An evidence-informed policymaking (EIPM) competency profile for the Brazilian Health System developed through consensus: process and outcomes.

BACKGROUND: Evidence-informed policymaking (EIPM) requires a set of individual and organizational knowledge, skills and attitudes that should be articulated with background factors and needs. In this regard, the development of an EIPM competency profile is important to support the diagnosis, planning and implementation of EIPM. PURPOSE: To present the process and outcomes of the development of an EIPM competency profile by an expert committee, to be applied in different contexts of the Brazilian Health System. METHODS: A committee of experts in EIPM shared different views, experiences and opinions to develop an EIPM competency profile for Brazil. In six consensus workshops mediated by facilitators, the committee defined from macro problems to key actions and performances essential for the competency profile. The development steps consisted of: (1) Constitution of the committee, including researchers, professionals with practical experience, managers, and educators; (2) Development of a rapid review on EIPM competency profiles; (3) Agreement on commitments and responsibilities in the processes; (4) Identification and definition of macro problems relating to the scope of the competency profile; and (5) Outlining of general and specific capacities, to be incorporated into the competency profile, categorized by key actions. RESULTS: The development of the EIPM competency profile was guided by the following macro problems: (1) lack of systematic and transparent decision-making processes in health policy management; (2) underdeveloped institutional capacity for knowledge management and translation; and (3) incipient use of scientific evidence in the formulation and implementation of health policies. A general framework of key actions and performances of the EIPM Competency Profile for Brazil was developed, including 42 specific and general key actions distributed by area of activity (Health Management, Scientific Research, Civil Society, Knowledge Translation, and Cross-sectional areas). CONCLUSIONS: The competency profile presented in this article can be used in different contexts as a key tool for the institutionalization of EIPM.

4-Nerolidylcatechol (4-NC) and Docetaxel Synergize in Controlling Androgen- independent Prostate Cancer Cells.

BACKGROUND: Effective cancer treatment still challenges medicine since the strategies employed so far are not sufficiently safe and capable of specifically eliminating tumor cells. Prostate cancer (PCa) is a highly incident malignant neoplasm, and the outcome of patients, especially those with advanced castration-resistant PCa (CRPC), depends directly on the efficacy of the therapeutic agents, such as docetaxel (DOC). OBJECTIVES: This study investigated the synergistic potentiation of 4-nerolidylcatechol (4-NC) with DOC in inhibiting androgen-independent PCa cells. METHODS: The cytotoxic effect of 4-NC was evaluated against non-tumorigenic (RWPE-01) and PCa cell lines (LNCaP and PC-3), and the antiproliferative potential of 4-NC was assessed by flow cytometry and colony formation. The Chou-Talalay method was applied to detect the synergistic effect of 4-NC and DOC, and the mechanism of anticancer activities of this combination was investigated by analyzing players in epithelial-mesenchymal transition (EMT). RESULTS: 4-NC significantly reduced the viability of PC-3 cells in a dose-dependent manner, decreasing colony formation and proliferation. The combination of 4-NC and DOC was synergistic in the androgen-independent cells and allowed the reduction of DOC concentration, with increased cytotoxicity and induction of apoptosis when compared to compounds alone. Furthermore, when 4- NC was co-administered with DOC, higher expression levels of proteins associated with the epithelial phenotype were observed, controlling EMT in PC-3 cells. CONCLUSION: Collectively, these data demonstrated, for the first time, that the combination of 4-NC with reduced doses of DOC could be especially valuable in the suppression of oncogenic mechanisms of androgen-independent PCa cells.

Perfil de competência do profissional em PIE no Brasil: relatório / Projeto ESPIE / Professional competency profile in PIE in Brazil: report / ESPIE Project

