Profile and Migration of Members of Residency Programs in Family Medicine.

OBJECTIVE: To describe the sociodemographic profile and analyze the migratory characteristics of the members of the Residency Programs in Family Medicine in 2020 in Brazil. METHODS: The study follows a cross-sectional observational design of a quantitative nature from the perspective of the members of the Residency Programs in Family Medicine. Questionnaires adapted for each participating group were developed, applied through an online platform. RESULTS: Most participants are female and white. Most supervisors and preceptors were residents of Residency Programs in Family Medicine, however, there are some who are not specialists in the field. Most participants are based in capitals or metropolitan regions. In relation to retention, 41.1% of supervisors and 73.1% of preceptors are affiliated to a program in the same municipality where they lived. For most resident physicians, the place of residence coincides with the place of birth and/or graduation (57.4%), and 48.5% are in the same place of graduation. CONCLUSIONS: The research reinforces the need for policies to promote the migration of residents to Residency Programs in Family Medicine outside capital cities and metropolitan regions, as well as encouraging the retention of graduates trained outside large urban centers so that they can contribute to distribution and provision of doctors where they are still needed.

Sulforaphane Effects on Cardiac Function and Calcium-Handling-Related Proteins in 2 Experimental Models of Heart Disease: Ischemia-Reperfusion and Infarction.

ABSTRACT: Sulforaphane (SFN) is a natural exogenous antioxidant from cruciferous vegetables already shown to improve cardiac function in cardiovascular diseases. The aim of this study was to analyze the effect of SFN treatment on the cardiac function in 2 experimental models of heart disease, ischemia/reperfusion (I/R) and myocardial infarction (MI), and whether an improvement of the cardiac function could be associated with a modulation of calcium-handling proteins. The study was divided into 2 main experiments: experiment 1, ex vivo with the I/R model and experiment 2, in vivo with the MI model. In the I/R model, rats were divided into control and SFN (0.5 mg/kg/d intraperitoneally for 3 days) groups, and the hearts were submitted to global ischemia (20 minutes) followed by reperfusion (20 minutes) in a Langendorff apparatus. SFN did not change left ventricle systolic and diastolic pressures but increased the contractility and relaxation indexes after 20 minutes of reperfusion. These functional changes were accompanied by a decreased protein expression of ryanodine receptor (RyR) and increased expression of p-phospholamban/phospholamban ratio, without alteration in the sarco/endoplasmic calcium ATPase expression. In the MI model, rats were randomly divided into Sham, MI (MI induced by left coronary artery ligation), Sham + SFN (5 mg/kg/d intraperitoneally for 25 days), and MI + SFN groups. Although SFN did not affect cardiac function, it led to a decreased RyR protein expression and reactive oxygen species levels in the left ventricular of the MI + SFN group. These data indicate that SFN modulates calcium-handling proteins and, thus, cardiac inotropism/lusitropism especially when administered previously to an ischemic event.

Profile and Migration of Members of Residency Programs in Family Medicine / Perfil e migração de membros dos Programas de Residência em Medicina de Família e Comunidade

ABSTRACT OBJECTIVE To describe the sociodemographic profile and analyze the migratory characteristics of the members of the Residency Programs in Family Medicine in 2020 in Brazil. METHODS The study follows a cross-sectional observational design of a quantitative nature from the perspective of the members of the Residency Programs in Family Medicine. Questionnaires adapted for each participating group were developed, applied through an online platform. RESULTS Most participants are female and white. Most supervisors and preceptors were residents of Residency Programs in Family Medicine, however, there are some who are not specialists in the field. Most participants are based in capitals or metropolitan regions. In relation to retention, 41.1% of supervisors and 73.1% of preceptors are affiliated to a program in the same municipality where they lived. For most resident physicians, the place of residence coincides with the place of birth and/or graduation (57.4%), and 48.5% are in the same place of graduation. CONCLUSIONS The research reinforces the need for policies to promote the migration of residents to Residency Programs in Family Medicine outside capital cities and metropolitan regions, as well as encouraging the retention of graduates trained outside large urban centers so that they can contribute to distribution and provision of doctors where they are still needed.

RESUMO OBJETIVO Caracterizar o perfil sociodemográfico e analisar as características migratórias dos integrantes dos Programas de Residência em Medicina de Família e Comunidade em 2020 no Brasil. MÉTODOS O estudo segue um delineamento observacional transversal de natureza quantitativa a partir da perspectiva dos integrantes dos Programas de Residência em Medicina de Família e Comunidade. Foram desenvolvidos questionários adaptados para cada grupo participante, aplicados por meio de plataforma on-line. RESULTADOS A maioria dos participantes é do sexo feminino e de cor branca. A maioria dos supervisores e preceptores foi residente de Programas de Residência em Medicina de Família e Comunidade, contudo, há alguns que não são especialistas na área. A maior parte dos participantes está vinculada às capitais ou regiões metropolitanas. Em relação à fixação, 41,1% dos supervisores e 73,1% dos preceptores estão vinculados a um programa no mesmo município onde foram residentes. Para a maioria dos médicos residentes, o local da residência coincide com o local de nascimento e/ou graduação (57,4%), sendo que 48,5% estão no mesmo local de graduação. CONCLUSÕES A pesquisa reforça a necessidade de políticas de promoção da migração de residentes para Programas de Residência em Medicina de Família e Comunidade fora das capitais e regiões metropolitanas, bem como estimula a fixação dos egressos formados fora dos grandes centros urbanos para que eles possam contribuir com a distribuição e com o provimento de médicos onde ainda é necessário.

Pesquisa: quando ética e a humanização se encontram / Research: when ethics and humanization meet

A Pesquisa Científica e Ética é um forte e principal fundamento para a realização de pesquisas, entretanto desde 2020 com a pandemia ocasionada pelo COVID-19, estamos podendo refletir de forma mais ampla e profunda, junto à sociedade, o significado de avaliações éticas na pesquisas e as suas repercussões para o Ser Humano. Nessa perspectiva e a partir da vivência de membros do Comitê de Ética em Pesquisa do Hospital Mãe de Deus surgiu esse livro que pretende dar início a Série Pesquisa: A Ética e Pesquisa no século XXI buscando estimular outros colegas com mais publicações que abordem essa temática.

Family and Community Medicine Residency Programs for training the health workforce: what do municipal health managers think? / Residência em Medicina de Família e Comunidade para a formação de recursos humanos: o que pensam gestores municipais?

The training, recruitment and retention of primary care professionals is a constant challenge in Brazil. The recent expansion of family and community medicine residency programs in the country coexists with gaps in the literature on the effects of this process. This article explores municipal health managers' understanding of these programs and the role they play in professional training and improving the quality of health care. We conducted a quantitative and qualitative analysis of the responses to questionnaires answered by 48 health managers working in municipal health services affiliated to residency programs. A descriptive statistical analysis of the quantitative data was performed and the qualitative data were analyzed using thematic analysis. The findings show that efforts were made to incorporate family and community doctors into the health care network and that managers recognized the potential residency program have to improve the quality of care and enhance professional training. Weaknesses were found in actions to improve infrastructure and facilities and the organization of the services affiliated to the programs. This study highlights the potential of residency programs for addressing longstanding problems in primary health care in Brazil when combined with actions to strengthen services, human resources and the programs.

