Macrophage migration inhibitory factor -173 G>C single nucleotide polymorphism and its association with active pulmonary tuberculosis

Purpose The establishment of candidate genes associated with susceptibility to TB is a challenge especially due to divergent frequencies among different populations. The objective of this study was to evaluate the association between macrophage migration inhibitory factor (MIF) -173 G>C single nucleotide polymorphism (SNP) and susceptibility to pulmonary TB in a population of southern Brazil. Methods Case-control study. Patients > 18 years old, diagnosed with pulmonary TB were included. The control group consisted of blood donors and household contacts, not relatives, healthy and > 18 years old. MIF -173 G>C SNPs were genotyped using real-time PCR using a TaqMan SNP Genotyping assay. Results 174 patients and 166 controls were included. There were no statistically significant differences between cases and controls regarding genotype prevalence (p>0.05). Comparing patients with normal genotype (GG) with those with at least one C allele, there was also no statistically significant difference (p = 0.135). Also, there was no statistically significant difference comparing the homozygous for the mutation (CC) with the other patients (GG and CG) (p = 0.864). Conclusions We did not find association between MIF -173 G>C polymorphism and susceptibility to pulmonary TB

Variant predictions in congenital adrenal hyperplasia caused by mutations in CYP21A2

CYP21A2 deficiency represents 95% of congenital adrenal hyperplasia (CAH) cases, a group of genetic disorders that affect steroid biosynthesis. The genetic and functional analysis provide critical tools to elucidate complex CAH cases. One of the most accessible tools to infer the pathogenicity of new variants is in silico prediction. Here, we analyzed the performance of in silico prediction tools to categorize missense single nucleotide variants (SNVs) of CYP21A2. SNVs of CYP21A2 characterized in vitro by functional assays were selected to assess the performance of online single and meta predictors. SNVs were tested separately or in combination with the related phenotype (severe or mild CAH form). In total, 103 SNVs of CYP21A2 (90 pathogenic and 13 neutral) were used to test the performance of 13 single-predictors and four meta-predictors. All SNVs associated with the severe phenotypes were well categorized by all tools, with an accuracy of between 0.69 (PredictSNP2) and 0.97 (CADD), and Matthews’ correlation coefficient (MCC) between 0.49 (PoredicSNP2) and 0.90 (CADD). However, SNVs related to the mild phenotype had more variation, with the accuracy between 0.47 (S3Ds&GO and MAPP) and 0.88 (CADD), and MCC between 0.18 (MAPP) and 0.71 (CADD). From our analysis, we identified four predictors of CYP21A2 variant pathogenicity with good performance, CADD, ConSurf, DANN, and PolyPhen2. These results can be used for future analysis to infer the impact of uncharacterized SNVs in CYP21A2

Alterações metabólicas associadas à terapia anti-retroviral em pacientes HIV-positivos

OBJECTIVE: To evaluate metabolic changes associated with highly active antiretroviral therapy (HAART) in HIV-positive patients, and to identify risk factors associated. METHODS: Retrospective study that included 110 HIV-positive patients who where on HAART in the city of Porto Alegre (Southern Brazil) between January 2003 and March 2004. Data on demographic variables, cigarette smoking, diabetes mellitus, cholesterol and triglyceride levels, stage of HIV infection, antiretroviral therapy and HCV coinfection were collected. General linear models procedure for repeated measures was used to test the interaction between HAART and HCV coinfection or protease inhibitor treatment. RESULTS: Total cholesterol, triglycerides, and glucose levels significantly increased after receiving HAART (pOBJETIVO: Evaluar las alteraciones metabólicas asociadas a la terapia anti-retroviral potente en pacientes HIV-positivos e identificar factores de riesgo asociados. MÉTODOS: Estudio retrospectivo con 110 pacientes HIV-positivos que estaban en terapia anti-retroviral potente (HAART) en la ciudad de Porto Alegre (Sur de Brasil), entre enero de 2003 y marzo de 2004. Los datos colectados incluyen variables demográficas, tabaquismo, diabetes mellitas, niveles de colesterol y triglicéridos, fase de la infección viral, terapia anti-retroviral y co-infección con hepatitis C. El análisis multivariado para medidas repetidas (General Linear Model procedure for Repeated Measures) fue utilizada para analizar la interacción entre el efecto de uso de HAART y el uso de inhibidores de proteasa o co-infección por hepatitis C. RESULTADOS: Fueron observados aumentos significativos en los niveles de colesterol total, triglicéridos y glucosa posterior al tratamiento con HAART (pOBJETIVO: Avaliar as alterações metabólicas associadas à terapia anti-retroviral potente em pacientes HIV-positivos e identificar fatores de risco associados. MÉTODOS: Estudo retrospectivo com 110 pacientes HIV-positivos que estavam sob terapia anti-retroviral potente (HAART) na cidade de Porto Alegre (RS), entre janeiro de 2003 e março de 2004. Os dados coletados incluem variáveis demográficas, tabagismo, diabetes mellitus, níveis de colesterol e triglicerídeos, estágio da infecção viral, terapia anti-retroviral e co-infecção com hepatite C. A análise multivariada para medidas repetidas (General Linear Model procedure for Repeated Measures) foi utilizada para testar a interação entre o efeito do uso de HAART e o uso de inibidores de protease ou co-infecção por hepatite C. RESULTADOS: Foram observados aumentos significativos nos níveis de colesterol total, triglicerídeos e glicose após o tratamento com HAART (

Role of the ENPP1 K121Q Polymorphism in Glucose Homeostasis

OBJECTIVE— To study the role of the ENPP1 Q121 variant on glucose homeostasis in whites from Italy

Detecção de DNA de Papilomavírus Humano (HPV) em mulheres grávidas utilizando a urina

Este trabalho foi realizado com o objetivo de investigar a incidência de DNA de Papilomavírus Humano(HPV) em urina de gestantes atendidas no Hospital Divina Providencia, do município de FredericoWestphalen da Região do Médio Uruguai. As amostras coletadas foram encaminhadas ao Laboratório deBiologia Molecular da ULBRA onde foram submetidas aos processos de extração de DNA e amplificaçãopor PCR (Polimerase Chain Reaction) utilizando primers específicos do genoma viral. Os fragmentosde DNA foram visualizados em eletroforese em gel de agarose (1,5%). Das 70 gestantes que participaramdo estudo, 9 apresentaram contaminação viral, sendo 12,9% da população estudada positiva paraHPV.Palavras-chave: Papilomavírus humano (HPV), gestantes, urina

LEISHMANIOSE VISCERAL CANINA: DETECÇÃO DE DNA EM SORO POR PCR EM TEMPO REAL

O diagnóstico de leishmaniose visceral canina (LVC) pelas técnicas imunológicas ainda não é satisfatório, uma vez que a detecção de anticorpos nem sempre corresponde a presença do parasita no animal. O objetivo deste trabalho foi detectar DNA de Leishmania em soro de caninos por PCR em tempo real e comparar os resultados com os obtidos pelos métodos imunológicos (DPP® e ELISA). O DNA foi extraído de soro de 60 caninos e analisado por PCR em tempo real utilizando como alvo a região do cinetoplasto. Na comparação dos resultados, o teste molecular mostrou uma sensibilidade e especificidade de 86,2% e 93,5%, respectivamente. É possível concluir que este método poderia auxiliar em um diagnóstico de LVC mais preciso, uma vez que confirma a presença do DNA de Leishmania nos cães infectados.

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-Week results of a randomized trial

Objectives Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm).Results In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. Conclusion Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therap