Serum osteoprotegerin and its gene polymorphisms in patients with Takayasu's arteritis: a bicentric cross-sectional study.

INTRODUCTION: Takayasu's arteritis (TAK) patients are at an elevated risk of metabolic syndrome and cardiovascular diseases (CVD). Currently, there are no well-validated biomarkers to assess this risk in this population. Previous research in different cohorts has linked serum levels of osteoprotegerin (OPG) and its polymorphisms to accelerated atherosclerosis and a marker of poor prognosis in CVD. Thus, we assessed this protein as a potential biomarker of CVD in TAK patients. OBJECTIVES: To evaluate the serum levels of OPG and its SNPs (single nucleotide polymorphisms) in TAK patients and healthy controls, and to associate these parameters with clinical data. METHODS: This bicentric cross-sectional study included TAK patients who were compared with healthy individuals (control group). The serum levels of OPG and the frequency of OPG SNPs [1181G > C (rs2073618), 245 A > C (rs3134069), 163T > C (rs3102735), and 209 C > T (rs3134070)] were compared between the both groups and associated with clinical data. RESULTS: In total, 101 TAK patients and 93 controls were included in the study. The serum levels of OPG (3.8 ± 1.9 vs. 4.3 ± 1.8pmol/L, respectively; P = 0.059), and its four polymorphisms were comparable between both groups. In an additional analysis of only TAK patients, serum OPG levels and its four genes were not associated with any CVD parameters, except for higher OPG levels among patients without dyslipidemia. CONCLUSION: No significant differences were observed in serum OPG levels or in the genotype frequencies of OPG SNPs between the patient and control groups. Similarly, no correlation was found between laboratory parameters and clinical data on CVD risk in TAK patients.

Potencialidades e desafios da formação em programas de residência em saúde mental realizados integralmente em serviços abertos e de base comunitária

A residência multiprofissional em saúde é considerada uma modalidade de formação estratégica para a qualificação de profissionais no campo da saúde coletiva e um espaço privilegiado de formação para o trabalho no Sistema Único de Saúde. No campo da saúde mental, é tida como uma aposta para o fortalecimento das práticas na perspectiva da atenção psicossocial, sobretudo quando não utiliza o hospital psiquiátrico como cenário de formação. Neste artigo, é discutida a formação para o trabalho em saúde mental a partir da percepção de ex-residentes de dois programas de residência em saúde mental realizados integralmente em serviços abertos e de base comunitária das redes de atenção psicossocial de dois municípios da Região Metropolitana de Belo Horizonte/MG. Foram realizadas entrevistas em profundidade com oito ex-residentes de diferentes categorias profissionais, que concluíram a formação entre os anos de 2012 e 2016. À luz das produções do campo da atenção psicossocial, as informações que emergiram foram analisadas em três grandes temas: formação em e na rede; suporte teórico-metodológico para o percurso formativo; e efeitos nas subjetividades e trajetórias dos entrevistados. Constata-se que os espaços mais potentes da atenção psicossocial são também os espaços mais potentes para a formação em saúde mental.

Conocimiento y conducta de las enfermeras de familia sobre la violencia contra la mujer / Knowledge and Behavior of Family Nurses with Respect to Violence against Women

Introducción: Los estudios indican una precariedad en la formación de las enfermeras, lo que limita sus conocimientos y comportamientos en el manejo de la violencia contra la mujer. Objetivo: Describir el conocimiento de las políticas de salud y la conducta de las enfermeras de familia en el cuidado de las mujeres víctimas de violencia. Métodos: Estudio transversal con 128 enfermeras de Teresina (Brasil). Se aplicó un cuestionario con variables sociodemográficas, ocupacionales y relacionadas con el tema. Para verificar la asociación entre variables cualitativas, se utilizó la prueba ji al cuadrado de Person ((²) o la prueba de Fisher. Se consideró un nivel de significación de 0,05. Resultados: El 95 por ciento respondió de forma correcta entre cinco y nueve de las diez preguntas sobre el tema. Hubo una asociación significativa entre el tiempo de entrenamiento y de cinco a diez respuestas correctas. El 82,8 por ciento respondió que suele observar signos indicativos de violencia durante las consultas. El 83,6 por ciento conoce el formulario de notificación, pero un 28 por ciento dijo que le fue difícil llenarlo. Se evidenció que el 59,10 por ciento no realizan actividades de enfrentamiento a la violencia con el equipo de salud y la comunidad. Conclusiones: Las enfermeras de familia que actúan en el municipio, en su mayoría, no realizaron actividades de capacitación o sensibilización sobre el enfrentamiento a la violencia, respondieron de forma correcta entre cinco y nueve de las diez preguntas relacionadas con el tema. Sin embargo, cuestionaron la necesidad de reportar esta lesión, importante instrumento que incentiva la construcción de políticas públicas para enfrentarlo(AU)

