Associations between neighborhood violence during pregnancy and birth outcomes: evidence from Sao Paulo's Western Region Birth Cohort

BACKGROUND: Low birth weight and prematurity remain leading causes of infant mortality and morbidity globally. Although extensive literature has highlighted the importance of socioenvironmental characteristics for birth outcomes, the role of indirect violence on health remains fairly understudied. METHODS: Using geocoded birth records from the ongoing Western Region Birth Cohort (Regiao Oeste Coorte - ROC-Cohort) of infants born between 2012 and 2014 and geocoded crime reports, we assessed the associations between exposure to violent crimes during pregnancy within a 1-km radius of the mother's residence and low birth weight, preterm delivery, and being born small-for-gestational-age. Violent crime exposure was categorized into quintiles. Multivariate logistic regressions were used to examine the associations between violence exposure and birth outcomes. Models were adjusted for sex, maternal age and education, socioeconomic status, and risk factors such as hypertension, diabetes, smoking, and drinking during pregnancy. RESULTS: Among the 5268 children included, the average crime exposure during the first two trimesters of pregnancy ranged from 0.44 violent crimes in the least exposed quintile to 12.74 crimes in the most exposed. Compared to children with the lowest violence exposure, children in the highest exposure quintile had higher odds of being born small-for-gestational-age (1.41[1.06-1.89]), preterm (1.35[1.01-1.80]), and low birth weight (1.42[1.03-1.98]). While socioeconomic status and maternal education were positively associated with lower violence exposure, no associations were found between these characteristics and birth outcomes. CONCLUSIONS: Higher exposure to violent crimes in the close vicinity of pregnant women's residence is associated with substantial increases in the odds of adverse birth outcomes. Policies to improve neighborhood safety can potentially contribute not only to the short-term wellbeing of populations but may also have large social, economic, and health benefits in the long term

Impact of COVID-19 on maternal health and child care behavior: evidence from a quasi-experimental study of vulnerable communities in Boa Vista, Brazil

BACKGROUND: COVID-19 related distress has been shown to have negative associations with family well-being. OBJECTIVES: To determine the immediate impact of acute COVID-19 infection on maternal well-being and parenting practices among Brazilian families. PARTICIPANTS AND SETTING: We studied 2'579 mothers (29'913 observations) of young children from vulnerable neighborhoods in Boa Vista, Brazil over 12 months. METHODS: We monitored family health and caregiving behavior including the incidence of COVID-19 infections in the surveyed households through bi-weekly phone interviews over 50 weeks, from June 2020 to May 2021. Primary outcomes were home-based child stimulation, positive parenting behavior, and parenting stress. We used fixed effects panel regressions to estimate the impact of household COVID-19 infections on parenting outcomes. RESULTS: Over the study period, 441 participants (17.1%; 831 (3.0%) observations) reported at least 1 positive COVID-19 infection in their household. Household COVID-19 infections significantly reduced home-based stimulation by 0.10 SDs (95%CI: -0.18, -0.01), positive parenting behaviors by 0.14 SDs (-0.21, -0.01), and increased parenting stress by 0.07 SDs (0.02, 0.12). The impact on home-based stimulation was most pronounced when the mother herself had a COVID-19 infection (-0.16; -0.29, -0.04). Parenting stress responded most strongly to mother or child COVID-19 infections. Effects were relatively short-lived, only children's infections' on parental stress was still detectable 2 weeks after initial infection. CONCLUSION: Our findings suggest that COVID-19 infections cause substantial disruptions in children's home environments - additional short-term support for families with acute infections could attenuate the negative impact on children's home environment during the pandemic

Tumor slices as a model to evaluate doxorubicin in vitro treatment and expression of trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 in canine mammary gland cancer

<p>Abstract</p> <p>Background</p> <p>In women with breast cancer submitted to neoadjuvant chemotherapy based in doxorubicin, tumor expression of groups of three genes (PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2) have classified them as responsive or resistant. We have investigated whether expression of these trios of genes could predict mammary carcinoma response in dogs and whether tumor slices, which maintain epithelial-mesenchymal interactions, could be used to evaluate drug response <it>in vitro</it>.</p> <p>Methods</p> <p>Tumors from 38 dogs were sliced and cultured with or without doxorubicin 1 μM for 24 h. Tumor cells were counted by two observers to establish a percentage variation in cell number, between slices. Based on these results, a reduction in cell number between treated and control samples ≥ 21.7%, arbitrarily classified samples, as drug responsive. Tumor expression of PRSS11, MTSS1, CLPTM1 and SMYD2, was evaluated by real time PCR. Relative expression results were then transformed to their natural logarithm values, which were spatially disposed according to the expression of trios of genes, comprising PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. Fisher linear discrimination test was used to generate a separation plane between responsive and non-responsive tumors.</p> <p>Results</p> <p>Culture of tumor slices for 24 h was feasible. Nine samples were considered responsive and 29 non-responsive to doxorubicin, considering the pre-established cut-off value of cell number reduction ≥ 21.7%, between doxorubicin treated and control samples. Relative gene expression was evaluated and tumor samples were then spatially distributed according to the expression of the trios of genes: PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. A separation plane was generated. However, no clear separation between responsive and non-responsive samples could be observed.</p> <p>Conclusion</p> <p>Three-dimensional distribution of samples according to the expression of the trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 could not predict doxorubicin <it>in vitro </it>responsiveness. Short term culture of mammary gland cancer slices may be an interesting model to evaluate chemotherapy activity.</p

Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure

BACKGROUND: Physiological maternal stress response, such as imbalance in the glucocorticoid pathway and immune system seems to be mediated by DNA methylation (DNAm) and might translate intrauterine stress exposures into phenotypic changes in a sex-specific manner. DNAm in specific sites can also predict newborn gestational age and gestational age acceleration (GAA). GAA occurs when the predicted biological age is higher than the chronological age. In adults, poor health outcomes related to this deviance are well documented and raise questions for the interpretation and prediction in early stages of life. Boys seem to be more vulnerable to intrauterine stress exposure than girls; however, the mechanisms of adaptive sex-specific responses are still unclear. We hypothesize that intrauterine stress exposure is associated with GAA and could be different in boys and girls if inflammatory or glucocorticoid pathways exposure is considered. RESULTS: Using the Western Region Birth Cohort (ROC-Sao Paulo, Brazil) (n = 83), we calculated DNAm age and GAA from cord blood samples. Two epigenetic risk scores were calculated as an indirect proxy for low-grade inflammation (i-ePGS) and for glucocorticoid exposure (GES). Multivariate linear regression models were applied to investigate associations of GAA with prenatal exposures. The i-ePGS and GES were included in different models with the same co-variates considering sex interactions. The first multivariate model investigating inflammatory exposure (adj. R(2) = 0.31, p = < 0.001) showed that GAA was positively associated with i-ePGS (CI, 0.26-113.87, p = 0.049) and negative pregnancy-related feelings (CI, 0.04-0.48 p = 0.019). No sex interaction was observed. The second model investigating glucocorticoid exposure (adj. R(2) = 0.32, p = < 0.001) showed that the higher was the GAA was associated with a lower the lower was the GES in girls (CI, 0.04-2.55, p = 0.044). In both models, maternal self-reported mental disorder was negatively associated with GAA. CONCLUSION: Prenatal epigenetic score of exposure to low-grade inflammatory was a predictor of GAA for both sexes. Glucocorticoid epigenetic score seems to be more important to GAA in girls. This study supports the evidence of sex-specificity in stress response, suggesting the glucocorticoid as a possible pathway adopted by girls to accelerate the maturation in an adverse condition

Land use regression modelling of NO2 in São Paulo, Brazil

BACKGROUND: Air pollution is a major global public health problem. The situation is most severe in low- and middle-income countries, where pollution control measures and monitoring systems are largely lacking. Data to quantify the exposure to air pollution in low-income settings are scarce. METHODS: In this study, land use regression models (LUR) were developed to predict the outdoor nitrogen dioxide (NO2) concentration in the study area of the Western Region Birth Cohort in Sao Paulo. NO2 measurements were performed for one week in winter and summer at eighty locations. Additionally, weekly measurements at one regional background location were performed over a full one-year period to create an annual prediction. RESULTS: Three LUR models were developed (annual, summer, winter) by using a supervised stepwise linear regression method. The winter, summer and annual models explained 52 %, 75 % and 66 % of the variance (R(2)) respectively. Cross-holdout validation tests suggest robust models. NO2 levels ranged from 43.2 mug/m(3) to 93.4 mug/m(3) in the winter and between 28.1 mug/m(3) and 72.8 mug/m(3) in summer. Based on our annual prediction, about 67 % of the population living in the study area is exposed to NO2 values over the WHO suggested annual guideline of 40 mug/m(3) annual average. CONCLUSION: In this study we were able to develop robust models to predict NO2 residential exposure. We could show that average measures, and therefore the predictions of NO2, in such a complex urban area are substantially high and that a major variability within the area and especially within the season is present. These findings also suggest that in general a high proportion of the population is exposed to high NO2 levels

Association between community noise and children's cognitive and behavioral development: a prospective cohort study

