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In 1973, the Velsicol Chemical Company, which manufactured FireMaster, a brominated flame retardant, and NutriMaster, a nutritional supplement, mistakenly shipped hundreds of pounds of FireMaster to grain mills around Michigan where it was incorporated into animal feed and then into the food chain across the state. An estimated 6.5 million Michigan residents consumed polybrominated biphenyl (PBB)-laced animal products leading to one of the largest agricultural accidents in U.S. history. To date, there have been no studies investigating the effects of PBB on epigenetic regulation in sperm, which could explain some of the endocrine-related health effects observed among children of PBB-exposed parents. Fusing epidemiological approaches with a novel in vitro model of human spermatogenesis, we demonstrate that exposure to PBB153, the primary component of FireMaster, alters the epigenome in human spermatogenic cells. Using our novel stem cell-based spermatogenesis model, we show that PBB153 exposure decreases DNA methylation at regulatory elements controlling imprinted genes. Furthermore, PBB153 affects DNA methylation by reducing de novo DNA methyltransferase activity at increasing PBB153 concentrations as well as reducing maintenance DNA methyltransferase activity at the lowest tested PBB153 concentration. Additionally, PBB153 exposure alters the expression of genes critical to proper human development. Taken together, these results suggest that PBB153 exposure alters the epigenome by disrupting methyltransferase activity leading to defects in imprint establishment causing altered gene expression, which could contribute to health concerns in the children of men exposed to PBB153. While this chemical is toxic to those directly exposed, the results from this study indicate that the epigenetic repercussions may be detrimental to future generations. Above all, this model may be expanded to model a multitude of environmental exposures to elucidate the effect of various chemicals on germline epigenetics and how paternal exposure may impact the health of future generations.

The Michigan Long-Term PBB Study was established following exposure to polybrominated biphenyls (PBBs) in the early 1970s. Serum samples from cohort members were analyzed for PBB during 1976–1993. More than 20 years following this industrial incident, some participants still had measurable serum PBB concentration levels. Thus, there is continuing interest in understanding the elimination of PBB from the body. In the present study, we estimated serum PBB decay and investigated the effects of covariates on serum PBB decay rates among 406 female cohort members. We developed a decay model using a general linear mixed model, which attributes unique intercept and slope estimates for each individual while borrowing information across individuals for predicting these quantities. Age at exposure and body mass index (BMI) at the initial measurement were time-independent covariates. Time since exposure, smoking history, pregnancy status, and breast-feeding status were time-dependent covariates. Higher BMI was associated with a slower decay rate; smokers had a faster decay rate than nonsmokers; and increasing age at exposure was marginally associated with a slower decay rate. Our results suggest a faster serum PBB decay rate for women who breast-fed during the interval between serum PBB measurements. To evaluate the predictive performance of our modeling approach, we compared the results from this model with those from a previously developed ordinary least squares (OLS) two-stage decay model. The mixed-effects decay model predicted the observed serum PBB concentration levels significantly better than the OLS two-stage decay model (mixed-effects model, r=0.93; OLS two-stage model, r=0.86; P

Background: In this review, the epidemiological evidence examining associations between upper extremity musculoskeletal symptoms and disorders and keyboard use intensity (hours of computer use-per day or per-week) and computer user posture was explored. Methods: An OVID Medline® literature search was conducted to identify papers published in the peer-reviewed medical literature between 1966 and November, 2005. A total of 558 citations were found and reviewed. Those papers in which associations between musculoskeletal outcomes and (1) posture (ascertained by a study investigator) or (2) computer use, in units of hours-per-day, hours-per-week, or as a percent of work-time, were included in the review. Results: Thirty-nine epidemiological studies examining associations between computer use and MSD outcomes were identified. While the observational epidemiological literature was heterogeneous, some trends did emerge. It appears that the most consistent finding was the association observed between hours keying and hand/arm outcomes. Associations between some postural effects and musculoskeletal outcomes may also be inferred from the literature. In particular, placing the keyboard below the elbow, limiting head rotation, and resting the arms appears to result in reduced risk of neck/shoulder outcomes. Minimizing ulnar deviation and keyboard thickness appears to result in reduced risk of hand/arm outcomes. Conclusions: Several methodological limitations, including non-representative samples, imprecise or biased measures of exposure and health outcome, incomplete control of confounding, and reversal of cause and effect, may contribute to the heterogeneity of observed results. Suggestions are made for improving the validity of future investigations.

Despite consensus recommendations the usse of screening mammography remins low. We examined physician and patient related variables associated with requests to undergo screening mammography in a primary care setting, in order to assess current barriers to screening mammography at the level of the physician-patient interaction. A sample of 261 women over the age of 50, whose primary care was provided by resident physician in a large, urban, academic medical center were examined. Data concerning patients and physicians demographic and clinical chracteristics were abstracted. The data were analyzed by Chi-square and stepwise logistic regression. Forty-five percent of the patients were offered screening mammography within the study year and 53% were offered mammography over the preceding two years. Variables significantly associated with a request for screening included a previous history of breast disease (p

Background Polybrominated biphenyl (PBB), a brominated flame retardant, was accidently mixed into animal feed in Michigan (1973–1974) resulting in human exposure through consumption of contaminated meat, milk and eggs. Beginning in 1976 individuals who consumed contaminated products were enrolled in the Michigan Long-Term PBB Study. This cohort presents a unique opportunity to study the association between parental exposures to PBB and offspring sex ratio. Methods We identified offspring of female PBB cohort participants (born 1975–1988) and obtained electronic birth records for those born in the state of Michigan. We linked this information to parental serum PBB and PCB concentrations collected at enrollment into the cohort. We modeled the odds of a male birth with generalized estimating equations accounting for the non-independence of siblings born to the same parents. We explored potential confounders: parental age and education at offspring's birth, parental body mass index at cohort enrollment, birth order, gestational age and year of offspring's birth. Results The overall proportion of male offspring among 865 live births to cohort mothers was 0.542. This was higher than the national male proportion of 0.514 (binomial test: p = 0.10). When both parents were in the cohort (n = 300), we found increased odds of a male birth with combined parents' enrollment PBB exposure ≥ the median concentrations (3 μg/L for mothers; 6 μg/L for fathers) compared to combined parents' PBB exposure < the median concentrations (AOR = 1.43, 95% CI: 0.89–2.29), although this did not reach statistical significance. In addition, there was a suggestion of increased odds of a male birth for combined parents' enrollment PCB exposure ≥ the median concentrations (6 μg/L for mothers; 8 μg/L for fathers) compared to combined parents' enrollment PCB exposure < the median concentrations (AOR = 1.53, 95% CI: 0.93–2.52). Conclusion This study adds to the body of literature on secondary sex ratio and exposure to environmental contaminants. In this population, combined parental exposure to PBBs or PCBs increased the odds of a male birth. Further research is needed to corroborate these findings and shed light on the biological mechanisms by which these types of chemicals may influence the secondary sex ratio.

Rats aged 15 to 19 days showed persistent locomotor activity when observed in a small open field at 22.8∘C. Higher ambient temperatures greatly curtailed the pups’ walking, however. Contrary to prior analyses, the relatively nonattenuating ambulation of rat pups seems to indicate no state of general arousal. The persistent activity among isolated pups does not appear to be a failure to adapt to a novel environment, nor is there much evidence that this behavior represents exploration. The hyperactive state of rat pups reflects a response to their being deprived of the thermal, olfactory, and tactile cues usually found within the litter.