Context: Perfluorocarbons (PFC) are man-made chemicals used in numerous household products. They have a long half-life in humans and complex animal toxicity, and accumulating evidence points toward associations with multiple human health endpoints. Objective: Our objective was to investigate whether PFC are associated with endocrine disruption in women. Design: Cross-sectional analyses were made between quintiles of serum PFC, serum estradiol, and menopause onset. Setting: The C8 Health Project, with cohort of 69,030 adults and children, was conducted due to PFC contamination of drinking water from six water districts in two states. Participants: Participants included 25,957 women aged 18–65 yr. Main Outcome Measures: Serum estradiol levels and onset of menopause were assessed. The survey was the result of a class action suit, and survey designers (an independent corporation) had no a priori hypotheses. All hypotheses have been formulated by other investigators after data collection. Results: After excluding women who reported hysterectomy and adjusting for age within the group, smoking, alcohol consumption, body mass index, and exercise, the odds of having experienced menopause were significantly higher in the highest quintile relative to the lowest quintile of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in the perimenopausal [PFOS odds = 1.4, confidence interval (CI) = 1.1–1.8; PFOA odds =1.4, CI = 1.1–1.8] and menopausal age groups (PFOS odds = 2.1, CI=1.6–2.8; PFOA odds = 1.7, CI = 1.3–2.3). After appropriate exclusions and adjustment for covariates, there was a significant inverse association between PFOS and estradiol in perimenopausal (β = −3.65; P < 0.0001) and menopausal age groups (β = −0.83; P = 0.007) but not between PFOA and estradiol. Conclusions: These data suggest that PFC are associated with endocrine disruption in women and that further research on mechanisms is warranted.

Cancer is a complex disease that involves a sequence of gene-environment interactions in a progressive process that cannot occur without dysfunction in multiple systems, including DNA repair, apoptotic and immune functions. Epigenetic mechanisms, responding to numerous internal and external cues in a dynamic ongoing exchange, play a key role in mediating environmental influences on gene expression and tumor development.

Perfluorocarbons from common household products such as food containers, stain- resistant protection for clothing, furniture and carpets, paints, and fire-fighting foams are found in soil, water, plants, animal and human serum worldwide. Previous research has shown a significant association between these chemicals and thyroid disease in women. The present data from the C8 Health Project assessed thyroid function in a cross-sectional analysis of 52,296 adults with a year or more of exposure to perfluorooctanoate (PFOA) from drinking water. Outcomes were: thyroxine, T3 uptake, and thyroid stimulating hormone (TSH). Analyses were stratified by gender and age group (< 20 - < 50 years and > 50). Both PFOA and perfluorooctane sulfonate (PFOS) were associated with significant elevations in serum thyroxine and a significant reduction in T3 uptake in all participants. There were also significant gender/PFOS interactions for T3 uptake and thyroxine, as well as gender/PFOA interactions for T3 uptake. Results provide evidence for disruption of thyroid function related to these common chemicals and possible mechanisms are discussed.

The ductal system of the salivary gland has long been postulated to be resistant to radiation-induced damage, a common side effect incurred by head and neck cancer patients receiving radiotherapy. Yet, whether the ducts are capable of regenerating after genotoxic injury, or if damage to ductal cells induces lineage plasticity, as has been reported in other organ systems, remains unknown. Here, we show that two ductal progenitor populations, marked exclusively by KRT14 and KIT, maintain non-overlapping ductal compartments after radiation exposure but do so through distinct cellular mechanisms. KRT14+ progenitor cells are fast cycling cells that proliferate in response to radiation-induced damage in a sustained manner and divide asymmetrically to produce differentiated cells of the larger granulated ducts. Conversely, KIT+ intercalated duct cells are long-lived progenitors for the intercalated ducts that undergo few cell divisions either during homeostasis or after gamma radiation, thus maintaining ductal architecture with slow rates of cell turnover. Together, these data illustrate the regenerative capacity of the salivary ducts and highlight the heterogeneity in the damage responses used by salivary progenitor cells to maintain tissue architecture.

Objectives: To examine barriers to initiation and continuation of treatment among individuals with common mental disorders in the Saudi National Mental Health Survey (SNMHS). Methods: The SNMHS is a community-based epidemiological survey in a nationally representative household sample of respondents aged 15–65 in the Kingdom of Saudi Arabia. The World Health Organization Composite International Diagnostic Interview (CIDI) 3.0 was used. Predictors of barriers to treatment were analyzed with multivariable logistic regression. Results: Among participants with a 12-month DSM-IV/CIDI disorder (n = 711), 86.1% reported no service use. Of those (n = 597), 50.7% did not think they needed any help (categorized as “low perceived need”) and 49.3% did perceive need. Of those who perceived need (n = 309), the majority (98.9%) reported attitudinal barriers to initiation. In contrast, 10.3% of those with a perceived need reported structural barriers. Respondents who were previously married or indicated below-average income were more likely to believe they needed help. Conclusions: Among people with a diagnosed mental disorder, low perceived need and attitudinal barriers are the primary barriers to mental health treatment in the KSA. The results suggest that addressing poor mental health literacy may be essential factor in reducing the unmet need for mental health treatment in the KSA.

Perfluoroalkyl substances (PFASs) have been associated with decreased immunity to childhood tetanus and diphtheria immunizations. If these vaccinations are vulnerable to influence from PFASs, questions arise about associations with other common inoculations. To examine whether serum PFASs were associated with reduced immunity to rubella immunization, and whether interactions with sex or ethnicity warranted analytic stratification. Usually, toxicology analyses are calculated controlling for race and sex. However, sex differences in immune function have been reported and a reduction of immunity to rubella in women could pose risks such miscarriage. We analyzed a nationally representative sample of individuals ≥ 12 years from the National Health and Nutrition Examination Survey (NHANES) for years 1999–2000 and 2003–2004 for whom PFAS measures were available. Our analytic strategy was to start with separate analyses for youth and adults controlling for several covariates including ethnicity and sex, as well as the interaction of these terms with PFASs. If there was a main effect of PFASs and an interaction term, we would stratify analyses of effect size. The outcome variable was Rubella IgG titers by quartile of perfluoroalkyl substances. After exclusion for missing data, the analyzed sample contained 581 adult women, 621 adult men, and 1012 youth. There was no significant effect of PFASs on immunity in youths but a significant effect of both PFOA and PFOS in adults, as well as a significant interaction of PFOA x sex and a borderline significant interaction of PFOS x sex. When effect size analyses were stratified by sex, a significant association between rubella titres and PFOA was found in men but not women and PFOS was not significant in either sex. These results support our earlier studies showing sex specific responses to PFASs and indicate the importance of thinking carefully about analytic strategies in population based toxicology research.