Associations between insomnia and pregnancy and perinatal outcomes: Evidence from mendelian randomization and multivariable regression analyses.

BACKGROUND: Insomnia is common and associated with adverse pregnancy and perinatal outcomes in observational studies. However, those associations could be vulnerable to residual confounding or reverse causality. Our aim was to estimate the association of insomnia with stillbirth, miscarriage, gestational diabetes (GD), hypertensive disorders of pregnancy (HDP), perinatal depression, preterm birth (PTB), and low/high offspring birthweight (LBW/HBW). METHODS AND FINDINGS: We used 2-sample mendelian randomization (MR) with 81 single-nucleotide polymorphisms (SNPs) instrumenting for a lifelong predisposition to insomnia. Our outcomes included ever experiencing stillbirth, ever experiencing miscarriage, GD, HDP, perinatal depression, PTB (gestational age <37 completed weeks), LBW (<2,500 grams), and HBW (>4,500 grams). We used data from women of European descent (N = 356,069, mean ages at delivery 25.5 to 30.0 years) from UK Biobank (UKB), FinnGen, Avon Longitudinal Study of Parents and Children (ALSPAC), Born in Bradford (BiB), and the Norwegian Mother, Father and Child Cohort (MoBa). Main MR analyses used inverse variance weighting (IVW), with weighted median and MR-Egger as sensitivity analyses. We compared MR estimates with multivariable regression of insomnia in pregnancy on outcomes in ALSPAC (N = 11,745). IVW showed evidence of an association of genetic susceptibility to insomnia with miscarriage (odds ratio (OR): 1.60, 95% confidence interval (CI): 1.18, 2.17, p = 0.002), perinatal depression (OR 3.56, 95% CI: 1.49, 8.54, p = 0.004), and LBW (OR 3.17, 95% CI: 1.69, 5.96, p < 0.001). IVW results did not support associations of insomnia with stillbirth, GD, HDP, PTB, and HBW, with wide CIs including the null. Associations of genetic susceptibility to insomnia with miscarriage, perinatal depression, and LBW were not observed in weighted median or MR-Egger analyses. Results from these sensitivity analyses were directionally consistent with IVW results for all outcomes, with the exception of GD, perinatal depression, and PTB in MR-Egger. Multivariable regression showed associations of insomnia at 18 weeks of gestation with perinatal depression (OR 2.96, 95% CI: 2.42, 3.63, p < 0.001), but not with LBW (OR 0.92, 95% CI: 0.69, 1.24, p = 0.60). Multivariable regression with miscarriage and stillbirth was not possible due to small numbers in index pregnancies. Key limitations are potential horizontal pleiotropy (particularly for perinatal depression) and low statistical power in MR, and residual confounding in multivariable regression. CONCLUSIONS: In this study, we observed some evidence in support of a possible causal relationship between genetically predicted insomnia and miscarriage, perinatal depression, and LBW. Our study also found observational evidence in support of an association between insomnia in pregnancy and perinatal depression, with no clear multivariable evidence of an association with LBW. Our findings highlight the importance of healthy sleep in women of reproductive age, though replication in larger studies, including with genetic instruments specific to insomnia in pregnancy are important.

Genome-wide association study of anti-Müllerian hormone levels in pre-menopausal women of late reproductive age and relationship with genetic determinants of reproductive lifespan.

Anti-Müllerian hormone (AMH) is required for sexual differentiation in the fetus, and in adult females AMH is produced by growing ovarian follicles. Consequently, AMH levels are correlated with ovarian reserve, declining towards menopause when the oocyte pool is exhausted. A previous genome-wide association study identified three genetic variants in and around the AMH gene that explained 25% of variation in AMH levels in adolescent males but did not identify any genetic associations reaching genome-wide significance in adolescent females. To explore the role of genetic variation in determining AMH levels in women of late reproductive age, we carried out a genome-wide meta-analysis in 3344 pre-menopausal women from five cohorts (median age 44-48 years at blood draw). A single genetic variant, rs16991615, previously associated with age at menopause, reached genome-wide significance at P = 3.48 × 10-10, with a per allele difference in age-adjusted inverse normal AMH of 0.26 standard deviations (SD) (95% confidence interval (CI) [0.18,0.34]). We investigated whether genetic determinants of female reproductive lifespan were more generally associated with pre-menopausal AMH levels. Genetically-predicted age at menarche had no robust association but genetically-predicted age at menopause was associated with lower AMH levels by 0.18 SD (95% CI [0.14,0.21]) in age-adjusted inverse normal AMH per one-year earlier age at menopause. Our findings provide genetic support for the well-established use of AMH as a marker of ovarian reserve.

