each unique context. This study aimed to discuss tools and strategies for qualifying managerial work at the local level of PHC in order to support the development of professional competences. The research was developed through an integrative literature review with data collection carried out from August to November 2020, through an advanced search in the PubMed, Lilacs, SciELO, Health Systems Evidence and Brazilian Digital Library of Theses and Dissertations. The research corpus consisted of 18 studies published between 2011 and 2020, 3 of which were of international origin and 15 were from national journals. The literature showed as tools and strategies to support the target audience of the study: permanent health education, management of relationships and learning, the use of health information technologies, matrix and institutional support, democratic and participatory practices, horizontal management, among others. Mario Testa's theoretical framework on strategic thinking was used to discuss the findings based on power relations in health work. Considering the need for changes in practices to consolidate the PHC care model, it was concluded that the knowledge, deepening and use of the findings can contribute to facing the difficulties and challenges experienced by local BHU managers and assist them in conducting the services of the SUS more effectively

    Core of the saliva microbiome: an analysis of the MG-RAST data

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    Background: Oral microbiota is considered as the second most complex in the human body and its dysbiosis can be responsible for oral diseases. Interactions between the microorganism communities and the host allow establishing the microbiological proles. Identifying the core microbiome is essential to predicting diseases and changes in environ‑ mental behavior from microorganisms. Methods: Projects containing the term “SALIVA”, deposited between 2014 and 2019 were recovered on the MG-RAST portal. Quality (Failed), taxonomic prediction (Unknown and Predicted), species richness (Rarefaction), and species diversity (Alpha) were analyzed according to sequencing approaches (Amplicon sequencing and Shotgun metagen‑ omics). All data were checked for normality and homoscedasticity. Metagenomic projects were compared using the Mann–Whitney U test and Spearman’s correlation. Microbiome cores were inferred by Principal Component Analysis. For all statistical tests, p<0.05 was used. Results: The study was performed with 3 projects, involving 245 Amplicon and 164 Shotgun metagenome datasets. All comparisons of variables, according to the type of sequencing, showed signifcant diferences, except for the Predicted. In Shotgun metagenomics datasets the highest correlation was between Rarefaction and Failed (r= −0.78) and the lowest between Alpha and Unknown (r= −0.12). In Amplicon sequencing datasets, the variables Rarefaction and Unknown (r=0.63) had the highest correlation and the lowest was between Alpha and Predicted (r= −0.03). Shotgun metagenomics datasets showed a greater number of genera than Amplicon. Propionibacterium, Lactobacil lus, and Prevotella were the most representative genera in Amplicon sequencing. In Shotgun metagenomics, the most representative genera were Escherichia, Chitinophaga, and Acinetobacter. Conclusions: Core of the salivary microbiome and genera diversity are dependent on the sequencing approaches. Available data suggest that Shotgun metagenomics and Amplicon sequencing have similar sensitivities to detect the taxonomic level investigated, although Shotgun metagenomics allows a deeper analysis of the microorganism diver‑ sity. Microbiome studies must consider characteristics and limitations of the sequencing approaches. Were identifed 20 genera in the core of saliva microbiome, regardless of the health condition of the host. Some bacteria of the core need further study to better understand their role in the oral cavity

    Tool development for analysis of scFv NGS data in databases related to 3D structures: evolution of antibodies In silico

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    Os autores externos submeteram sua publicação para apresentação de trabalho no evento “International Symposium on Immunobiologicals”, que foi coordenado e organizado pelo Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), da Fundação Oswaldo Cruz

    γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

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    Recently, many discoveries have elucidated the cellular and molecular diversity in the leukemic microenvironment and improved our knowledge regarding their complex nature. This has allowed the development of new therapeutic strategies against leukemia. Advances in biotechnology and the current understanding of T cell-engineering have led to new approaches in this fight, thus improving cell-mediated immune response against cancer. However, most of the investigations focus only on conventional cytotoxic cells, while ignoring the potential of unconventional T cells that until now have been little studied. gd T cells are a unique lymphocyte subpopulation that has an extensive repertoire of tumor sensing and may have new immunotherapeutic applications in a wide range of tumors. The ability to respond regardless of human leukocyte antigen (HLA) expression, the secretion of antitumor mediators and high functional plasticity are hallmarks of gd T cells, and are ones that make them a promising alternative in the field of cell therapy. Despite this situation, in particular cases, the leukemic microenvironment can adopt strategies to circumvent the antitumor response of these lymphocytes, causing their exhaustion or polarization to a tumor-promoting phenotype. Intervening in this crosstalk can improve their capabilities and clinical applications and can make them key components in new therapeutic antileukemic approaches. In this review, we highlight several characteristics of gd T cells and their interactions in leukemia. Furthermore, we explore strategies for maximizing their antitumor functions, aiming to illustrate the findings destined for a better mobilization of gd T cells against the tumor. Finally, we outline our perspectives on their therapeutic applicability and indicate outstanding issues for future basic and clinical leukemia research, in the hope of contributing to the advancement of studies on gd T cells in cancer immunotherapy

    Th17 Cells in Viral Infections—Friend or Foe?

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    Th17 cells are recognized as indispensable in inducing protective immunity against bacteria and fungi, as they promote the integrity of mucosal epithelial barriers. It is believed that Th17 cells also play a central role in the induction of autoimmune diseases. Recent advances have evaluated Th17 effector functions during viral infections, including their critical role in the production and induction of pro-inflammatory cytokines and in the recruitment and activation of other immune cells. Thus, Th17 is involved in the induction both of pathogenicity and immunoprotective mechanisms seen in the host’s immune response against viruses. However, certain Th17 cells can also modulate immune responses, since they can secrete immunosuppressive factors, such as IL-10; these cells are called non-pathogenic Th17 cells. Here, we present a brief review of Th17 cells and highlight their involvement in some virus infections. We cover these notions by highlighting the role of Th17 cells in regulating the protective and pathogenic immune response in the context of viral infections. In addition, we will be describing myocarditis and multiple sclerosis as examples of immune diseases triggered by viral infections, in which we will discuss further the roles of Th17 cells in the induction of tissue damage

    Unveiling the relevance of the redox character of nitroaromatic and nitroheteroaromatic compounds as Q6 potential medicines

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    This review discusses the state of the art, challenges, and perspectives in recent applications of nitroaromatics and nitroheteroaromatics, which are redox-bio-activated drugs or leads, in Medicinal Chemistry. It deals mainly with the elec trochemical approach toward the electron transfer-based mo lecular mechanisms of drug action, drug design, estimation and measurement of redox potentials, correlation of physico chemical and pharmacological data, and electrochemical studies of the main representatives of nitro-containing prodrugs, along with approaches to combat their toxicity issues, aiming at a better therapeutic profile. Electrochemical investigation plays essential roles, being strategic in the design and discovery of potential medicines.202

    Trabalhadores da Saúde atuam em condições precárias diante da pandemia, concluem pesquisas apresentadas em debate do CNS

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    O Conselho Nacional de Saúde (CNS), por meio da Comissão Intersetorial de Recursos Humanos e Relações de Trabalho (Cirhrt), se reuniu nesta segunda (30/03) com o Ministério da Saúde e com pesquisadores para debater as condições de trabalho dos profissionais da Saúde em meio à pandemia. Os dados apresentados mostram que a situação caótica do país, em meio às negligências governamentais agravadas pela pandemia, estão trazendo muitos problemas aos profissionais da linha de frente contra a Covid-19. A pesquisadora Maria Helena Machado, da ENSP/Fiocruz, participou da atividade

    Effect of seasonal and temperature variation on hospitalizations for stroke over a 10-year period in Brazil

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    Background: Seasonal variation in stroke incidence remains controversial. Aims: We aimed to describe the pattern of seasonality in hospitalizations for stroke in Brazil. Methods: We evaluated age-adjusted hospitalization rates for stroke per month using data from the Brazilian Unified Healthcare System and median monthly temperature data obtained from the National Institute of Meteorology. To detect a seasonality pattern in time series, we used seasonal-trend decomposition using LOESS. We calculated a seasonal strength statistic and used Kruskal-Wallis test to evaluate the presence of seasonality in Brazil and its five regions. We also assessed the association of temperature and stroke hospitalization rates using Spearman's rho correlation. Results: We identified 1,422,496 stroke-related hospitalizations between 2009 and 2018. Mean age was 67 years, 51% were male and 77.5% of stroke diagnoses were not specified as ischemic or hemorrhagic. Median temperature was 23.8℃ (IQR 22.3-24.4). Age-adjusted hospitalizations demonstrated significant seasonal variation during all the years analyzed, with increased rates during the winter. When regional differences were analyzed, seasonal behavior was present in the south, southeast and northeast regions of the country. These were also the regions with lower median temperatures during the winter months and greater amplitude of average temperatures between warmer and colder months. Conclusions: In this large national cohort of stroke patients in Brazil, we demonstrated the presence of seasonal variation in the age-adjusted hospitalization rate, with peak rates during the winter months. The regional gradient of incidence of stroke was directly associated with colder winters and greater amplitude of temperature

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