Mortality in the agricultural health study, 1993-2007

Comparing agricultural cohorts with the general population is challenging because the general healthiness of farmers may mask potential adverse health effects of farming. Using data from the Agricultural Health Study, a cohort of 89,656 pesticide applicators and their spouses (N = 89, 656) in North Carolina and Iowa, the authors computed standardized mortality ratios (SMRs) comparing deaths from time of the enrollment (1993-1997) through 2007 to state-specific rates. To compensate for the cohort's overall healthiness, relative SMRs were estimated by calculating the SMR for each cause relative to the SMR for all other causes. In 1,198,129 person-years of follow-up, 6,419 deaths were observed. The all-cause mortality rate was less than expected (SMR(applicators) = 0.54, 95% confidence interval (CI): 0.52, 0.55; SMR(spouses) = 0.52, 95% CI: 0.50, 0.55). SMRs for all cancers, heart disease, and diabetes were significantly below 1.0. In contrast, applicators experienced elevated numbers of machine-related deaths (SMR = 4.15, 95% CI: 3.18, 5.31), motor vehicle nontraffic accidents (SMR = 2.80, 95% CI: 1.81, 4.14), and collisions with objects (SMR = 2.12, 95% CI: 1.25, 3.34). In the relative SMR analysis for applicators, the relative mortality ratio was elevated for lymphohematopoietic cancers, melanoma, and digestive system, prostate, kidney, and brain cancers. Among spouses, relative SMRs exceeded 1.0 for lymphohematopoietic cancers and malignancies of the digestive system, brain, breast, and ovary. Unintentional fatal injuries remain an important risk for farmers; mortality ratios from several cancers were elevated relative to other causes.     

Oral Lead Bullet Fragment Exposure in Northern Bobwhite (<Emphasis Type="Italic">Colinus virginianus</Emphasis>)

Lead (Pb) is a worldwide environmental contaminant known to adversely affect multiple organ systems in both mammalian and avian species. In birds, a common route of exposure is via oral ingestion of lead particles. Data are currently lacking for the retention and clearance of Pb bullet fragments in gastrointestinal (GI) tract of birds while linking toxicity with blood Pb levels. In the present study, northern bobwhite quail fed a seed-based diet were orally gavaged with Pb bullet fragments (zero, one or five fragments/bird) and evaluated for rate of fragment clearance, and changes in peripheral blood, renal, immune, and gastrointestinal parameters. Based on radiographs, the majority of the birds cleared or absorbed the fragments by seven days, with the exception of one five-fragment bird which took between 7 and 14 days. Blood Pb levels were higher in males than females, which may be related to egg production in females. In males but not females, feed consumption, body weight gain, packed cell volume (PCV), plasma protein concentration, and δ-aminolevulinic acid dehydratase (δ-ALAD) activity were all adversely affected by five Pb fragments. Birds of both sexes that received a single Pb fragment displayed depressed δ-ALAD, suggesting altered hematologic function, while all birds dosed with five bullet fragments exhibited greater morbidity.     

Trauma in the neighborhood: a geospatial analysis and assessment of social determinants of major injury in North America