Sex differences in systemic metabolites at four life stages: cohort study with repeated metabolomics.

BACKGROUND: Males experience higher rates of coronary heart disease (CHD) than females, but the circulating traits underpinning this difference are poorly understood. We examined sex differences in systemic metabolites measured at four life stages, spanning childhood to middle adulthood. METHODS: Data were from the Avon Longitudinal Study of Parents and Children (7727 offspring, 49% male; and 6500 parents, 29% male). Proton nuclear magnetic resonance (1H-NMR) spectroscopy from a targeted metabolomics platform was performed on EDTA-plasma or serum samples to quantify 229 systemic metabolites (including lipoprotein-subclass-specific lipids, pre-glycaemic factors, and inflammatory glycoprotein acetyls). Metabolites were measured in the same offspring once in childhood (mean age 8 years), twice in adolescence (16 years and 18 years) and once in early adulthood (25 years), and in their parents once in middle adulthood (50 years). Linear regression models estimated differences in metabolites for males versus females on each occasion (serial cross-sectional associations). RESULTS: At 8 years, total lipids in very-low-density lipoproteins (VLDL) were lower in males; levels were higher in males at 16 years and higher still by 18 years and 50 years (among parents) for medium-or-larger subclasses. Larger sex differences at older ages were most pronounced for VLDL triglycerides-males had 0.19 standard deviations (SD) (95% CI = 0.12, 0.26) higher at 18 years, 0.50 SD (95% CI = 0.42, 0.57) higher at 25 years, and 0.62 SD (95% CI = 0.55, 0.68) higher at 50 years. Low-density lipoprotein (LDL) cholesterol, apolipoprotein-B, and glycoprotein acetyls were generally lower in males across ages. The direction and magnitude of effects were largely unchanged when adjusting for body mass index measured at the time of metabolite assessment on each occasion. CONCLUSIONS: Our results suggest that males begin to have higher VLDL triglyceride levels in adolescence, with larger sex differences at older ages. Sex differences in other CHD-relevant metabolites, including LDL cholesterol, show the opposite pattern with age, with higher levels among females. Such life course trends may inform causal analyses with clinical endpoints in specifying traits which underpin higher age-adjusted CHD rates commonly seen among males.

Pharmacokinetics of amoxicillin in obese and nonobese subjects.

AIMS: To compare the pharmacokinetics of amoxicillin (AMX) in obese and nonobese subjects, given as single dose 875-mg tablets. METHODS: A prospective, single-centre, open-label, clinical study was carried out involving 10 nonobese and 20 obese subjects given a dose of an AMX 875-mg tablet. Serial blood samples were collected between 0 and 8 hours after administration of AMX and plasma levels were quantified by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters (PK) were calculated by noncompartmental analysis and means of the 2 groups were compared using Student t-test. Analysis of correlation between covariates and PK was performed using Pearson's correlation coefficient. RESULTS: Ten nonobese subjects (mean age 30.6 ± 7.12 y; body mass index 21.56 ± 1.95 kg/m2 ) and 20 obese subjects (mean age 34.47 ± 7.03 y; body mass index 33.17 ± 2.38 kg/m2 ) participated in the study. Both maximum concentration (Cmax ; 12.12 ± 4.06 vs. 9.66 ± 2.93 mg/L) and area under the curve (AUC)0-inf (34.18 ± 12.94 mg.h/L vs. 26.88 ± 9.24 mg.h/L) were slightly higher in nonobese than in obese subjects, respectively, but differences were not significant. The volume of distribution (V/F) parameter was statistically significantly higher in obese compared to nonobese patients (44.20 ± 17.85 L vs. 27.57 ± 12.96 L). Statistically significant correlations were observed for several weight metrics vs. AUC, Cmax , V/F and clearance, and for creatinine clearance vs. AUC, Cmax and clearance. CONCLUSION: In obese subjects, the main altered PK was V/F as a consequence of greater body weight. This may result in antibiotic treatment failure if standard therapeutic regimens are administered.

A comparison of the associations between adiposity and lipids in Malawi and the United Kingdom.