O projeto Apoio à Formulação e Implementação de Políticas Públicas de Saúde Informadas por Evidências (ESPIE) é desenvolvido pelo Instituto Sírio-Libanês de Ensino e Pesquisa do Hospital Sírio-Libanês (IEP/HSL), no âmbito do Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde (PROADI-SUS), em parceria com o Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos do Ministério da Saúde (DECIT/SCTIE/MS). O projeto ESPIE desenvolveu o Perfil de Competência do Profissional de PIE para o Brasil, com o objetivo de subsidiar atividades educacionais relacionadas com Políticas Informadas por Evidências (PIE), mas também apoiar o planejamento e ações de diferentes organizações no contexto da gestão da saúde no Sistema Único de Saúde (SUS). O perfil de competência foi desenvolvido e validado por um grupo de autoria constituído por técnicos das instituições envolvidas e especialistas convidados. O objetivo de criação do grupo de autoria foi agregar diferentes visões, experiências e opiniões ao processo de construção do perfil de competência em PIE. O grupo de autoria discutiu e definiu, ao longo de seis oficinas realizadas no ano de 2021, desde os macroproblemas até as ações-chave e desempenhos considerados essenciais. O processo de elaboração deste perfil foi orientado pelos seguintes macroproblemas: 1) processos decisórios na gestão das políticas de saúde pouco sistemáticos e transparentes; 2) capacidade institucional para gestão e tradução do conhecimento pouco desenvolvida e 3) incipiente incorporação das evidências científicas ao processo de formulação e implementação de políticas de saúde. Este documento consiste um meta-ponto de vista sobre o perfil de competência do profissional de PIE no Brasil e está endereçado aos macroproblemas no âmbito do SUS e inclui ações-chave e desempenhos que compõem um conjunto de conhecimentos, habilidades e atitudes, necessário para uma atuação institucional competente em PIE.

Interleukin-6 Signaling in Triple Negative Breast Cancer Cells Elicits the Annexin A1/Formyl Peptide Receptor 1 Axis and Affects the Tumor Microenvironment.

Annexin A1 (AnxA1) is a pleiotropic protein that exerts essential roles in breast cancer (BC) growth and aggressiveness. In our previous work, we described the autocrine signaling of AnxA1 through formyl peptide receptor 1 (FPR1) in the triple-negative (TN) BC cell line, MDA-MB-231. Here, we aimed to describe the interaction between the AnxA1/FPR1 and the Interleukin-6 (IL-6) signaling pathways and their role in the tumor microenvironment (TME). First, we demonstrated that AnxA1 and IL-6 expression levels are correlated in BC tissue samples. In three TNBC cell lines, overexpression of both AnxA1 and IL-6 was also identified. Next, we inhibited FPR1, the IL-6 receptor and STAT3 in both MDA-MB-231 and MDA-MB-157 cells. The FPR1 inhibition led to increased levels of IL-6 and secreted AnxA1 in both cell lines. On the other side, inhibition of the IL-6 receptor or STAT3 led to the impairment of AnxA1 secretion, suggesting the essential role of the IL-6 signaling cascade in the activation of the AnxA1/FPR1 autocrine axis. Finally, we described the interaction between IL-6 and the AnxA1/FPR1 pathways and their role on the TME by analyzing the effect of supernatants derived from MDA-MB-231 and MDA-MB-157 cells under the inhibition of FPR1 or IL-6 signaling on fibroblast cell motility.

Annexin A1 as a Regulator of Immune Response in Cancer.

Annexin A1 is a 37 kDa phospholipid-binding protein that is expressed in many tissues and cell types, including leukocytes, lymphocytes and epithelial cells. Although Annexin A1 has been extensively studied for its anti-inflammatory activity, it has been shown that, in the cancer context, its activity switches from anti-inflammatory to pro-inflammatory. Remarkably, Annexin A1 shows pro-invasive and pro-tumoral properties in several cancers either by eliciting autocrine signaling in cancer cells or by inducing a favorable tumor microenvironment. Indeed, the signaling of the N-terminal peptide of AnxA1 has been described to promote the switching of macrophages to the pro-tumoral M2 phenotype. Moreover, AnxA1 has been described to prevent the induction of antigen-specific cytotoxic T cell response and to play an essential role in the induction of regulatory T lymphocytes. In this way, Annexin A1 inhibits the anti-tumor immunity and supports the formation of an immunosuppressed tumor microenvironment that promotes tumor growth and metastasis. For these reasons, in this review we aim to describe the role of Annexin A1 in the establishment of the tumor microenvironment, focusing on the immunosuppressive and immunomodulatory activities of Annexin A1 and on its interaction with the epidermal growth factor receptor.

Overview of Beneficial Effects of (Poly)phenol Metabolites in the Context of Neurodegenerative Diseases on Model Organisms.

