Characterization of Torquetenovirus in amniotic fluid at the time of in utero fetal surgery: correlation with early premature delivery and respiratory distress

Torquetenovirus (TTV) is a commensal virus present in many healthy individuals. Although considered to be non-pathogenic, its presence and titer have been shown to be indicative of altered immune status in individuals with chronic infections or following allogeneic transplantations. We evaluated if TTV was present in amniotic fluid (AF) at the time of in utero surgery to correct a fetal neurological defect, and whether its detection was predictive of adverse post-surgical parameters. AF was collected from 27 women by needle aspiration prior to a uterine incision. TTV titer in the AF was measured by isolation of viral DNA followed by gene amplification and analysis. The TTV genomes were further characterized and sequenced by metagenomics. Pregnancy outcome parameters were subsequently obtained by chart review. Three of the AFs (11.1%) were positive for TTV at 3.36, 4.16, and 4.19 log10 copies/mL. Analysis of their genomes revealed DNA sequences similar to previously identified TTV isolates. Mean gestational age at delivery was >2  weeks earlier (32.5 vs. 34.6  weeks) and the prevalence of respiratory distress was greater (100% vs. 20.8%) in the TTV-positive pregnancies. TTV detection in AF prior to intrauterine surgery may indicate elevated post-surgical risk for earlier delivery and newborn respiratory distress

Variabilidade genética nos genes do sistema tioredoxina e txnip e fatores de risco e doença cardiovascular na população brasileira

o sistema tioredoxina está envolvido em importantes processos da homeostase cardiovascular. Em especial, suas duas mais importantes proteínas, tioredoxina e tioredoxina redutase, em interação com a proteína TXNIP são vias centrais nesse processo, regulando a expressão de diversos genes em resposta a estresse oxidativo ou sinalização de vias de relevância para o sistema. O presente trabalho, investigou o potencial preditivo dos marcadores polimórficos nos genes TXNIP, Tioredoxina Redutase e Tioredoxina, através de sua associação a fenótipos é fatores de risco cardiovascular em amostras de indivíduos selecionados na população brasileira. Para o TXNIP, a análise univariada de variáveis categóricas e contínuas, mostrou uma associação significativa entre níveis de glicose em jejum e fenótipos da pressão arterial com os marcadores genéticos rs7211 e rs7212 do gene TXNIP. O modelo de regressão logística, foi capaz de demonstrar uma capacidade preditora, independente entre os marcadores, mesmo após o ajuste para outras covariáveis. Finalmente o haplótipo TG (presente em aproximadamente 17% dos indivíduos da população estudada) modulou o risco de diabetes (OR 1.95 95% IC 1.23-3.08 p=0.004) e de hipertensão (OR 1.41 95% IC 1.02-1.93 p=0.049). Estes resultados foram confirmados em uma segunda população independente. Ainda foi analisado o impacto destes marcadores em crianças da população brasileira e uma associação com glicemia de jejum e insulina foi encontrada. Foi realizado também, ensaio funcional em população de células de músculo liso de vaso, nessa, o TXNIP mostrou ser mais expresso no grupo genotípico CG comparado ao grupo CC (pValor=0,031). Em última etapa, a análise dos marcadores no gene Tioredoxina redutase, mostraram valores significativos para uréia e ácido úrico. Em conclusão, nossos dados sugerem que indivíduos normais homozigotos para o alelo G e o alelo T do gene TXNIP possuem riscos aumentados de desenvolveram diabetes e hipertensão na população geral. XVI o haplótipo TG confere maior risco para Diabetes Mellifus tipo 2 e alteração de fenótipos associados a homeostase glicêmica desde a infância. Indivíduos do grupo genotípico CG têm maior expressão de TXNIP no tecido vascular. Assim,desta forma, o TXNIP evidencia um link comum entre o sistema tioredoxina e doenças multifatoriais, como diabetes e hipertensão. XVIIDados abertos - Sucupira - Teses e dissertações (2013 a 2016

Encephalopathy Caused by Human Parvovirus B19 Genotype 1 Associated with <i>Haemophilus influenzae</i> Meningitis in a Newborn

Parvovirus B19 infection is associated with a wide range of clinical manifestations, from asymptomatic to severe neurological disorders. Its major clinical symptoms, fever and rash, are common to multiple viruses, and laboratory tests to detect B19 are frequently not available. Thus, the impact of B19 on public health remains unclear. We report the case of a 38-day old girl admitted to São Paulo Clinical Hospital, Brazil, with an initial diagnosis of bacterial meningitis, seizures, and acute hydrocephalus. Antibiotic therapy was maintained for one week after admission and discontinued after negative laboratory results were obtained. Nine days after symptoms onset, a cerebral spinal fluid (CSF) sample revealed persistent pleocytosis. The complete B19 complete genome was subsequently identified in her CSF by a metagenomic next-generation sequencing approach. This report highlights the possible involvement of B19 in the occurrence of acute neurological manifestations and emphasizes that its possible involvement might be better revealed by the use of metagenomic technology to detect viral agents in clinical situations of unknown or uncertain etiology

Higher incidence of death in multi-vessel coronary artery disease patients associated with polymorphisms in chromosome 9p21

<p>Abstract</p> <p>Background</p> <p>We investigated whether 9p21 polymorphisms are associated with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function.</p> <p>Methods</p> <p>The participants of the MASS II were genotyped for 9p21 polymorphisms (rs10757274, rs2383206, rs10757278 and rs1333049). Survival curves were calculated with the Kaplan–Meier method and compared with the log-rank statistic. We assessed the relationship between baseline variables and the composite end-point of death, death from cardiac causes and myocardial infarction using a Cox proportional hazards survival model.</p> <p>Results</p> <p>We observed significant differences between patients within each polymorphism genotype group for baseline characteristics. The frequency of diabetes was lower in patients carrying GG genotype for rs10757274, rs2383206 and rs10757278 (29.4%, 32.8%, 32.0%) compared to patients carrying AA or AG genotypes (49.1% and 39.2%, p = 0.01; 52.4% and 40.1%, p = 0.01; 47.8% and 37.9%, p = 0.04; respectively).</p> <p>Significant differences in genotype frequencies between double and triple vessel disease patients were observed for the rs10757274, rs10757278 and rs1333049. Finally, there was a higher incidence of overall mortality in patients with the GG genotype for rs2383206 compared to patients with AA and AG genotypes (19.5%, 11.9%, 11.0%, respectively; p = 0.04). Moreover, the rs2383206 was still significantly associated with a 1.75-fold increased risk of overall mortality (p = 0.02) even after adjustment of a Cox multivariate model for age, previous myocardial infarction, diabetes, smoking and type of coronary anatomy.</p> <p>Conclusions</p> <p>Our data are in accordance to previous evidence that chromosome 9p21 genetic variation may constitute a genetic modulator in the cardiovascular system in different scenarios. In patients with established CAD, we observed an association between the rs2383206 and higher incidence of overall mortality and death from cardiac causes in patients with multi-vessel CAD.</p