BACKGROUND: The prevalence of excess adiposity, as measured by elevated body mass index (BMI) and waist-hip ratio (WHR), is increasing in sub-Saharan African (SSA) populations. This could add a considerable burden of cardiovascular and metabolic diseases for which these populations are currently ill-prepared. Evidence from white, European origin populations shows that higher adiposity leads to an adverse lipid profile; whether these associations are similar in all SSA populations requires further exploration. This study compared the association of BMI and WHR with lipid profile in urban Malawi with a contemporary cohort with contrasting socioeconomic, demographic, and ethnic characteristics in the United Kingdom (UK). METHODS: We used data from 1248 adolescents (mean 18.7 years) and 2277 Malawian adults (mean 49.8 years), all urban-dwelling, and from 3201 adolescents (mean 17.8 years) and 6323 adults (mean 49.7 years) resident in the UK. Adiposity measures and fasting lipids were assessed in both settings, and the associations of BMI and WHR with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were assessed by sex and age groups in both studies. RESULTS: Malawian female adults were more adipose and had more adverse lipid profiles than their UK counterparts. In contrast, Malawian adolescent and adult males were leaner and had more favourable lipid profiles than in the UK. Higher BMI and WHR were associated with increased TC, LDL-C and TG and reduced HDL-C in both settings. The magnitude of the associations of BMI and WHR with lipids was mostly similar or slightly weaker in the Malawian compared with the UK cohort in both adolescents and adults. One exception was the stronger association between increasing adiposity and elevated TC and LDL-C in Malawian compared to UK men. CONCLUSIONS: Malawian adult women have greater adiposity and more adverse lipid profiles compared with their UK counterparts. Similar associations of adiposity with adverse lipid profiles were observed for Malawian and UK adults in most age and sex groups studied. Sustained efforts are urgently needed to address the excess adiposity and adverse lipid profiles in Malawi to mitigate a future epidemic of cardio-metabolic disease among the poorest populations.

Changes in six domains of cognitive function with reproductive and chronological ageing and sex hormones: a longitudinal study in 2411 UK mid-life women.

BACKGROUND: There may be changes in cognitive function in women going through the menopause. The current evidence remains unclear, however, whether these changes occur over and above those of general ageing. We aimed to evaluate the potential impact of the menopause (assessed by reproductive age and hormone levels) on cognitive function in women in mid-life accounting for the underlying effects of ageing. METHODS: The study was based on the follow up of women originally enrolled in pregnancy in a birth cohort when resident in the South West of England, UK between 1991 and 1992. Using up to three repeated measurements in 2411 women (mean age 51 at first assessment), we modelled changes in six cognitive function domains: immediate and delayed verbal episodic memory, working memory, processing speed, verbal intelligence and verbal fluency. The exposures of interest were reproductive age measured as years relative to the final menstrual period (FMP), chronological age and reproductive hormones (follicle-stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH)). RESULTS: Processing speed (- 0.21 (95% CI - 0.36 to - 0.06) standard deviation (SD) difference per 10 years since FMP), immediate verbal episodic memory (- 0.15 (95% CI - 0.35 to 0.06)) and delayed verbal episodic memory (- 0.17 (95% CI - 0.37 to 0.03)) declined with reproductive age. Reproductive hormones were not robustly associated with processing speed, but FSH and LH were both negatively associated with immediate (- 0.08 (95% CI - 0.13 to - 0.02) SD difference per SD difference in hormone level) and delayed verbal episodic memory (- 0.08 (95% CI - 0.13 to - 0.03)). There was little consistent evidence of cognitive function declining with menopause in other cognitive domains. CONCLUSIONS: Of the cognitive domains tested only verbal episodic memory declined both in relation to age since the menopause and in conjunction with the reproductive hormones that reflect the menopause. This decline was independent of normal ageing and suggests that the menopause is associated with a mild impact on this specific domain of cognitive function.

[Breastfeeding and externalizing behaviors in childhood and adolescence in a birth cohort]. / Amamentação e comportamentos externalizantes na infância e adolescência em uma coorte de nascimentos.

