Germline Mutations Landscape in a Cohort of the State of Minas Gerais, Brazil, in Patients Who Underwent Genetic Counseling for Gynecological and Breast Cancer / Cenário de mutações germinativas em uma coorte do estado de Minas Gerais, Brasil, em pacientes submetidas ao aconselhamento genético para câncer ginecológico e de mama

Abstract Objective The present study evaluated the profile of germline mutations present in patients who underwent genetic counseling for risk assessment for breast cancer (BC), ovarian cancer (OC), and endometrial cancer (EC) with a possible hereditary pattern. Methods Medical records of 382 patients who underwent genetic counseling after signing an informed consent form were analyzed. A total of 55.76% of patients (213/382) were symptomatic (personal history of cancer), and 44.24% (169/382) were asymptomatic (absence of the disease). The variables analyzed were age, sex, place of birth, personal or family history of BC, OC, EC, as well as other types of cancer associated with hereditary syndromes. The Human Genome Variation Society (HGVS) nomenclature guidelines were used to name the variants, and their biological significance was determined by comparing 11 databases. Results We identified 53 distinct mutations: 29 pathogenic variants, 13 variants of undetermined significance (VUS), and 11 benign. The most frequent mutations were BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T, and BRCA2 c.2T> G. Furthermore, 21 variants appear to have been described for the first time in Brazil. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. Conclusion This study allowed a deeper understanding of the main mutations identified in families in the state of Minas Gerais and demonstrates the need to assess the family history of non-gynecological cancer for risk assessment of BC, OC, and EC. Moreover, it is an effort that contributes to population studies to evaluate the cancer risk mutation profile in Brazil.

Resumo Objetivo O presente estudo avaliou o perfil de mutações germinativas presentes em pacientes submetidas a aconselhamento genético para avaliação de risco para câncer de mama (CM), câncer de ovário (OC) e câncer de endométrio (CE) com possível padrão hereditário. Métodos Foram analisados os prontuários de 382 pacientes que realizaram aconselhamento genético após consentimento informado. Um total de 55,76% dos pacientes (213/382) eram sintomáticos (história pessoal de câncer), e 44,24% (169/382) eram assintomáticos (ausência da doença). As variáveis analisadas foram idade, sexo, naturalidade, história pessoal ou familiar de CM, OC, CE bem como outros tipos de câncer associados a síndromes hereditárias. As diretrizes de nomenclatura da Human Genome Variation Society (HGVS) foram usadas para nomear as variantes e seu significado biológico foi determinado pela comparação de 11 bancos de dados. Resultados Identificamos 53 mutações distintas: 29 variantes patogênicas, 13 variantes de significado indeterminado e 11 benignas. As mutações mais frequentes foram BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T e BRCA2 c.2T > G. Além disso, 21 variantes parecem ter sido descritas pela primeira vez no Brasil. Além das mutações BRCA1/2, foram encontradas variantes em outros genes relacionados a síndromes hereditárias que predispõem a cânceres ginecológicos. Conclusão Este estudo permitiu conhecer melhor as principais mutações identificadas nas famílias do estado de Minas Gerais e demonstra a necessidade de avaliar a história familiar de câncer não ginecológico para avaliação do risco de CM, OC e CE. Além disso, é um esforço que contribui com estudos populacionais para avaliar o perfil de mutações de risco para câncer no Brasil.

Association of human papillomavirus (HPV), p16, p53 and p63 expression with non-bilharzia-associated squamous cell carcinoma of the bladder and algorithm construction for histopathological grading prediction

