Time and dose-dependent effects of phenobarbital on the rat liver miRNAome.

In a previous study we had shown that treatment of male Fischer rats with exogenous chemicals for three months resulted in prominent, mode-of-action dependent effects on liver microRNA (miRNA) (Koufaris et al., 2012). Here we investigated how the effects of chemicals on liver miRNA in male Fischer rats relate to the length and dose of exposure to phenobarbital (PB), a drug with multiple established hepatic effects. Importantly, although acute PB treatment (1-7 days) had significant effects on liver mRNA and the expected effects on the liver phenotype (transient hyperplasia, hepatomegaly, cytochrome P450 induction), limited effects on liver miRNA were observed. However, at 14 days of PB treatment clear dose-dependent effects on miRNA were observed. The main effect of PB treatment from days 1 to 90 on liver miRNA was found to be the persistent, progressive, and highly correlated induction of the miR-200a/200b/429 and miR-96/182 clusters, occurring after the termination of the xenobiotic-induced transient hyperplasia. Moreover, in agreement with their reported functions in the literature we found associations between perturbations of miR-29b and miR-200a/200b by PB with global DNA methylation and zeb1/zeb2 proteins respectively. Our data suggest that miRNA are unlikely to play an important role in the acute responses of the adult rodent liver to PB treatment. However, the miRNA responses to longer PB exposures suggest a potential role for maintaining liver homeostasis in response to sub-chronic and chronic xenobiotic-induced perturbations. Similar studies for more chemicals are needed to clarify whether the temporal and dose pattern of miRNA-toxicant interaction identified here for PB are widely applicable to other xenobiotics. © 2013 Elsevier Ireland Ltd

Associations between socioeconomic status and environmental toxicant concentrations in adults in the USA: NHANES 2001-2010

This is the final version, also available from Elsevier via the DOI in this record.Low level chronic exposure to toxicants is associated with a range of adverse health effects. Understanding the various factors that influence the chemical burden of an individual is of critical importance to public health strategies. We investigated the relationships between socioeconomic status (SES) and bio-monitored chemical concentration in five cross-sectional waves of the U.S. National Health and Nutrition Examination Survey (NHANES).We utilised adjusted linear regression models to investigate the association between 179 toxicants and the poverty income ratio (PIR) for five NHANES waves. We then selected a subset of chemicals associated with PIR in 3 or more NHANES waves and investigated potential mediating factors using structural equation modelling.PIR was associated with 18 chemicals in 3 or more NHANES waves. Higher SES individuals had higher burdens of serum and urinary mercury, arsenic, caesium, thallium, perfluorooctanoic acid, perfluorononanoic acid, mono(carboxyoctyl) phthalate and benzophenone-3. Inverse associations were noted between PIR and serum and urinary lead and cadmium, antimony, bisphenol A and three phthalates (mono-benzyl, mono-isobutyl, mono-n-butyl). Key mediators included fish and shellfish consumption for the PIR, mercury, arsenic, thallium and perfluorononanoic acid associations. Sunscreen use was an important mediator in the benzophenone-3/PIR relationship. The association between PIR and cadmium or lead was partially mediated by smoking, occupation and diet.These results provide a comprehensive analysis of exposure patterns as a function of socioeconomic status in US adults, providing important information to guide future public health remediation measures to decrease toxicant and disease burdens within society. © 2013 Elsevier Ltd.University of ExeterEuropean Social Fund Convergence Programme for Cornwall and the Isles of ScillyEuropean Regional Development Fund Programme 2007 to 201

Research note: Urban street tree density and antidepressant prescription rates—A cross-sectional study in London, UK

This is the author’s version of a work that was accepted for publication in Landscape and Urban Planning. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published at doi:10.1016/j.landurbplan.2014.12.005.Abstract: Growing evidence suggests an association between access to urban greenspace and mental health and wellbeing. Street trees may be an important facet of everyday exposure to nature in urban environments, but there is little evidence regarding their role in influencing population mental health. In this brief report, we raise the issue of street trees in the nature-health nexus, and use secondary data sources to examine the association between the density of street trees (trees/km street) in London boroughs and rates of antidepressant prescribing. After adjustment for potential confounders, and allowing for unmeasured area-effects using Bayesian mixed effects models, we find an inverse association, with a decrease of 1.18 prescriptions per thousand population per unit increase in trees per km of street (95% credible interval 0.00, 2.45). This study suggests that street trees may be a positive urban asset to decrease the risk of negative mental health outcomes.European Regional Development Fund Programme 2007 to 2013 and European Social Fund Convergence Programme for Cornwall and the Isles of Scill

Dermatitis associated with exposure to a marine cyanobacterium during recreational water exposure

<p>Abstract</p> <p>Background</p> <p>Anecdotal evidence reported an outbreak of symptoms on Fraser Island during the late 1990s similar to those expected from exposure to dermotoxins found in the cyanobacterium <it>L. majuscula</it>. This coincided with the presence of a bloom of <it>L. majuscula</it>.</p> <p>Methods</p> <p>Records from the Fraser Island National Parks First aid station were examined. Information on cyanobacterial blooms at Fraser Island were obtained from Queensland National Parks rangers.</p> <p>Results</p> <p>Examination of first aid records from Fraser Island revealed an outbreak of symptoms predominantly in January and February 1998.</p> <p>Conclusion</p> <p>During a bloom of <it>L. majuscula </it>there were numerous reports of symptoms that could be attributed to dermotoxins found in <it>L. majuscula</it>. The other four years examined had no <it>L. majuscula </it>blooms and the number of <it>L. majuscula </it>symptoms was much reduced. These cases comprised a high percentage of the cases treated at the first aid station.</p

High urinary tungsten concentration is associated with stroke in the National Health and Nutrition Examination Survey 1999-2010.

Published onlineClinical TrialMulticenter StudyResearch Support, Non-U.S. Gov'tBACKGROUND: In recent years there has been an exponential increase in tungsten demand, potentially increasing human exposure to the metal. Currently, the toxicology of tungsten is poorly understood, but mounting evidence suggests that both the elemental metal and its alloys have cytotoxic effects. Here, we investigate the association between tungsten and cardiovascular disease (CVD) or stroke using six waves of the National Health and Nutrition Examination Survey (NHANES). METHODS: We investigated associations using crude and adjusted logistic regression models in a cohort of 8614 adults (18-74 years) with 193 reported stroke diagnoses and 428 reported diagnoses of CVD. We also stratified our data to characterize associations in a subset of younger individuals (18-50 years). RESULTS: Elevated tungsten concentrations were strongly associated with an increase in the prevalence of stroke, independent of typical risk factors (Odds Ratio (OR): 1.66, 95% Confidence Interval (95% CI): 1.17, 2.34). The association between tungsten and stroke in the young age category was still evident (OR: 2.17, 95% CI: 1.33, 3.53). CONCLUSION: This study represents the most comprehensive analysis of the human health effects of tungsten to date. Individuals with higher urinary tungsten concentrations have double the odds of reported stroke. We hypothesize that the pathological pathway resulting from tungsten exposure may involve oxidative stress.This work was supported by funding from University of Exeter Medical School. No funding organization or sponsor played any part in the design or conduct of the study, in the analysis or interpretation of the data, or preparation, review, or approval of the manuscript. The European Centre for the Environment and Human Health (part of the University of Exeter Medical School) is supported by investment from the ERDF (European Regional Development Fund) and ESF (European Social Fund) Convergence Programmed for Cornwall and the Isles of Scilly. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

What accounts for ‘England’s green and pleasant land’? A panel data analysis of mental health and land cover types in rural England

This is the author’s version of a work that was accepted for publication in Landscape and Urban Planning. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published at doi:10.1016/j.landurbplan.2015.05.008.Exposure to green space is associated with a variety of positive health states. Research to date has focused primarily on ‘generic’ green space in urban areas, where green space is relatively scarce and where it is dominated by playing fields and parks. The current research adds to our understanding with an examination of relationships between different types of green space and mental health in rural areas in England (approximate rural population = 4 million). The aggregate land cover classes of Land Cover Map 2007 were linked to rural residential areas (Lower-level Super Output Areas) and then linked to rural participants (n = 2020) in the 18-year longitudinal British Household Panel Survey. Random effects regression of mental health (as measured by GHQ12 scores) against land cover enabled effects to be simultaneously estimated from both mean between-individual differences and from within-individual differences over time. The nine natural land cover classes (Broadleaved woodland; Coniferous woodland; Arable; Improved grassland; Semi-natural grassland; Mountain, heath and bog; Saltwater; Freshwater; Coastal) were not significantly associated with differences in mental health between individuals. However, significant relationships were observed between some types of land cover and within-individual change in mental health amongst individuals who relocated during the 18 annual waves of the panel. These findings indicate the presence of important health related ecosystem services from different land cover types that have not previously been investigated and which help more effective spatial planning and land use management.Economic and Social Research CouncilNational Institute for Health Research Health Protection Research Unit (NIHR HPRU

