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Arbuckle T.E.,Environmental Health Science and Research Bureau
Birth defects research. Part A, Clinical and molecular teratology | Year: 2010

There is growing concern about the potential health effects of exposure to various environmental chemicals during pregnancy and infancy. One of the key limitations of past epidemiologic research in this field has been the potential for exposure misclassification to lead to biases in the health risk estimate. The use of biomarkers in pregnancy cohort or case-control studies has significantly advanced the field; however, this is true only if the biomarker is a true measurement of exposure for the relevant time period of interest. There are a number of theoretical and practical constraints to their use, including difficulty interpreting biomonitoring data, high analytical and collection costs, potential participant selection biases, and ethical challenges in reporting results to study subjects. Identifying a representative sample and collecting biospecimens in the developmental window of interest can be problematic. Various strategies for identifying pregnant women range from the more representative but least efficient sampling of the general population to recruitment through early ultrasound clinics and local advertising. Whereas measurement of xenobiotic chemicals in cord blood, amniotic fluid, or meconium provides unequivocal evidence that the chemical has entered the fetal environment, analysis of maternal blood and urine can be used as a surrogate for fetal exposure. Use of stored midpregnancy serum collected for fetal screening and of large-cohort biobanks offer unique opportunities for biomonitoring data for birth defects studies. Future research is needed to explore less invasive matrices for biomonitoring of infants and to develop less costly analytical methods that require smaller sample volumes. © 2010 Wiley-Liss, Inc. Source

Cakmak S.,Environmental Health Science and Research Bureau | Dales R.E.,University of Ottawa | Coates F.,Aerobiology Research Laboratories
Journal of Allergy and Clinical Immunology | Year: 2012

Background: Clinical experiments demonstrate that the asthmatic response to an aeroallergen can be enhanced by prior exposure to an air pollutant. Objective: We sought to compare the effects of ambient aeroallergens on hospitalization for asthma between high and low air pollution days in 11 large Canadian cities. Methods: Daily time-series analysis was used, and results were adjusted for day of the week, temperature, barometric pressure, and relative humidity. Results: The relative risk of admission for an interquartile increase in tree pollen levels was 1.124 (95% CI, 1.101-1.147) on days of lower values of fine particulate matter with a median aerodynamic diameter less than or equal to 2.5 μm (PM 2.5) compared with 1.179 (95% CI, 1.149-1.21) on days of higher PM 2.5 values. Significant (P ≤.05) differences in the relative risks of admission between lower versus higher values of particulate matter with a median aerodynamic diameter less than or equal to 10 μm in diameter were 1.149 (95% CI, 1.118-1.181) versus 1.210 (95% CI, 1.161-1.261) for ascomycetes, 1.112 (95% CI, 1.085-1.14) versus 1.302 (95% CI, 1.242-1.364) for basidiomycetes, 1.159 (95% CI, 1.125-1.195) versus 1.149 (95% CI, 1.129-1.169) for deuteromycetes, and 1.061 (95% CI, 1.016-1.107) versus 1.117 (95% CI, 1.092-1.143) for weeds. Conclusion: We identified an association between aeroallergens and hospitalizations for asthma, which was enhanced on days of higher air pollution. Minimizing exposure to air pollution might reduce allergic exacerbations of asthma. © 2011 American Academy of Allergy, Asthma & Immunology. Source

Abdou H.-S.,Research Center | Atlas E.,Environmental Health Science and Research Bureau | Hache R.J.G.,York University
Endocrinology | Year: 2013

Glucocorticoids promote adipogenesis and contribute to the metabolic syndrome through a number of mechanisms. One of the effectors of glucocorticoid action is the CCAAT/enhancer binding protein β (C/EBPβ). C/EBPβ is a basic leucine-zipper transcription factor involved in diverse processes including differentiation, cellular proliferation, and inflammation. C/EBPβ transcriptional activity is regulated, in part, by its acetylation profile resulting from its dynamic interaction with either acetylases general control nonrepressed protein 5/p300/CBP associated factor (GCN5/PCAF) or deacetylase complexes (mSin3A/histone deacetylase 1 [HDAC1]). Glucocorticoid treatment of preadipocytes promotes C/EBPβ acetylation, leading to mSin3A/HDAC1 dissociation from C/EBPβ and resulting in C/ebpα promoter activation at the onset of adipogenesis, thus increasing the differentiation rate. We recently showed that the regulatory domain 1 (RD1) of C/EBPβ contains four residues (153-156) required for its interaction with HDAC1, therefore supporting RD1 proposed inhibitory role. In an attempt to further elucidate the intrinsic regulatory property of RD1, we sought to characterize the regulatory potential of the N terminus region of RD1 (residues 141-149). In this study, we show that C/EBPβΔ141-149 transcriptional activity was compromised on the C/ebpα, but not on the Pparγ, promoter. Additionally, the ability of C/EBPβΔ141-149 to induce adipogenesis in NIH 3T3 cells was compromised when compared with C/EBPβwt owing to a delayed expression of C/ebpα at the onset of differentiation. Furthermore, the data suggest that the reduced expression of C/ebpα in cells expressing C/EBPβ Δ141-149 was due to a persistent recruitment of HDAC1 to the C/ebpα promoter after glucocorticoid treatment. Together, these results suggest that amino acids 141-149 of C/EBPβ act as a positive regulatory domain required for maximum transcriptional activity. Copyright © 2013 by The Endocrine Society. Source

Vanos J.K.,Environmental Health Science and Research Bureau | Vanos J.K.,Texas Tech University | Hebbern C.,Environmental Health Science and Research Bureau | Cakmak S.,Environmental Health Science and Research Bureau
Environmental Pollution | Year: 2014

Synoptic weather and ambient air quality synergistically influence human health. We report the relative risk of mortality from all non-accidental, respiratory-, and cardiovascular-related causes, associated with exposure to four air pollutants, by weather type and season, in 10 major Canadian cities for 1981 through 1999. We conducted this multi-city time-series study using Poisson generalized linear models stratified by season and each of six distinctive synoptic weather types. Statistically significant relationships of mortality due to short-term exposure to carbon monoxide, nitrogen dioxide, sulphur dioxide, and ozone were found, with significant modifications of risk by weather type, season, and mortality cause. In total, 61% of the respiratory-related mortality relative risk estimates were significantly higher than for cardiovascular- related mortality. The combined effect of weather and air pollution is greatest when tropical-type weather is present in the spring or summer. © 2013 Published by Elsevier Ltd. All rights reserved. Source

Singer T.M.,Environmental Health Science and Research Bureau | Yauk C.L.,Environmental Health Science and Research Bureau
Environmental and Molecular Mutagenesis | Year: 2010

Heritable mutations may result in a wide variety of detrimental outcomes, from embryonic lethality to genetic disease in the offspring. Despite this, today's commonly used test batteries do not include assays for germ cell mutation. Current challenges include a lack of practical assays and concrete evidence for human germline mutagens, and large data gaps that often impede risk assessment. Moreover, most regulatory assessments are based on the assumption that somatic cell mutation assays also protect the germline by default, which has not been adequately confirmed. The field is also faced with new challenges aimed at dramatically reducing animal testing, and attempts to rapidly classify thousands of chemicals using high throughput in vitro assays. These approaches may not adequately capture effects that may be particular to gametes, since many aspects of the germline are unique. In light of these challenges, an urgent need exists to develop new approaches to evaluate the potential of toxicants to cause germline mutation. The application of new technologies will greatly enhance our understanding of mutation in humans exposed to environmental mutagens. However, we must be poised to collect and interpret these data, and facilitate risk translation to regulators and the public. Genetic toxicologists must also become actively involved in the development of high-throughput tools to study germline mutation. Appropriate attention to these areas will result in the development of policies that prioritize the protection of the germline and future generations from DNA sequence mutations. © 2010 Government of Canada. Source

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