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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. Author summary: ZIKV is a neurotropic virus associated with congenital abnormalities that have been grouped under congenital Zika syndrome (CZS), the most prominent being microcephaly. Recent studies have uncovered a spectrum of other abnormalities. However, what remains unclear is the Population Attributable Fraction (PAF) of developmental alterations attributable to ZIKV intrauterine exposure in children (> one year of life). In this population-based cohort study, we found that children (without microcephaly) exposed in utero to ZIKV have an increased incidence of mild cognitive delay and auditory behavior abnormalities, with over half of these events attributable to intrauterine exposure. The results of this study suggest that more than half of alterations found in the population study can be attributed to intrauterine ZIKV exposure, thus demonstrating the importance of monitoring apparently healthy children born during the epidemic, even to asymptomatic mothers. Health services should implement early interventions to limit the morbidity of congenital ZIKV infection. [ABSTRACT FROM AUTHOR]

Aim: To identify potential predictors of community integration in individuals after stroke using a residential setting-based strategy. Method: A prospective cohort of post-stroke individuals was recruited from the Stroke Unit of the Roberto Santos General Hospital (UAVC-HGRS). All included individuals were aged over 18 years, received a diagnosis of ischemic stroke confirmed by neuroimaging and resided in the city of Salvador (Bahia, Brazil). Following discharge from the stroke unit, the individuals themselves, or their responsible parties, were contacted by telephone to schedule a home visit no less than three months after discharge. All subjects were examined in their homes, at which time the Community Integration Questionnaire (CIQ) was also applied. A robust linear regression model was used to assess community reintegration using CIQ score as the outcome variable. Results: A total of 124 individuals effectively fulfilled the eligibility criteria: 51.6% were females, the median (IQR) age was 63(53–69) years, 82.3% were non-white, 53.2% were married, the median (IQR) of years of schooling was 6 (4–12) and family income averaged two minimum monthly wages. Investigated individuals presented a median (IQR) NIH Stroke Scale (NIHSS) score of 7 (4–12). Multivariate linear regression identified the following independent predictors of community integration: age (β = -0.095; 95% CI = -0.165 to -0.025; p = 0.008), diabetes mellitus (β = -2.348; 95% CI = -4.125 to -0.571; p = 0.010), smoking habit (β = -2.951; 95% CI = -5.081 to -0.821; p = 0.007), functional capacity upon hospital discharge (β = 0.168; 95% CI = 0.093 to 0.242; p = <0.001) and stroke severity (β = -0.163; CI = -0.318 to -0.009); p = 0.038). Conclusions: Regardless of length of time since stroke, individuals present restrictions that compromise their reintegration into their respective communities. The demographic, clinical and functional factors identified herein as potential predictors should be considered when conducting regular follow-up, as well as in the rehabilitation of individuals after stroke with the purpose to identify the interventions necessary to optimize their reintegration into the community. [ABSTRACT FROM AUTHOR]

Background and Objective: Recently, we have shown that the Parkinson’s disease (PD) susceptibility locus MAPT (microtubule associated protein tau) is associated with parkinsonism in older adults without a clinical diagnosis of PD. In this study, we investigated the relationship between parkinsonian signs and MAPT transcripts by assessing the effect of MAPT haplotypes on alternative splicing and expression levels of the most common isoforms in two prospective clinicopathologic studies of aging. Materials and Methods: using regression analysis, controlling for age, sex, study and neuropathology, we evaluated 976 subjects with clinical, genotyping and brain pathology data for haplotype analysis. For transcript analysis, we obtained MAPT gene and isoform-level expression from the dorsolateral prefrontal cortex for 505 of these subjects. Results: The MAPT H2 haplotype was associated with lower total MAPT expression (p = 1.2x10-14) and global parkinsonism at both study entry (p = 0.001) and proximate to death (p = 0.050). Specifically, haplotype H2 was primarily associated with bradykinesia in both assessments (p<0.001 and p = 0.008). MAPT total expression was associated with age and decreases linearly with advancing age (p<0.001). Analysing MAPT alternative splicing, the expression of 1N/4R isoform was inversely associated with global parkinsonism (p = 0.008) and bradykinesia (p = 0.008). Diminished 1N/4R isoform expression was also associated with H2 (p = 0.001). Conclusions: Overall, our results suggest that age and H2 are associated with higher parkinsonism score and decreased total MAPT RNA expression. Additionally, we found that H2 and parkinsonism are associated with altered expression levels of specific isoforms. These findings may contribute to the understanding of the association between MAPT locus and parkinsonism in elderly subjects and in some extent to age-related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

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 (β = 0.29; CI 95% = 0.02-0.57) and motor raw scores (β = 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 (β = 1.27; CI 95% = 0.01-2.53) and motor raw scores (β = 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., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: The authors declare that there is no conflict of interest.