ABSTRACT Objective To investigate the expression of human papillomavirus (HPV), p16, p53, and p63 in non-schistosomiasis-related squamous cell carcinoma of the bladder and to develop an accurate and automated tool to predict histological classification based on clinicopathological features. Methods Twenty-eight patients with primary bladder pure squamous cell carcinoma who underwent cystectomy or transurethral resection of bladder tumor (TURBT) for bladder cancer between January 2011 and July 2017 were evaluated. Clinical data and follow-up information were obtained from medical records. Formalin-fixed, paraffin-embedded surgical specimens were used for immunohistochemical staining for p16, p53, and p63. Human papillomavirus detection was evaluated by PCR. Statistical analysis was performed, and statistical significance was set at p<0.05. Finally, decision trees were built to classify patients' prognostic features. Leave-one-out cross-validation was used to test the generalizability of the model. Results Neither direct HPV detection nor its indirect marker (p16 protein) was identified in most cases. The absence of p16 was correlated with less aggressive histological grading (p=0.040). The positive p16 staining detection found only in pT1 and pT2 cases in our sample suggests a possible role for this tumor suppressor protein in the initial stages of bladder squamous cell carcinoma. The decision trees constructed described the relationship between clinical features, such as hematuria/dysuria, the level of tumor invasion, HPV status, lymphovascular invasion, gender, age, compromised lymph nodes, and tumor degree differentiation, with high classification accuracy. Conclusion The algorithm classifier approach established decision pathways for semi-automatic tumor histological classification, laying the foundation for tailored semi-automated decision support systems for pathologists.

Sexual, reproductive health and health status of female sex workers in 12 Brazilian cities, 2016 / Saúde sexual, reprodutiva e estado de saúde de mulheres trabalhadoras do sexo em 12 cidades brasileiras, 2016

ABSTRACT: Objective: To investigate differences in sexual, reproductive health and health status indicators of female sex workers in 12 Brazilian cities. Methods: Cross-sectional study of biological and behavioral surveillance survey with a minimum sample of 350 female sex workers per city, recruited by respondent driven sampling, in 2016. Complex sample design was considered in the data analysis. Indicators and 95% confidence intervals related to sexual and reproductive health, and health status were described separately by city and for the total sample. Results: The total sample consisted of 4,328 female sex workers. The coverage of Pap smear exam, human immunodeficiency virus and syphilis tests and antenatal care indicators varied by 20 percentages points or more. Pap smear exam coverage ranged from 53.4% in Recife to 73.0% in Porto Alegre. The highest percentage of female sex workers who had never been tested for human immunodeficiency virus and syphilis was in Fortaleza (36.8 and 63.8%, respectively). Antenatal coverage ranged from 61.1% in Salvador to 99.0% in Curitiba. In five cities, the proportion of female sex workers who disclosed their sex work status in health services was over 20.0%. Conclusion: The differences between the indicators in the 12 cities followed the Brazilian population profile, with more vulnerable sex workers in the North and Northeast regions. The results show that it is essential to consider the barriers to accessing health, such as stigma and discrimination, which restrict the addressing of female sex workers specific needs.

RESUMO: Objetivo: Investigar diferenças nos indicadores de saúde sexual, reprodutiva e de estado de saúde de mulheres trabalhadoras do sexo em 12 cidades brasileiras. Métodos: Estudo de corte transversal comportamental e biológico, com amostra mínima de 350 mulheres trabalhadoras do sexo por cidade, recrutadas por Respondent-Driven Samplig, em 2016. Na análise de dados, foi considerado o desenho complexo de amostragem. Foram apresentados indicadores e respectivos intervalos de 95% de confiança relacionados à saúde sexual, reprodutiva e ao estado de saúde separadamente por cidade e para a amostra total. Resultados: A amostra total foi de 4.328 mulheres trabalhadoras do sexo. A cobertura de exame de Papanicolau e teste para vírus da imunodeficiência humana e sífilis, e os indicadores de pré-natal apresentaram variação igual ou superior a 20 pontos percentuais. A cobertura de exame de Papanicolau variou de 53,4%, em Recife, a 73%, em Porto Alegre. O maior percentual de mulheres trabalhadoras do sexo que nunca realizaram o teste para vírus da imunodeficiência humana e sífilis foi registrado em Fortaleza (36,8 e 63,8%, respectivamente). A cobertura de pré-natal variou de 61,1%, em Salvador, a 99%, em Curitiba. Em cinco cidades, o percentual de participantes que afirmou já ter sentido discriminação no serviço de saúde por ser trabalhadora do sexo foi superior a 20%. Conclusões: As diferenças entre os indicadores nas 12 cidades acompanharam o perfil da população brasileira, com mulheres trabalhadoras do sexo mais vulneráveis nas regiões Norte e Nordeste. Os resultados mostram que é fundamental considerar as barreiras de acesso à saúde, como o estigma e a discriminação, que impedem a contemplação das necessidades específicas dessas mulheres.