The rise of neurodegenerative diseases in an aging population is an increasing problem of health, social and economic consequences. Epidemiological and intervention studies have demonstrated that diets rich in (poly)phenols can have potent health benefits on cognitive decline and neurodegenerative diseases. Meanwhile, the role of gut microbiota is ever more evident in modulating the catabolism of (poly)phenols to dozens of low molecular weight (poly)phenol metabolites that have been identified in plasma and urine. These metabolites can reach circulation in higher concentrations than parent (poly)phenols and persist for longer periods of time. However, studies addressing their potential brain effects are still lacking. In this review, we will discuss different model organisms that have been used to study how low molecular weight (poly)phenol metabolites affect neuronal related mechanisms gathering critical insight on their potential to tackle the major hallmarks of neurodegeneration.

Primary care-based health surveillance actions in response to the COVID-19 pandemic: contributions to the debate. / Ações de vigilância à saúde integradas à Atenção Primária à Saúde diante da pandemia da COVID-19: contribuições para o debate.

We conducted an integrated literature review aimed at reflecting on the challenges related to primary care-based health surveillance actions in response to the COVID-19 pandemic in selected countries. The study included countries with different PHC models that adopted surveillance as an approach to control the transmission of COVID-19. We performed a search in October 2020 for relevant literature and norms and guidelines related to the organization of primary health care (PHC) in response to the pandemic on official government websites and the databases Web of Science and Science Direct. The integrated health surveillance actions demonstrated that efforts were more focused on risks, with some countries adopting innovative and effective measures to respond to COVID-19, considering emerging needs within PHC. However, in addition to ethical controversies and operational difficulties, access to technology was a challenge in actions developed by some countries due to social inequalities.

Trata-se de uma revisão de síntese integrativa com objetivo de refletir sobre os desafios atinentes às ações de vigilância em saúde no enfrentamento da COVID-19, no âmbito da Atenção Primária à Saúde (APS), em sistemas de saúde de países selecionados. Foram incluídos, no estudo, países com modelos de APS distintos, mas que adotaram a vigilância nos territórios como premissa para o controle da transmissão da COVID-19. Houve a revisão bibliográfica da literatura científica e a análise documental de normas e diretrizes relacionadas à organização da APS para enfrentamento da pandemia. A produção dos dados ocorreu no período entre abril e julho de 2020 e envolveu a busca de documentos sobre o enfrentamento da COVID-19, no que se refere à APS, nos sites oficiais governamentais de cada país e nas bases de dados científicas Web of Science e Science Direct. Ações integradas de vigilância em saúde demonstraram atuação mais direcionada sobre riscos, sendo possível respostas inovadoras e mais efetivas para enfrentamento da COVID-19, considerando necessidades emergentes no âmbito da APS. Contudo, experiências desenvolvidas por alguns países apresentaram controvérsias éticas e operacionais além dos desafios de acesso às tecnologias decorrente das desigualdades sociais.

Phospholipase A2 Drives Tumorigenesis and Cancer Aggressiveness through Its Interaction with Annexin A1.

Phospholipids are suggested to drive tumorigenesis through their essential role in inflammation. Phospholipase A2 (PLA2) is a phospholipid metabolizing enzyme that releases free fatty acids, mostly arachidonic acid, and lysophospholipids, which contribute to the development of the tumor microenvironment (TME), promoting immune evasion, angiogenesis, tumor growth, and invasiveness. The mechanisms mediated by PLA2 are not fully understood, especially because an important inhibitory molecule, Annexin A1, is present in the TME but does not exert its action. Here, we will discuss how Annexin A1 in cancer does not inhibit PLA2 leading to both pro-inflammatory and pro-tumoral signaling pathways. Moreover, Annexin A1 promotes the release of cancer-derived exosomes, which also lead to the enrichment of PLA2 and COX-1 and COX-2 enzymes, contributing to TME formation. In this review, we aim to describe the role of PLA2 in the establishment of TME, focusing on cancer-derived exosomes, and modulatory activities of Annexin A1. Unraveling how these proteins interact in the cancer context can reveal new strategies for the treatment of different tumors. We will also describe the possible strategies to inhibit PLA2 and the approaches that could be used in order to resume the anti-PLA2 function of Annexin A1.