BACKGROUND: Noise exposure has been associated with adverse cognitive and behavioral outcomes in children, but evidence on longitudinal associations between community noise and child development in low- and middle-income countries is rare. We investigated associations between community noise and behavioral and cognitive development in preschool children in Sao Paulo. METHODS: We linked child development data from the Sao Paulo Western Region Birth Cohort with average (Lden) and night-time (Lnight) community noise exposure at children's home, estimated by means of a land use regression model using various predictors (roads, schools, greenness, residential and informal settlements). Outcomes were the Strengths and Difficulties Questionnaire (SDQ) and Regional Project on Child Development Indicators (PRIDI) at 3 years of age and the Child Behavior Checklist (CBCL) and International Development and Early Learning Assessment (IDELA) at 6 years of age. We investigated the relationship between noise exposure and development using cross-sectional and longitudinal regression models. RESULTS: Data from 3385 children at 3 years of age and 1546 children at 6 years of age were analysed. Mean Lden and Lnight levels were 70.3 dB and 61.2 dB, respectively. In cross-sectional analyses a 10 dB increase of Lden above 70 dB was associated with a 32% increase in the odds of borderline or abnormal SDQ total difficulties score (OR = 1.32, 95% CI: 1.04; 1.68) and 0.72 standard deviation (SD) increase in the CBCL total problems z-score (95% CI: 0.55; 0.88). No cross-sectional association was found for cognitive development. In longitudinal analyses, each 10 dB increase was associated with a 0.52 SD increase in behavioral problems (95% CI: 0.28; 0.77) and a 0.27 SD decrease in cognition (95%-CI: 0.55; 0.00). Results for Lnight above 60 dB were similar. DISCUSSION: Our findings suggest that community noise exposure above Lden of 70 dB and Lnight of 60 dB may impair behavioral and cognitive development of preschool children

Land use regression modelling of community noise in São Paulo, Brazil

Noise pollution has negative health consequences, which becomes increasingly relevant with rapid urbanization. In low- and middle-income countries research on health effects of noise is hampered by scarce exposure data and noise maps. In this study, we developed land use regression (LUR) models to assess spatial variability of community noise in the Western Region of Sao Paulo, Brazil.We measured outdoor noise levels continuously at 42 homes once or twice during one week in the summer and the winter season. These measurements were integrated with various geographic information system variables to develop LUR models for predicting average A-weighted (dB(A)) day-evening-night equivalent sound levels (Lden) and night sound levels (Lnight). A supervised mixed linear regression analysis was conducted to test potential noise predictors for various buffer sizes and distances between home and noise source.Noise exposure levels in the study area were high with a site average Lden of 69.3 dB(A) ranging from 60.3 to 82.3 dB(A), and a site average Lnight of 59.9 dB(A) ranging from 50.7 to 76.6 dB(A). LUR models had a good fit with a R(2) of 0.56 for Lden and 0.63 for Lnight in a leave-one-site-out cross validation. Main predictors of noise were the inverse distance to medium roads, count of educational facilities within a 400 m buffer, mean Normalized Difference Vegetation Index (NDVI) within a 100 m buffer, residential areas within a 50 m (Lden) or 25 m (Lnight) buffer and slum areas within a 400 m buffer. Our study suggests that LUR modelling with geographic predictor data is a promising and efficient approach for noise exposure assessment in low- and middle-income countries, where noise maps are not available

GeoHealth: A Georeferenced System for Health Data Analysis in Primary Care

The Primary Care Information System (SIAB) concentrates basic healthcare information from all different regions of Brazil. The information is collected by primary care teams on a paper-based procedure that degrades the quality of information provided to the healthcare authorities and slows down the process of decision making. To overcome these problems we propose a new data gathering application that uses a mobile device connected to a 3G network and a GPS to be used by the primary care teams for collecting the families' data. A prototype was developed in which a digital version of one SIAB form is made available at the mobile device. The prototype was tested in a basic healthcare unit located in a suburb of Sao Paulo. The results obtained so far have shown that the proposed process is a better alternative for data collecting at primary care, both in terms of data quality and lower deployment time to health care authorities

Transcriptome signature of the adult mouse choroid plexus

<p>Abstract</p> <p>Background</p> <p>Although the gene expression profile of several tissues in humans and in rodent animal models has been explored, analysis of the complete choroid plexus (CP) transcriptome is still lacking. A better characterization of the CP transcriptome can provide key insights into its functions as one of the barriers that separate the brain from the periphery and in the production of cerebrospinal fluid.</p> <p>Methods</p> <p>This work extends further what is known about the mouse CP transcriptome through a microarray analysis of CP tissue from normal mice under physiological conditions.</p> <p>Results</p> <p>We found that the genes most highly expressed are those implicated in energy metabolism (oxidative phosphorylation, glycolysis/gluconeogenesis) and in ribosomal function, which is in agreement with the secretory nature of the CP. On the other hand, genes encoding for immune mediators are among those with lower expression in basal conditions. In addition, we found genes known to be relevant during brain development, and not previously identified to be expressed in the CP, including those encoding for various axonal guidance and angiogenesis molecules and for growth factors. Some of these are known to influence the neural stem cell niche in the subventricular zone, highlighting the involvement of the CP as a likely modulator of neurogenesis. Interestingly, our observations confirm that the CP transcriptome is unique, displaying low homology with that of other tissues. Of note, we describe here that the closest similarity is with the transcriptome of the endothelial cells of the blood-brain barrier.</p> <p>Conclusions</p> <p>Based on the data presented here, it will now be possible to further explore the function of particular proteins of the CP secretome in health and in disease.</p