Treinamento especializado, provimento e fixação de profissionais na Atenção Primária à Saúde são desafios prementes no Brasil. A recente expansão dos Programas de Residência em Medicina de Família e Comunidade coexiste com lacunas na literatura sobre o efeito deste processo. O objetivo do trabalho é explorar a perspectiva do gestor municipal de saúde acerca das estratégias para o fortalecimento das residências e do papel destas na formação profissional e na qualificação da atenção. Trata-se de um estudo de análise quantitativa e qualitativa, com aplicação de questionário a gestores de municípios cenários destes programas. As respostas de 48 sujeitos foram submetidas a estatística descritiva e análise de conteúdo. Os resultados revelam um esforço em incorporar o Médico de Família e Comunidade na rede de atenção à saúde, uma percepção do potencial das residências no incremento da qualidade da atenção e da formação profissional e fragilidades nas ações para melhoria da estrutura e organização dos serviços com residentes. Vislumbra-se assim o potencial das residências para a superação de problemas históricos da Atenção Primária à Saúde brasileira, se atrelada a ações de fortalecimento do serviço, dos recursos humanos e do próprio programa.

Residência em Medicina de Família e Comunidade para a formação de recursos humanos: o que pensam gestores municipais? / Family and Community Medicine Residency Programs for training the health workforce: what do municipal health managers think?

Resumo Treinamento especializado, provimento e fixação de profissionais na Atenção Primária à Saúde são desafios prementes no Brasil. A recente expansão dos Programas de Residência em Medicina de Família e Comunidade coexiste com lacunas na literatura sobre o efeito deste processo. O objetivo do trabalho é explorar a perspectiva do gestor municipal de saúde acerca das estratégias para o fortalecimento das residências e do papel destas na formação profissional e na qualificação da atenção. Trata-se de um estudo de análise quantitativa e qualitativa, com aplicação de questionário a gestores de municípios cenários destes programas. As respostas de 48 sujeitos foram submetidas a estatística descritiva e análise de conteúdo. Os resultados revelam um esforço em incorporar o Médico de Família e Comunidade na rede de atenção à saúde, uma percepção do potencial das residências no incremento da qualidade da atenção e da formação profissional e fragilidades nas ações para melhoria da estrutura e organização dos serviços com residentes. Vislumbra-se assim o potencial das residências para a superação de problemas históricos da Atenção Primária à Saúde brasileira, se atrelada a ações de fortalecimento do serviço, dos recursos humanos e do próprio programa.

Abstract The training, recruitment and retention of primary care professionals is a constant challenge in Brazil. The recent expansion of family and community medicine residency programs in the country coexists with gaps in the literature on the effects of this process. This article explores municipal health managers' understanding of these programs and the role they play in professional training and improving the quality of health care. We conducted a quantitative and qualitative analysis of the responses to questionnaires answered by 48 health managers working in municipal health services affiliated to residency programs. A descriptive statistical analysis of the quantitative data was performed and the qualitative data were analyzed using thematic analysis. The findings show that efforts were made to incorporate family and community doctors into the health care network and that managers recognized the potential residency program have to improve the quality of care and enhance professional training. Weaknesses were found in actions to improve infrastructure and facilities and the organization of the services affiliated to the programs. This study highlights the potential of residency programs for addressing longstanding problems in primary health care in Brazil when combined with actions to strengthen services, human resources and the programs.

The progression of pulmonary arterial hypertension induced by monocrotaline is characterized by lung nitrosative and oxidative stress, and impaired pulmonary artery reactivity.

The time-course of pulmonary arterial hypertension in the monocrotaline (MCT) model was investigated. Male rats were divided into two groups: MCT (received a 60 mg/kg i.p. injection) and control (received saline). The MCT and control groups were further divided into three cohorts, based on the follow-up interval: 1, 2, and 3 weeks. Right ventricle (RV) catheterization was performed and RV hypertrophy (RVH) was estimated. The lungs were used for biochemical, histological, molecular, and immunohistochemical analysis, while pulmonary artery rings were used for vascular reactivity. MCT promoted lung perivascular edema, inflammatory cells exudation, greater neutrophils and lymphocytes profile, and arteriolar wall thickness, compared to CTR group. Increases in pulmonary artery pressure and in RVH were observed in the MCT 2- and 3-week groups. The first week was marked by the presence of nitrosative stress (50% moderate and 33% accentuated staining by nitrotyrosine). These alterations lead to an adaptation of NO production by NO synthase activity after 2 weeks. Oxidative stress was evident in the third week, probably by an imbalance between endothelin-1 receptors, resulting in extracellular matrix remodeling, endothelial dysfunction, and RVH. Also, it was found a reduced pulmonary arterial vasodilatory response to acetylcholine after 2 (55%) and 3 (45%) weeks in MCT groups. The relevance of this study is precisely to show that nitrosative and oxidative stress predominate in distinct time windows of the disease progression.

