CONTRIBUIÇÃO DA EDUCAÇÃO PERMANENTE PARA A EFETIVIDADE DA INTERSETORIALIDADE NO SISTEMA ÚNICO DE SAÚDE

Introdução: a educação permanente em saúde (EPS) é o processo de qualificação profissional para atuação na assistência à saúde, previsto na Política Nacional de Educação Permanente em Saúde, a ser desenvolvido em consonância com o que foi preconizado pelo Sistema Único de Saúde (SUS) quanto à sua diretriz de integralidade. Objetivo: analisar a contribuição da educação permanente na efetividade da intersetorialidade no SUS. Metodologia: trata-se de uma revisão integrativa, fundamentada em seis etapas: identificação do tema e questão de pesquisa; estabelecimento de critérios para inclusão e exclusão de estudos; categorização dos estudos; avaliação dos estudos incluídos na revisão; interpretação dos resultados e; apresentação da síntese do conhecimento. Resultados e Discussão: foram selecionados 16 artigos que atenderam às especificações de análise, posteriormente organizados em três temáticas de discussão: a mudança no processo de trabalho, empoderamento da gestão e educação permanente como indutora da qualificação profissional. Considerações finais: notou-se a relevância das ações de EPS para a promoção da intersetorialidade no SUS através dos encontros entre profissionais de diversas esferas da atenção à saúde ou da gestão setorial, da integração entre o conhecimento e a vivência dos participantes das ações, culminando na organização integralizada do sistema de saúde.

Contribuições de um projeto de Extensão para a promoção da saúde do idoso com demência

The extension project “Gerontological Practices: health care for the elderly with dementia, their families and the community” works to promote the health of the elderly with dementia, to care for family caregivers and to disclose information about dementias to the community. The objective of this experience report is to present the strategies used by the project to achieve the aforementioned purpose and describe the contributions of this project to the student development at the institution, based on interdisciplinary practices. The method used is a document analysis carried out in three stages: exploratory, analytical, and interpretive reading of the social responsibility reports of the project from 2018 and 2019. Regarding the results, the project uses three main strategies to reach its objective, which includes the support group, the neurodegenerative diseases ambulatory and the lectures at the university and community. In 2018, there were 115 people benefited through the support group and 120 through lectures in the community; 09 neurocognitive assessments conducted, 07 interviews with family members and 12 referrals of patients to the clinic. In 2019, it benefited 136 people through the support group and 336 through lectures in the community; 10 neurocognitive assessments conducted, 8 interviews with family members and 4 referrals. The project is extremely important to promote the health of the elderly with dementia, supporting them with better diagnosis and care.O projeto de extensão “Práticas Gerontológicas: atenção à saúde do idoso com demência, seus familiares e comunidade” atua na promoção da saúde do idoso com demência, no cuidado com os familiares cuidadores e na difusão da informação para a comunidade sobre essa doença. Objetiva-se por este relato de experiência apresentar as estratégias utilizadas pelo projeto para alcançar o propósito supracitado e descrever as contribuições deste estudo para o desenvolvimento discente na instituição, baseado nas práticas interdisciplinares. A metodologia utilizada é a análise documental realizada em três etapas: leitura exploratória, analítica e interpretativa dos relatórios de responsabilidade social do projeto dos anos de 2018 e 2019. Com relação aos resultados, o projeto utiliza três estratégias principais para o alcance do seu objetivo: o grupo de apoio, o ambulatório de doenças neurodegenerativas e as palestras na universidade e comunidade. Em 2018, o projeto beneficiou 115 pessoas pelo grupo de apoio, e 120 por palestras na comunidade; realizou 09 avaliações neurocognitivas, 07 entrevistas com familiares e 12 encaminhamentos de pacientes ao ambulatório. Já em 2019, beneficiou 136 pessoas pelo grupo de apoio e 336 por palestras na comunidade; realizou 10 avaliações neurocognitivas, 08 entrevistas com familiares e 04 encaminhamentos. O projeto mostrou ser de extrema importância para a promoção da saúde do idoso com demência, subsidiando melhor diagnóstico e cuidado para tal

Epistemologias do Sul e a experiência do Projeto Vidas Paralelas Migrantes Brasil-França

