519 research outputs found

    Zika virus infection in the returning traveller: what every neurologist should know

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    Zika virus has been associated with a wide range of neurological complications. Neurologists in areas without current active transmission of the virus may be confronted with Zika-associated neurological disease, as a large number of returning travellers with Zika virus infection have been reported and the virus continues to spread to previously unaffected regions. This review provides an overview of Zika virus-associated neurological disease and aims to support neurologists who may encounter patients returning from endemic areas

    Guillain-Barré syndrome related to Zika virus infection: A systematic review and meta-analysis of the clinical and electrophysiological phenotype

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    BACKGROUND: The Zika virus (ZIKV) has been associated with Guillain-Barré syndrome (GBS) in epidemiological studies. Whether ZIKV-associated GBS is related to a specific clinical or electrophysiological phenotype has not been established. To this end, we performed a systematic review and meta-analysis of all published s

    RELATO DE EXPERIÊNCIA: DIREITOS HUMANOS E JUSTIÇA “ENREDANDO SABERES: IMPASSES DA PRÁTICA”: O TRABALHO EM REDE NA SOCIOEDUCAÇÃO

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    O projeto “Em nome do Sujeito: encontros de psicanálise, educação, literatura e artes”, que integra o programa de extensão “Enredando Saberes: impasses da prática”, da Universidade Federal do Estado do Rio de Janeiro – UNIRIO, em parceria com o Serviço de Psicologia da Vara de Execução de Medidas Socioeducativas do Rio de Janeiro – VEMSE/RJ, compondo o Programa “Eu apoio a voz do adolescente”, objetiva fomentar novas estratégias de atendimento e acolhimento aos adolescentes que estão em cumprimento de medidas socioeducativas. Trata-se de uma proposta que abrange a dimensão psicológica, cultural, política, pedagógica e jurídica com vistas a integrar esses jovens na dimensão simbólica de seu tempo, promovendo desta forma a reflexão e elaboração de seu lugar na cidade. Em execução desde 2018, o projeto passou por várias fases, aqui descritas, atingindo aproximadamente 200 jovens em cumprimento de diferentes medidas socioeducativas e seus familiares. Entre as suas principais ações, destacam-se as visitas mediadas realizadas em museus e centros culturais, ações educativas, esquetes teatrais, sempre acompanhadas de rodas de conversas, nas quais são produzidos documentos individuais com os relatos dos jovens acerca da experiência na socioeducação e das atividades realizadas. Tais documentos, se autorizados pelos jovens, poderão ser anexados aos seus autos processuais, fazendo reverberar a voz desses adolescentes no espaço jurídico.&nbsp

    RELATO DE EXPERIÊNCIA: DIREITOS HUMANOS E JUSTIÇA “ENREDANDO SABERES: IMPASSES DA PRÁTICA”: O TRABALHO EM REDE NA SOCIOEDUCAÇÃO

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    O projeto “Em nome do Sujeito: encontros de psicanálise, educação, literatura e artes”, que integra o programa de extensão “Enredando Saberes: impasses da prática”, da Universidade Federal do Estado do Rio de Janeiro – UNIRIO, em parceria com o Serviço de Psicologia da Vara de Execução de Medidas Socioeducativas do Rio de Janeiro – VEMSE/RJ, compondo o Programa “Eu apoio a voz do adolescente”, objetiva fomentar novas estratégias de atendimento e acolhimento aos adolescentes que estão em cumprimento de medidas socioeducativas. Trata-se de uma proposta que abrange a dimensão psicológica, cultural, política, pedagógica e jurídica com vistas a integrar esses jovens na dimensão simbólica de seu tempo, promovendo desta forma a reflexão e elaboração de seu lugar na cidade. Em execução desde 2018, o projeto passou por várias fases, aqui descritas, atingindo aproximadamente 200 jovens em cumprimento de diferentes medidas socioeducativas e seus familiares. Entre as suas principais ações, destacam-se as visitas mediadas realizadas em museus e centros culturais, ações educativas, esquetes teatrais, sempre acompanhadas de rodas de conversas, nas quais são produzidos documentos individuais com os relatos dos jovens acerca da experiência na socioeducação e das atividades realizadas. Tais documentos, se autorizados pelos jovens, poderão ser anexados aos seus autos processuais, fazendo reverberar a voz desses adolescentes no espaço jurídico.

    Predictive and therapeutic implications of a novel PLCγ1/SHP2-driven mechanism of cetuximab resistance in metastatic colorectal cancer