Ações de vigilância à saúde integradas à Atenção Primária à Saúde diante da pandemia da COVID-19: contribuições para o debate / Primary care-based health surveillance actions in response to the COVID-19 pandemic: contributions to the debate

Resumo Trata-se de uma revisão de síntese integrativa com objetivo de refletir sobre os desafios atinentes às ações de vigilância em saúde no enfrentamento da COVID-19, no âmbito da Atenção Primária à Saúde (APS), em sistemas de saúde de países selecionados. Foram incluídos, no estudo, países com modelos de APS distintos, mas que adotaram a vigilância nos territórios como premissa para o controle da transmissão da COVID-19. Houve a revisão bibliográfica da literatura científica e a análise documental de normas e diretrizes relacionadas à organização da APS para enfrentamento da pandemia. A produção dos dados ocorreu no período entre abril e julho de 2020 e envolveu a busca de documentos sobre o enfrentamento da COVID-19, no que se refere à APS, nos sites oficiais governamentais de cada país e nas bases de dados científicas Web of Science e Science Direct. Ações integradas de vigilância em saúde demonstraram atuação mais direcionada sobre riscos, sendo possível respostas inovadoras e mais efetivas para enfrentamento da COVID-19, considerando necessidades emergentes no âmbito da APS. Contudo, experiências desenvolvidas por alguns países apresentaram controvérsias éticas e operacionais além dos desafios de acesso às tecnologias decorrente das desigualdades sociais.

Abstract We conducted an integrated literature review aimed at reflecting on the challenges related to primary care-based health surveillance actions in response to the COVID-19 pandemic in selected countries. The study included countries with different PHC models that adopted surveillance as an approach to control the transmission of COVID-19. We performed a search in October 2020 for relevant literature and norms and guidelines related to the organization of primary health care (PHC) in response to the pandemic on official government websites and the databases Web of Science and Science Direct. The integrated health surveillance actions demonstrated that efforts were more focused on risks, with some countries adopting innovative and effective measures to respond to COVID-19, considering emerging needs within PHC. However, in addition to ethical controversies and operational difficulties, access to technology was a challenge in actions developed by some countries due to social inequalities.

Effectiveness of the use of non-woven face mask to prevent coronavirus infections in the general population: a rapid systematic review. / Eficácia da máscara facial (TNT) na população para a prevenção de infecções por coronavírus: revisão sistemática.

OBJECTIVES: to evaluate the effectiveness of non-woven face masks for the prevention of respiratory infections (MERS CoV, SARS-CoV, and SARS-CoV-2) in the population. METHODS: search in Medline, Embase, Cinahl, The Cochrane Library, Trip databases. Google Scholar, Rayyan and medRxiv were also consulted for complementary results. No filters related to date, language or publication status were applied. Titles and abstracts were screened, and later, full texts were evaluated. RESULTS: three studies were included: a randomized cluster clinical trial and two systematic reviews. The clinical trial indicates a potential benefit of medical masks to control the source of clinical respiratory disease infection. In one of the systematic reviews, it was not possible to establish a conclusive relationship between the use of the mask and protection against respiratory infection. Finally, another systematic review indicated that masks are effective in preventing the spread of respiratory viruses. CONCLUSION: Evidence points to the potential benefit of standard non-woven face masks. For the current pandemic scenario of COVID-19, education on the appropriate use of masks associated with individual protection measures is recommended.

Annexin A1 promotes the nuclear localization of the epidermal growth factor receptor in castration-resistant prostate cancer.

Epidermal growth factor receptor is a cancer driver whose nuclear localization has been associated with the progression of prostate cancer to the castration-resistant phenotype. Previous reports indicated a functional interaction between this receptor and the protein Annexin A1, which has also been associated with aggressive tumors. The molecular pathogenesis of castration-resistant prostate cancer remains largely unresolved, and herein we have demonstrated the correlation between the expression levels and localization of the epidermal growth factor receptor and Annexin A1 in prostate cancer samples and cell lines. Interestingly, a higher expression of both proteins was detected in castration-resistant prostate cancer cell lines and the strongest correlation was seen at the nuclear level. We verified that Annexin A1 interacts with the epidermal growth factor receptor, and by using prostate cancer cell lines knocked down for Annexin A1, we succeeded in demonstrating that Annexin A1 promotes the nuclear localization of epidermal growth factor receptor. Finally, we showed that Annexin A1 activates an autocrine signaling in castration-resistant prostate cells through the formyl peptide receptor 1. The inhibition of such signaling by Cyclosporin H inhibits the nuclear localization of epidermal growth factor receptor and its downstream signaling. The present work sheds light on the functional interaction between nuclear epidermal growth factor receptor and nuclear Annexin A1 in castration-resistant prostate cancer. Therefore, strategies to inhibit the nuclear localization of epidermal growth factor receptor through the suppression of the Annexin A1 autocrine loop could represent an important intervention strategy for castration-resistant prostate cancer.

