In deep bioinformatic characterization of a novel fumarate hydratase variant FH c.199T > G; (p.Tyr67Asp) in hereditary leiomyomatosis and renal cell carcinoma.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare, autosomal dominant tumor predisposition syndrome characterized by variable development of multiple skin and uterus leiomyomas and aggressive forms of renal cell carcinoma (RCC). Mutations in fumarate hydratase (FH), one of the proteins in homologous recombination repair, precede the development of HLRCC with high penetrance. Considering the risk of early metastasis of RCC, FH has been included in mutation screening panels. The identification of a pathogenic FH variant guides the screening for tumors in the carriers. However, variants of uncertain significance (VUS) are frequent findings, limiting the clinical value of the mutation screening. Here, we describe the associated phenotype and an in-depth, multi-step Bioinformatic evaluation of the germline FH c.199T > G (p.Tyr67 > Asp) variant segregated in an HLRCC family. Evidence for FH c.199T > G; (p.Tyr67Asp) pathogenicity includes the variant segregation with the disease in three affected family members, its absence in populational databases, and the deep evolutionary conservation of the Tyr67 residue. At the protein level, this residue substitution causes the loss of molecular bonds and ionic interactions, affecting molecular dynamics and protein stability. Considering ACMG/AMP criteria, we propose the reclassification of the FH c.199T > G; (p.Tyr67Asp) variant to "likely pathogenic". In addition, the in-depth, in silico approach used here allowed us to understand how and why FH c.199T > G; (p.Tyr67Asp) could cause HLRCC. This could help in clinical management decisions concerning the monitoring of unaffected family members having this variant.

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.

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.

Germline Mutations Landscape in a Cohort of the State of Minas Gerais, Brazil, in Patients Who Underwent Genetic Counseling for Gynecological and Breast Cancer.

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.

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.

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.

Exploring electronic, structural and dynamics parameters of phenylbenzothiazole complexes with Mn2+, Cu2+ and Zn2+ for designing new magnetic resonance imaging (MRI) probes: congruence between computation and spectroscopic data.

Cancer is one of the leading causes of human death worldwide, being one of the most serious problems faced by mankind. For the diagnosis, Magnetic Resonance Imaging (MRI), through effective contrast agents (Cas), has greatly helped in the diagnosis at the initial stages. However, it is necessary to include new compounds more effective and selective for cancer diagnosis. The complexes with Mn2+, Cu2+ and Zn2+ have received great attention due to their applications as CAs for MRI. Those materials can shorten the T2 and T2* transverse relaxation times. Thus, the representative structures for hyperfine coupling constants (HFCCs) were selected from docking results by frequency of occupancy calculations. From the Multivariate Analysis to obtain the PCA graphs in the choice of a representative conformations. it is possible to notice that the variable energy does not present a high correlation with the other variables, and structural factors, such as the spatial positions of the metal atoms, seem to be important in the reactivity of the complexes. Structural factors, such as the spatial positions of the metal atoms, seem to be important in the reactivity of the complexes. Theoretical findings suggest that the compounds are capable of increasing the Aiso values of the water molecules, but the complex [Zn(H2O)(NNO)] shows a greater influence, being more sensitive to the Electron paramagnetic resonance parameters than the complexes [CuCl(H2O)NNO] and [MnCl2(H2O)(NNO)] with the explicit solvent and the enzyme. MRI contrast agents have generated various problems due to their high toxicity. In this perspective, this compound may be a promising alternative for transporting the CAs into diseased tissue.Communicated by Ramaswamy H. Sarma.

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.

Health vulnerabilities in female sex workers in Brazil, 2016.

Female sex workers (FSW) suffer stigma and discrimination that negatively impact their physical and mental health and affect access to health care services. This paper aims to describe selected health indicators among FSW in 12 Brazilian cities in 2016. Brazilian cross-sectional Biological Behavioral Surveillance Survey was conducted in 2016 among 4328 FSW recruited by respondent-driven sampling. The sample weighing was inversely proportional to participant's network sizes and the seeds were excluded from the analysis. Health indicators were estimated with 95% confidence interval and included indicators of health status, symptoms of depression, antenatal care, pap smear coverage, signs and symptoms of sexually transmitted infection, contraception and regular condom use, number of births and children alive per women, human immunodeficiency virus and syphilis testing, usual source of care, and perception of discrimination. Most participants self-rated their health as very good/good (65.8%) and 27.7% were positively screened for major depressive disorder episode on Patient Health Questionnaire-2. Antenatal coverage was 85.8% and 62.3% of FSW had access to pap smear exam in the past 3 years. A total of 67.0% of FSW were using some contraceptive method at the time of the study. Male condom was the most common method (37.1%), followed by oral pill (28.9%). A total of 22.5% FSW had never been tested for HIV and the main reasons were "not feeling at risk" (40.4%) and "being afraid or ashamed" (34.0%). The vast majority of FSW used Brazilian National Health System as their usual source of health care (90.2%). Approximately one-fifth of the participants felt discriminated against or were treated worse for being FSW (21.4%) and only 24.3% disclose their sex work status in health services. The vulnerability of FSW is expressed in all health indicators. Indicators of health status, antenatal care, pap smear coverage, and contraception were worse than in the Brazilian population, and point out to the importance of increase FSW's access to health care services. Also, stigma and discrimination emerged as an important barrier to FSW's health care in all dimensions and need to be struggled.