This article addresses the experience of the Migrant Parallel Lives Project (“PVP Migrantes”), whose action subjects are people in migration situation in both countries. Funded by CAPES-COFECUB, this project is an international research cooperation between the University of Brasília, University of the State of Rio de Janeiro, Université Paris XIII and Université Paul Valery. The method of the project is structured in the performance of photography and human rights workshops and has as a guide the reflection from the image and the sharing of meanings, paths, destinations, impacts and possibilities of collective construction of forms of intervention in the world, capable of guaranteeing the human rights of the migrants. This article emerges from the experiences developed in order to reflect on the convergences and crossings with the perspectives of the epistemologies of the South. The project starts from the praxis of the workshops and from the potential of incorporating the image as an emancipatory device in order to discuss the theoretical-methodological aspects and their epistemological dialogues. Thus, the workshops are catalysts for a powerful encounter mediated by two important actants inscribed in the project method: photographs and a world map, through which migration experiences are told and shared, embodying a common object that does not seek to homogenize the experiences, since the logic of the epistemologies of the South is not to work with single stories and unquestionable truths, but to allow the emergence of epistemological, cultural, political and social diversities.Este artículo analiza la experiencia del Proyecto Vidas Paralelas Migrantes Brasil- Francia, que tiene como temas de acción personas en situaciones de migración en ambos países. Esta es una cooperación internacional de investigación entre la Universidad de Brasilia, la Universidad del Estado de Río de Janeiro, la Universidad Paris XIII y la Universidad Paul Valery, financiada por CAPES-COFECUB. El método del proyecto se estructura en la realización de «Talleres de fotografía y derechos humanos», que tienen como hilo conductor la reflexión desde la imagen y el intercambio de significados, caminos, destinos, impactos y posibilidades de construcción colectiva de formas de intervención en el mundo, capaces de garantizar los derechos humanos de los sujetos migrantes involucrados. Este artículo se sumerge en las experiencias desarrolladas para reflexionar sobre sus convergencias y atravesamientos con las perspectivas de las epistemologías del sur. Partimos de reflexiones teóricas y metodológicas para pensar en la práctica de los talleres y el uso de fotografías como una forma propositiva de construir vínculos entre todos los que se articulan en esta red. Por lo tanto, los talleres se entienden como catalizadores de una reunión mediada por dos importantes actores registrados en el método del proyecto: fotografías y un mapa del mundo. A través de estos actores, se construye una conversación, se cuenta y comparte las experiencias de migración, dando forma a un significado común que no busca homogeneizar las experiencias, ya que la lógica de las epistemologías del sur no es trabajar con historias únicas y verdades incuestionables, pero precisamente para permitir el surgimiento de diversidades, ya sean epistemológicas, culturales, políticas y sociales.Esse artigo aborda a experiência do Projeto Vidas Paralelas Migrantes Brasil-França, que tem como sujeitos da ação as pessoas em situação de migração em ambos países. Esse projeto é uma cooperação internacional de pesquisa entre a Universidade de Brasília, Universidade do Estado do Rio de Janeiro, Université Paris XIII e Université Paul Valery, financiado pela CAPES-COFECUB via edital. O método do projeto estrutura-se na realização de oficinas de fotografia e direitos humanos e tem como fio condutor a reflexão a partir da imagem e da partilha de sentidos, trajetos, destinos, impactos e possibilidades de construção coletiva de formas de intervenção no mundo, capazes de garantir os direitos humanos dos sujeitos migrantes envolvidos. Este artigo emerge nas experiências desenvolvidas, a fim de refletir sobre suas convergências e atravessamentos com as perspectivas das epistemologias do Sul. Partimos então da práxis das oficinas e das potencialidades da incorporação da imagem enquanto dispositivo emancipatório para discutir os aspectos teórico-metodológicos e seus diálogos epistemológicos. Assim, as oficinas são catalisadoras de um potente encontro mediado por dois importantes actantes inscritos no método do projeto: fotografias e um mapa do mundo. Por meio destes, as experiências de migração vão sendo contadas e partilhadas, dando corpo a um comum que não busca homogeneizar as experiências, uma vez que a lógica das epistemologias do Sul não é trabalhar com histórias únicas e verdades inquestionáveis, mas permitir a emersão das diversidades epistemológicas, culturais, políticas e sociais

Reduced SLIT2 is Associated with Increased Cell Proliferation and Arsenic Trioxide Resistance in Acute Promyelocytic Leukemia

Simple Summary In solid tumors, the altered expression of embryonic genes such as the SLIT-ROBO family has been associated with poor prognosis, while little is known about their role in acute myeloid leukemia (AML). Previous studies reported frequent hypermethylation of SLIT2 mediated by the methyltransferase enzyme EZH2 and more recently the PML protein, which are commonly found to be aberrantly expressed in AML. Here, we aim to assess retrospectively the clinical relevance of the SLIT2 gene in acute promyelocytic leukemia, a homogenous subtype of AML. We demonstrated that reduced SLIT2 expression was associated with high leukocyte counts and reduced overall survival in different APL cohorts. STLI2 treatment decreased APL growth, while SLIT2 knockdown accelerated cell cycle progression and proliferation. Finally, reduced expression of SLIT2 in murine APL blasts resulted in fatal leukemia associated with increased leukocyte counts in vivo. These findings demonstrate that SLIT2 can be considered as a prognostic marker in APL, and a potential candidate for clinical studies of a more heterogeneous disease, such as AML. The SLIT-ROBO axis plays an important role in normal stem-cell biology, with possible repercussions on cancer stem cell emergence. Although the Promyelocytic Leukemia (PML) protein can regulate SLIT2 expression in the central nervous system, little is known about SLIT2 in acute promyelocytic leukemia. Hence, we aimed to investigate the levels of SLIT2 in acute promyelocytic leukemia (APL) and assess its biological activity in vitro and in vivo. Our analysis indicated that blasts with SLIT2(high) transcript levels were associated with cell cycle arrest, while SLIT2(low) APL blasts displayed a more stem-cell like phenotype. In a retrospective analysis using a cohort of patients treated with all-trans retinoic acid (ATRA) and anthracyclines, high SLIT2 expression was correlated with reduced leukocyte count (p = 0.024), and independently associated with improved overall survival (hazard ratio: 0.94; 95% confidence interval: 0.92-0.97; p <0.001). Functionally, SLIT2-knockdown in primary APL blasts and cell lines led to increased cell proliferation and resistance to arsenic trioxide induced apoptosis. Finally, in vivo transplant of Slit2-silenced primary APL blasts promoted increased leukocyte count (p = 0.001) and decreased overall survival (p = 0.002) compared with the control. In summary, our data highlight the tumor suppressive function of SLIT2 in APL and its deteriorating effects on disease progression when downregulated

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery