As reported by the CDC, birth defects remain a common occurrence in the United States, with malformations originating in many places in the developing organism. Furthermore, the etiology of many of these defects remain unknown, with some factors consisting of genetics, environmental pollutants and teratogens. In our study, we examined whether insults by teratogenic agents, ethanol in particular, can be mitigated by hyperpolarizing agents acting to restore the cell’s potential. We first evaluated whether three hyperpolarizing drugs (Lamotrigine, Gabapentin, and Ivermectin) induced teratogenic effects on CD-1 mice and found that Ivermectin induced craniofacial malformations, and exposure to Lamotrigine and Gabpentin resulted in limb defects in the offspring. For the second part of our study, pregnant CD-1 mice were orally dosed with Lamotrigine or Gabapentin from gestational day (GD) 0 till parturition. On GD 8, we exposed females to one hit of ethanol, creating four treatment groups: Vehicle, EtOH only, Lamotrigine + EtOH and Gabapentin + EtOH. We evaluated a variety of different endpoints: gestational outcomes, maternal outcomes, neonatal outcomes, behavioral outcomes in pups at prepuberty, and changes in brain weight, shape, and morphology. We observed that both Gabapentin and Lamotrigine, although in varied ways, mitigate some of the perturbations resulting from ethanol, but not all. Our study provides a preliminary, but insightful, look into the role of hyperpolarizing agents on teratogenic insults induced by ethanol. It highlights the future directions of research which include, but are not limited to, understanding the mode of action through which teratogens alter individual cell behavior and the interactions between hyperpolarizing agents on the cell’s potential when this alteration occurs.

Background: Kathmandu Valley is one of the largest and most polluted metropolitan regions in the Himalayan foothills. Rapidly expanding urban sprawl and growing fleet of vehicles, and industrial facilities such as brick factories across the valley have led to conditions where ambient concentrations of key gaseous air pollutants are expected to exceed Nepal’s National Ambient Air Quality Standards and World Health Organization guidelines. Objectives: The aim of this study is to quantify the distribution of gaseous pollutants across the valley characterized by different emission sources, and also assess influence of meteorology in the region on the temporal variability and spatial distribution of these gases, including differences at sites upwind and/or downwind of three major cities in the Kathmandu Valley. Methods: In order to understand the spatial variation of the trace gases in the Kathmandu Valley, passive samples of SO2, NOx, NO2, NH3, and O3 were simultaneously collected from fifteen locations between March and May 2013. A follow-up study during two separate campaigns in 2014 sampled these gases, except ammonia, one site at a time from thirteen urban, suburban and rural stationary sites. Results: In 2013, urban sites were observed to have higher weekly averaged NO2 and SO2 (22.4 ± 8.1 µg/m3 and 14.5 ± 11.1 µg/m3, respectively) than sub-urban sites (9.2 ± 3.9 µg/m3 and 7.6 ± 2.8 µg/m3, respectively). Regions located within 3 km of brick factories exhibited higher SO2 concentrations (22.3 ± 14.7 µg/m3) than sites at least than 3 km away (5.8 ± 1.1 µg/m3). Increased NH3 levels were observed at sites downstream from polluted rivers (25.8 ± 5.5 µg/m3) compared to upstream sites (19.9 ± 3.6 µg/m3). Increased O3 was observed in rural locations (108.5 ± 31.4 µg/m3) compared to urban sites (87.1 ± 9.2 µg/m3) (ANOVA, p Conclusions: Parallel to previous studies that found O3 levels that exceeded guideline, these results suggest that ground-level O3, as its levels frequently exceeded guidelines throughout the sampling periods, is an important concern throughout the valley. NH3 near polluted rivers, NO2 near high traffic activity and SO2 around brick factories are also important pollutants that need more intensive monitoring, primarily due to their importance in particulate matter formation chemistry.

