Protocol of the baseline assessment for the Environments for Healthy Living (EHL) Wales cohort study

Background Health is a result of influences operating at multiple levels. For example, inadequate housing, poor educational attainment, and reduced access to health care are clustered together, and are all associated with reduced health. Policies which try to change individual people's behaviour have limited effect when people have little control over their environment. However, structural environmental change and an understanding of the way that influences interact with each other, has the potential to facilitate healthy choices irrespective of personal resources. The aim of Environments for Healthy Living (EHL) is to investigate the impact of gestational and postnatal environments on health, and to examine where structural change can be brought about to optimise health outcomes. The baseline assessment will focus on birth outcomes and maternal and infant health. Methods/Design EHL is a longitudinal birth cohort study. We aim to recruit 1000 pregnant women in the period April 2010 to March 2013. We will examine the impact of the gestational environment (maternal health) and the postnatal environment (housing and neighbourhood conditions) on subsequent health outcomes for the infants born to these women. Data collection will commence during the participants' pregnancy, from approximately 20 weeks gestation. Participants will complete a questionnaire, undergo anthropometric measurements, wear an accelerometer, compile a food diary, and have environmental measures taken within their home. They will also be asked to consent to having a sample of umbilical cord blood taken following delivery of their baby. These data will be complemented by routinely collected electronic data such as health records from GP surgeries, hospital admissions, and child health and development records. Thereafter, participants will be visited annually for follow-up of subsequent exposures and child health outcomes. Discussion The baseline assessment of EHL will provide information concerning the impact of gestational and postnatal environments on birth outcomes and maternal and infant health. The findings can be used to inform the development of complex interventions targeted at structural, environmental factors, intended to reduce ill-health. Long-term follow-up of the cohort will focus on relationships between environmental exposures and the later development of adverse health outcomes, including obesity and diabetes

The role of proteomics in depression research

Depression is a severe neuropsychiatric disorder affecting approximately 10% of the world population. Despite this, the molecular mechanisms underlying the disorder are still not understood. Novel technologies such as proteomic-based platforms are beginning to offer new insights into this devastating illness, beyond those provided by the standard targeted methodologies. Here, we will show the potential of proteome analyses as a tool to elucidate the pathophysiological mechanisms of depression as well as the discovery of potential diagnostic, therapeutic and disease course biomarkers

Gene expression patterns in the hippocampus and amygdala of endogenous depression and chronic stress models

The etiology of depression is still poorly understood, but two major causative hypotheses have been put forth: the monoamine deficiency and the stress hypotheses of depression. We evaluate these hypotheses using animal models of endogenous depression and chronic stress. The endogenously depressed rat and its control strain were developed by bidirectional selective breeding from the Wistar–Kyoto (WKY) rat, an accepted model of major depressive disorder (MDD). The WKY More Immobile (WMI) substrain shows high immobility/despair-like behavior in the forced swim test (FST), while the control substrain, WKY Less Immobile (WLI), shows no depressive behavior in the FST. Chronic stress responses were investigated by using Brown Norway, Fischer 344, Lewis and WKY, genetically and behaviorally distinct strains of rats. Animals were either not stressed (NS) or exposed to chronic restraint stress (CRS). Genome-wide microarray analyses identified differentially expressed genes in hippocampi and amygdalae of the endogenous depression and the chronic stress models. No significant difference was observed in the expression of monoaminergic transmission-related genes in either model. Furthermore, very few genes showed overlapping changes in the WMI vs WLI and CRS vs NS comparisons, strongly suggesting divergence between endogenous depressive behavior- and chronic stress-related molecular mechanisms. Taken together, these results posit that although chronic stress may induce depressive behavior, its molecular underpinnings differ from those of endogenous depression in animals and possibly in humans, suggesting the need for different treatments. The identification of novel endogenous depression-related and chronic stress response genes suggests that unexplored molecular mechanisms could be targeted for the development of novel therapeutic agents