Objectives. We sought to identify and characterize areas with high rates of major trauma events in 9 diverse cities and counties in the United States and Canada.Methods. We analyzed a prospective, population-based cohort of injured individuals evaluated by 163 emergency medical service agencies transporting patients to 177 hospitals across the study sites between December 2005 and April 2007. Locations of injuries were geocoded, aggregated by census tract, assessed for geospatial clustering, and matched to sociodemographic measures. Negative binomial models were used to evaluate population measures.Results. Emergency personnel evaluated 8786 major trauma patients, and data on 7326 of these patients were available for analysis. We identified 529 (13.7%) census tracts with a higher than expected incidence of major trauma events. In multivariable models, trauma events were associated with higher unemployment rates, larger percentages of non-White residents, smaller percentages of foreign-born residents, lower educational levels, smaller household sizes, younger age, and lower income levels.Conclusions. Major trauma events tend to cluster in census tracts with distinct population characteristics, suggesting that social and contextual factors may play a role in the occurrence of significant injury events.Injury is a major public health problem and one of the most common reasons for emergency department visits, health care expenses, morbidity, and mortality.^1–4 Although a growing body of literature has assessed individual-level injury factors and outcomes, relatively little research has evaluated how broader geographic, environmental, social, and cultural factors influence the occurrence of injury.Better understanding such macroscopic influences may improve health policy strategies for injury prevention, including community planning to reduce violence, defining the interplay between contextual and individual-level injury factors, efficient deployment of emergency medical service (EMS) resources, and more targeted public health efforts to reduce injury-related morbidity and mortality. Geographic information systems (GIS) analysis has been suggested as a novel tool in evaluating such geospatial and contextual components of injury events,^5–7 yet the number of GIS-based injury studies remains relatively sparse.Injury disproportionately affects individuals in certain racial, ethnic, and socioeconomic groups.^8–10 However, whether such differences function through individual-level mechanisms or are indicative of larger societal and environmental influences is unknown. Previous geospatial injury studies evaluated intentional injury (i.e., assault)^11–13 and violent crime¹⁴ rates, falls among the elderly,⁷ pedestrian injuries,^15,16 and trauma system patients.¹⁷ These studies suggested that the locations where injuries occur are not random and that certain environmental (e.g., density of alcohol outlets), demographic, socioeconomic (e.g., poverty), and racial/ethnic factors, as well as time of day, are associated with higher injury and crime rates.However, previous research has been limited to single geographic areas, patients with certain mechanisms of injury, and hospitalized patients.^7,11–17 It remains unclear whether similar geospatial clustering exists among patients affected by additional injury mechanisms across diverse regions and communities and whether specific environmental and sociocultural factors can reliably identify high-risk populations.We sought to identify geospatial clusters of major trauma patients accessing 911 emergency services and to characterize socioeconomic, cultural, and demographic population measures in such locations across 9 diverse North American sites. These sites were Birmingham, Alabama; Dallas, Texas; Milwaukee, Wisconsin; Pittsburgh, Pennsylvania; Portland, Oregon; King County, Washington; Ottawa, Ontario; Toronto, Ontario; and Vancouver, British Columbia. Our overall aim was to combine both geospatial and population information to evaluate the contextual basis and broader social determinants of serious injury.     

Atrazine and cancer incidence among pesticide applicators in the agricultural health study (1994-2007)

Background: Atrazine is a triazine herbicide used widely in the United States. Although it is an animal carcinogen, the mechanism in rodents does not appear to operate in humans. Few epidemiologic studies have provided evidence for an association.Methods: The Agricultural Health Study (AHS) is a prospective cohort that includes 57,310 licensed pesticide applicators. In this report, we extend a previous AHS analysis of cancer risk associated with self-reported atrazine use with six additional years of follow-up and more than twice as many cancer cases. Using Poisson regression, we calculated relative risk estimates and 95% confidence intervals for lifetime use of atrazine and intensity-weighted lifetime days, which accounts for factors that impact exposure.Results: Overall, 36,357 (68%) of applicators reported using atrazine, among whom there were 3,146 cancer cases. There was no increase among atrazine users in overall cancer risk or at most cancer sites in the higher exposure categories compared with the lowest. Based on 29 exposed cases of thyroid cancer, there was a statistically significant risk in the second and fourth quartiles of intensity-weighted lifetime days. There was a similar pattern for lifetime days, but neither the risk estimates nor the trend were statistically significant and for neither metric was the trend monotonic.Conclusions: Overall, there was no consistent evidence of an association between atrazine use and any cancer site. There was a suggestion of increased risk of thyroid cancer, but these results are based on relatively small numbers and minimal supporting evidence.     

Restaurant challenge offers healthful meal options and builds diabetes awareness

PURPOSE: The Frederick Restaurant Challenge is an innovative project based on a collaborative effort among community organizations and partners designed to offer delicious healthful meal options at local restaurants during the month of November for American Diabetes Month. Local restaurants were challenged to participate and submitted recipes for healthful meals to the Frederick County Diabetes Coalition for review by registered dietitians. Diners voted on meals to determine the challenge winner(s), and were eligible to win prizes as well. Publicity prior to and during the month was effective in creating positive news about healthful meals when eating out, raised awareness about diabetes, and provided restaurants with desirable advertising opportunities. Feedback from restaurants and diners was overwhelmingly positive. The purpose of this article is to describe this successful low-budget project to encourage its replication in local communities. CONCLUSIONS: The Frederick Restaurant Challenge proved to be a very successful, innovative, low-budget project that met its intended goals: to develop healthful meal options for people with diabetes (or for anyone wishing to eat healthier); to demonstrate that healthful food can taste delicious; and to encourage restaurants to continue offering healthful options on their menus beyond the challenge month. Community interventions such as the Frederick Restaurant Challenge offer unique and important strategies for affecting change and raising awareness not only for people with diabetes but also for the entire community.     