Apoptosis-related gene expression can predict the response of ovarian cancer cell lines to treatment with recombinant human TRAIL alone or combined with cisplatin

OBJECTIVES: The objectives of this study were to determine the sensitivity of ovarian cancer (OC) cell lines (TOV-21G and SKOV-3) to cisplatin and to the recombinant human TRAIL (rhTRAIL), and to evaluate the expression profile of TNFRSF10B, TNFRSF10C, TP53TG5, MDM2, BAX, BCL-2 and CASPASE-8 genes and their participation in the resistance/susceptibility mechanism of these tumor cell lines. METHODS: To determine the IC50 values associated with Cisplatin and rhTRAIL, inhibition of cell growth was observed using MTT assays in two human OC cell lines (SKOV-3 and TOV-21G). The analysis of gene expression was performed using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Both cell lines had different susceptibility profiles to the tested drugs. In the SKOV-3 cell line, the IC50 values for cisplatin and for rhTRAIL were 270.83 ug/mL and 196.5 ng/mL, respectively. The same concentrations were used for TOV-21G. Different gene expression profiles were observed in each tested cell line. CASPASE-8 and TNFRSF10B expression levels could predict the response of both the cell lines to rhTRAIL alone or the response to a combination of rhTRAIL and cisplatin. In addition, we observed a relationship between BCL-2 and BAX expression that may be helpful in estimating the proliferation rate of the OC cell lines. CONCLUSION: SKOV-3 and TOV-21G respond differently to cisplatin and rhTRAIL exposure, and expression of CASPASE-8 and TNFRSF10B are good predictors of responses to these treatments.

Orientações em alimentação e nutrição para adultos e idosos com COVID-19 em isolamento domiciliar e após alta hospitalar / Série Nutricionistas em Ação com a Ciência / Guidelines on food and nutrition for adults and the elderly with COVID-19 in home isolation and after hospital discharge / Nutritionists In Action Series with Science

Orientações em alimentação e nutrição para adultos e idosos com COVID-19 em isolamento domiciliar e após alta hospitalar, com suspeita ou diagnóstico do novo Coronavírus, também às pessoas que apresentam sintomas leves ou moderados e que não precisam ficar internadas em hospitais, direcionada também para os cuidadores e pessoas que convivem no mesmo ambiente e demais interessados no tema. Em uma linguagem acessível e usando ótimas ilustrações e tabelas, esclarece sobre os cuidados nutricionais e também sobre alguns alimentos e nutrientes importantes para a imunidade. Instrui como fazer em situações de falta de apetite, perda de paladar (Disgeusia), dificuldade para engolir (Disfagia), perda de olfato (Anosmia) e diarréia. Orienta sobre as compras dos alimentos, sobre os riscos de contaminação, tempo de validade e armazenagem na geladeira e freezer, bem como os cuidados no preparo dos mesmos. Apresenta instruções sobre a higienização das mãos com água e sabonete e como fazer a fricção anti-séptica das mãos com preparação alcoólicas, sobre o manuseio adequado na retirada do lixo e instruções para diluição da solução clorada para superfícies e para embalagens e alimentos. Por fim, apresenta sete passos para manter a alimentação saudável para adultos e idosos

Guidelines on food and nutrition for adults and the elderly with COVID-19 in home isolation and after hospital discharge, with suspicion or diagnosis of the new coronavirus, also those with mild or moderate symptoms and who do not need to be hospitalized, also directed to the caregivers and people who live in the same environment and others interested in the topic. In an accessible language and using great illustrations and tables, it clarifies about nutritional care and also about some foods and nutrients important for immunity. Instructs you how to do it in situations of poor appetite, loss of taste (dysgeusia), difficulty swallowing (dysphagia), loss of smell (anosmia) and diarrhea. It advises on food purchases, on the risks of contamination, expiration time and storage in the refrigerator and freezer, as well as care in preparing them. It presents instructions on hand hygiene with soap and water and how to rub hands with alcoholic preparations, on proper handling of waste removal and instructions for diluting the chlorinated solution to surfaces and to packaging and food. Finally, it presents seven steps to maintain healthy eating for adults and the elderly

