The “Hypertension Approaches in the Elderly: a Lifestyle study” multicenter, randomized trial (HAEL Study): rationale and methodological protocol

Background: Hypertension is a clinical condition highly prevalent in the elderly, imposing great risks to cardiovascular diseases and loss of quality of life. Current guidelines emphasize the importance of nonpharmacological strategies as a first-line approach to lower blood pressure. Exercise is an efficient lifestyle tool that can benefit a myriad of health-related outcomes, including blood pressure control, in older adults. We herein report the protocol of the HAEL Study, which aims to evaluate the efficacy of a pragmatic combined exercise training compared with a health education program on ambulatory blood pressure and other health-related outcomes in older individuals. Methods: Randomized, single-blinded, multicenter, two-arm, parallel, superiority trial. A total of 184 subjects (92/center), ≥60 years of age, with no recent history of cardiovascular events, will be randomized on a 1:1 ratio to 12-week interventions consisting either of a combined exercise (aerobic and strength) training, three times per week, or an active-control group receiving health education intervention, once a week. Ambulatory (primary outcome) and office blood pressures, cardiorespiratory fitness and endothelial function, together with quality of life, functional fitness and autonomic control will be measured in before and after intervention. Discussion: Our conceptual hypothesis is that combined training intervention will reduce ambulatory blood pressure in comparison with health education group. Using a superiority framework, analysis plan prespecifies an intention-to-treat approach, per protocol criteria, subgroups analysis, and handling of missing data. The trial is recruiting since September 2017. Finally, this study was designed to adhere to data sharing practices. Trial registration: NCT03264443. Registered on 29 August, 2017

Representações sociais de mulheres frente a descoberta do diagnóstico do HIV / Women social representations in face to HIV diagnosis disclosure

Objetivo: descrever as representações sociais de mulheres diante do recebimento do diagnóstico de HIV. Método: Estudo descritivo, exploratório com abordagem qualitativa, realizado com 21 mulheres que se encontravam em dois centros de referência para pessoas que vivem com HIV/aids. Os dados foram coletados de maio a junho de 2016. Utilizou-se como referencial teórico a Teoria das Representações Sociais, e os dados foram analisados por meio da técnica de análise de conteúdo na perspectiva de Bardin. Resultados: Demonstraram as representações sociais das mulheres frente à descoberta do diagnóstico do HIV. O diagnóstico do HIV é recebido com grande impacto pela mulher que apresenta sentimentos distintos no momento da descoberta, como: angústia, medo, tristeza, terror, surpresa, incredibilidade, injustiça e vergonha.  Conclusão: Existe uma complexa representação social que gera impacto no modo de viver e conviver das mulheres que vivem com HIV, como a culpabilização, isolamento, estigmatização e preconceit

Representações sociais de mulheres frente a descoberta do diagnóstico do HIV / Women social representations in face to HIV diagnosis disclosure

Objetivo: descrever as representações sociais de mulheres diante do recebimento do diagnóstico de HIV. Método: Estudo descritivo, exploratório com abordagem qualitativa, realizado com 21 mulheres que se encontravam em dois centros de referência para pessoas que vivem com HIV/aids. Os dados foram coletados de maio a junho de 2016. Utilizou-se como referencial teórico a Teoria das Representações Sociais, e os dados foram analisados por meio da técnica de análise de conteúdo na perspectiva de Bardin. Resultados: Demonstraram as representações sociais das mulheres frente à descoberta do diagnóstico do HIV. O diagnóstico do HIV é recebido com grande impacto pela mulher que apresenta sentimentos distintos no momento da descoberta, como: angústia, medo, tristeza, terror, surpresa, incredibilidade, injustiça e vergonha.  Conclusão: Existe uma complexa representação social que gera impacto no modo de viver e conviver das mulheres que vivem com HIV, como a culpabilização, isolamento, estigmatização e preconceit

The RNA-binding protein hnRNP K mediates the effect of BDNF on dendritic mRNA metabolism and regulates synaptic NMDA receptors in hippocampal neurons

