Unequal burden of Zika-associated microcephaly among populations with public and private healthcare in Salvador, Brazil.

OBJECTIVES: To describe the differences in clinical presentation and relative disease burden of congenital Zika syndrome (CZS)-associated microcephaly at 2 large hospitals in Salvador, Brazil that serve patients of different socioeconomic status (SES). METHODS: Clinical and serologic data were collected prospectively from pregnant women and their infants, who delivered at 2 study centers during the 2015-2016 Zika virus (ZIKV) epidemic in Salvador, Brazil. RESULTS: Pregnant women from Salvador, Brazil delivering in a low SES hospital had 3 times higher ZIKV exposure rate than women at a high SES hospital. However, different SES hospitals had similar prevalence of infants with CZS-associated microcephaly (10% vs 6%, p = 0.16) after controlling for ZIKV exposure in their mothers. CONCLUSIONS: Our study supports the positive association between low SES, high maternal ZIKV exposure, and high rates of CZS-associated microcephaly.

Heterogeneous development of children with Congenital Zika Syndrome-associated microcephaly.

OBJECTIVE: To describe the neurological and neurodevelopmental outcomes of children with Congenital Zika Syndrome (CZS) associated microcephaly beyond 2 years of age. METHOD: We followed children with CZS-associated microcephaly in an outpatient clinic in Salvador, Brazil. Neurological and neurodevelopmental assessments were performed using the Hammersmith Infant Neurological Examination (HINE) and Bayley Scales of Infant and Toddler Neurodevelopment (Bayley-III) respectively. RESULTS: Of the 42 children included, 19 were male (45.2%); median (interquartile range) age at neurological evaluation was 28 (25-32) months, and 36 (85.7%) had severe microcephaly. HINE and Bayley-III results were completed for 35/42 (83.3%) and 33/42 (78.5%) children respectively. Bayley-III identified a severe developmental delay in 32/33 (97.0%) children while 1/33 (3.0%) had only a mild delay. In the multivariable analysis, we found that Bayley-III and HINE scores were correlated. Better HINE scores were associated with higher Bayley-III cognitive raw scores (ß = 0.29; CI 95% = 0.02-0.57) and motor raw scores (ß = 0.43; CI 95% = 0.04-0.82) after adjusting for head circumference, prematurity, and age at neurodevelopmental evaluation. Furthermore, we found that greater head circumference at follow up was associated with higher cognitive (ß = 1.27; CI 95% = 0.01-2.53) and motor raw scores (ß = 2.03; CI 95% = 0.25-3.81). CONCLUSION: Children with CZS-associated microcephaly demonstrate severe neurodevelopmental delays and slower growth rates than their peers over time. Still, they have remarkably heterogeneous neurodevelopmental profiles according to neurological exam scores which correlate with their long-term outcomes. We found that HINE scores effectively captured the heterogeneity of neurological capabilities among these children and could be predictive of cognitive and motor development progress.

Social determinants associated with Zika virus infection in pregnant women.

This study aims to describe the sociodemographic determinants associated with exposure to Zika Virus (ZIKV) in pregnant women during the 2015-2016 epidemic in Salvador, Brazil. METHODS: We recruited women who gave birth between October 2015 and January 2016 to a cross-sectional study at a referral maternity hospital in Salvador, Brazil. We collected information on their demographic, socioeconomic, and clinical characteristics, and evaluated their ZIKV exposure using a plaque reduction neutralization test. Logistic regression was then used to assess the relationship between these social determinants and ZIKV exposure status. RESULTS: We included 469 pregnant women, of whom 61% had a positive ZIKV result. Multivariate analysis found that lower education (adjusted Prevalence Rate [aPR] 1.21; 95%CI 1.04-1.35) and food insecurity (aPR 1.17; 95%CI 1.01-1.30) were positively associated with ZIKV exposure. Additionally, age was negatively associated with the infection risk (aPR 0.99; 95%CI 0.97-0.998). CONCLUSION: Eve after controlling for age, differences in key social determinants, as education and food security, were associated with the risk of ZIKV infection among pregnant women in Brazil. Our findings elucidate risk factors that can be targeted by future interventions to reduce the impact of ZIKV infection in this vulnerable population.

Developmental outcomes in children exposed to Zika virus in utero from a Brazilian urban slum cohort study.

BACKGROUND: The prevalence of developmental alterations associated with in-utero Zika virus (ZIKV) exposure in children is not well understood. Furthermore, estimation of the Population Attributable Fraction (PAF) of developmental alterations attributed to ZIKV has not been performed due to lack of population-based cohorts with data on symptomatic and asymptomatic ZIKV exposures and an appropriate control group. The aim of this study was to characterize neurodevelopmental outcomes of children at 11 to 32 months of age with intrauterine ZIKV exposure and estimate the PAF of alterations secondary to ZIKV exposure. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cohort of biannual community-based prospective serosurveys in a slum community in Salvador, Brazil. We recruited women participating in our cohort, with a documented pregnancy from January 2015 to December 2016 and children born to those mothers. Children were classified as ZIKV exposed in utero (born from women with ZIKV seroconversion during pregnancy) or unexposed (born from women without ZIKV seroconversion or that seroconverted before/after pregnancy) by using an IgG monoclonal antibody blockade-of-binding (BoB). We interviewed mothers and performed anthropometric, audiometric, ophthalmological, neurologic, and neurodevelopmental evaluations of their children at 11 to 32 months of age. Among the 655 women participating in the cohort, 66 (10%) were pregnant during the study period. 46 (70%) of them completed follow-up, of whom ZIKV seroconversion occurred before, during, and after pregnancy in 25 (54%), 13 (28%), and 1 (2%), respectively. The rest of women, 7 (21.2%), did not present ZIKV seroconversion. At 11 to 32 months of life, the 13 ZIKV-exposed children had increased risk of mild cognitive delay (RR 5.1; 95%CI 1.1-24.4) compared with the 33 children unexposed, with a PAF of 53.5%. Exposed children also had increased risk of altered auditory behavior (RR 6.0; 95%CI 1.3-26.9), with a PAF of 59.5%. CONCLUSIONS: A significant proportion of children exposed in utero to ZIKV developed mild cognitive delay and auditory behavioral abnormalities even in the absence of gross birth defects such as microcephaly and other neurodevelopmental domains. Furthermore, our findings suggest that over half of these abnormalities could be attributed to intrauterine ZIKV exposure.

Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.

Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with pre-existing reactivity to DENV1 in humans.

Parámetros de composición corporal en pacientes VIH mediante el análisis de la biompedancia eléctrica

Se han descrito cambios en la composición corporal en pacientes VIH mediante el análisis de la bioimpedancia eléctrica (ABE). Hay pocos estudios que describan estos cambios en la composición corporal en pacientes VIH en Venezuela. Objetivo: Conocer cuáles son las características de la composición corporal de los pacientes VIH (Hospitalizados y Ambulatorios), período enero - agosto 2015. Materiales y Métodos: Estudio descriptivo - transversal. Tres grupos: Hospitalizados: pacVIH-h (n=22), Ambulatorio: pacVIH-a (n=47) y No VIH: Control (n=28). Se registraron género, peso, talla y LCD4+. Mediante ABE se obtuvo: Masa grasa (MG), Tejido adiposo abdominal (TAA), Agua corporal total (ACT), Agua intracelular (AIC), Agua extracelular (AEC), Masa celular corporal (MCC), Masa libre de grasa (MLG), Potasio corporal total (KCT), Ángulo de Fase (AF). Resultados: Peso, IMC, LCD4+ fue menor en pacVIH-h. La MG y TAA fue menor en grupos de pacientes VIH con respecto al Control. No hubo diferencias en Agua Corporal. MMC fue menor en pacVIH-a. AF fue menor en pacVIH. Una correlación significativa entre MG y TAA, y LCD4+. Conclusión: Este estudio ha permitido exponer y reconocer los aspectos relacionados con los cambios en la composición corporal que ocurren en el paciente VIH adulto. La relación entre el compartimento graso y CD4+ permitiría explorar el papel del tejido adiposo en la reconstitución inmune.

Body composition in HIV patients have been assessed previously using bioelectrical impedance analysis (BIA). Lack of studies that describes changes in body composition in Venezuelan HIV patients. Objective: To assess body composition characteristic of HIV patients (hospitalized, ambulatory) , period January-August 2015. Methods: Descriptive-transversal study. Three groups: hospitalized: HIV-h (n=22), ambulatory: HIV-a (n=47) and Control (n=28). Gender, weight, height, CD4+ were measured. By BIA: Fat Mass (FM), Abdominal Adipose Tissue (AAT), Total body water (TBW), Intracellular water (ICW), Extracellular water (ECW), Body cell mass (BCM),Free Fat Mass (FFM), Total body potassium (TBK), Phase angle (PA). Results: Weight, BMI, CD4+ were lower in HIV-h. FM and AAT were lower in HIV patients. Water compartment showed no differences. BCM were lower in HIV-a. PA was lower in HIV patients. Significant relationship between FM, ATT and CD4+ was found. Conclusions: This study let us expose and recognize body composition changes that occur in HIV patients. Relationship between FAT, AAT and CD4+ can let us explore the possible role of adipose tissue in immune reconstitution.

Zika Virus Infection and Stillbirths: A Case of Hydrops Fetalis, Hydranencephaly and Fetal Demise.

BACKGROUND: The rapid spread of Zika virus in the Americas and current outbreak of microcephaly in Brazil has raised attention to the possible deleterious effects that the virus may have on fetuses. METHODOLOGY/PRINCIPAL FINDINGS: We report a case of a 20-year-old pregnant woman who was referred to our service after a large Zika virus outbreak in the city of Salvador, Brazil with an ultrasound examination that showed intrauterine growth retardation of the fetus at the 18th gestational week. Ultrasound examinations in the 2nd and 3rd trimesters demonstrated severe microcephaly, hydranencephaly, intracranial calcifications and destructive lesions of posterior fossa, in addition to hydrothorax, ascites and subcutaneous edema. An induced labor was performed at the 32nd gestational week due to fetal demise and delivered a female fetus. ZIKV-specific real-time polymerase chain reaction amplification products were obtained from extracts of cerebral cortex, medulla oblongata and cerebrospinal and amniotic fluid, while extracts of heart, lung, liver, vitreous body of the eye and placenta did not yield detectable products. CONCLUSIONS/SIGNIFICANCE: This case report provides evidence that in addition to microcephaly, there may be a link between Zika virus infection and hydrops fetalis and fetal demise. Given the recent spread of the virus, systematic investigation of spontaneous abortions and stillbirths may be warranted to evaluate the risk that ZIKV infection imparts on these outcomes.

Iatrogenic aortic pseudoaneurysm: a forgotten complication.

Pseudoaneurysms of the ascending aorta are a rare complication of cardiac surgery. However, the poor prognosis associated with this condition if untreated makes early diagnosis and treatment important. We present the case of a 66-year-old woman who had undergone mitral valvuloplasty 12 days previously, who was admitted with a diagnosis of new-onset atrial fibrillation. The transthoracic echocardiogram showed a clot in the right atrium and anticoagulation was initiated, followed by antibiotic therapy. After further investigation, the patient was diagnosed with a pseudoaneurysm of the ascending aorta and underwent surgical repair, followed by six weeks of antibiotic therapy. She was readmitted six months later for an abscess of the lower sternum and mediastinum. After a conservative approach with antibiotics and local drainage failed, recurrence of a large pseudoaneurysm compressing the superior vena cava was documented. A third operation was performed to debride the infected tissue and to place an aortic allograft. There were no postoperative complications.

Improving RBC K transport and hemoglobin-O2 binding by amiloride: A novel therapeutic approach for reversion of angina and myocardial ischemia in coronary heart diseases.

UNLABELLED: Coronary heart disease (CHD) is the leading cause of morbidity and mortality across the entire world, in which reversion of angina or improvement of ECG remains an unrealistic therapeutic option for most patients, suggesting that microvascular dysfunction or impaired oxygen delivery might be critical factors in CHD. This research article, thus presents the rationale basis, clinical and experimental, for the first therapeutic innovation addressing the role of red blood cell (RBC) H/K and O2/CO2 exchanges in CHD. It is followed by a randomized single-blind trial of Amiloride and Optimal Medical Therapy (OMT, n=35 cases) vs OMT alone (n=35 cases) in patients having angina, ST-T alteration and a defective RBC-K transport. All patients had serial clinical evaluation, Ion Transport Studies, ECGs and non-invasive aortic waveform and cardiovascular hemodynamic recordings. Statistical analysis was performed by SAS. RESULTS: Amiloride rapidly improved RBC-K (93.5 ±4 vs 84.5 ±4 mmol/lc, p= < 0.001), angina (80% of cases, 1.5 ±0.3 weeks, CI:1.72 to 1.45), CCS Class (1.3 ±0.5 vs 3.1 ±0.8, p < 0.001) vs patients with OMT alone CCS Class (3.2 ± 0.4 vs 3.3 ± 0.5, p =0.21). Reversion of angina was sustained through the next 6-months (87% vs 26 % in OMT, RR 2.1, odds ratio 6.31, Pearson x2 34.6,p < 0.0001 at 95% CI) and 1-year (85% vs 37% OMT). At 6-months of amiloride, ECG became normal (29% vs 0%, RR ∞ uncalculated-time, odds ratio ∞, Pearson x2 42.4 at 95% CI, p < 0.0001), improved (55% vs 29%; RR2.1, odds ratio 3.16, 95% CI, p < 0.0001) or unchanged (15% vs 67% OMT). At 1-year, seven patients on amiloride (18%) exhibited evidence of electrical regeneration of the heart, not observed with placebo. IN CONCLUSION: This therapeutical innovation of amiloride improves RBC H/K and O2/CO2 function, and reverses angina, ST-T alterations while inducing electrical regeneration of the heart, in patients receiving optimal medical treatment for angina. The article has short discussion on the relevant patents to the topic.

Atribuições causais e nível educativo familiar na compreensão do desempenho escolar em alunos portugueses / Causal attributions and educational level of the family in understanding school performance in Portuguese students / Atribuciones causales y nivel educativo familiar en la comprensión del desempeño escolar en alumnos portugueses

Este artigo analisa o contributo específico do nível educativo familiar e das atribuições causais para o bom e fraco rendimento escolar dos alunos na explicação do seu desempenho nas disciplinas de Língua Portuguesa e de Matemática numa amostra de 2.082 alunos do ensino público de 11 escolas de Portugal, incluindo as Regiões Autónomas dos Açores e da Madeira. As atribuições causais foram avaliadas por meio do Questionário das Atribuições Causais para os Resultados Escolares (QARE). O nível educativo familiar foi estimado levando em conta o nível escolar do progenitor com maior habilitação escolar. As classificações obtidas pelos alunos nas disciplinas de língua portuguesa e matemática foram também examinadas. Os resultados apontam para correlações estatisticamente significativas, destacando as atribuições na capacidade para a explicação do rendimento escolar, situação que contrasta com a atribuição dos níveis de rendimento a variáveis externas ao aluno. A análise de regressão permite associar 34,5% da variância no rendimento conjunto em Língua Portuguesa e em Matemática no ensino básico, assim como 21,3% no ensino secundário, às dimensões atribucionais e ao nível educativo familiar. Implicações educacionais são derivadas a partir dos achados.

This paper analyzes the contribution of both family educational level and causal attributions in explaining students´ academic performance in Mathematics and Portuguese Language in a sample of 2.082 public school students from mainland Portugal and the Azores and Madeira regions. Causal attributions were assessed by the Causal Attributions Questionnaire for School Results (QARE). The family educational level was estimated taking into account the educational level of the parent with higher academic degree. The academic grades obtained by students in mathematics and portuguese language were also considered. The results show statistically significant correlations between variables. Internal causal attributions such as capacity and study methods were predominant to explain school performance in the sample and stood out in contrast to external attributions explanations. Regression analyses revealed that 34.5% of the variance in the combined achievement on Portuguese Language and Mathematics in primary education and 21.3% in secondary education could be explained by both the attributional dimensions and family education level. Some educational implications are present taking these data.

Este artículo analiza la contribución específica del nivel educativo familiar y de las atribuciones causales para el buen y el flaco rendimiento escolar de los alumnos en la explicación de su desempeño en las disciplinas de Lengua Portuguesa y Matemáticas en una muestra de 2.082 alumnos de enseñanza pública de 11 escuelas de Portugal, incluyendo las Regiones Autónomas de Açores y Madeira. Las atribuciones causales fueron evaluadas por medio del "Questionário das Atribuições Causais para os Resultados Escolares" (QARE). El nivel educativo familiar fue estimado teniendo en cuenta el nivel escolar del progenitor con mayor habilitación escolar. Las clasificaciones obtenidas por los alumnos en las disciplinas de lengua portuguesa y matemáticas fueron también examinadas. Los resultados señalaron correlaciones estadísticamente significativas, destacando las atribuciones en la capacidad para la explicación del rendimiento escolar, situación que contrasta con la atribución de los niveles de rendimiento a variables externas al alumno. El análisis de regresión permite asociar 34.5% de la variancia en el rendimiento conjunto de la Lengua Portuguesa y las Matemáticas en la enseñanza básica, así como 21.3% en la enseñanza secundaria, a las dimensiones de atribución y al nivel educativo familiar. Implicaciones educacionales son derivadas a partir de los hallazgos.