Introduction: Studies show deprivation in the training of nurses, which limits their knowledge and behaviors for the management of violence against women. Objective: To describe the knowledge about health policies and the behavior of family nurses as part of the care of women victims of violence. Methods: A cross-sectional study was conducted with 128 nurses from Teresina, Brazil. A questionnaire was applied, including sociodemographic and occupational variables, as well as others related to the topic. To verify the association between qualitative variables, the Person's chi-squared test (χ2) or Fisher's test were used. A significance level of 0.05 was considered. Results: 95 percent answered correctly between five and nine of the ten questions on the subject. There was a significant association between training time and five to ten correct answers. 82.8 percent answered that, during consultations, they usually observe signs indicative of violence. 83.6 percent know the notification form, but 28 percent expressed that filling it out was difficult for them. It was evident that 59.10 percent do not carry out activities to confront violence together with the health team and the community. Conclusions: Most of the family nurses working in the municipality did not carry out training or awareness-raising activities on confronting violence; they answered correctly between five and nine of the ten questions related to the topic. However, they questioned the need for such damage notification as an important instrument encouraging the construction of public policies to confront the phenomenon(AU)

Screening of ABCG5 and ABCG8 Genes for Sitosterolemia in a Familial Hypercholesterolemia Cascade Screening Program.

BACKGROUND: Sitosterolemia is a rare autosomal recessive disorder caused by homozygous or compound heterozygous variants in ABCG5/ABCG8. The disease is characterized by increased plasma plant sterols. Small case series suggest that patients with sitosterolemia have wide phenotypic heterogeneity with great variability on either plasma cholesterol levels or development of atherosclerotic cardiovascular disease. The present study aims to characterize the prevalence and clinical features of sitosterolemia participating in a familial hypercholesterolemia genetic cascade screening program. METHODS: From 443 familial hypercholesterolemia index cases, 260 were negative for familial hypercholesterolemia genes and were sequenced for the ABCG5/8 genes. Clinical and laboratory characteristics of affected individuals were determined. RESULTS: Eight (3.1%) index cases were found to be homozygous or compound heterozygous variant for ABCG5/ABCG8 genes, confirming the genetic diagnosis of sitosterolemia. Screening their relatives led to the identification of 6 additional confirmed sitosterolemia cases (3 homozygous and 3 compound heterozygous variant) and 18 carriers (heterozygous). The mean age of identified sitosterolemia cases (n=14) was 37.2±19.8 years, 50% were females, and 78.6% (all adults) presented either clinical or subclinical atherosclerotic cardiovascular disease. As expected, affected individuals presented elevated plasma plant sterol levels (mean ß-Sitosterol and campesterol, respectively, 160.3±107.1 and 32.0±19.6 µg/mL) and the highest plasma LDL (low-density lipoprotein)-cholesterol was 269.0±120.0 mg/dL (range: 122-521 mg/dL). LDL-cholesterol mean reduction with therapy among cases was 65%. Eighty-three percent (83%) of identified sitosterolemia patients presented hematologic abnormalities. CONCLUSIONS: Testing genes associated with sitosterolemia in the molecular routine workflow of a familial hypercholesterolemia cascade screening program allowed the precise diagnosis of sitosterolemia in a substantial number of patients with varying LDL-C levels and high incidence of early atherosclerotic cardiovascular disease and hematologic abnormalities.

Electroacupuncture reduces weight, skinfold thickness and waist circumference and increases skin temperature of the abdominal region in women: a randomized controlled trial.

BACKGROUND: Acupuncture, as a complementary and alternative medical treatment, has shown some promise as a therapeutic option for obesity and weight control. The aim of the current study was to investigate the effects of electroacupuncture (EA) on body weight, body mass index (BMI), skin fold thickness, waist circumference and skin temperature of the abdominal region in non-obese women with excessive abdominal subcutaneous fat. METHODS: A total of 50 women with excessive abdominal subcutaneous fat (and average BMI of 22) were randomly assigned to one of two groups: an EA group (n = 25) receiving 10 EA sessions (insertion of needles connected to an electrical stimulator at a frequency of 40 Hz for 40 min) and a control group (n = 25) that received no treatment. Outcome measures evaluated included waist circumference, supra-iliac and abdominal skinfolds, body composition and superficial skin temperature (measured by cutaneous thermography) before and after treatment. RESULTS: Compared with the untreated group, women in the EA group exhibited decreased supra-iliac and abdominal skin folds (p < 0.001), waist circumference (p < 0.001), percentage body fat (p = 0.001) and percentage abdominal fat (p < 0.001). In addition, the EA group showed an elevated skin temperature at the site of the treatment. However, EA did not significantly impact body weight (p = 0.01) or BMI (p = 0.2). CONCLUSION: EA promoted a reduction in abdominal waist circumference, supra-iliac and abdominal skin folds, and percentage body and abdominal fat in women of normal BMI with excessive abdominal subcutaneous fat, as well as an increase in the superficial skin temperature of the abdominal region. TRIAL REGISTRATION NUMBER: RBR-9tsmpp (Brazilian Registry of Clinical Trials).

