Maternal Arsenic Exposure,Arsenic Methylation Efficiency,and Birth Outcomes in the Biomarkers of Exposure to ARsenic (BEAR) Pregnancy Cohort in Mexico

Background: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations.Objectives: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children.Methods: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals.Results: DW-iAs for the study subjects ranged from < 0.5 to 236 μg As/L. More than half of the women (53%) had DW-iAs that exceeded the World Health Organization’s recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length.Conclusions: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations.Citation: Laine JE, Bailey KA, Rubio-Andrade M, Olshan AF, Smeester L, Drobná Z, Herring AH, Stýblo M, García-Vargas GG, Fry RC. 2015. Maternal arsenic exposure, arsenic methylation efficiency, and birth outcomes in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico. Environ Health Perspect 123:186–192; http://dx.doi.org/10.1289/ehp.1307476     

Using care plans to better manage multimorbidity

Background

The health care for patients having two or more long-term medical conditions is fragmented between specialists, allied health professionals, and general practitioners (GPs), each keeping separate medical records. There are separate guidelines for each disease, making it difficult for the GP to coordinate care. The TrueBlue model of collaborative care to address key problems in managing patients with multimorbidity in general practice previously reported outcomes on the management of multimorbidities. We report on the care plan for patients with depression, diabetes, and/or coronary heart disease that was embedded in the TrueBlue study.

Methods

A care plan was designed around diabetes, coronary heart disease, and depression management guidelines to prompt implementation of best practices and to provide a single document for information from multiple sources. It was used in the TrueBlue trial undertaken by 400 patients (206 intervention and 194 control) from 11 Australian general practices in regional and metropolitan areas.

Results

Practice nurses and GPs successfully used the care plan to achieve the guideline-recommended checks for almost all patients, and successfully monitored depression scores and risk factors, kept pathology results up to date, and identified patient priorities and goals. Clinical outcomes improved compared with usual care.

Conclusion

The care plan was used successfully to manage and prioritise multimorbidity. Downstream implications include improving efficiency in patient management, and better health outcomes for patients with complex multimorbidities.     

Autistic-Like Syndrome in Mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity

The etiology of Autism Spectrum Disorders (ASDs) remains largely unknown. Identifying vulnerability genes for autism represents a major challenge in the field and allows the development of animal models for translational research. Mice lacking the mu opioid receptor gene (Oprm1^−/−) were recently proposed as a monogenic mouse model of autism, based on severe deficits in social behavior and communication skills. We confirm this hypothesis by showing that adult Oprm1^−/− animals recapitulate core and multiple comorbid behavioral symptoms of autism and also display anatomical, neurochemical, and genetic landmarks of the disease. Chronic facilitation of mGluR4 signaling, which we identified as a novel pharmacological target in ASDs in these mice, was more efficient in alleviating behavioral deficits than the reference molecule risperidone. Altogether, our data provide first evidence that disrupted mu opioid receptor signaling is sufficient to trigger a comprehensive autistic syndrome, maybe through blunted social reward processes, and this mouse model opens promising avenues for therapeutic innovation.     

Multilevel examination of diabetes in modernising China: what elements of urbanisation are most associated with diabetes?

Aims/hypothesis

The purpose of this study was to examine the association between urbanisation-related factors and diabetes prevalence in China.

Methods

Anthropometry, fasting blood glucose (FBG) and community-level data were collected for 7,741 adults (18–90?years) across 217 communities and nine provinces in the 2009 China Health and Nutrition Survey to examine diabetes (FBG ≥7.0?mmol/l or doctor diagnosis). Sex-stratified multilevel models, clustered at the community and province levels and controlling for individual-level age and household income were used to examine the association between diabetes and: (1) a multicomponent urbanisation measure reflecting overall modernisation and (2) 12 separate components of urbanisation (e.g., population density, employment, markets, infrastructure and social factors).

Results

Prevalent diabetes was higher in more-urbanised (men 12%; women 9%) vs less-urbanised (men 6%; women 5%) areas. In sex-stratified multilevel models adjusting for residential community and province, age and household income, there was a twofold higher diabetes prevalence in urban vs rural areas (men OR 2.02, 95% CI 1.47, 2.78; women, OR 1.94, 95% CI 1.35, 2.79). All urbanisation components were positively associated with diabetes, with variation across components (e.g. men, economic and income diversity, OR 1.42, 95% CI 1.20, 1.66; women, transportation infrastructure, OR 1.18, 95% CI 1.06, 1.32). Community-level variation in diabetes was comparatively greater for women (intraclass correlation [ICC] 0.03–0.05) vs men (ICC ≤0.01); province-level variation was greater for men (men 0.03–0.04; women 0.02).

Conclusions/interpretation

Diabetes prevention and treatment efforts are needed particularly in urbanised areas of China. Community economic factors, modern markets, communications and transportation infrastructure might present opportunities for such efforts.     

Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: A Canadian Thoracic Society clinical practice guideline

Alpha-1 antitrypsin (A1AT) functions primarily to inhibit neutrophil elastase, and deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD). Severe A1AT deficiency occurs in one in 5000 to one in 5500 of the North American population. While the exact prevalence of A1AT deficiency in patients with diagnosed COPD is not known, results from small studies provide estimates of 1% to 5%. The present document updates a previous Canadian Thoracic Society position statement from 2001, and was initiated because of lack of consensus and understanding of appropriate patients suitable for targeted testing for A1AT deficiency, and for the use of A1AT augmentation therapy. Using revised guideline development methodology, the present clinical practice guideline document systematically reviews the published literature and provides an evidence-based update. The evidence supports the practice that targeted testing for A1AT deficiency be considered in individuals with COPD diagnosed before 65 years of age or with a smoking history of <20 pack years. The evidence also supports consideration of A1AT augmentation therapy in nonsmoking or exsmoking patients with COPD (forced expiratory volume in 1 s of 25% to 80% predicted) attributable to emphysema and documented A1AT deficiency (level ≤11 μmol/L) who are receiving optimal pharmacological and nonpharmacological therapies (including comprehensive case management and pulmonary rehabilitation) because of benefits in computed tomography scan lung density and mortality.