Orientações em alimentação e nutrição para crianças e adolescentes com COVID-19 em isolamento domiciliar e após alta hospitalar / Série Nutricionistas em Ação com a Ciência / Guidelines on food and nutrition for children and adolescents with COVID-19 in home isolation and after hospital discharge / Nutritionists in Action with Science Series

Orientações em alimentação e nutrição para crianças e adolescentes com COVID-19 em isolamento domiciliar e após alta hospitalar, considerando que os cuidados com crianças e adolescentes em casa envolvem convivência harmoniosa na família, o distanciamento entre as pessoas, os cuidados com a casa, com a alimentação, cuidados estes que implicam em zelar para que a doença não comprometa o crescimento e desenvolvimento adequados deste grupo específico. Neste sentido, as orientações presentes no texto prestam sua contribuição com a saúde de crianças e adolescentes diagnosticados ou com suspeita de COVID-19

Guidelines on food and nutrition for children and adolescents with COVID-19 in home isolation and after hospital discharge, considering that care for children and adolescents at home involves harmonious coexistence in the family, the distance between people, care with the home, with food, care that implies ensuring that the disease does not compromise the proper growth and development of this specific group. In this sense, the guidelines present in the text contribute to the health of children and adolescents diagnosed or suspected of having COVID-19

Monitoring HIV infection in Minas Gerais state: 15-year assessment of adults living with HIV initiating Antiretroviral Therapy

Abstract INTRODUCTION The first Brazilian HIV treatment recommendation was put forward in 1996, resulting in 12 subsequent guidelines. Several changes were made regarding "when" and "how" to begin treatment. The latest guideline recommends immediate initiation of antiretroviral therapy (ART). This study aimed to describe the evolution of HIV treatment among people living with HIV (PLHIV) who initiated ART between 2004 and 2018 based on the national guideline recommendations concerning T-CD4+ and VL measurements. METHODS A cross-sectional analysis of data of PLHIV aged >18 years, in Minas Gerais who received ART between 2004 and 2018 was conducted. Clinical, therapeutic, and demographic information were obtained from national healthcare databases. The study was divided into four periods: 2004-2007, 2008-2012, 2013-2016, and 2017-2018. Descriptive analyses were performed. RESULTS A total of 60,618 PLHIV initiated ART (67% male and 48% aged 25-39 years), 36% of whom had CD4 counts at ART initiation and 51% documented VL after ART initiation. The median CD4 count ranged from 288 to 373 cells/µL. The median time to ART initiation decreased from 604 to 28 days and was lower among males (p <0.01). The median time from ART initiation to the first VL result decreased from 101 to 62 days over the study period, while the median VL after ART initiation ranged from 2.3 to 1.7 log10 copies/ml. CONCLUSIONS Although our results demonstrated that most recommendations were followed, there seemed to be little impact on CD4 counts and VL testing. This may result in an inadequate evaluation of ART effectiveness.

Caracterização de mulheres trabalhadoras do sexo em capitais brasileiras, 2016 / Caracterización de las mujeres trabajadoras sexuales en las capitales brasileñas, 2016 / Characterization of female sex workers in Brazilian state capitals, 2016

Objetivo: Descrever as características das mulheres trabalhadoras do sexo (MTS) de 12 capitais brasileiras. Métodos: Estudo transversal de vigilância biológica e comportamental com MTS recrutadas por respondent-driven sampling (RDS), em 2016. Foram estimadas, por cidade, as prevalências de HIV, características sociodemográficas, comportamentais e da profissão. Utilizou-se o teste do Qui-Quadrado para comparar essas distribuições. Resultados: Entre 4.328 MTS, a prevalência da infecção pelo HIV foi de 5,3% (IC95% 4,5;6,3), variando de 0,2% (IC95% 0,0;1,2), em Campo Grande, a 18,2% (IC95%13,2;24,7) em Salvador. Em metade das cidades, a prevalência de HIV nas amostras foi >5,0%, enquanto Campo Grande, Brasília e Belo Horizonte apresentaram prevalências <1,0%. Diferenças significativas entre as cidades foram encontradas nas distribuições segundo escolaridade, renda, local de trabalho, idade de início do trabalho sexual, e uso de drogas ilícitas. Conclusão: As características das amostras em cada cidade foram distintas, e influenciaram a prevalência local de HIV.