Rastreamento para Hipercolesterolemia Familiar em Pequenos Municípios: A Experiência do Programa HipercolBrasil em 11 Municípios Brasileiros / Screening for Familial Hypercholesterolemia in Small Towns: Experience from 11 Brazilian Towns in the Hipercolbrasil Program

Resumo Fundamento A hipercolesterolemia familiar (HF) é uma doença genética dominante que se caracteriza por níveis sanguíneos elevados de colesterol de lipoproteína de baixa densidade (LDL-C), e está associada à ocorrência de doença cardiovascular precoce. No Brasil, o HipercolBrasil, que é atualmente o maior programa de rastreamento em cascata para HF, já identificou mais de 2.000 indivíduos com variantes genéticas causadoras de HF. A abordagem padrão baseia-se no rastreamento em cascata de casos índices referidos, indivíduos com hipercolesterolemia e suspeita clínica de HF. Objetivos Realizar rastreamento direcionado de 11 pequenos municípios brasileiros com suspeita de alta prevalência de indivíduos com HF. Métodos A seleção dos municípios ocorreu de 3 maneiras: 1) municípios em que houve suspeita de efeito fundador (4 municípios); 2) municípios em uma região com altas taxas de infarto do miocárdio precoce, conforme descrito pelo banco de dados do Sistema Único de Saúde (2 municípios); e 3) municípios geograficamente próximos a outros municípios com alta prevalência de indivíduos com HF (5 municípios). A significância estatística foi considerada como valor p < 0,05. Resultados Foram incluídos 105 casos índices e 409 familiares de primeiro grau. O rendimento dessa abordagem foi de 4,67 familiares por caso índice, o qual é significativamente melhor (p < 0,0001) do que a taxa geral do HipercolBrasil (1,59). Identificamos 36 CIs com variante patogênica ou provavelmente patogênica para HF e 240 familiares de primeiro grau afetados. Conclusão: Nossos dados sugerem que, uma vez detectadas, regiões geográficas específicas justificam uma abordagem direcionada para a identificação de aglomerações de indivíduos com HF.

Abstract Background Familial hypercholesterolemia (FH) is a genetic disease characterized by elevated serum levels of low-density lipoprotein cholesterol (LDL-C), and it is associated with the occurrence of early cardiovascular disease. In Brazil, HipercolBrasil, which is currently the largest FH cascade screening program, has already identified more than 2000 individuals with causal genetic variants for FH. The standard approach is based on cascade screening of referred index cases, individuals with hypercholesterolemia and clinical suspicion of FH. Objectives To perform targeted screening of 11 small Brazilian cities with a suspected high prevalence of people with FH. Methods The selection of cities occurred in 3 ways: 1) cities in which a founder effect was suspected (4 cities); 2) cities in a region with high rates of early myocardial infarction as described by the National Health System database (2 cities); and 3) cities that are geographically close to other cities with a high prevalence of individuals with FH (5 cities). Statistical significance was considered as p value < 0.05. Results One hundred and five index cases and 409 first-degree relatives were enrolled. The yield of such approach of 4.67 relatives per index case was significantly better (p < 0.0001) than the general HipercolBrasil rate (1.59). We identified 36 IC with a pathogenic or likely pathogenic variant for FH and 240 affected first-degree relatives. Conclusion Our data suggest that, once detected, specific geographical regions warrant a target approach for identification of clusters of individuals with FH.

Screening for Familial Hypercholesterolemia in Small Towns: Experience from 11 Brazilian Towns in the Hipercolbrasil Program. / Rastreamento para Hipercolesterolemia Familiar em Pequenos Municípios: A Experiência do Programa HipercolBrasil em 11 Municípios Brasileiros.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disease characterized by elevated serum levels of low-density lipoprotein cholesterol (LDL-C), and it is associated with the occurrence of early cardiovascular disease. In Brazil, HipercolBrasil, which is currently the largest FH cascade screening program, has already identified more than 2000 individuals with causal genetic variants for FH. The standard approach is based on cascade screening of referred index cases, individuals with hypercholesterolemia and clinical suspicion of FH. OBJECTIVES: To perform targeted screening of 11 small Brazilian cities with a suspected high prevalence of people with FH. METHODS: The selection of cities occurred in 3 ways: 1) cities in which a founder effect was suspected (4 cities); 2) cities in a region with high rates of early myocardial infarction as described by the National Health System database (2 cities); and 3) cities that are geographically close to other cities with a high prevalence of individuals with FH (5 cities). Statistical significance was considered as p value < 0.05. RESULTS: One hundred and five index cases and 409 first-degree relatives were enrolled. The yield of such approach of 4.67 relatives per index case was significantly better (p < 0.0001) than the general HipercolBrasil rate (1.59). We identified 36 IC with a pathogenic or likely pathogenic variant for FH and 240 affected first-degree relatives. CONCLUSION: Our data suggest that, once detected, specific geographical regions warrant a target approach for identification of clusters of individuals with FH.