OBJECTIVE: To assess the association between breastfeeding duration and externalizing behaviors in childhood and adolescence. METHODS: Data from the 1993 Pelotas Birth Cohort was used. Information on breastfeeding was assessed at 12 months of age. Behavior was assessed at 4 years of age using the Child Behavior Checklist (CBCL), and at ages 11 and 15 years using the Strengths and Difficulties Questionnaire (SDQ), both administered to the mother or caretaker. Of 5 249 cohort participants, those with complete data on breastfeeding and externalizing behaviors were included: 630 children at 4 years of age, 1 277 adolescents at 11 years, and 1 199 at 15 years. Poisson regression with robust variance was used to assess the association between breastfeeding duration and externalizing behaviors. RESULTS: After adjustment for confounders, children who were breastfed for least 6 months had lower risk of hyperactivity (RR = 0.54; 95%CI: 0.32-0.91) at age 11 compared to those breastfed for less than 1 month. However, no association was observed between breastfeeding duration and externalizing behaviors at ages 4 and 15. CONCLUSIONS: Although breastfeeding for at least 6 months was inversely associated with hyperactivity at 11 years of age no association was observed at 4 and 15 years of age. Further longitudinal studies should focus on other aspects influencing externalizing behaviors, such as presence of the father in the family, domestic violence and abuse, and the quality of mother-child relationship.

Parental Separation and Cardiometabolic Risk Factors in Late Adolescence: A Cross-Cohort Comparison.

The aim of this study was to explore the association between parental separation during childhood (up to 18 years of age) and cardiometabolic risk factors (body mass index, fat mass index, blood pressure, physical activity, smoking, and alcohol consumption) in late adolescence using a cross-cohort comparison and to explore whether associations differ according to the age at which the parental separation occurred and the presence or absence of parental conflict prior to separation. Data from the Avon Longitudinal Study of Parents and Children (ALSPAC, United Kingdom) (1991-2011) and the 1993 Pelotas Birth Cohort (Brazil) (1993-2011) were used. The associations of parental separation with children's cardiometabolic risk factors were largely null. Higher odds of daily smoking were observed in both cohorts for those adolescents whose parents separated (for ALSPAC, odds ratio = 1.46; for Pelotas Birth Cohort, odds ratio = 1.98). Some additional associations were observed in the Pelotas Birth Cohort but were generally in the opposite direction to our a priori hypothesis: Parental separation was associated with lower blood pressure and fat mass index, and with more physical activity. No consistent differences were observed when analyses were stratified by child's age at parental separation or parental conflict.

Evaluation of violations in water quality standards in the monitoring network of São Francisco River basin, the third largest in Brazil.

The São Francisco River is the largest river located entirely within Brazil, and water scarcity problems have been a major concern of Brazilian society and government. Water quality issues are also a concern and have worsened with the recent intensification of urbanization and industrialization. In this study, violations to water quality standards established by local legislation were calculated as a percentage for 26 selected parameters over a monitoring period of 14 years. The violation percentages were analyzed spatially using the Kruskal-Wallis test, followed by multiple comparison analysis. Temporal analysis was performed using the Mann-Kendall test and Spearman correlation. Some parameters could be identified as cause for concern due to high violation levels, such as the fecal coliform indicator (FCI) and phosphorus-both related to domestic and effluent disposal without treatment or with insufficient treatment-and color, turbidity, manganese, and total suspended solids-which can be affected by erosive processes of natural and anthropogenic causes. The study found that these violations are concentrated in the most urbanized and industrialized areas of the basin. Some metallic parameters, such as iron and arsenic violations, may be related to mining activities in the rich soil of the Iron Quadrangle area located within the Minas Gerais State. Trend analysis results indicated that most monitoring stations did not have significant modification (elevation or reduction) trends over time, which, together with the high violation percentages, might indicate the maintenance of a scenario of constant pressure upon water resources, in particular in those more urbanized areas.

Prevalence, co-occurrence, and associated factors of intimate partner violence among Brazilian university students.

Intimate Partner Violence (IPV) among youth is a public health problem worldwide because of its high prevalence and lifelong serious consequences in health and quality of life. This cross-sectional census aimed to describe the IPV victimization among all freshman students in a Brazilian university (n=1,509), which was selected from a larger population of 2,706 freshmen. We created a 10-item questionnaire inspired by established instruments to measure the prevalence of IPV. Multivariate logistic regression assessed the association between demographic, socioeconomic, and behavioral factors with various types of IPV. We visualized co-occurrence using a Venn diagram and employed multinomial logistic regression to examine the relationship between covariates and the cooccurrence of IPV types. The chance of IPV was higher in males, those who were currently in a relationship, and those with a higher risk of alcohol abuse. These same characteristics were also associated with an increased likelihood of experiencing the co-occurrence of two or more types of IPV. Prevention strategies should consider those groups and monitoring of those who abuse alcohol, which can be a predictor behavior or a mechanism to deal with the stress arising from IPV.

Why are pregnant women physically inactive? A qualitative study on the beliefs and perceptions about physical activity during pregnancy.

This study aimed to describe the beliefs and perceptions of pregnant women and healthcare providers about physical activity during pregnancy. Using a qualitative approach, 30 pregnant women and the 14 healthcare providers caring for them were interviewed in the second trimester of pregnancy. We included women who maintained, decreased, or stopped physical activity since becoming pregnant. They were divided into low (≤ 8 years) and high schooling (> 8 years). Semi-structured, in-depth interviews were conducted and guided by three key questions: (1) When does physical activity during pregnancy start to be considered a wrong behavior?; (2) What are the main barriers (biological or others) to physical activity?; and (3) Do the actions of healthcare providers and people close to pregnant women reinforce barriers? Interviews were audio recorded, transcribed, and analyzed based on recurring themes. All women changed their physical activity behavior (decreased or stopped) when they discovered their pregnancy. Fear of miscarriage, contractions, bleeding, and of causing malformations in the baby were the most reported reasons for decreasing or stopping physical activity. Participants also lacked access to consistent information and healthcare providers' support on the benefits of physical activity. Despite the current international recommendations to regular physical activity during pregnancy, uncertainty regarding its benefits remains. Interventions to promote physical activity during this period should include the training of healthcare providers so they can advise and discard ideas contrary to mother-child health benefits.

Biomedical and Biotechnological Potential of Animal Venoms: Bothrops Snake Venoms and their Antimicrobial Applications.

The pursuit of novel treatment alternatives to address the accumulated resistance to antimicrobials over the years has prompted the scientific community to explore biodiversity, particularly animal venom, as a potential source of new antimicrobial drugs. Snake venoms, with their complex mixtures of components, are particularly promising targets for investigation in this regard. The search for novel molecules exhibiting antimicrobial activity against multidrug-resistant strains is of paramount importance for public health and numerous research groups worldwide. High expectations within the healthcare field are supported by the scientific literature, which highlights the potential development of innovative drugs through in vivo and in vitro application, depending on dose titration. Snake venoms and their molecules and peptides offer exponential possibilities for biotechnological applications as antimicrobial agents. However, many uncertainties and unexplored avenues remain, presenting opportunities for discoveries and research.

The Brazilian version of the telehealth usability questionnaire (telehealth usability questionnaire Brazil): translation, cross-cultural adaptation, and psychometric properties.

OBJECTIVE: The objectives of this study were to translate and cross-culturally adapt the telehealth usability questionnaire into Brazilian Portuguese and to evaluate its psychometric properties. METHODS: This was a methodological validation study carried out in two phases. In phase 1, the telehealth usability questionnaire was cross-culturally adapted with 10 participants comprising the expert committee members, including 5 healthcare professionals with theoretical and practical knowledge of telehealth, 1 methodologist, and 4 translators. This phase was performed at Universidade Federal de Juiz de Fora Physiotherapy Clinic School. In phase 2, the psychometric properties of telehealth usability questionnaire Brazil were analyzed. This phase included in-person assessments at Márcio Cunha Hospital, Minas Gerais. The recruitment period for both phases was from April 2020 to February 2021. Content validity, reliability, internal consistency, and criterion validity were analyzed. The criterion validity was evaluated using correlation with a validated instrument: the system usability scale. RESULTS: The telehealth usability questionnaire was adequately translated and cross-culturally adapted. The telehealth usability questionnaire Brazil presented an excellent content validity index of 0.96 with percentages of understanding higher than 90%. The telehealth usability questionnaire Brazil demonstrated great internal consistency (α=0.94 and ω=0.94), excellent intra-rater reliability (intraclass correlation coefficient=0.85, 95%CI 0.75-0.91), no difference between the test and retest [T (0.425), p>0.673], and no proportional bias (p=0.205). There was a moderate correlation between telehealth usability questionnaire Brazil and the system usability scale (r=0.52, p<0.0001). CONCLUSION: The telehealth usability questionnaire was adequately translated and cross-culturally adapted into Brazilian Portuguese and showed adequate psychometric properties for use in telehealth clinical practice and research in Brazilian-Portuguese-speaking individuals.

Child maltreatment and substances use throughout adolescence and adulthood: Data from a Brazilian Birth Cohort.

BACKGROUND: Child maltreatment has been associated with substance use later in life, but few studies have used repeated measures. OBJECTIVE: To assess the association between child maltreatment and use of psychoactive substances from adolescence to early adulthood, and whether this differs by sex. PARTICIPANTS AND SETTING: 3641 participants from the 1993 Pelotas Birth Cohort, Brazil. METHODS: Child maltreatment (psychological, physical and sexual abuse, and physical neglect) was assessed up to age 15 and use of psychoactive substances (smoking, harmful use of alcohol and use of illicit drugs) was assessed at ages 15, 18, and 22 years. Associations between child maltreatment and use of substances at each time point were analyzed using logistic regression, adjusted for confounders. RESULTS: Overall, child maltreatment was associated with substance use, and the strength of the associations decreased over time. E.g., the association between psychological abuse and harmful use of alcohol was OR 2.17 (95%CI 1.80, 2.62; p-value < 0.001) at 15 years, OR 1.61 (95%CI 1.31, 1.97; p-value < 0.001) at 18 years, and OR1.55 (95%CI 1.22, 1.96; p-value < 0.001) at 22 years. When sex differences were evident, stronger associations were observed among females. E.g., the association between physical abuse and smoking at 15 years was OR 3.49 (95%CI 2.17, 5.62) in females and OR 0.87 (95%CI 0.30, 2.52) in males (p-value for sex interaction = 0.041). CONCLUSIONS: Child maltreatment was associated with psychoactive substance in adolescence and early adulthood. Strategies to prevent use of substances could benefit those who suffered maltreatment in childhood.

Evidence of Lactobacillus reuteri to reduce colic in breastfed babies: Systematic review and meta-analysis.

OBJECTIVE: To investigate evidence for the treatment of childhood colic by supplementing Lactobacillus reuteri in infants breastfed with breast milk. METHODS: The study was conducted according to the PRISMA protocol. The databases used for acquiring data were PubMed and Web of Science, applying MeSH terms and free terms. Meta-analysis was conducted using Stata ™ 12.0. The risk of bias was evaluated by the Review Manager (RevMan) 5.3 tool, and the strength of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Ten clinical trials were included in the review. The administration of L. reuteri (DSM 17938 or ATCC55730) was tested in infants (n = 248) versus the control/placebo group (n = 229). Eight articles were included in the meta-analysis. There was a significant response in reducing crying time (minutes/day) and treatment effectiveness (reduction ≥ 50% in average daily crying time) in the first week (p = 0.001 and p = 0.003, respectively). These results were similar in the second, third weeks (p < 0.001 for both outcomes) and fourth weeks (p<0.001 and p = 0.002, respectively). The risk of bias was low for the majority of the studies. Confidence in evidence was considered very low for crying time and low for effectiveness treatment. CONCLUSIONS: The evidence shows that the administration of Lactobacillus reuteri to babies fed with breast milk reduces the crying time in babies diagnosed with colic. But our confidence in the effect estimate is limited.

Impacts of anthropogenic activities and calculation of the relative risk of violating surface water quality standards established by environmental legislation: a case study from the Piracicaba and Paraopeba river basins, Brazil.

The nonparametric test of Kruskal-Wallis and relative risk were used to evaluate surface water quality allowed to an identification of the most degraded water bodies in Piracicaba River and Paraopeba River basins, two important hydrographic basins in Brazil. Total manganese, dissolved iron, and fecal contamination indicator were considered the most relevant parameters for the characterization of water quality in the basins. The Peixe River, in Nova Era, and Pedras Creek, in Betim, were considered the most impacted water bodies in the Piracicaba River and Paraopeba River basins, respectively. The analysis of violations and the relative risk confirmed that both basins are subject to impacts resulting from economic activities. On comparing the relative risks, the Paraopeba River basin showed a higher risk of violation for 5-day biological oxygen demand (BOD5), total manganese, total phosphorus, total suspended solids, and turbidity, while the Piracicaba River basin showed a higher risk of violation for fecal contamination indicator. The release of domestic sewage and industrial effluents, mining activities, and diffuse pollution from agriculture and pasture areas were responsible for the surface water quality deterioration in these basins. The results show the need for investment in basic sanitation, improved treatment efficiency for industrial effluents, adequate soil management, riparian vegetation preservation, and environmental education actions.

Sex differences in the association between childhood maltreatment and cardiovascular disease in the UK Biobank.

OBJECTIVES: To assess and compare associations between childhood maltreatment and cardiovascular disease (CVD) in men and women in the UK. In secondary analyses, we also explored possible age differences and associations with early onset CVD (<50 years). METHODS: We included 157 311 participants from the UK Biobank who had information on physical, sexual or emotional abuse, emotional or physical neglect. CVD outcomes were defined as any CVD, hypertensive disease, ischaemic heart disease (IHD) and cerebrovascular disease. These were extracted from self-report, blood pressure measurements, hospital register and death register. The associations between maltreatment and CVD were assessed using Poisson regression with robust variance to estimate risk ratios, stratified by sex and adjusted for socioeconomic and demographic factors. RESULTS: All types of maltreatment were associated with increased risk of CVD and IHD in both sexes. Additionally, in women all types of maltreatment were associated with higher risk of hypertensive disease, and all, except emotional neglect, were associated with cerebrovascular disease. In men, all but sexual abuse, were associated with higher risk of hypertensive disease, and all, except physical and sexual abuse, were associated with cerebrovascular disease. Associations were generally stronger in women, and individuals who were younger at baseline had stronger associations of childhood maltreatment with any CVD and IHD, but age differences were less evident when only early onset CVD was considered. CONCLUSIONS: Childhood maltreatment was consistently associated with CVD and stronger associations were generally observed in women and seemed to be stronger for early onset CVD.

[Dietary patterns of elderly Brazilians and associated determinants: a population-based study in the south of Brazil]. / Padrões alimentares de idosos e seus determinantes: estudo de base populacional no sul do Brasil.

This cross-sectional study sought to assess the effect of demographic and socioeconomic factors, chronic diseases, and health counseling on dietary patterns of the elderly. Food consumption was assessed by means of a reduced eating frequency questionnaire distributed to 1,426 elderly residents in Pelotas, State of Rio Grande do Sul, Brazil, and dietary patterns were obtained using main component analysis. Two dietary patterns were identified: healthy diet (wholegrain food, fruits, vegetables, and milk) and Western diet (sweet snacks, fried foods, frozen foods, processed meats, and fast food). Females, non-smokers, and alcohol-free individuals tended more toward the healthy diet, whereas males, smokers, alcohol-dependent, and overweight individuals tended more toward the Western diet. Higher income and schooling were associated with a higher tendency toward both diets, and chronic diseases were not associated with either diet. Receiving counseling for adopting healthy habits was associated with a higher tendency toward a healthy diet and a lower tendency toward the Western diet. There is a need to increase effective guidance on healthy habits by health services to promote healthier eating practices, with special attention to elderly males, smokers, alcohol-dependent and overweight individuals.

Este estudo teve como objetivo avaliar o efeito de fatores demográficos e socioeconômicos, de doenças crônicas e do recebimento de orientações em saúde no padrão alimentar de idosos. O consumo alimentar foi avaliado por meio de questionário de frequência alimentar reduzido aplicado a 1.426 idosos residentes em Pelotas, RS, Brasil e os padrões alimentares foram obtidos por análise de componentes principais. Dois padrões foram identificados: saudável (alimentos integrais, frutas, legumes/verduras e leite) e ocidental (doces, frituras, alimentos congelados, embutidos e "fast food"). Mulheres, não fumantes e não dependentes alcoólicos aderiam mais ao padrão saudável, enquanto que homens, fumantes, dependentes alcóolicos e indivíduos com sobrepeso aderiam mais ao padrão ocidental. Maior renda e escolaridade estiveram associadas à maior adesão de ambos os padrões e a presença de doenças crônicas não esteve associada a nenhum padrão. O recebimento de orientações para hábitos saudáveis esteve associado à maior adesão ao padrão saudável e menor ao padrão ocidental. Há necessidade do fortalecimento de orientações eficazes sobre hábitos saudáveis nos serviços de saúde, com especial atenção para idosos do sexo masculino, tabagistas, dependentes alcoólicos e indivíduos com sobrepeso.

Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan.

The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes.

The genetic architecture of sporadic and multiple consecutive miscarriage.

Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P = 3.2 × 10-8, odds ratio (OR) = 1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF = 6.4%, P = 1.3 × 10-8, OR = 1.7; rs143445068, MAF = 0.8%, P = 5.2 × 10-9, OR = 3.4; rs183453668, MAF = 0.5%, P = 2.8 × 10-8, OR = 3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.