Brain-derived neurotrophic factor (BDNF) is an important mediator of long-term synaptic potentiation (LTP) in the hippocampus. The local effects of BDNF depend on the activation of translation activity, which requires the delivery of transcripts to the synapse. In this work, we found that neuronal activity regulates the dendritic localization of the RNA-binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP K) in cultured rat hippocampal neurons by stimulating BDNF-Trk signaling. Microarray experiments identified a large number of transcripts that are coimmunoprecipitated with hnRNP K, and about 60% of these transcripts are dissociated from the protein upon stimulation of rat hippocampal neurons with BDNF. In vivo studies also showed a role for TrkB signaling in the dissociation of transcripts from hnRNP K upon high-frequency stimulation (HFS) of medial perforant path-granule cell synapses of male rat dentate gyrus (DG). Furthermore, treatment of rat hippocampal synaptoneurosomes with BDNF decreased the coimmunoprecipitation of hnRNP K with mRNAs coding for glutamate receptor subunits, Ca2+- and calmodulin-dependent protein kinase IIβ (CaMKIIβ) and BDNF. Downregulation of hnRNP K impaired the BDNF-induced enhancement of NMDA receptor (NMDAR)-mediated mEPSC, and similar results were obtained upon inhibition of protein synthesis with cycloheximide. The results demonstrate that BDNF regulates specific populations of hnRNP-associated mRNAs in neuronal dendrites and suggests an important role of hnRNP K in BDNF-dependent forms of synaptic plasticity.publishe

Representações de puérperas sobre o cuidado recebido no trabalho de parto e parto

Objetivo: descrever as representações sociais de puérperas sobre o cuidado recebido durante o trabalho de parto e parto.Metodologia: trata-se de um estudo descritivo baseado na Teoria do Núcleo Central, desenvolvido com 119 puérperas em uma maternidade pública localizada no Brasil, na cidade de Fortaleza, Ceará. Os dados foram coletados por meio do Teste de Associação Livre de Palavras, que continha como estímulos indutores: trabalho de parto, parto, cuidado no trabalho de parto e parto, sendo transcritos e analisados pelo software Evoc.Resultados: a partir da análise estrutural, os vocábulos dor, felicidade e orientação apresentaram maior frequência como elemento central dos respectivos termos indutores.Conclusão: por meio dos resultados obtidos, é possível afirmar que o momento do trabalho de parto e do parto é crucial para que o enfermeiro planeje e execute uma adequada assistência durante o processo de parturição a fim de reduzir o impacto das representações negativas em relação a esse processo.Objective: to describe the social representations puerperal women have about the care they received during labor and delivery.Methodology: this is a descriptive study, based on the Theory of the Central Nucleus, which was undertaken with 119 women in the postpartum period in a public maternity hospital, located in the city of Fortaleza, Ceará, Brazil. The data were collected through the Free Word Association Test, which included as inductive stimuli: care, labor, delivery and care in labor and delivery. The data were transcribed and analyzed with Evoc software.Results: the structural analysis showed that the words “pain”, “happiness” and “guidance” ocurred more frequency as a central feature of the respective inducing terms.Conclusion: the results confirm that the moment of labor and delivery is crucial for nurses in the planning and implementation of adequate care during parturition insofar, as such measures lessen the impact of negative representations of childbirth.Objetivo: describir las representaciones sociales de puérperas sobre el cuidado recibido durante el trabajo de parto y parto.Metodología: se trata de un estudio descriptivo basado en la Teoría del Núcleo Central, desarrollado con 119 madres, en un hospital público de Fortaleza, Ceará, Brasil. Los datos fueron recolectados por medio del Test de Asociación de Palabras, que contenía como estímulos inductores: cuidado, trabajo de parto, parto, cuidado en el trabajo de parto y en el parto, siendo transcritos y analizados por el software Evoc.Resultados: a partir del análisis estructural, los vocablos dolor, felicidad y orientación presentaron mayor frecuencia como elemento central de los respectivos términos inductores.Conclusión: por medio de los resultados obtenidos, es posible afirmar que el momento del trabajo de parto y el parto es crucial para que el enfermero planee y ejecute una adecuada asistencia durante el proceso de parto con el fin de reducir el impacto de las representaciones negativas en relación con ese proceso

Is the proteome of bronchoalveolar lavage extracellular vesicles a marker of advanced lung cancer?

Funding: R.M. is supported by Fundação para a Ciência e a Tecnologia (CEEC position, 2019–2025 investigator). This article is a result of the projects (iNOVA4Health—UID/Multi/04462/2013), supported by Lisboa Portugal Regional Operational Programme (Lisboa2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work is also funded by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT—Portuguese Foundation for Science and Technology under the projects number PTDC/BTM-TEC/30087/2017 and PTDC/BTM-TEC/30088/2017. This work was supported by the Wellcome Trust/DBT India Alliance Margdarshi Fellowship (grant number IA/M/15/1/502023) awarded to A.P. B.C.-S., M.C.S.C. and C.B. are supported by the Champalimaud Foundation and the EMBO Installation Grant 3921.Acellular bronchoalveolar lavage (BAL) proteomics can partially separate lung cancer from non-lung cancer patients based on principal component analysis and multivariate analysis. Furthermore, the variance in the proteomics data sets is correlated mainly with lung cancer status and, to a lesser extent, smoking status and gender. Despite these advances BAL small and large extracellular vehicles (EVs) proteomes reveal aberrant protein expression in paracrine signaling mechanisms in cancer initiation and progression. We consequently present a case-control study of 24 bronchoalveolar lavage extracellular vesicle samples which were analyzed by state-of-the-art liquid chromatography-mass spectrometry (LC-MS). We obtained evidence that BAL EVs proteome complexity correlated with lung cancer stage 4 and mortality within two years´ follow-up (p value = 0.006). The potential therapeutic target DNMT3B complex is significantly up-regulated in tumor tissue and BAL EVs. The computational analysis of the immune and fibroblast cell markers in EVs suggests that patients who deceased within the follow-up period display higher marker expression indicative of innate immune and fibroblast cells (four out of five cases). This study provides insights into the proteome content of BAL EVs and their correlation to clinical outcomes.publishersversionpublishe

Conditional cash transfer program and child mortality: A cross-sectional analysis nested within the 100 Million Brazilian Cohort.

BACKGROUND: Brazil has made great progress in reducing child mortality over the past decades, and a parcel of this achievement has been credited to the Bolsa Família program (BFP). We examined the association between being a BFP beneficiary and child mortality (1-4 years of age), also examining how this association differs by maternal race/skin color, gestational age at birth (term versus preterm), municipality income level, and index of quality of BFP management. METHODS AND FINDINGS: This is a cross-sectional analysis nested within the 100 Million Brazilian Cohort, a population-based cohort primarily built from Brazil's Unified Registry for Social Programs (Cadastro Único). We analyzed data from 6,309,366 children under 5 years of age whose families enrolled between 2006 and 2015. Through deterministic linkage with the BFP payroll datasets, and similarity linkage with the Brazilian Mortality Information System, 4,858,253 children were identified as beneficiaries (77%) and 1,451,113 (23%) were not. Our analysis consisted of a combination of kernel matching and weighted logistic regressions. After kernel matching, 5,308,989 (84.1%) children were included in the final weighted logistic analysis, with 4,107,920 (77.4%) of those being beneficiaries and 1,201,069 (22.6%) not, with a total of 14,897 linked deaths. Overall, BFP participation was associated with a reduction in child mortality (weighted odds ratio [OR] = 0.83; 95% CI: 0.79 to 0.88; p < 0.001). This association was stronger for preterm children (weighted OR = 0.78; 95% CI: 0.68 to 0.90; p < 0.001), children of Black mothers (weighted OR = 0.74; 95% CI: 0.57 to 0.97; p < 0.001), children living in municipalities in the lowest income quintile (first quintile of municipal income: weighted OR = 0.72; 95% CI: 0.62 to 0.82; p < 0.001), and municipalities with better index of BFP management (5th quintile of the Decentralized Management Index: weighted OR = 0.76; 95% CI: 0.66 to 0.88; p < 0.001). The main limitation of our methodology is that our propensity score approach does not account for possible unmeasured confounders. Furthermore, sensitivity analysis showed that loss of nameless death records before linkage may have resulted in overestimation of the associations between BFP participation and mortality, with loss of statistical significance in municipalities with greater losses of data and change in the direction of the association in municipalities with no losses. CONCLUSIONS: In this study, we observed a significant association between BFP participation and child mortality in children aged 1-4 years and found that this association was stronger for children living in municipalities in the lowest quintile of wealth, in municipalities with better index of program management, and also in preterm children and children of Black mothers. These findings reinforce the evidence that programs like BFP, already proven effective in poverty reduction, have a great potential to improve child health and survival. Subgroup analysis revealed heterogeneous results, useful for policy improvement and better targeting of BFP