Metabolic comorbidities and systemic arterial hypertension: the challenge faced by HIV patients on long-term use of antiretroviral therapy.

OBJECTIVE: Our objective was to estimate the frequency of comorbidities and assess its relationship with exposure factors after long-term ART use. METHODS: A cross-sectional study with PLHIV (≥18 years-old), who initiated ART between 2001 and 2005 and attended an HIV/AIDS public referral center (Belo Horizonte/Brazil), was performed. Demographic, clinical, therapeutic, and lifestyle data were obtained through interviews, medical charts, public database, routine laboratory examinations, and bone densitometry. The outcome was the number of comorbidities: hyperglycemia, dyslipidemia, systemic arterial hypertension (SAH), and low bone mineral density (BMD). Absolute/relative frequencies were calculated. Factors associated with the outcome were assessed by quasi-Poisson regression. RESULTS: Of the 98 participants, 53% were male and 79% and over 43 years-old. Moderate physical activity was observed in 82%, overweight/obesity in 50%, and 58% used ART based on two nucleoside reverse transcriptase inhibitors (NRTIs) plus one non-nucleoside reverse transcriptase inhibitor (NNRTI). After a mean of 15.6 years of ART exposure, 207 comorbidities were identified and 93% participants presented at least one comorbidity (mean = 2.1/participant). The most frequent overlapping constituted two co-occurrences: dyslipidemia + hyperglycemia or dyslipidemia + SAH, n = 36 for each co-occurrence. The quasi-Poisson regression showed an increase of 3% in the number of comorbidities per year of age (OR = 1.03; 95%CI = 1.02-1.04) and 84% among PLHIV on moderate physical activity (ref = heavy physical-activity) (OR = 1.84; 95%CI = 1.08-3.13). CONCLUSIONS: Our study shows that the aging slightly contributed to comorbidities. However, the practice of physical-activities is crucial to prevent chronic-diseases. Treatment and preventive measures should be encouraged to diminish the burden of disease and improve quality of life among PLHIV.

Identification of best housekeeping genes for the normalization of RT-qPCR in human cell lines.

The identification of the best reference gene is a critical step to evaluate the relative change in mRNA expression of a target gene by RT-qPCR. In this work, we evaluated nineteen genes of different functional classes using Real Time Human Reference Gene Panel (Roche Applied Sciences), to identify the internal housekeeping genes (HKGs) most suitable for gene expression normalization data in human cell lines. Normal cell lines CCD-19LU (lung fibroblast), HEK-293 (epithelial cell of embryonic kidney), WI-26 VA4 (lung fibroblast), and human cancer cells, BT-549 (breast cancer), Hs 578T (breast cancer), MACL-1 (breast cancer), HeLa (cervical carcinoma), U-87 MG (glioblastoma/astrocytoma), RKO-AS45-1 (colorectal carcinoma), and TOV-21G (ovarian adenocarcinoma) were cultivated according to manufacturer's protocol. Twelve candidate reference genes were commonly expressed in five cell lines (CCD-19Lu, HEK-293, RKO-AS45-1, TOV-21G, and U-87 MG). To verify the expression stability, we used the RefFinder web tool, which integrates data from the computational programs Normfinder, BestKeeper, geNorm, and the comparative Delta-Ct method. The ACTB was the most stable reference gene to the CCD-19Lu and HEK-293 cells. The best combination of HKGs for the RKO-AS45-1 and TOV-21G cell lines were B2M/GAPDH and PBGD/B2M, respectively. For the U-87 MG cells, GAPDH and IPO8 were the most suitable HKGs. Thus, our findings showed that it is crucial to use the right HKGs to precise normalize gene expression levels in cancer studies, once a suitable HKG for one cell type cannot be to the other.

Sexual, reproductive health and health status of female sex workers in 12 Brazilian cities, 2016.

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.

Cervical Cancer Stem-Like Cell Transcriptome Profiles Predict Response to Chemoradiotherapy.

Cervical cancer (CC) represents a major global health issue, particularly impacting women from resource constrained regions worldwide. Treatment refractoriness to standard chemoradiotheraphy has identified cancer stem cells as critical coordinators behind the biological mechanisms of resistance, contributing to CC recurrence. In this work, we evaluated differential gene expression in cervical cancer stem-like cells (CCSC) as biomarkers related to intrinsic chemoradioresistance in CC. A total of 31 patients with locally advanced CC and referred to Mário Penna Institute (Belo Horizonte, Brazil) from August 2017 to May 2018 were recruited for the study. Fluorescence-activated cell sorting was used to enrich CD34+/CD45- CCSC from tumor biopsies. Transcriptome was performed using ultra-low input RNA sequencing and differentially expressed genes (DEGs) using Log2 fold differences and adjusted p-value < 0.05 were determined. The analysis returned 1050 DEGs when comparing the Non-Responder (NR) (n=10) and Responder (R) (n=21) groups to chemoradiotherapy. These included a wide-ranging pattern of underexpressed coding genes in the NR vs. R patients and a panel of lncRNAs and miRNAs with implications for CC tumorigenesis. A panel of biomarkers was selected using the rank-based AUC (Area Under the ROC Curve) and pAUC (partial AUC) measurements for diagnostic sensitivity and specificity. Genes overlapping between the 21 highest AUC and pAUC loci revealed seven genes with a strong capacity for identifying NR vs. R patients (ILF2, RBM22P2, ACO16722.1, AL360175.1 and AC092354.1), of which four also returned significant survival Hazard Ratios. This study identifies DEG signatures that provide potential biomarkers in CC prognosis and treatment outcome, as well as identifies potential alternative targets for cancer therapy.

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.

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

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.

Epithelial-to-mesenchymal transition markers are differentially expressed in epithelial cancer cell lines after everolimus treatment.

The epithelial-to-mesenchymal transition (EMT) is a phenomenon during which cancer epithelial cells undergo changes in plasticity and lose cell-cell adhesion with consequent remodeling of the extracellular matrix and development of mesenchymal characteristics. Long non-coding RNAs (lncRNAs) have been described as EMT modulation markers, becoming a promising target in the development of new therapies for cancer. The present study aimed to investigate the role of everolimus at 100 nM as inductor of the EMT phenomenon in cell lines derived from human breast (BT-549), colorectal (RKO-AS45-1) and ovary (TOV-21G) cancer. The integrity of cellular junctions was monitored using an in vitro model of epithelial resistance. The results demonstrated that the EMT genes ZEB1, TWIST1 and TGFB1 were differentially expressed in cells treated with everolimus compared with in untreated cells. lncRNA HOTAIR was upregulated post-treatment only in BT-549 cells compared with in untreated cells. After treatment with everolimus, the intensity of fluorescence of P-cadherin decreased, and that of fibronectin increased in RKO-AS45-1 and TOV-21G cells compared with control cells. The transepithelial electrical resistance at the RKO-AS45-1 monolayer treated with everolimus started to decrease at 48 h. The changes in the gene expression and epithelial resistance may confirm the role of everolimus in EMT.

Characterization of female sex workers in Brazilian state capitals, 2016. / Caracterização de mulheres trabalhadoras do sexo em capitais brasileiras, 2016.

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.

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

Objective. To describe the characteristics of female sex workers (FSW) from 12 Brazilian cities. Methods. Cross-sectional study of Biological and Behavioral Surveillance Survey (BBSS) with FSW recruited by Respondent-Driven Sampling (RDS), in 2016. HIV prevalence, sociodemographic, behavioral, and variables related to sex work were estimated by city. 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 the distributions according to educational level, income, workplace, starting age of sex work, and illicit drugs use. Conclusion. The characteristics of the samples in each city were distinct and have influenced local HIV prevalence.

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, 2016. La prevalencia del VIH, las características sociodemográficas, de comportamiento y relacionadas con la profesión se estimaron por ciudad. Se utilizó chi-cuadrado para comparar essas 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 <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. Palabras-clave: VIH; Trabajo Sexual; Muestreo; Red Social; Poblaciones Vulnerables; Brasil.

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 de 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.

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.

HSPA1A, HSPA1L and TRAP1 heat shock genes may be associated with prognosis in ovarian epithelial cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, with the presence of chemoresistance contributing to the poor prognosis. Heat Shock Proteins (HSPs) genes are activated in response to pathophysiological stress and serve a role in a variety of stages in carcinogenesis, acting primarily as anti-apoptotic agents and in chemotherapy resistance in a variety of tumor types. The current study evaluated the HSP gene expression profile in women with ovarian cancer (OC) and their correlation with clinical and pathological aspects of patients with OC. A total of 51 patients included in the current study were divided into four groups: Primary Epithelial Ovarian Cancer (EOC; n=14), metastatic EOC (n=11), ovarian serous cystadenoma (n=7) and no evidence of ovarian malignancy or control groups (n=19). RNA extraction and reverse transcription-quantitative (RT-q) PCR was then performed on the samples obtained. RT-qPCR was performed to compare TNF receptor associated protein 1 (TRAP1), heat shock protein family (HSP) HSPB1, HSPD1, HSPA1A and HSPA1L expression in primary and metastatic EOCs. TRAP1, HSPB1, HSPD1, HSPA1A and HSPA1L gene expression did not differ among groups. HSPA1A, HSPA1L and TRAP1 were revealed to be underexpressed in the primary and metastatic EOC groups, with HSPA1L exhibiting the lowest expression. TRAP1 expression was higher in tumors at stages I/II compared with those at stages III/IV. No correlation was exhibited between HSP expression and age, menarche, menopause, parity, period after menopause initiation, cytoreduction, CA-125 or overall and disease-free survival. HSPA1A was negatively correlated with the risk of mortality from OC. The results indicated that the downregulation of HSPA1A, HSPA1L and TRAP1 could be associated with the clinical prognostic features of women with EOC.

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.

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.