FUNDAMENTO: A hipercolesterolemia familiar (HF) é uma doença genética dominante que se caracteriza por níveis sanguíneos elevados de colesterol de lipoproteína de baixa densidade (LDL-C), e está associada à ocorrência de doença cardiovascular precoce. No Brasil, o HipercolBrasil, que é atualmente o maior programa de rastreamento em cascata para HF, já identificou mais de 2.000 indivíduos com variantes genéticas causadoras de HF. A abordagem padrão baseia-se no rastreamento em cascata de casos índices referidos, indivíduos com hipercolesterolemia e suspeita clínica de HF. OBJETIVOS: Realizar rastreamento direcionado de 11 pequenos municípios brasileiros com suspeita de alta prevalência de indivíduos com HF. MÉTODOS: A seleção dos municípios ocorreu de 3 maneiras: 1) municípios em que houve suspeita de efeito fundador (4 municípios); 2) municípios em uma região com altas taxas de infarto do miocárdio precoce, conforme descrito pelo banco de dados do Sistema Único de Saúde (2 municípios); e 3) municípios geograficamente próximos a outros municípios com alta prevalência de indivíduos com HF (5 municípios). A significância estatística foi considerada como valor p < 0,05. RESULTADOS: Foram incluídos 105 casos índices e 409 familiares de primeiro grau. O rendimento dessa abordagem foi de 4,67 familiares por caso índice, o qual é significativamente melhor (p < 0,0001) do que a taxa geral do HipercolBrasil (1,59). Identificamos 36 CIs com variante patogênica ou provavelmente patogênica para HF e 240 familiares de primeiro grau afetados. Conclusão: Nossos dados sugerem que, uma vez detectadas, regiões geográficas específicas justificam uma abordagem direcionada para a identificação de aglomerações de indivíduos com HF.

Polygenic risk score for hypercholesterolemia in a Brazilian familial hypercholesterolemia cohort.

Background and aims: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of LDL-C leading to premature cardiovascular disease (CAD). Only about 40% of individuals with a clinical diagnosis of FH have a causative genetic variant identified, and a proportion of genetically negative cases may have a polygenic cause rather than a still unidentified monogenic cause. This work aims to evaluate and validate the role of a polygenic risk score (PRS) associated with hypercholesterolemia in a Brazilian FH cohort and its clinical implications. Methods: We analyzed a previously derived PRS of 12 and 6 SNPs (Single Nucleotide Polymorphism) in 684 FH individuals (491 mutation-negative [FH/M-], 193 mutation-positive [FH/M+]) and in 1605 controls. Coronary artery calcium (CAC) score was also evaluated. Results: The PRS was independently associated with LDL-C in control individuals (p < 0.001). Within this group, in individuals in the highest quartile of the 12 SNPs PRS, the odds ratio for CAC score >100 was 1.7 (95% CI: 1.01-2.88, p = 0.04) after adjustment for age and sex. Subjects in the FH/M- group had the highest mean score in both 12 and 6 SNPs PRS (38.25 and 27.82, respectively) when compared to the other two groups (p = 2.2 × 10-16). Both scores were also higher in the FH/M+ group (36.48 and 26.26, respectively) when compared to the control group (p < 0.001 for the two scores) but inferior to the FH/M- group. Within FH individuals, the presence of a higher PRS score was not associated with LDL-C levels or with CAD risk. Conclusion: A higher PRS is associated with significantly higher levels of LDL-C and it is independently associated with higher CAC in the Brazilian general population. A polygenic cause can explain a fraction of FH/M- individuals but does not appear to be a modulator of the clinical phenotype among FH individuals, regardless of mutation status.

Genome-Wide Association of Proprotein Convertase Subtilisin/Kexin Type 9 Plasma Levels in the ELSA-Brasil Study.

Pharmacological inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is an established therapeutic option to treat hypercholesterolemia, and plasma PCSK9 levels have been implicated in cardiovascular disease incidence. A number of genetic variants within the PCSK9 gene locus have been shown to modulate PCSK9 levels, but these only explain a very small percentage of the overall PCSK9 interindividual variation. Here we present data on the genetic association structure between PCSK9 levels and genom-wide genetic variation in a healthy sample from the general population. We performed a genome-wide association study of plasma PCSK9 levels in a sample of Brazilian individuals enrolled in the Estudo Longitudinal de Saude do Adulto cohort (n=810). Enrolled individuals were free from cardiovascular disease, diabetes and were not under lipid-lowering medication. Genome-wide genotyping was conducted using the Axiom_PMRA.r3 array, and imputation was performed using the TOPMED multi-ancestry sample panel as reference. Total PCSK9 plasma concentrations were determined using the Quantikine SPC900 ELISA kit. We observed two genome-wide significant loci and seven loci that reached the pre-defined value of p threshold of 1×10-6. Significant variants were near KCNA5 and KCNA1, and LINC00353. Genetic variation at the PCSK9 locus was able to explain approximately 4% of the overall interindividual variations in PCSK9 levels. Colocalization analysis using eQTL data suggested RWDD3, ATXN7L1, KCNA1, and FAM177A1 to be potential mediators of some of the observed associations. Our results suggest that PCSK9 levels may be modulated by trans genetic variation outside of the PCSK9 gene and this may have clinical implications. Understanding both environmental and genetic predictors of PCSK9 levels may help identify new targets for cardiovascular disease treatment and contribute to a better assessment of the benefits of long-term PCSK9 inhibition.