Effectiveness of the facial mask (non-woven) in the population to prevent coronavirus infections: A systematic review / Eficácia da máscara facial (TNT) na população para prevenção de infecções por coronavírus: Revisão sistemática

Objectives: To evaluate the effectiveness of non-woven face masks for the prevention of respiratory diseases (MERS CoV, SARS-CoV and SARS-CoV-2) in the population. Methods: search in Medline, Embase, Cinahl, The Cochrane Library, Trip databases. It also seeks to complement Google Scholar, Rayyan and medRxiv. No filters related to date, language or publication status were applied. Titles and abstracts were screened, and later, full texts were evaluated. Results: three studies were included: a randomized cluster clinical trial and two systematic reviews. The clinical trial indicates the potential benefit of medical masks to control the source of infection for clinical respiratory disease. In one of the systematic reviews, it was not possible to establish a conclusive relationship between the use of the mask and protection against respiratory infection. Finally, another systematic review has shown that masks are effective in preventing the spread of respiratory viruses. Conclusion: Evidence points to the potential benefit of standard non-woven face masks. For the current pandemic scenario due to COVID 19, education on the appropriate use of masks, associated with individual protection measures, is recommended.

Objetivos: avaliar a eficácia das máscaras padrão de tecido (TNT) para a prevenção de doenças respiratórias (MERS CoV, SARS-CoV e SARS-CoV-2) na população. Métodos: busca nas bases de dados Medline, Embase, Cinahl, The Cochrane Library, Trip. Também busca complementar no Google Acadêmico, Rayyan e medRxiv. Não foram aplicados filtros relacionados a dados, idioma ou status de publicação. Títulos e resumos foram rastreados, e posteriormente textos completos foram usados. Resultados: foram incluídos três estudos: um ensaio clínico randomizado tipo cluster e duas análises sistemáticas. O ensaio clínico indica o benefício potencial de máscaras médicas para o controle da fonte de infecção, para a doença respiratória clínica.Em uma das revisões sistemáticas, não foi possível definir uma relação conclusiva entre o uso da Máscara e proteção contra a infecção respiratória. Por fim, outra revisão sistemática demonstrou que máscaras são usadas na prevenção da propagação de vírus respiratórios. Conclusão: Como indicado para o benefício potencial das máscaras padrão TNT. Para o cenário atual de pandemia por COVID 19, recomenda-se a educação sobre o uso adequado de máscaras, relacionadas a medidas individuais de proteção.

Eficácia da máscara facial (TNT) na população para a prevenção de infecções por coronavírus: revisão sistemática / Effectiveness of the use of non-woven face mask to prevent coronavirus infections in the general population: a rapid systematic review

Resumo O objetivo deste artigo é avaliar a eficácia das máscaras faciais padrão tecido não tecido (TNT) para a prevenção de doenças respiratórias (MERS CoV, SARS-CoV e SARS-CoV-2) na população. Foi realizada busca nas bases de dados Medline, Embase, Cinahl, The Cochrane Library, Trip. Também busca complementar no Google Acadêmico, Rayyan e medRxiv. Não foram aplicados filtros relacionados a data, idioma ou status de publicação. Títulos e resumos foram rastreados e, posteriormente, textos completos foram avaliados. Foram incluídos três estudos: um ensaio clínico randomizado tipo cluster e duas revisões sistemáticas. O ensaio clínico indica benefício potencial de máscaras médicas para controle da fonte de infecção, para a doença respiratória clínica. Em uma das revisões sistemáticas, não foi possível estabelecer relação conclusiva entre uso da máscara e proteção contra infecção respiratória. Por fim, outra revisão sistemática demonstrou que máscaras são eficazes na prevenção da propagação de vírus respiratórios. As evidências apontam para benefício potencial das máscaras faciais padrão TNT. Para o cenário atual de pandemia por COVID 19, recomenda-se educação sobre uso adequado de máscaras, associado a medidas individuais de proteção.