Urinary bisphenol A concentration and risk of future coronary artery disease in apparently healthy men and women

addresses: Epidemiology and Public Health Group, Peninsula College of Medicine and Dentistry, Barrack Road, Exeter, United Kingdom. [email protected]: Comparative Study; Journal Article; Research Support, Non-U.S. Gov'tThe endocrine-disrupting chemical bisphenol A (BPA) is widely used in food and beverage packaging. Higher urinary BPA concentrations were cross-sectionally associated with heart disease in National Health and Nutrition Examination Survey (NHANES) 2003-2004 and NHANES 2005-2006, independent of traditional risk factors.Medical Research Council UKCancer Research UKBritish Heart FoundationPeninsula Medical School, University of ExeterEuropean Regional Development FundEuropean Social Fund Convergence Programme for Cornwall and the Isles of ScillyNational Institute for Health Research Collaborations for Leadership in Applied Health Research and Car

Beyond greenspace: an ecological study of population general health and indicators of natural environment type and quality.

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.BACKGROUND: Many studies suggest that exposure to natural environments ('greenspace') enhances human health and wellbeing. Benefits potentially arise via several mechanisms including stress reduction, opportunity and motivation for physical activity, and reduced air pollution exposure. However, the evidence is mixed and sometimes inconclusive. One explanation may be that "greenspace" is typically treated as a homogenous environment type. However, recent research has revealed that different types and qualities of natural environments may influence health and wellbeing to different extents. METHODS: This ecological study explores this issue further using data on land cover type, bird species richness, water quality and protected or designated status to create small-area environmental indicators across Great Britain. Associations between these indicators and age/sex standardised prevalence of both good and bad health from the 2011 Census were assessed using linear regression models. Models were adjusted for indicators of socio-economic deprivation and rurality, and also investigated effect modification by these contextual characteristics. RESULTS: Positive associations were observed between good health prevalence and the density of the greenspace types, "broadleaf woodland", "arable and horticulture", "improved grassland", "saltwater" and "coastal", after adjusting for potential confounders. Inverse associations with bad health prevalence were observed for the same greenspace types, with the exception of "saltwater". Land cover diversity and density of protected/designated areas were also associated with good and bad health in the predicted manner. Bird species richness (an indicator of local biodiversity) was only associated with good health prevalence. Surface water quality, an indicator of general local environmental condition, was associated with good and bad health prevalence contrary to the manner expected, with poorer water quality associated with better population health. Effect modification by income deprivation and urban/rural status was observed for several of the indicators. CONCLUSIONS: The findings indicate that the type, quality and context of 'greenspace' should be considered in the assessment of relationships between greenspace and human health and wellbeing. Opportunities exist to further integrate approaches from ecosystem services and public health perspectives to maximise opportunities to inform policies for health and environmental improvement and protection.Economic and Social Research CouncilEuropean Regional Development Fund Programme 2007 to 2013 and European Social Fund Convergence Programme for Cornwall and the Isles of Scill

Transdifferentiated rat pancreatic progenitor cells (AR42J-B13/H) respond to phenobarbital in a rat hepatocyte-specific manner

Phenobarbital (PB) is known to produce species-specific effects in the rat and mouse, being carcinogenic in certain mouse strains, but only in rats if treated after a DNA damaging event. PB treatment in the rat and mouse also produces disparate effects on cell signalling and miRNA expression profiles. These responses are induced by short term and prolonged PB exposure, respectively, with the latter treatments being difficult to examine mechanistically in primary hepatocytes due to rapid loss of the original hepatic phenotype and limited sustainability in culture. Here we explore the rat hepatocyte-like B13/H cell line as a model for hepatic response to PB exposure in both short-term and longer duration treatments. We demonstrate that PB with Egf treatment in the B13/H cells, resulted in a significant increase in Erk activation, as determined by the ratio of phospho-Erk to total Erk, compared to Egf alone. We also show that an extended treatment with PB in the B13/H cells produces a miRNA response similar to that seen in the rat in vivo, via the time-dependent induction of miR-182/96. Additionally, we confirm that B13/H cells respond to Car activators in a typical rat-specific manner. These data suggest that the B13/H cells produce temporal responses to PB that are comparable to those reported in short-term primary rat hepatocyte cultures and in the longer term are similar to those in the rat in vivo. Finally, we also show that Car-associated miR-122 expression is decreased by PB treatment in B13/H cells, a PB-induced response that is common to the rat, mouse and human. We conclude that the B13/H cell system produces a qualitative response comparable to the rat, which is different to the response in the mouse, and that this model could be a useful tool for exploring the functional consequences of PB-sensitive miRNA changes and resistance to PB-mediated tumours in the rat