Adherence to a Mediterranean diet, dyslipidemia and inflammation in familial hypercholesterolemia.

BACKGROUND AND AIMS: Familial Hypercholesterolemia (FH) is characterized by elevated LDL-cholesterol (LDL-C) and high atherosclerosis risk. The impact of different dietary patterns on atherosclerosis biomarkers has been poorly studied in FH. This study verified the association of adherence to a Mediterranean diet with biomarkers of dyslipidemia and low-grade inflammation in molecularly proven FH adults from Brazil (BR) and Spain (SP). METHODS AND RESULTS: In this cross-sectional study adherence to the Mediterranean diet was assessed by a validated score and generalized estimating equations were used to evaluate its association with plasma LDL-C, apolipoprotein-B (ApoB) and high sensitivity C-reactive protein (hs-CRP) concentrations. We included 92 (mean age 45 years, 58.7% females) and 98 FH individuals (mean age 46.8 years, 60.2% females) respectively from BR and SP. FH causing variants did not differ between countries. LDL-C, ApoB and hs-CRP concentrations were higher in BR than in SP: 179 (135-250) and 161 (133-193) mg/dL; 141 (109-181) and 103 (88-134) mg/dL; and 1.6 (0.8-4.0) and 0.8 (0.4-1.5) mg/L respectively (all p < 0.001). Most of BR had low adherence (n = 77, 83.7%), while the majority of SP were divided into moderate (n = 35, 35.7%) and strong adherence to the Mediterranean diet (n = 37, 37.8%), p < 0.001. There was a significant inverse association of adherence to the Mediterranean diet score with higher LDL-C, ApoB, and hs-CRP after adjusting for socio economic parameters, caloric and fatty acid intakes as well as pharmacological lipid lowering therapies. CONCLUSIONS: Higher adherence to a Mediterranean diet was associated with better dyslipidemia and low-grade inflammation profiles in FH.

Familial hypercholesterolemia and cardiovascular disease in older individuals.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is characterized by high LDL-cholesterol (LDL-C) and early atherosclerotic cardiovascular disease (ASCVD). With a lipid lowering therapy (LLT), most individuals with FH may have a longer ASCVD-free survival. However, there is scant data about older individuals with FH. METHODS: We compared characteristics of genetically defined FH older individuals with age-matched non-FH counterparts. RESULTS: From 4111 genotyped individuals, 462 older than 60 years were included (198 positive and 264 negative for FH variants). There were no differences regarding median age [%25; 75%] 66.0 (62.0; 71.0) and 66.0 (62.2; 71.0) years, p = 0.68 for FH and non-FH, respectively. In both groups, there was a higher frequency of females, however, there were more males in the FH group 37.4% vs. 24.2%, p = 0.002. No differences were seen between FH and non-FH in LLT use: 88.5% vs. 91.5%, p = 0.29. Despite a longer LLT duration in FH patients (with 11.0 (7.0; 20.0) vs. 7.0 (3.0; 13.0) years, p < 0.001), treatment was started late in both groups: at 54.0 (47.0; 61.0) and 59.0 (52.0; 64.0) years, p < 0.001, in FH and non-FH, respectively. FH had greater frequencies of previous and early ASCVD (40.9% vs. 27.3%, p = 0.002, and 22.2% vs. 9.0%, p < 0.001). In FH, male sex [HR (95%CI)] 2.67 (1.50-4.73), p = 0.001, and LLT onset age 0.96 (0.93-0.99), p = 0.009, were independently associated with ASCVD. CONCLUSIONS: Among hypercholesterolemic older individuals participating in a cascade screening program, the genetic diagnosis of FH was associated with higher ASCVD rates, emphasizing the relevance of a monogenic defect as the cause of long-lasting hypercholesterolemia and ASCVD risk, particularly in men.

Cascade screening and genetic diagnosis of familial hypercholesterolemia in clusters of the Southeastern region from Brazil.

