Developing small-area predictions for smoking and obesity prevalence in the United States for use in Environmental Public Health Tracking.

BACKGROUND: Globally and in the United States, smoking and obesity are leading causes of death and disability. Reliable estimates of prevalence for these risk factors are often missing variables in public health surveillance programs. This may limit the capacity of public health surveillance to target interventions or to assess associations between other environmental risk factors (e.g., air pollution) and health because smoking and obesity are often important confounders. OBJECTIVES: To generate prevalence estimates of smoking and obesity rates over small areas for the United States (i.e., at the ZIP code and census tract levels). METHODS: We predicted smoking and obesity prevalence using a combined approach first using a lasso-based variable selection procedure followed by a two-level random effects regression with a Poisson link clustered on state and county. We used data from the Behavioral Risk Factor Surveillance System (BRFSS) from 1991 to 2010 to estimate the model. We used 10-fold cross-validated mean squared errors and the variance of the residuals to test our model. To downscale the estimates we combined the prediction equations with 1990 and 2000 U.S. Census data for each of the four five-year time periods in this time range at the ZIP code and census tract levels. Several sensitivity analyses were conducted using models that included only basic terms, that accounted for spatial autocorrelation, and used Generalized Linear Models that did not include random effects. RESULTS: The two-level random effects model produced improved estimates compared to the fixed effects-only models. Estimates were particularly improved for the two-thirds of the conterminous U.S. where BRFSS data were available to estimate the county level random effects. We downscaled the smoking and obesity rate predictions to derive ZIP code and census tract estimates. CONCLUSIONS: To our knowledge these smoking and obesity predictions are the first to be developed for the entire conterminous U.S. for census tracts and ZIP codes. Our estimates could have significant utility for public health surveillance.

Cyclist route choice, traffic-related air pollution, and lung function: a scripted exposure study.

BACKGROUND: A travel mode shift to active transportation such as bicycling would help reduce traffic volume and related air pollution emissions as well as promote increased physical activity level. Cyclists, however, are at risk for exposure to vehicle-related air pollutants due to their proximity to vehicle traffic and elevated respiratory rates. To promote safe bicycle commuting, the City of Berkeley, California, has designated a network of residential streets as "Bicycle Boulevards." We hypothesized that cyclist exposure to air pollution would be lower on these Bicycle Boulevards when compared to busier roads and this elevated exposure may result in reduced lung function. METHODS: We recruited 15 healthy adults to cycle on two routes - a low-traffic Bicycle Boulevard route and a high-traffic route. Each participant cycled on the low-traffic route once and the high-traffic route once. We mounted pollutant monitors and a global positioning system (GPS) on the bicycles. The monitors were all synced to GPS time so pollutant measurements could be spatially plotted. We measured lung function using spirometry before and after each bike ride. RESULTS: We found that fine and ultrafine particulate matter, carbon monoxide, and black carbon were all elevated on the high-traffic route compared to the low-traffic route. There were no corresponding changes in the lung function of healthy non-asthmatic study subjects. We also found that wind-speed affected pollution concentrations. CONCLUSIONS: These results suggest that by selecting low-traffic Bicycle Boulevards instead of heavily trafficked roads, cyclists can reduce their exposure to vehicle-related air pollution. The lung function results indicate that elevated pollutant exposure may not have acute negative effects on healthy cyclists, but further research is necessary to determine long-term effects on a more diverse population. This study and broader field of research have the potential to encourage policy-makers and city planners to expand infrastructure to promote safe and healthy bicycle commuting.

Sodium butyrate activates Notch1 signaling, reduces tumor markers, and induces cell cycle arrest and apoptosis in pheochromocytoma.

BACKGROUND: Pheochromocytoma is a neuroendocrine (NE) tumor of the adrenal medulla for which surgical resection is the only therapy. However, 10-46% of tumors are metastatic or have malignant features, and are often inoperable. Our lab has demonstrated the importance of the Notch1 signaling pathway in NE neoplasia, indicating that this pathway could be a target for emergent treatments in pheochromocytoma. It has recently become clear that histone deacetylase (HDAC) inhibitors influence Notch1 signaling. We hypothesized that the HDAC inhibitor Sodium Butyrate (NaB) might activate Notch1 in pheochromocytoma resulting in altered tumor cell proliferation. METHODS: Pheochromocytoma (PC-12) cells were treated with increasing concentrations of NaB. MTT cellular proliferation assay was used to determine the effect of NaB on PC-12 cell growth. Expression of Notch1, NE markers, and cell cycle proteins was studied using Western analysis. RESULTS: Untreated PC-12 cells lack Notch1 activity. Treatment with NaB led to a dose-dependent induction of Notch1 signaling, reduction of NE markers ASCL1 and CgA, and a significant reduction in cellular proliferation. Levels of expression of cyclin D1, p21, cleaved PARP, and cleaved caspase 3 proteins indicated the presence of cell cycle arrest and apoptosis following NaB treatment. CONCLUSION: NaB activated Notch1 signaling, inhibited cellular proliferation, reduced NE markers, and induced cell cycle arrest and apoptosis in pheochromocytoma cells. This data indicates that activation of Notch1 signaling is a promising potential therapy or palliative measure for pheochromocytoma that warrants further investigation.