Objetivos: Describir las características de las mujeres trabajadoras sexuales (MTS) de 12 ciudades brasileñas. Métodos: Estudio transversal de vigilancia biológica y conductual con MTS reclutadas por Respondent-Driven Sampling (RDS) 2016. La prevalencia del VIH, las características sociodemográficas, de comportamiento y relacionadas con la profesión se estimaron por ciudad. Se utilizó la prueba de Chi cuadrado para comparar esas distribuciones. Resultados: Entre 4,328 MTS, la prevalencia del VIH fue 5,3% (IC95%4,5; 6,3), variando de 0,2% (IC95% 0,0;1,2) en Campo Grande a 18,2% (IC95% 13,2; 24,7) en Salvador. En la mitad de las ciudades, la prevalencia del VIH fue >5,0%, mientras que Campo Grande, Brasíla y Belo Horizonte tuvieron prevalencia de, <1,0%. Se encontraron diferencias significativas entre las ciudades en las distribuciones, de acuerdo con la escolaridad, ingresos, lugar de trabajo, edad de inicio del trabajo sexual y uso de drogas ilícitas. Conclusión: Las características de las muestras locales fueron diferentes e influyeron en la prevalencia local del VIH.

Objective: To describe the characteristics of female sex workers (FSW) in 12 Brazilian cities. Methods: This was a cross-sectional biological and behavioral surveillance study with FSW recruited by respondent-driven sampling (RDS) in 2016. HIV prevalence, sociodemographic, behavioral and sex work profession variables were estimated by city. The chi-square test was used to compare these distributions. Results: Among 4,328 FSW, HIV prevalence was 5.3% (95%CI 4.5;6.3), ranging from 0.2% (95% CI 0.0;1.2), in Campo Grande, to 18.2 (95%CI 13.2;24.7) in Salvador. In half of the cities, HIV prevalence in the samples was >5.0%, while Campo Grande, Brasília and Belo Horizonte had prevalence rates <1.0%. Significant differences between cities were found in distributions according to educational level, income, workplace, age sex work started, and illicit drug use. Conclusion: The characteristics of the samples in each city were distinct and have influenced local HIV prevalence.

Correlation between parameters of self-monitoring of blood glucose and the perception of health-related quality of life in patients with type 1 diabetes mellitus

ABSTRACT Objective The aim of this study was to evaluate how different parameters of short-term glycemic control would correlate with the perception of health-related quality of life (HRQoL) in patients with type 1 diabetes mellitus (T1D). Subjects and methods A total of 50 T1D patients aged 18 to 50 years were evaluated with the questionnaires Problem Areas in Diabetes (PAID) scale and Diabetes Quality of Life (DQOL) measure after 30 days of self-monitoring of blood glucose (SMBG). Glycemic control was evaluated using glycated hemoglobin (HbA1c), mean glucose levels (MGL) in the prior month's data from SMBG (Accu-Check 360o), number of hypoglycemic episodes (< 70 mg/dL and < 50 mg/dL), and glycemic variability (GV). Results PAID correlated positively with MGL (r = 0.52; p < 0.001) and HbA1c (r = 0.36; p < 0.0097), but not with GV (r = 0.17; p = 0.23) or number of hypoglycemic episodes (r = 0.15; p = 0.17 for glucose < 70 mg/dL and r = 0.02; p = 0.85 for glucose < 50 mg/dL). After multiple linear regression, only MGL remained independently related to PAID scores. DQOL scores had a positive correlation with MGL (r = 0.45; p = 0.001), but not with HbA1c (r = 0.23; p = 0.09), GV (r = 0.20; p = 0.16), or number of hypoglycemic episodes (r = 0.06 p = 0.68). Conclusion In T1D patients, MGL, but not HbA1c or number hypoglycemic episodes, was the glycemic control parameter that best correlated with short-term perception of HRQoL.

Adverse reactions to antiretroviral therapy: a prevalent concern / Las reacciones adversas al tratamiento antirretroviral: una preocupación frecuente / Reações adversas à terapia antirretroviral: uma preocupação frequente

ABSTRACT The risk-benefit ratio of antiretroviral therapy (ART) is usually considered favorable due to the urgent need to control the HIV/AIDS epidemic. Current studies have shown that combined ART (two or more drugs, from two different classes) is the most effective, with benefits that go beyond clinical management of the disease playing a crucial role in preventing HIV transmission. Therefore, early identification of HIV infection followed by immediate initiation of ART has been encouraged worldwide. However, the success of this strategy has been threatened by poor engagement of patients in HIV care, which may be related to drug harms. In addition, ART is required for the life course, creating the potential for adverse drug reactions (e.g., lipodystrophies). Therefore, adverse drug reactions are a prevalent concern among people living with HIV/AIDS, even in the current era of early initiation of ART ("early ART"), with most drugs considered much safer than those used in previous eras. Accurate diagnosis, recording, and reporting, followed up with proper management and prevention, and intensive surveillance, of new and known adverse reactions to ART, should be strongly encouraged as part of the care continuum.

RESUMEN La relación entre los riesgos y beneficios del tratamiento antirretroviral (TAR) generalmente se considera favorable debido a la urgente necesidad de controlar la epidemia de VIH/SIDA. Los estudios actuales han revelado que la politerapia antirretrovírica (dos o más medicamentos de dos clases diferentes) es la más eficaz porque no solo trata la enfermedad, sino que tiene una función crucial como método preventivo de la transmisión del VIH. Por consiguiente, en todo el mundo se ha promovido el diagnóstico temprano de la infección por el VIH seguido del inicio inmediato del TAR. Sin embargo, la efectividad de esta estrategia ha sido comprometida por la baja retención de pacientes en los servicios de salud, que puede estar asociada a seguridad en el uso de los medicamentos. Además, dado que estos pacientes deben recibir TAR durante toda la vida, aumenta la probabilidad de que presenten reacciones adversas a los medicamentos (por ejemplo, lipodistrofias). De esta forma, las reacciones adversas a los antirretrovirales se tornaron una constante preocupación, incluso en la era actual de inicio precoz de la TAR, en que los medicamentos son considerados más seguros que aquellos utilizados en el pasado. El diagnóstico preciso, registro y notificación de las reacciones adversas, seguidos de manejo y prevención adecuados, y vigilancia intensiva para detectar reacciones adversas (nuevas y conocidas) deben ser fuertemente recomendadas como parte de la cascada del cuidado continuado.

RESUMO A relação risco-benefício da terapia antirretroviral (TARV) é considerada favorável devido à urgente necessidade de controlar a epidemia de HIV/aids. Estudos recentes demonstram que a TARV combinada (dois ou mais medicamentos de duas classes distintas) é altamente efetiva, apresentando benefícios que ultrapassam o objetivo do manejo clínico da doença, pois contribui de forma significativa para a prevenção da transmissão do HIV. Recomenda-se, portanto, o diagnóstico precoce da infecção pelo HIV e o início imediato da TARV em todo o mundo. Todavia, a efetividade dessa estratégia tem sido comprometida pela baixa retenção de pacientes nos serviços de saúde, que pode estar associada à segurança no uso dos medicamentos. Além disso, o uso da TARV se faz necessário por toda a vida, o que possibilita a ocorrência de reações adversas (como lipodistrofias). Dessa forma, as reações adversas aos antirretrovirais se tornaram uma constante preocupação, mesmo na era atual de início precoce da TARV, em que os medicamentos são considerados mais seguros do que aqueles utilizados no passado. O diagnóstico preciso, o registro e a notificação das reações adversas, acompanhados de tratamento e prevenção adequados, além de intensiva vigilância para detecção de reações adversas (novas e conhecidas) devem ser fortemente recomendadas como parte da cascata do cuidado contínuo.