Ergodic and nonergodic processes coexist in the plasma membrane as observed by single-molecule tracking

Diffusion in the plasma membrane of living cells is often found to display anomalous dynamics. However, the mechanism underlying this diffusion pattern remains highly controversial. Here, we study the physical mechanism underlying Kv2.1 potassium channel anomalous dynamics using single-molecule tracking. Our analysis includes both time series of individual trajectories and ensemble averages. We show that an ergodic and a nonergodic process coexist in the plasma membrane. The ergodic process resembles a fractal structure with its origin in macromolecular crowding in the cell membrane. The nonergodic process is found to be regulated by transient binding to the actin cytoskeleton and can be accurately modeled by a continuous-time random walk. When the cell is treated with drugs that inhibit actin polymerization, the diffusion pattern of Kv2.1 channels recovers ergodicity. However, the fractal structure that induces anomalous diffusion remains unaltered. These results have direct implications on the regulation of membrane receptor trafficking and signaling.     

Pesticide exposure and amyotrophic lateral sclerosis

Our objectives were to summarize literature on the association of amyotrophic lateral sclerosis (ALS) with pesticides as a group and to evaluate associations of ALS with specific pesticides. We conducted a meta-analysis of published studies of ALS and pesticides as a group and investigated the association of ALS with specific pesticides, using data from the Agricultural Health Study (AHS), a cohort including 84,739 private pesticide applicators and spouses. AHS participants provided information on pesticide use at enrollment in 1993-1997. In mortality data collected through February 2010, ALS was recorded on death certificates of 41 individuals whom we compared to the remaining cohort (controls), using unconditional logistic regression adjusted for age and gender to calculate odds ratios (ORs) and 95% confidence intervals. In the meta-analysis, ALS was associated with use of pesticides as a group (1.9, 1.1-3.1). In the AHS, ALS was not associated with pesticides as a group, but was associated with use of organochlorine insecticides (OCs) (1.6, 0.8-3.5), pyrethroids (1.4, 0.6-3.4), herbicides (1.6, 0.7-3.7), and fumigants (1.8, 0.8-3.9). ORs were elevated forever use of the specific OCs aldrin (2.1, 0.8-5.1), dieldrin (2.6, 0.9-7.3), DDT (2.1, 0.9-5.0), and toxaphene (2.0, 0.8-4.9). None of these associations was statistically significant. Similar results were observed in an analysis restricted to men. In conclusion, the meta-analysis suggests that ALS risk is associated with use of pesticides as a group, and our analysis of AHS data points to OC use in particular. The latter results are novel but based on a small number of cases and require replication in other populations.     

Age-dependent neurovascular abnormalities and altered microglial morphology in the YAC128 mouse model of Huntington disease

Central nervous system (CNS) inflammatory processes including microglial activation have been implicated in the pathogenesis of neurodegenerative diseases such as Huntington Disease (HD). We report age-dependent changes in striatal microglial morphology and vasculature in the YAC128 mouse model of HD. Decreases in microglial ramification along with a decrease in vessel diameter and increased vessel density and length suggest the presence of microgliosis and proangiogenic activity in YAC128 mice. Our hypothesis for this study was that the changes in microglial morphology and perturbations in vasculature may be involved in the pathogenesis of HD and that peripheral challenge with the bacterial endotoxin, lipopolysaccharide (LPS), will exacerbate these microglial and vascular changes as well as the HD phenotype in YAC128 mice at 12 months. Chronic peripheral LPS (1 mg/kg) potentiated microglial activation indicated by an increase in microglial cell body size and retraction of processes. This potentiation in microglial activation with chronic peripheral LPS challenge was paralleled with vascular remodeling including dilatation, increased vessel wall thickness, increased BBB permeability and fibrinogen deposition in YAC128 striatum. Although peripheral LPS caused an increase in microglial activation and degenerative changes in cerebrovasculature, the phenotypic hallmarks of HD in YAC128 mice such as motor coordination deficits and decreased striatal volume were not exacerbated by chronic peripheral LPS exposure. This study identifies age-dependent increases in microglial activation and angiogenesis in YAC128 at 12 months. Peripheral inflammation induced by chronic LPS causes similar changes but does not influence the HD phenotype in YAC128 mice.