Lactato como preditor de gravidade no paciente crítico

Objetivo: investigar a literatura acerca do papel do lactato sanguíneo como marcador prognóstico de mortalidade em pacientes graves. Método: A busca dos estudos foi realizada nas plataformas de busca LILACS e Pubmed. Foram utilizadas as palavras-chave “lactato”, “paciente grave”, “mortalidade” e “prognóstico”. As palavras-chaves foram ainda traduzidas para o idioma inglês da seguinte forma: “lactate”, “critical patient”, “mortality” and “prognosis”. Todas as palavras-chave estão registradas nos Descritores em Ciências da Saúde (DeCs) e Medical Subject Headings (MeSh). Discussão: Em indivíduos saudáveis, a produção e a metabolização do lactato ocorrem de forma continua em tecidos cerebrais, estomacais, no músculo esquelético e em eritrócitos. Os pacientes com hiperlactatemia persistente (&gt;2mmol/L) por um período ≥72 horas apresentaram maior mortalidade em 90 dias quando comparados aos pacientes com lactato ≤2,0 mmol/L e, valores médios de lactato ponderado pelo tempo foram maiores em não sobreviventes. Considerações finais: O manejo de pacientes graves orientados pelo lactato é considerado como um método que pode ser capaz de promover a redução da mortalidade. A hiperlactatemia esteve associada à maiores taxas de mortalidade em pacientes gravemente enfermos, especialmente quando acima ou iguais a 5mmol/L no momento da admissão. Dessa forma, o lactato é um preditor considerado confiável e que prediz a gravidade da doença e a falência de múltiplos órgãos

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study.

BACKGROUND: The microcephaly epidemic, which started in Brazil in 2015, was declared a Public Health Emergency of International Concern by WHO in 2016. We report the preliminary results of a case-control study investigating the association between microcephaly and Zika virus infection during pregnancy. METHODS: We did this case-control study in eight public hospitals in Recife, Brazil. Cases were neonates with microcephaly. Two controls (neonates without microcephaly), matched by expected date of delivery and area of residence, were selected for each case. Serum samples of cases and controls and cerebrospinal fluid samples of cases were tested for Zika virus-specific IgM and by quantitative RT-PCR. Laboratory-confirmed Zika virus infection during pregnancy was defined as detection of Zika virus-specific IgM or a positive RT-PCR result in neonates. Maternal serum samples were tested by plaque reduction neutralisation assay for Zika virus and dengue virus. We estimated crude odds ratios (ORs) and 95% CIs using a median unbiased estimator for binary data in an unconditional logistic regression model. We estimated ORs separately for cases with and without radiological evidence of brain abnormalities. FINDINGS: Between Jan 15, 2016, and May 2, 2016, we prospectively recruited 32 cases and 62 controls. 24 (80%) of 30 mothers of cases had Zika virus infection compared with 39 (64%) of 61 mothers of controls (p=0·12). 13 (41%) of 32 cases and none of 62 controls had laboratory-confirmed Zika virus infection; crude overall OR 55·5 (95% CI 8·6-∞); OR 113·3 (95% CI 14·5-∞) for seven cases with brain abnormalities; and OR 24·7 (95% CI 2·9-∞) for four cases without brain abnormalities. INTERPRETATION: Our data suggest that the microcephaly epidemic is a result of congenital Zika virus infection. We await further data from this ongoing study to assess other potential risk factors and to confirm the strength of association in a larger sample size. FUNDING: Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations