Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Use of vascular Doppler ultrasound to detect acute estradiol vascular effect in postmenopausal women

OBJECTIVES: To report on a simple practical test for assessing acute estradiol vascular effects on healthy and unhealthy postmenopausal women. INTRODUCTION: Estradiol acts in the endothelium to promote vasodilatation through genomic and non-genomic mechanisms, but its vascular action may be impaired in diabetes mellitus, hypertension, smoking and obesity. METHODS: Nineteen postmenopausal women (nine healthy and 10 with two or more of the above factors) of similar age and time since menopause were examined with vascular Doppler ultrasound. Resistance indexes and systolic and diastolic flow velocities were determined for the brachial and internal carotid arteries at baseline and 20 minutes after administration of a nasal estradiol formulation, available on the market, which reaches 1,200-1,500 pg/ml in the serum in 10-30 minutes. Estradiol blood levels were measured at 30 minutes. RESULTS: The carotid resistance index increased 14.2% (vasoconstriction) in the unhealthy group after estradiol, from a mean ± S.E. of 0.56 ± 0.016 at baseline to 0.64 ± 0.05 (p=0.033), and remained unchanged in healthy women. Brachial diastolic flow velocity increased 19.7% (vasodilatation) in healthy women, from 16.2 ± 1.93 to 19.4 ± 0.64 cm/s (p=0.046), and did not change in the unhealthy subjects. Estradiol levels were similar in both groups. DISCUSSION: Healthy postmenopausal women showed brachial vasodilatation while unhealthy postmenopausal women displayed vasoconstriction at the carotid artery. Vascular responses to estradiol were divergent between the groups. CONCLUSIONS: The acute estradiol test, coupled with Doppler ultrasound, seemed to be able to differentiate women with normal and abnormal endothelial function in a simple, non-invasive manner.OBJETIVO: Descrever um teste simples e prático para avaliar o efeito vascular agudo do estradiol em mulheres saudáveis e não-saudáveis na menopausa. INTRODUÇÃO: O estradiol atua no endotélio promovendo vasodilatação através de mecanismos genômicos e não-genômicos e esta ação pode estar prejudicada em morbidades como diabetes mellitus, hipertensão, tabagismo e obesidade. MÉTODOS: Dezenove mulheres na pós-menopausa (9 saudáveis e 10 com dois ou mais dos fatores acima), com idade e tempo de menopausa semelhantes foram examinadas por Doppler vascular. O índice de resistência e as velocidades de fluxo sistólico e diastólico foram medidos nas artérias braquial e carótida, em condições basais e 20 min após a administração de uma preparação nasal de estradiol, disponível comercialmente, que atinge 1200 a 1500 pg/ml no soro, entre 10 e 30 min após a aplicação. Os níveis séricos de estradiol foram determinados 30 min após a aplicação nasal. RESULTADOS: O índice de resistência da artéria carótida aumentou em 14,2% (vasoconstricção) após o estradiol no grupo não-saudável, partindo da média ± SE de 0,56 ± 0,016 para 0,64 ± 0,05 (p=0,033) e não se modificou nas mulheres saudáveis. A velocidade de fluxo diastólico da artéria braquial aumentou 19,7% (vasodilatação) nas mulheres saudáveis, partindo de 16,2 ± 1,93 para 19,4 ± 0,64 cm/s (p=0,046) e não apresentou alteração nas não saudáveis. Os níveis de estradiol foram semelhantes nos dois grupos. DISCUSSÃO: Nas mulheres saudáveis na menopausa houve vasodilatação da artéria braquial e nas não-saudáveis vasoconstricção na artéria carótida. A resposta vascular ao estradiol foi divergente entre os grupos estudados. CONCLUSÃO: O teste com estradiol agudo, associado ao Doppler vascular, parecem diferenciar, de forma simples e não-invasiva, mulheres com função endotelial normal e anormal

Reductions in the Prevalence and Incidence of Geohelminth Infections following a City-wide Sanitation Program in a Brazilian Urban Centre

In the city of Salvador, a large urban centre in Northeast Brazil, a city-wide sanitation intervention started in 1997, aiming to improve the sewerage coverage of households from 26% to 80%. Our aim was to study the impact of the intervention on the prevalence and incidence of geohelminths in the school-aged population. The longitudinal study comprised two cohorts: from the beginning of 1997 to 1998, where data was collected before the intervention, and at the end of 2003 to 2004, after the intervention. Copro-parasitological examinations were carried out on every individual from both cohorts, at the start and nine months later. Demographic, socio-economic, and environmental data were collected using semi-structured questionnaires. The variables utilized to demonstrate the effects of intervention, when utilized together in a multivariate model, accounted for a 100% observed reduction in the prevalence ratio (PR) and incidence ratio (IR). As well as proving that the variables associated with the effect of the program intervention were mediators in this reduction, the reduction in the PR and IR between these periods demonstrated that modifications to the urban environment, particularly those associated with sanitary sewage systems, affected the health of the population, significantly reducing the prevalence of geohelminths