The role of epigenetic dysregulation in the epidemic of allergic disease

The epidemic of allergic disease in early life is one of the clearest indicators that the developing immune system is vulnerable to modern environmental changes. A range of environmental exposures epidemiologically associated with allergic disease have been shown to have effects on the foetal immune function in pregnancy, including microbial burden, dietary changes and environmental pollutants. Preliminary studies now suggest that these early effects on immune development may be mediated epigenetically through a variety of processes that collectively modify gene expression and allergic susceptibility and that these effects are potentially heritable across generations. It is also possible that rising rates of maternal allergy, a recognised direct risk factor for infant allergic disease, may be further amplifying the effects of environmental changes. Whilst effective prevention strategies are the ultimate goal in reversing the allergy epidemic, the specific environmental drivers, target genes, and intracellular pathways and mechanisms of early life immune programming are still unclear. It is hoped that identifying genes that are differentially regulated in association with subsequent allergic disease will assist in identifying causal pathways and upstream contributing environmental factors. In this way, epigenetic paradigms are likely to provide valuable insights into how the early environment can be modified to more favourably drive immune development and reverse the allergic epidemic

Genetic variants linked to education predict longevity

Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members’ polygenic profile score for education to predict their parents’ longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total ndeaths = 79,702) and ∼2.4% lower risk for fathers (total ndeaths = 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity.</p

Prevalência de asma brônquica e de sintomas a ela relacionados em escolares do Distrito Federal e sua relação com o nível socioeconômico Prevalence of bronchial asthma and related symptoms in schoolchildren in the Federal District of Brazil: correlations with socioeconomic levels

OBJETIVO: Avaliar a prevalência de asma e sintomas a ela relacionados no Distrito Federal e sua relação com o nível socioeconômico, utilizando o questionário escrito do International Study of Asthma and Allergies in Childhood. MÉTODOS: Foram avaliadas 6.437 crianças, em escolas públicas e particulares, divididas em: 3.183 crianças de seis a sete anos e 3.254 de treze a catorze anos. Os dados foram analisados por sexo e grupo socioeconômico (teste do qui-quadrado). RESULTADOS: A prevalência encontrada de asma brônquica no Distrito Federal foi de 12,1% e 13,8% nas faixas etárias de seis a sete anos e treze a catorze anos, respectivamente (p < 0,04). Na faixa etária de seis a sete anos, o sexo masculino apresentou prevalências significativamente maiores de asma diagnosticada e de sintomas (p < 0,001), enquanto que na de treze a catorze anos, a maior prevalência de sintomas ocorreu no sexo feminino (p < 0,05). O grupo de piores condições socioeconômicas apresentou maiores taxas de sintomas relacionados à asma nas duas faixas etárias (p < 0,05). O diagnóstico de asma foi mais freqüente na classe social menos favorecida (p < 0,001) para o questionário respondido pelos pais. Entre os adolescentes, houve maior número de diagnósticos de asma no grupo de nível socioeconômico mais elevado (p = 0,001). CONCLUSÃO: O grupo economicamente desfavorecido apresentou prevalências maiores de sintomas de asma, assim como crises de maior gravidade. Também a prevalência de asma provável foi maior neste grupo que a de asma diagnosticada, o que sugere seu subdiagnóstico.<br>OBJECTIVE: To evaluate the asthma prevalence in the Federal District of Brazil, using the questionnaire developed for the International Study of Asthma and Allergies in Childhood to look for correlations with socioeconomic levels. METHODS: A total of 6437 children (3183 from six to seven years old and 3254 from thirteen to fourteen years old), attending public or private schools, were evaluated. The data were analyzed by gender and socioeconomic status (chi-square test). RESULTS: The prevalence of asthma in the Federal District was 12.1% among the six- and seven-year-olds and 13.8% among the thirteen- and fourteen-year-olds (p < 0.04). In the six-to-seven age bracket, asthma prevalence was significantly greater, and asthma-related symptoms were more frequent, among males (p < 0.001). In contrast, asthma-related symptoms were more frequent among females in the thirteen-to-fourteen age bracket (p < 0.05). Children belonging to the lowest socioeconomic class, as determined by the responses given on the questionnaire completed by the parents, presented the highest prevalence of asthma, regardless of age bracket (p < 0.001). Among such children, asthma-related symptoms were also more frequent (p < 0.05). In the thirteen-to-fourteen age bracket, the prevalence of asthma was greater among those belonging to the highest socioeconomic class (p = 0.001). CONCLUSIONS: Overall, economically disadvantaged children more frequently presented asthma-related symptoms and experienced asthma attacks that were of greater severity. In addition, the prevalence of suspected asthma was higher than that of diagnosed asthma in this group, suggesting that asthma is underdiagnosed in children belonging to the lowest socioeconomic class