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by high levels of low-density lipoprotein-cholesterol (LDLc), associated to premature cardiovascular disease. The detection of the variants related to FH is important to improve the early diagnosis in probands / index-cases (ICs) and their relatives. We included ICs with FH and their relatives, living in a small region of Minas Gerais state-Brazil, which were classified according to Dutch Lipid Clinic Network Criteria (DLCNC) and submitted to sequencing of genes related to FH (LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, APOE, ABCG5 e ABCG8). In a total of 143 subjects (32 ICs and 111 relatives), eight variants were identified in 91 individuals. From these variants, five were in LDLR [p.(Asp224Asn), p.(Ser854Gly), p.(Cys34Arg), p.(Asp601His), deletion of exon15 in LDLR)], one in APOB [p.(Met499Val)], one in PCSK9 [p.(Arg237Trp)] and one in APOE [p.(Pro28Leu)] genes. The variants were detected in 100% of those subjects classified as definitive, 87% as probable and 69% as possible FH cases based on DLCNC. The LDLc level was higher in individuals with corneal arch and xanthomas or xanthelasmas, as well as in pathogenic or probably pathogenic variants carriers. This study showed higher frequency of LDLR gene variants compared to other genes related to LDL metabolism in individuals with FH in Minas Gerais - Brazil and the presence of FH in relatives without previous diagnosis. Our data reinforce the importance of molecular and clinical evaluation of FH relatives in order to early diagnosis the FH, as well as cardiovascular diseases prevention.

Melanopsin mediates UVA-dependent modulation of proliferation, pigmentation, apoptosis, and molecular clock in normal and malignant melanocytes.

Cutaneous melanocytes and melanoma cells express several opsins, of which melanopsin (OPN4) detects temperature and UVA radiation. To evaluate the interaction between OPN4 and UVA radiation, normal and malignant Opn4WT and Opn4KO melanocytes were exposed to three daily low doses (total 13.2 kJ/m2) of UVA radiation. UVA radiation led to a reduction of proliferation in both Opn4WT cell lines; however, only in melanoma cells this effect was associated with increased cell death by apoptosis. Daily UVA stimuli induced persistent pigment darkening (PPD) in both Opn4WT cell lines. Upon Opn4 knockout, all UVA-induced effects were lost in three independent clones of Opn4KO melanocytes and melanoma cells. Per1 bioluminescence was reduced after 1st and 2nd UVA radiations in Opn4WT cells. In Opn4KO melanocytes and melanoma cells, an acute increase of Per1 expression was seen immediately after each stimulus. We also found that OPN4 expression is downregulated in human melanoma compared to normal skin, and it decreases with disease progression. Interestingly, metastatic melanomas with low expression of OPN4 present increased expression of BMAL1 and longer overall survival. Collectively, our findings reinforce the functionality of the photosensitive system of melanocytes that may subsidize advancements in the understanding of skin related diseases, including cancer.

Association of dietary components with dyslipidemia and low-grade inflammation biomarkers in adults with heterozygous familial hypercholesterolemia from different countries.

The association of components of a low saturated fat (SFA) and of a Mediterranean diet was tested with atherosclerosis biomarkers in 190 familial hypercholesterolemia adults (FH) from Brazil (BR) and Spain (SP). Median blood LDL-C, Apolipoprotein B (apoB), and C reactive protein (hs-CRP) concentrations were higher in BR than in SP: 179.0 vs.161 mg/dL; 141 vs. 103 mg/dL; and 1.6 vs. 0.8 mg/L respectively (all p < 0.001). In BR there was lower median total fat (22.3 vs. 38.3%) and SFA (8.1 vs. 12.5%) but higher cholesterol (283.3 mg vs.188.9 mg) and carbohydrate (57.1 vs. 42.5%) consumption (all p < 0.001). Inverse associations were encountered between fibers, mono, and polyunsaturated fats and their ratios to SFA with LDL-C and ApoB (all p < 0.001). There was a direct association respectively of cholesterol with lipid biomarkers and of carbohydrates and trans-fatty acids with hs-CRP while other fats showed inverse relations with the latter (p < 0.001).

Residências integradas em saúde mental: para além do tecnicismo / Integrated residencies in mental health: beyond technicism / Residencias integradas en salud mental: yendo más allá del tecnicismo

Resumo Este estudo objetivou analisar, à luz das discussões sobre educação interprofissional e práticas colaborativas no contexto da reforma psiquiátrica, o projeto político-pedagógico de um programa de residências integradas em saúde mental em curso em Belo Horizonte, Minas Gerais. Mediante abordagem qualitativa, foi realizada análise de conteúdo temática do projeto político-pedagógico do programa, que resultou em três temas amplos: perspectiva teórico-pedagógica; diversificação das estratégias de cuidado; trabalho multiprofissional na lógica interdisciplinar. As informações que emergiram foram complementadas e aprofundadas com a realização de entrevistas semiestruturadas com atores envolvidos na preceptoria e na coordenação do programa. Entre os achados, destacamos a potencialidade do programa para o fortalecimento do processo de desinstitucionalização e de qualificação da política pública de saúde mental, ao possibilitar uma aprendizagem conjunta entre residentes de diferentes áreas e trabalhadores dos serviços envolvidos. Por meio do desenvolvimento de competências necessárias para a realização de um trabalho coletivo e comprometido com a integralidade da assistência em saúde, o programa reforça a necessidade da interprofissionalidade e das práticas colaborativas, indo além do tecnicismo. A aposta na rede de atenção psicossocial como local privilegiado para processos de ensino-aprendizagem, sem a utilização do hospital psiquiátrico, questiona práticas de formação estagnadas e possibilita a ampliação das formas de cuidado.

Abstract The present study had the goal of analyzing, based on the discussions about interprofessional education and collaborative practices in the context of the psychiatric reform, the political-pedagogical project of an integrated residency in mental health program taking place in the city of Belo Horizonte, in the state of Minas Gerais, Brazil. Through a qualitative approach, we performed the analysis of the thematic content of the political-pedagogical project of the program, which resulted in three broad themes: theoretical-pedagogical perspective; diversification of the care strategies; multiprofessional work in the interdisciplinary logic. The information found was complemented and delved into with the performance of semistructured interviews with the actors involved in the tutorship and coordination of the program. Among the findings, we highlight the potential of the program to strengthen the process of deinstitutionalization and of qualification of the mental health public policy, by enabling a joint learning among residents of different areas and workers at the services involved. Through the creation of the necessary competences for the development of a work that is collective and committed to the comprehensiveness of the care in health, the program emphasizes the need for interprofessionality and collaborative practices, going beyond technicism. The choice of the psychosocial care network as a privilege space for teaching-learning processes, without using the psychiatric hospital, questions the stagnant training practices and enables the expansion of forms of care.

Resumen A través de este estudio el objetivo fue analizar, a la luz de las discusiones sobre educación interprofesional y prácticas colaborativas en el contexto de la reforma psiquiátrica, el proyecto político-pedagógico de un programa de residencias integradas en salud mental en curso en la ciudad de Belo Horizonte, estado de Minas Gerais, Brasil. Mediante el abordaje cualitativo se efectuó el análisis de contenido temático del proyecto político-pedagógico del programa, dando lugar a tres temas principales: perspectiva teórico-pedagógica; diversificación de las estrategias de cuidado; trabajo multiprofesional desde la lógica interdisciplinaria. Se ahondó en la información obtenida y se complementó a través de la realización de entrevistas semiestructuradas con actores involucrados en la tutoría y coordinación del programa. Entre los resultados encontrados se destaca el potencial del programa para el fortalecimiento del proceso de desinstitucionalización y cualificación de la política pública de salud mental, al posibilitar un aprendizaje conjunto entre residentes de diferentes áreas y trabajadores de los servicios involucrados. Por medio del desarrollo de competencias necesarias para la realización de un trabajo colectivo y comprometido con la integralidad de la asistencia en salud, el programa refuerza la necesidad de la interprofesionalidad y de las prácticas colaborativas, yendo más allá del tecnicismo. La apuesta en la red de atención psicosocial como espacio privilegiado para procesos de enseñanza-aprendizaje, sin el uso del hospital psiquiátrico, cuestiona prácticas de formación estancadas y posibilita la ampliación de las formas de cuidado.

O Grupo de Suporte como espaço promotor de holding para mulheres com câncer de mama / The Suport Group as a holding promoter for women with breast cancer / Le Groupe de Soutien comme espace promoteur de holding pour des femmes ayant un cancer du sein / El Grupo de Apoyo como un espacio de promoción de sostén (holding) entre mujeres con cáncer de mama

Fundamentado na psicanálise e no conceito de suporte social, este trabalho busca explorar as repercussões psíquicas do adoecimento de mulheres com câncer de mama e o potencial de reintegração do Grupo de Suporte. Os resultados apontam para o fortalecimento das defesas psicossomáticas, através dos vínculos estabelecidos no Grupo, considerado um espaço promotor de holding, por propiciar suporte social, compartilhamento de sentimentos e melhor integração entre psíquico e somático, possibilitando a reinserção social e o enfrentamento da doença.

Anchored on psychoanalysis and on the concept of social support, this paper aims to explore the psychic repercussions of the illness of women with breast cancer and the reintegration potential by the Support Group. The results point to the strengthening of the women's psychosomatic defenses, by means of the ties created in the Group, regarded as a space that promotes holding, by providing social support, sharing of feelings and better psychological and somatic integration, making social reintegration and the confrontation of the disease possible.

Sur la base de la psychanalyse et du concept de soutien social, ce travail vise à explorer les répercussions psychologiques de la maladie des femmes atteintes du cancer du sein et de la réinsertion potentielle du Groupe de Soutien. Les résultats indiquent un renforcement des défenses psychosomatiques à travers des liens établis au sein du groupe, considéré comme un espace promoteur de maintien, pour apporter un soutien social, partage de sentiments et une meilleure intégration entre le psychique et le somatique, rendant ainsi possible la réinsertion sociale et la lutte contre la maladie.

Basado en el psicoanálisis y en el concepto de apoyo social, este trabajo pretende explorar las repercusiones psíquicas, entre las mujeres, repercusiones provenientes del diagnóstico de cáncer de mama, y el potencial de reintegración del Grupo de Apoyo. Los resultados apuntan al fortalecimiento de las defensas psicosomáticas de las mujeres, a través de los vínculos establecidos dentro del Grupo, que es considerado un espacio que promueve el sostén (holding) al proporcionar apoyo social, permitir compartir sentimientos y promover una mejor integración entre lo psíquico y lo somático, haciendo posible la reintegración social y el manejo de la enfermedad.

Basierend auf die Psychoanalyse und auf das Konzept der sozialen Unterstützung, zielt diese Arbeit darauf ab, die psychischen Auswirkungen der Erkrankung bei Frauen mit Brustkrebs und das Wiedereingliederungspotential einer Unterstützungsgruppe zu erforschen. Die Ergebnisse deuten darauf hin, dass die psychosomatische Widerstandskraft der Frauen durch die in der Gruppe geknüpften Verhältnisse gestärkt wurde. Die Gruppe wird als Raum beschrieben, der das Holding fördert, da sie soziale Unterstützung leistet, es erlaubt Gefühle zu teilen, die Integration psychologischer und somatischer Aspekte fördert, die soziale Wiedereingliederung ermöglicht und den Patientinnen hilft, die Krankheit zu konfrontieren.

Isolation of infectious Zika virus from a urine sample cultured in SIRC cells from a patient suspected of having rubella virus.

A great variety of viruses which cause exanthema share other clinical manifestations, making the etiologic identification a very difficult task, relying exclusively on the clinical examination. Rubella virus (RV) infection during the early stages of pregnancy can lead to serious birth defects, known as congenital rubella syndrome (CRS). In the present report, we described the presence of Zika virus (ZIKV) particles in urine samples and also ZIKV isolation in SIRC cells from the urine of a patient in acute phase of suspected rubella disease. The 50-year-old unvaccinated woman living in Sao Paulo, Brazil, was admitted to the emergency room with fever, headache, rash, arthralgia and prostration. Urine samples were collected for virus isolation and RT-qPCR. SIRC and Vero cells were inoculated with urine samples during 7 days. RT-qPCR was performed using measles virus (MV) and RV primers and both were found to be negative. After this result, RT-qPCR was performed for parvovirus B19, herpes virus 6 and ZIKV. The urine sample and the isolate were positive by Real Time PCR for ZIKV and negative for all other viruses tested. The sequences isolated are from the Asiatic lineage.

[The mental health promotion of children and teenagers in vulnerability and social violence: the challenges for an intersectoral network]. / La promotion de la santé mentale des enfants et adolescents en situation de vulnérabilité et violence sociale : les défis pour un réseau intersectoriel.

This paper presents and discusses the results of an intervention research conducted in Ouro Preto, Brazil from August 2014 to March 2016. The main objective was to contribute to the development of an intersectoral and interdisciplinary network to face psychosocial vulnerabilities of children and teenagers, especially related to sexual violence and drug use. To achieve this, we identified the difficulties faced by the Sistema de Garantia de Direitos Humanos da Criança e do Adolescente (SGDHCA) implemented by the municipality which take care of this population. We also identified protective and promotion factors accomplished to empower them. The methodology used combines Deleuze and Guattari Cartography, Institutional Analysis and the Cross Training. This latter methodology was developed by a group of researchers of Douglas Institute, in Montreal, which we met through scientific co-operation with our laboratory. On account of the practical-theoric and co-participative activities with the professional network of Ouro Preto, we produced a detailed diagnosis of the SGDHCA and a document proposing short, medium and long-term strategies. As final result, we intend to help the local collective-the Forum Intersetorial da Infância e Juventude-to develop a work plan from the proposed actions. In this paper we will concentrate the potential of the methodology used by presenting outcome from two important moments of the research: the discussions of successful and unsuccessful cases that elucidate the network operation and the potential and difficulties arising from the Rotation Positional, important technical of the Cross Training.

Guidelines for the treatment of antiphospholipid syndrome.

The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombosis, gestational morbidity and presence of elevated and persistently positive serum titers of antiphospholipid antibodies. The treatment of APS is still controversial, because any therapeutic decision potentially faces the risk of an insufficient or excessive antithrombotic coverage associated with anticoagulation and its major adverse effects. This guideline was elaborated from nine relevant clinical questions related to the treatment of APS by the Committee of Vasculopathies of the Brazilian Society of Rheumatology. Thus, this study aimed at establishing a guideline that included the most relevant and controversial questions in APS treatment, based on the best scientific evidence available. The questions were structured by use of the PICO (patient, intervention or indicator, comparison and outcome) process, enabling the generation of search strategies for evidence in the major primary scientific databases (MEDLINE/PubMed, Embase, Lilacs, Scielo, Cochrane Library, Premedline via OVID). A manual search for evidence and theses was also conducted (BDTD and IBICT). The evidence retrieved was selected based on critical assessment by using discriminatory instruments (scores) according to the category of the therapeutic question (JADAD scale for randomized clinical trials and Newcastle-Ottawa scale for non-randomized studies). After defining the potential studies to support the recommendations, they were selected according to level of evidence and grade of recommendation, according to the Oxford classification.