Lapatinib Inhibits Amphiregulin-induced BeWo Choriocarcinoma Cell Proliferation by Reducing ERK1/2 and AKT Signaling Pathways.

BACKGROUND: Human choriocarcinoma is the most aggressive type of gestational trophoblastic neoplasia. The expression of epidermal growth factor receptor (EGFR) in choriocarcinomas is significantly higher than those of trophoblastic cells in healthy placentas. Lapatinib is a potent EGFR and human epidermal growth factor receptor 2 (HER2) inhibitor that inhibits cell proliferation and induces apoptosis in various human cancer cells. Amphiregulin (AREG) is the most abundant EGFR ligand in amniotic fluid during human pregnancy. AIM: To explore the role of AREG in human choriocarcinoma cell proliferation. MATERIALS AND METHODS: The effect of lapatinib and AREG on cell proliferation was examined by the MTT assay. Western blots were used to investigate EGFR and HER2 expression, and the activation of caspase-3, extracellular signal-regulated kinases 1/2 (ERK1/2) and phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT) signaling pathways. RESULTS: Treatment with lapatinib reduced BeWo cell proliferation by inducing apoptosis. Moreover, AREG treatment stimulated BeWo cell proliferation by activating ERK1/2 and PI3K/AKT signaling pathways, which was blocked by lapatinib. CONCLUSION: Targeting EGFR/HER2 might be a useful therapeutic strategy for human choriocarcinoma.

Influence of HLA-G polymorphisms in human immunodeficiency virus infection and hepatitis C virus co-infection in Brazilian and Italian individuals.

OBJECTIVE: This study aimed to investigate the role of Human Leukocyte Antigen (HLA)-G in the susceptibility to HIV-1 infection through the analysis of the HLA-G 3' untranslated region (UTR) polymorphisms 14 bp insertion/deletion (rs66554220) and +3142C>G (rs1063320). DESIGN: We analyzed 582 HIV-1 infected patients and 626 uninfected individuals from Brazil and Italy in a case-control study. METHODS: HLA-G polymorphisms were genotyped using PCR, PCR-RFLP assays or direct sequencing. All analyses were stratified by ethnicity. Genotypic, allelic and diplotypic frequencies were compared between HIV-1 infected subjects and controls using Chi-square or Fischer exact tests. Also, haplotypic frequencies were estimated using MLocus software. RESULTS: African-derived HIV-infected individuals presented a higher frequency of the 14 bp insertion allele as compared to non-infected individuals (0.468 versus 0.373, respectively; p(Bonf) = 0.010). A higher frequency of the 14 bp insertion +3142G (insG) haplotype (0.456 versus 0.346, p<0.001) and the insG/insG diplotype (OR=1.88, 95%CI = 1.08-3.23, p=0.021) was observed among African-derived patients as compared to uninfected controls. Also, we observed a higher frequency of the ins/ins genotype among African-derived HIV patients co-infected with HCV (OR=2.78, 95%CI = 1.20-6.49, p = 0.008). CONCLUSIONS: Our data point out to an increased frequency of alleles and genotypes associated with low HLA-G expression among African-derived patients, suggesting a potential role for HLA-G in the susceptibility to HIV-1 infection and HCV co-infection in those individuals.

Reviewing and updating the major molecular markers for stem cells.