Abstract Objectives: to evaluate the effectiveness of non-woven face masks for the prevention of respiratory infections (MERS CoV, SARS-CoV, and SARS-CoV-2) in the population. Methods: search in Medline, Embase, Cinahl, The Cochrane Library, Trip databases. Google Scholar, Rayyan and medRxiv were also consulted for complementary results. No filters related to date, language or publication status were applied. Titles and abstracts were screened, and later, full texts were evaluated. Results: three studies were included: a randomized cluster clinical trial and two systematic reviews. The clinical trial indicates a potential benefit of medical masks to control the source of clinical respiratory disease infection. In one of the systematic reviews, it was not possible to establish a conclusive relationship between the use of the mask and protection against respiratory infection. Finally, another systematic review indicated that masks are effective in preventing the spread of respiratory viruses. Conclusion: Evidence points to the potential benefit of standard non-woven face masks. For the current pandemic scenario of COVID-19, education on the appropriate use of masks associated with individual protection measures is recommended.

New Insights into the Role of Polybromo-1 in Prostate Cancer.

The human protein Polybromo-1 (PBMR1/BAF180) is a component of the SWI/SNF chromatin-remodeling complex that has been reported to be deregulated in tumors. However, its role in prostate cancer (PCa) is largely unknown. In this study, we described the PBRM1 transcriptional levels and the protein expression/localization in tissues of PCa patients and in prostatic cell lines. Increased PBRM1 mRNA levels were found in PCa samples, when compared to benign disease, and were correlated with higher Gleason score. We also verified that only the nuclear localization of PBRM1 protein is correlated with a more aggressive disease and high Prostate-Specific Antigen (PSA) levels in tissue microarrays. Intriguing expression patterns of mRNA and protein were identified in the cell lines. Although PBRM1 protein was restricted to the nuclei, in tumor cell lines in non-neoplastic cells, it was also present in vesicular-like structures that were dispersed within the cytoplasm. We knocked-down PBRM1 in the castration-resistant PCa (CRPC) cell line PC-3 and we verified that PBRM1 promotes the expression of several markers of aggressiveness, including EpCAM, TGF-ß, and N-Cadherin. Therefore, our data supported the hypothesis that PBRM1 displays a pivotal role in the promotion and maintenance of the malignant behavior of PCa, especially in CRPC.

Inhibition of Triple-Negative Breast Cancer Cell Aggressiveness by Cathepsin D Blockage: Role of Annexin A1.

Triple-negative breast cancers (TNBCs) are more aggressive than other breast cancer (BC) subtypes and lack effective therapeutic options. Unraveling marker events of TNBCs may provide new directions for development of strategies for targeted TNBC therapy. Herein, we reported that Annexin A1 (AnxA1) and Cathepsin D (CatD) are highly expressed in MDA-MB-231 (TNBC lineage), compared to MCF-10A and MCF-7. Since the proposed concept was that CatD has protumorigenic activity associated with its ability to cleave AnxA1 (generating a 35.5 KDa fragment), we investigated this mechanism more deeply using the inhibitor of CatD, Pepstatin A (PepA). Fourier Transform Infrared (FTIR) spectroscopy demonstrated that PepA inhibits CatD activity by occupying its active site; the OH bond from PepA interacts with a CO bond from carboxylic acids of CatD catalytic aspartate dyad, favoring the deprotonation of Asp33 and consequently inhibiting CatD. Treatment of MDA-MB-231 cells with PepA induced apoptosis and autophagy processes while reducing the proliferation, invasion, and migration. Finally, in silico molecular docking demonstrated that the catalytic inhibition comprises Asp231 protonated and Asp33 deprotonated, proving all functional results obtained. Our findings elucidated critical CatD activity in TNBC cell trough AnxA1 cleavage, indicating the inhibition of CatD as a possible strategy for TNBC treatment.

Análise crítica da interculturalidade na Política Nacional de Atenção às Populações Indígenas no Brasil

[RESUMO]. A preocupação com um cuidado culturalmente apropriado e intercultural, baseado na articulação e complementariedade entre saberes em saúde, vem sendo uma prioridade para garantir a atenção primária à saúde (APS) dos povos indígenas desde a Conferência de Alma-Ata. No Brasil, país de significativa variedade sociocultural no contexto indígena sul-americano, existe há 16 anos uma Política Nacional de Atenção à Saúde das Populações Indígenas (PNASPI) focada no conceito de atenção diferenciada. Esse conceito, considerado como incompleto e contraditório, é variavelmente operacionalizado na APS de indígenas. Sendo assim, o presente artigo propõe uma análise da formulação e operacionalização desse conceito na PNASPI. Essa análise torna evidente o caráter etnocêntrico da PNASPI, as numerosas contradições e negligências que não contemplam de fato o intercâmbio e articulação com o saber tradicional e as visões êmicas indígenas de saúde e dos processos de padecimento/cura. A reversão dessas limitações exigirá maior reflexividade, questionamento e vigilância epistemológicos tanto das ciências sociais e políticas quanto dos movimentos sociais e de controle social indígenas para redefinir em termos interculturais a APS de indígenas no Brasil.