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    © 2022 The Authors; Published by the American Association for Cancer Research. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 International (CC BY-NC-ND)Purpose: Cetuximab is an EGFR-targeted therapy approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC). However, about 60% of these patients show innate resistance to cetuximab. To increase cetuximab efficacy, it is crucial to successfully identify responder patients, as well as to develop new therapeutic approaches to overcome cetuximab resistance. Experimental design: We evaluated the value of EGFR effector phospholipase C gamma 1 (PLCγ1) in predicting cetuximab responses, by analyzing progression-free survival (PFS) of a multicentric retrospective cohort of 94 treated patients with mCRC (log-rank test and Cox regression model). Furthermore, we used in vitro and zebrafish xenotransplant models to identify and target the mechanism behind PLCγ1-mediated resistance to cetuximab. Results: In this study, levels of PLCγ1 were found increased in RAS WT tumors and were able to predict cetuximab responses in clinical samples and in vitro and in vivo models. Mechanistically, PLCγ1 expression was found to bypass cetuximab-dependent EGFR inhibition by activating ERK and AKT pathways. This novel resistance mechanism involves a noncatalytic role of PLCγ1 SH2 tandem domains in the propagation of downstream signaling via SH2-containing protein tyrosine phosphatase 2 (SHP2). Accordingly, SHP2 inhibition sensitizes PLCγ1-resistant cells to cetuximab. Conclusions: Our discoveries reveal the potential of PLCγ1 as a predictive biomarker for cetuximab responses and suggest an alternative therapeutic approach to circumvent PLCγ1-mediated resistance to cetuximab in patients with RAS WT mCRC. In this way, this work contributes to the development of novel strategies in the medical management and treatment of patients with mCRC.M. Martins' research was supported by Liga Portuguesa Contra o Cancro (LPCC): Terry Fox Fundation; Investigador FCT- Fundação para a Ciência e Technologia (IF/00409/2014) and IMM Bridge grant; RC-D research was supported by Fundação para a Ciência e Technologia (SFRH/BD/139138/2018). A. Fernandes was supported by LPCC-IMM BIOBANK; R. Fior was supported by Champalimaud Foundation and L. Costa was supported by Merck Serono.info:eu-repo/semantics/publishedVersio

    The legacy of ZikaPLAN: a transnational research consortium addressing Zika

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    Global health research partnerships with institutions from high-income countries and low- and middle-income countries are one of the European Commission's flagship programmes. Here, we report on the ZikaPLAN research consortium funded by the European Commission with the primary goal of addressing the urgent knowledge gaps related to the Zika epidemic and the secondary goal of building up research capacity and establishing a Latin American-European research network for emerging vector-borne diseases. Five years of collaborative research effort have led to a better understanding of the full clinical spectrum of congenital Zika syndrome in children and the neurological complications of Zika virus infections in adults and helped explore the origins and trajectory of Zika virus transmission. Individual-level data from ZikaPLAN`s cohort studies were shared for joint analyses as part of the Zika Brazilian Cohorts Consortium, the European Commission-funded Zika Cohorts Vertical Transmission Study Group, and the World Health Organization-led Zika Virus Individual Participant Data Consortium. Furthermore, the legacy of ZikaPLAN includes new tools for birth defect surveillance and a Latin American birth defect surveillance network, an enhanced Guillain-Barre Syndrome research collaboration, a de-centralized evaluation platform for diagnostic assays, a global vector control hub, and the REDe network with freely available training resources to enhance global research capacity in vector-borne diseases

    Factors Associated with Tuberculosis Treatment Default in an Endemic Area of the Brazilian Amazon: A Case Control-Study

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    SETTING: Treatment default is a serious problem in tuberculosis control because it implies persistence of infection source, increased mortality, increased relapse rates and facilitates the development of resistant strains. OBJECTIVE: This study analyzed tuberculosis treatment default determinants in the Amazonas State to contribute in planning appropriate control interventions. DESIGN: Observational study with a retrospective cohort using Brazilian Disease Notification System data from 2005 to 2010. A nested case control study design was used. Patients defaulting from treatment were considered as 'cases' and those completing treatment as 'controls'. In the analysis, 11,312 tuberculosis patients were included, 1,584 cases and 9,728 controls. RESULTS: Treatment default was observed to be associated to previous default (aOR 3.20; p<0.001), HIV positivity (aOR 1.62; p<0.001), alcoholism (aOR 1.51; p<0.001), low education level (aOR 1.35; p<0.001) and other co-morbidities (aOR 1.31; p = 0.05). Older patients (aOR 0.98; p = 0.001) and DOT (aOR 0,72; p<0.01) were considered as protective factor for default. CONCLUSIONS: Associated factors should be considered in addressing care and policy actions to tuberculosis control. Information on disease and treatment should be intensified and appropriate to the level of education of the population, in order to promote adherence to treatment and counter the spread of multidrug resistance to anti-TB drugs

    Spondias purpurea

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    Spondias purpurea is used in folk medicine to treat diarrhea and diuresis. The objective of this study was to evaluate the phytochemical profile and antioxidant and antiulcer activities of the hexane extract of the leaves of S. purpurea (SpHE). Phytochemical profile was evaluated via thin layer chromatography (TLC) and HPLC. SpHE was screened for antioxidant activities using DPPH, ABTS, FRAP, and phosphomolybdenum assays. To determine its antiulcer properties, animals were pretreated with injured control, lansoprazole, ranitidine, carbenoxolone, or SpHE (12.5, 25, and 50 mg/kg) and were screened; acute ulcers were induced by HCl/ethanol, absolute ethanol, and nonsteroidal anti-inflammatory drug (NSAID). TLC revealed the presence of flavonoids, whereas HPLC analysis showed the presence of caffeic acid and epigallocatechin. The phenolic compounds and in vitro assays showed antioxidant activity. After gastric ulcer induction by using HCl/ethanol, SpHE reduced the area of ulcerative lesions by 82, 91, and 88%, respectively. In ethanol, SpHE reduced the area of ulcerative lesions by 77, 93, and 92%, respectively. In the NSAID, the percentages of protection were 70, 76, and 78%, respectively. SpHE promoted the minimization of ulcers, increased the levels of reduced glutathione, and decreased tumor necrosis factor. S. purpurea has antioxidant and antiulcer properties
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