High incidence of hypertriglyceridemia in a Brazilian cohort of people living with HIV/AIDS undergoing antiretroviral treatment in Belo Horizonte, 2001-2010

Abstract INTRODUCTION: Hypertriglyceridemia incidence should be estimated in HIV-infected patients after antiretroviral therapy (ART) initiation. METHODS: We retrospectively analyzed clinical data of HIV-infected adults at 3 public referral centers. Cumulative and person-time incidences were estimated for patients without hypertriglyceridemia. Survival time and hazard ratio (HR) were estimated by Kaplan-Meier analysis and Cox proportional regression, respectively. RESULTS: Cumulative and person-time incidences were 40.4% and 1.4 cases/100 person-months, respectively. The median period for hypertriglyceridemia occurrence was 47 months. Men and patients with switched ART regimens had increased hypertriglyceridemia risk (HR=3.05 and 3.34, respectively). CONCLUSIONS: Hypertriglyceridemia incidence is high in HIV-infected patients undergoing ART.

Determinação do perfil de expressão e metilação dos receptores tipo TRAIL, caspase 8 e Bcl-2 em câncer epitelial de ovário / Determination of expression profile of receivers and methylation TRAIL, capase 8 and Bcl-2 in ephithelial ovarian cancer

Dentre as patologias do trato genital feminino, o câncer epitelial de ovário (CEO) representa a sétima causa mais relevante de morbidade e mortalidade no mundo. Apesar dos avanços no tratamento dessa neoplasia, não houve melhorias equivalentes nas tax as de sobrevida das mulheres afetadas. O presente estudo visa analisar o perfil de expressão e metilação dos genes receptor es tipo TRAIL ( TRAIL-R2 e TRAIL-R3) , CASPASE- 8 e BCL -2 em pacientes com CEO a fim de prover uma melhor compreensão da biologia molecular deste tumor e da predição de respostas terapêuticas numa medicina person alizada. Para as análises, foram coletadas amostras de pacientes atendidas no Hospital Vera Cruz, em Belo Horizonte, Minas Gerais. Estas amostras foram destinadas à extração simultânea do R NA e DNA genômico pelo reagente TR Izol®. A expressão gênica de TRAIL-R2, TRAIL-R3, BCL-2 e CASPASE-8 foi avaliada por meio da reação em cadeia da polimerase (PCR) quantitativa em tempo real e o padrão de metilação dos promotores de TRAIL-R2, TRAIL-R3 e C ASPASE-8 foi analisado por PCR metilação específica. Observou-se que o grupo de pacientes com CEO metastático superexpressou todos os genes avaliados, enquanto que, pacientes com cistoadenoma seroso ovariano apenas não superex pressar am BCL-2. O grupo de pacientes com CEO primário expressou níveis reduzidos dos marcadores antiapoptóticos, TRAIL-R3 eBCL-2¸ que aliados a superex pressão de CASPASE -8, sugerem completamente não metiladas para o marcador TRAIL-R3 e que difer enças significativas foram encontradas entre a metilação presente nas ilhas CpG dos promotores de TRAILR3 eCASPASE-8 e os grupos histológicos. Entretanto, esse evento não se correlacionou com o silenciamento epigenético desses genes, o que sugere o envolvimento de outros mecanismos de controle transcricional...

The epithelial ov arian cancer (EOC) represents the seventh most important cause of morbidity and mortality worldwide among the female genital tract diseases. Despite the advances in the treatment of this malignancy, there were no equivalent improvements in the survival rates of affected women. The present study aims to analyze the expression and methylation profiles of TRAIL receptors ( TRAIL-R2 and TRAIL-R3 ), CASPASE-8 and BCL-2 genes in p atients with EOC in order to provide a better understanding of the molecular biology of this pathology and to predict therapeutic responses in a personalized medicine. Samples were collected from patients treated at Vera Cruz Hospital in Belo Horizonte, state of Minas Gerais. Those samples were used for simultaneous extraction of RNA and genomic DNA b y TRIzol ® reagent. The genetic expression of TRAIL-R2, TRAIL-R3, BCL-2 and CASPASE-8 were evaluated by realtime quantitative polymerase chain reaction and the meth ylation profile of TRAIL-R2, TRAIL-R3 and CASPASE-8 promoters were analyzed b y methylation specific PCR. Higher expression levels of all four markers were observed in metastatic EOC. In contrast, serous cystoad enoma overexpressed all markers, ex cept for BCL-2. The primary tumors underexpressed anti-apoptotic gen es, TRAIL-R3 and BCL-2 , and overexpressed proapoptotic genes C ASPASE -8 which suggest a genetic signature in TRAIL signaling pathway in EOC...