[ABSTRACT]. Concern for culturally appropriate and intercultural care, based on the articulation and complementarity among health knowledges, has been a priority for ensuring primary health care for indigenous peoples since the Alma-Ata Conference. In Brazil, a country with significant sociocultural variety in the South American indigenous context, a National Policy for the Care of Indigenous Peoples (PNASPI) was established 16 years ago, focusing on the notion of differentiated care. This concept, considered incomplete and contradictory, has been variably operationalized in indigenous primary health care. Therefore, the present article proposes an analysis of the formulation and operationalization of this concept in PNASPI. The analysis brings to light the ethnocentric nature of PNASPI, the numerous contradictions and oversights that fail to encompass the interchange and articulation with traditional knowledges and the indigenous emic views of health and the processes of illness/cure. The reversal of these limitations will require greater reflexivity, problematization, and epistemological surveillance of both the social and political sciences as well as social movements and indigenous social control to redefine indigenous primary health care in Brazil in intercultural terms.

[RESUMEN]. La preocupación por un cuidado culturalmente apropiado e intercultural, basado en la articulación y complementariedad entre saberes en salud, es una prioridad para garantizar la atención primaria de salud de los pueblos indígenas desde la Conferencia de Alma-Ata. En Brasil, un país con una significativa variedad sociocultural en el contexto indígena de América del Sur, existe desde hace 16 años una Política Nacional de Atención a la Salud de las Poblaciones Indígenas (PNASPI) enfocada en el concepto de atención diferenciada. Este concepto, considerado incompleto y contradictorio, es ejecutado de manera variable en la atención primaria de salud de las poblaciones indígenas. Este artículo propone un análisis de la formulación y ejecución de ese concepto en la PNASPI. Este análisis hace evidente el carácter etnocéntrico de la PNASPI, las numerosas contradicciones y negligencias que no contemplan de hecho el intercambio y la articulación con el saber tradicional y las visiones émicas indígenas de salud y de los procesos de enfermedad/curación. La reversión de esas limitaciones requerirá mayor reflexividad, cuestionamiento y vigilancia epistemológica tanto desde las ciencias sociales y políticas como desde los movimientos sociales y de control social indígenas para redefinir en términos interculturales la atención primaria de salud de estas poblaciones en Brasil.

Inhibition of the AnxA1/FPR1 autocrine axis reduces MDA-MB-231 breast cancer cell growth and aggressiveness in vitro and in vivo.

Breast Cancer (BC) is a highly heterogeneous disease whose most aggressive behavior is displayed by triple-negative breast cancer (TNBC), which lacks an efficient targeted therapy. Despite its controversial role, one of the proteins that having been linked with BC is Annexin A1 (AnxA1), which is a Ca+2 binding protein that acts modulating the immune system, cell membrane organization and vesicular trafficking. In this work we analyzed tissue microarrays of BC samples and observed a higher expression of AnxA1 in TNBCs and in lymph node metastasis. We also observed a positive correlation in primary tumors between expression levels of AnxA1 and its receptor, FPR1. Despite displaying a lesser strength, this correlation also exists in BC lymph node metastasis. In agreement, we have found that AnxA1 was highly expressed and secreted in the TNBC cell line MDA-MB-231 that also expressed high levels of FPR1. Furthermore, we demonstrated, by using the specific FPR1 inhibitor Cyclosporin H (CsH) and the immunosuppressive drug Cyclosporin A (CsA), the existence of an autocrine signaling of AnxA1 through the FPR1. Such signaling, elicited by AnxA1 upon its secretion, increased the aggressiveness and survival of MDA-MB-231 cells. In this manner, we demonstrated that CsA works very efficiently as an FPR1 inhibitor. Finally, by using CsA, we demonstrated that FPR1 inhibition decreased MDA-MB-231 tumor growth and metastasis formation in nude mice. These results indicate that FPR1 inhibition could be a potential intervention strategy to manage TNBCs displaying the characteristics of MDA-MB-231 cells. FPR1 inhibition can be efficiently achieved by CsA.