Stem cells (SC) are able to self-renew and to differentiate into many types of committed cells, making SCs interesting for cellular therapy. However, the pool of SCs in vivo and in vitro consists of a mix of cells at several stages of differentiation, making it difficult to obtain a homogeneous population of SCs for research. Therefore, it is important to isolate and characterize unambiguous molecular markers that can be applied to SCs. Here, we review classical and new candidate molecular markers that have been established to show a molecular profile for human embryonic stem cells (hESCs), mesenchymal stem cells (MSCs), and hematopoietic stem cells (HSCs). The commonly cited markers for embryonic ESCs are Nanog, Oct-4, Sox-2, Rex-1, Dnmt3b, Lin-28, Tdgf1, FoxD3, Tert, Utf-1, Gal, Cx43, Gdf3, Gtcm1, Terf1, Terf2, Lefty A, and Lefty B. MSCs are primarily identified by the expression of CD13, CD29, CD44, CD49e, CD54, CD71, CD73, CD90, CD105, CD106, CD166, and HLA-ABC and lack CD14, CD31, CD34, CD45, CD62E, CD62L, CD62P, and HLA-DR expression. HSCs are mainly isolated based on the expression of CD34, but the combination of this marker with CD133 and CD90, together with a lack of CD38 and other lineage markers, provides the most homogeneous pool of SCs. Here, we present new and alternative markers for SCs, along with microRNA profiles, for these cells.

Sensitization of glioma cells by X-linked inhibitor of apoptosis protein knockdown.

OBJECTIVE: Glioblastomas are a kind of cancer with high resistance to treatments, requiring more efficient alternatives of treatment. X-linked inhibitor of apoptosis (XIAP) is highly expressed in gliomas and, due to its inhibition of caspases, can participate in resistance to therapy. Here we test the sensitization of glioma cells with XIAP gene knockdown (KD) to drugs used in chemotherapy. METHODS: We silenced XIAP expression in U87MG glioblastoma using stable shRNA, and cells were treated with taxol, BCNU, temozolomide, cisplatin, etoposide, resveratrol (Rsv), vincristine and doxorubicin. We analyzed cell viability, cell cycle, apoptosis and senescence. RESULTS: XIAP KD cells were more sensitive to etoposide, Rsv, vincristine and doxorubicin compared to wild-type (WT) cells. Doxorubicin 1 µM and vincristine 100 nM induced higher activation of caspases after 24 h and doxorubicin induced a higher degree of senescence induction in XIAP KD cells in relation to WT cells. Phospho-p53 and phospho-H2Ax Western blot indicate subsequent DNA damage as an important effector of doxorubicin-induced death. CONCLUSIONS: This study suggests that XIAP inhibitors may sensitize gliomas to certain drugs and induce death and that the mechanisms of sensitization involve apoptosis, senescence and p53 signaling.

Interaction between normal and CML hematopoietic progenitors and stroma influences abnormal hematopoietic development.

Several studies have shown defective progenitor-stromal interactions in chronic myeloid leukemia (CML), and adhesive defects induced by BCR/ABL have been described. However, controversial results have been reported, and the role of the stroma in abnormal development of the hematopoietic system is not clear. In this study, CML hematopoietic and irradiated stromal cells were co-cultured in different combinations for 10 or 21 days. Maintenance of viable cells was dependent both on the sources of hematopoietic progenitors and stromal adherent layers, with normal cells performing better than their leukemic counterparts. The frequency of CD34(+) CD38(-) cells in the non-adherent fraction was more related to the source of hematopoietic cells than of stroma, and hematopoietic cells from normal subjects showed better performance. The simultaneous analysis of different combinations of normal and leukemic precursor cells and stromal layers, as done in the present work, suggests that the outcome of the interaction depends on characteristics of both compartments. This hematopoietic system development is influenced by intrinsic qualities of both hematopoietic stem cells and the supportive stroma.