The primary goal of this PhD research was to obtain critical information needed to further calibrate the novel glass-based retrospective radon detectors (RRDs) by characterizing the quantitative relationship between radon gas concentrations, the surface-deposited activities of various radon progeny, the airborne dose rate, and various residential environmental factors through both actual field measurements and Monte-Carlo simulation. Radon and radon progeny concentrations were measured, from May 2005 to May 2007, in 38 Iowa houses occupied by either smokers or nonsmokers. The investigation took into account several important indoor environmental factors, which have crucial influences on the radon progeny deposition process in homes. The long-term (3 months) surface-deposited radon progeny by species and implanted 210Po were measured using a RRD. During the 3 months, the short-term (3-7 days) airborne radon progeny by species and bimodal size fraction were measured using a recently developed active detector. Both passive and active detectors are solid state nuclear track detectors. Airborne dose rates were calculated from unattached and attached potential alpha energy concentrations (PAECs) based on both Porstendörfer's effective dose conversion factor and that of James. Correlation analysis and multiple linear regression analysis were applied to analyze both field study results and Monte-Carlo simulation study results. Temporal and spatial variations among airborne dose rates and surface-deposited radon progeny were also investigated in actual field settings. Overall, deposited radon progeny were useful in predicting airborne dose rate in addition to the radon gas concentration. The occurrence of smoking was the most crucial environmental factor influencing the deposition process. In addition, other environmental factors were identified that served as useful covariates predicting airborne dose rates by smoking status. The results from our current study will greatly aid the future resolution of the final reanalysis of the lung cancer risks for the Iowa Radon Lung Cancer Study (IRLCS) based on radon progeny exposure estimates obtained from RRD measurements. In addition, the results of this study will be used as the basis for a large-scale pooled analysis of the Iowa and Missouri Residential Radon Studies, both of which incorporated the use of the glass-based detectors within their study designs.

Four in ten people in the US will be diagnosed with cancer during their lifetime. Environmental exposures are important determinants of cancer risk, causing as many as 19% of cancers worldwide. Phthalates are a group of chemicals used to increase the flexibility of plastics and vinyl in household materials such as food packaging, plastic toys, wood finishes and adhesives. Some phthalates may act as endocrine disruptors with hypothesized links to endometriosis, breast cancer, and reproductive outcomes. However, no research yet exists on phthalate exposure and all-cancer mortality. We investigated the relationship between seven urinary phthalate metabolites among 5,205 adults in National Health and Nutrition Examination Survey (NHANES), from 1999 to 2006 with mortality data through 2011. Urinary phthalate metabolites were measured in spot urine samples using HPLC-MS/MS and HPLC-ESI-MS/MS. Cox proportional hazard regressions were conducted to calculate hazard ratios and 95 percent confidence intervals for all-cancer mortality, stratified by gender. Mean creatinine adjusted metabolite concentrations ranged from 0.03 – 3.86 ug/mg in males and 0.07 – 4.37 ug/mg in females. Age-adjusted and multivariate Cox proportional hazard models did not yield statistically significant results for any metabolites. Hazard ratios in the multivariate model for continuous, creatinine adjusted, log transformed metabolite concentrations, ranged from 0.90 to 1.27 in men and 0.86 to 1.07 in women. There was no evidence for a dose-response relationship in the quartile analyses, with p-values for trend above 0.12. This research contributes to the limited cancer literature on phthalate exposure that helps direct future regulations on plasticizers in consumer products.

Farmworkers play an integral role in the production and availability of tomato fruit for consumption. Yet the work activities of farmworkers present risk factors for musculoskeletal disorders. Tasks involving stake pounding, picking, bucket toss, and trellising entail risk factors such as repetitive motions, lifting/carrying of heavy loads, and working in flexed trunk postures. These physically demanding activities are typically associated with musculoskeletal disorders (MSDs). Presently, quantitative assessments of these jobs and health risks to the workers are rare. Access to the workers who are often migrant and seasonal can pose an impediment to such investigations. This research examines three tasks performed by tomato farmworkers using objective quantitative tools such as electromyography and physical activity monitoring. It also studies the relationship between self-reported and/or clinically diagnosed chronic health conditions among tomato farmworkers in the region, and risks for developing musculoskeletal disorders in the workplace. Finally, it provides models for studying risk factors of migrant farmworkers via cooperation with a migrant health center and the construction of a tomato test plot. The results of the test plot study show that the anterior deltoid and upper trapezius muscles are disproportionately impacted by tomato farm work activity, even though the three tasks studied are of moderate physical intensity. A high prevalence of musculoskeletal pain was found to exist among tomato farmworkers with the age of the worker influencing the presence or absence of chronic and comorbid conditions. Diabetes, obesity and hypertension were studied in relation to musculoskeletal disorders. The studies described in this dissertation lay the groundwork for future studies and may also encourage policy makers to support programs and collaborative partnerships that address the needs of migrant agricultural workers. We recommend longitudinal studies to research the interplay between comorbidities, jobs performed, and musculoskeletal conditions. We also recommend the use of test plots and full-shift evaluations to better characterize the degree of overexertion in tomato industry tasks.

Public health effects associated with rising temperatures resulting from global climate change are expected to increase significantly in this century. Projecting future heat-related mortality is challenging due to considerable uncertainties, and national-level, large-scale impacts under the latest greenhouse gas emission scenarios remain largely unexplored. Here I estimate excess heat-related mortality in the continental United States and in 50 largest metropolitan areas in China in the 2050s under two Representative Concentration Pathways (RCPs) emission scenarios: RCP4.5 and RCP8.5. Using model-simulated future and present climate variables that were dynamically downscaled by regional meteorology models, this study quantifies the potential increase in heat-related mortality during the warm season (May-September) in mid-century relative to the base period of 2000s. The projections are based on an integrated assessment framework that combines high-resolution climate model outputs, location specific temperature-mortality relationships, population projections and baseline mortality rates. Heat mortality risk estimates for both countries are derived from systematic reviews of current literature on temperature-mortality relationships. Potential human adaptation is likely to decrease heat-related mortality in the future. I evaluate future adaptation assumption with a scenario analysis based on empirical evidence of adaptation to heat in both countries. Findings from this study will provide valuable information to support climate policy decision making and heat-related risk management in both countries and globally

Infamous for “Mad hatter syndrome” and “Minamata disease”, mercury (Hg) is ranked high on the Agency for Toxic Substances and Disease Registry's priority list of hazardous substances for its potent neurologic, renal, and developmental toxicities. Most typical exposures are via contaminated water and food. Although regulations and advisories are exercised at various levels, Hg pollution from both natural and anthropogenic sources has remained a major public health and safety concern. Rapid detection of solvated aqueous Hg2+ ions at low levels is critical for immediate response and protection of those who are vulnerable (young children, pregnant and breast-feeding women) to acute and chronic exposures to Hg2+. Various types of sensors capable of detecting Hg in water have been developed. In particular, the novel use of engineered carbon nanotubes (CNTs) has garnered attention due to their specificity and sensitivity towards Hg2+ detection in solution. In this focused review, we describe the sensitivity, selectivity and mechanisms of Hg2+ ion sensing at trace levels by employing CNT-based various sensor designs, and appraise the open literature on the currently applied and “proof-of-concept” methods. Five different types of CNT-based sensor systems are described: potentiometric, DNA-based fluorescence, surface plasmon resonance (SPR), colorimetric, and stripping voltammetric assays. In addition, the recognized merits and shortcomings for each type of electrochemical sensors are discussed. The knowledge from this succinct review shall guide the development of the next generation CNT-based biochemical sensors for rapid Hg2+ detection in the environment, which is a significant first step towards human health risk analysis of this legacy toxicant.

No description available.

No description available.

Numerous investigators have studied sound communication in animals in recent years. Most of these studies have been on birds, insects, or cetaceans, particularly the dolphin. Most of the studies on terrestrial mammals have been of the natural history type, and the authors have given an orthographic rendition of any sounds produced by that particular species. Few definitive studies have been done. There have been a few attempts to determine cause and function of sounds in mammals (Arvola, lImen, and Koponen, 1962; Bartholomew and Collias, 1962; Rowell and Hinde, 1962; Andrew, 1963). No quantitative studies on sound communication in Citellus have been made. Balph and Stokes (1963), Burnett (1931), Fitch (1948), Gordon (1943), Linsdale (1946), and Manville (1959) have described the natural history and ecology of various ground squirrels. The purpose of my study was to catalog the sounds given by the Uinta ground squirrel (Citellus armatus), to determine the cause and function of each sound, and to see how these sounds represent adaptations to life in the animal's habitat.