Ethanolic Extracts from Azadirachta indica Leaves Modulate Transcriptional Levels of Hormone Receptor Variant in Breast Cancer Cell Lines.

Breast Cancer (BC) encompasses numerous entities with different biological and behavioral characteristics, favored by tumor molecular complexity. Azadirachta indica (neem) presents phenolic compounds, indicating its potential as an antineoplastic compound. The present study aimed to evaluate the cellular response of MCF10, MCF7, and MDA-MB-231 breast cell lines to ethanolic extracts of neem leaves (EENL) obtained by dichloromethane (DCM) and ethyl acetate (EA) solvent. Extracts' antiproliferative activities were evaluated against MCF 10A, MCF7, and MDA-MB-231 for 24 and 48 h using MTT assay. ESR1, ESR2, AR, AR-V1, AR-V4, and AR-V7 transcripts were quantified through qPCR for 0.03125 µg/mL of DCM and 1.0 µg/mL for EA for 48 h. The EENL was tested on Drosophila melanogaster as a sole treatment and then also together with doxorubicin. Antiproliferative effect on tumor cell lines without affecting MCF 10A were 1.0 µg/mL (P < 0.001) for EA, and 0.03125 µg/mL (P < 0.0001) for DCM, both after 48 h. Transcriptional levels of AR-V7 increased after treatment. In vivo assays demonstrated that EENL induced fewer tumors at a higher concentration with doxorubicin (DXR). The behavior of AR-V7 in the MDA-MB-231 tumor lineage indicates new pathways involved in tumor biology and this may have therapeutic value for cancer.

Por uma atenção diferenciada e menos desigual: o caso do Distrito Sanitário Especial Indígena da Bahia / For differentiated and less uneven health care practices: the case of the Special Indigenous Sanitary District of Bahia

Nesse estudo buscou-se conhecer os significados do princípio da "atenção diferenciada" por meio da análise dos enunciados e da observação das práticas de gestores do Subsistema de Atenção à Saúde dos Povos Indígenas na Bahia, a fim de revelar as bases sociais, políticas e culturais que os sustentam e analisar como contribuem, ou não, para a sua operacionalização. Parte-se do pressuposto de que a prestação de ações de atenção à saúde efetivamente diferenciadas, que considerem as especificidades socioculturais dos povos indígenas e sua medicina tradicional, pode contribuir para maior resolutividade do cuidado à saúde desses povos e mitigação de algumas implicações de determinantes sociais sobre os modos de viver, adoecer e morrer na população indígena. Optou-se pela realização de um estudo qualitativo, de abordagem etnográfica, com aplicação das técnicas de observação participante e de entrevistas semiestruturadas entre gestores do Subsistema na Bahia. A coleta de informações ocorreu entre setembro de 2014 e março de 2017. As narrativas revelaram frequentemente um tom retórico da ideia de "atenção diferenciada" como uma iniciativa de respeito às especificidades culturais indígenas, as quais foram mais insistentemente utilizadas como justificativa para a não realização de práticas diferenciadas de cuidado (por exemplo, protocolos específicos). A presença de indígenas na gestão contribuiu para a produção de práticas mais contextualizadas e orientadas para os problemas vivenciados pelas comunidades, mas o esforço de legitimação nesse espaço social ratifica a hegemonia "branca" na pauta principal de discussões.(AU)

In this study, we sought to know the meanings of the principle of "differentiated health care" through the analysis of narratives and practices from managers of the Subsystem of Indigenous People's Health Care in Bahia, Brazil, to reveal how their social, political, and cultural bases can contribute or not to its operationalization. It is assumed that the provision of effectively differentiated health care actions, which consider the socio-cultural specificities of indigenous peoples and their traditional medicine, can contribute to a greater resolution of health services targeted for these peoples and mitigation of some social determinants of their ways of living and dying. Thus, a qualitative study with an ethnographic approach was developed, using participant observation techniques and semi-structured interviews with managers of the Subsystem in Bahia. Data collection took place between September 2014 and March 2017. The narratives often revealed a rhetorical tone of the idea of "differentiated health care" as an initiative to respect indigenous cultural specificities, which were insistently used as a justification for not conducting differentiated practices (as specific protocols, for example). The presence of indigenous people in the management contributed for producing more contextualized practices, oriented to the problems experienced by the communities, but the effort to legitimize themselves in this social space ratifies a "white" hegemony in the main topic of discussions.(AU)