Modeled PFOA Exposure and Coronary Artery Disease,Hypertension, and High Cholesterol in Community and Worker Cohorts

Background: Several previous studies, mostly cross-sectional, have found associations between perfluorooctanoic acid (PFOA) and high cholesterol levels, but studies of hypertension and heart disease have had inconsistent findings.Objectives: In this study we examined the association between modeled PFOA exposure and incident hypertension, hypercholesterolemia, and coronary artery disease among workers at a Mid-Ohio Valley chemical plant that used PFOA, and residents of the surrounding community.Methods: Community- and worker-cohort participants completed surveys during 2008–2011 covering demographics, health-related behaviors, and medical history. Cox proportional hazard models, stratified by birth year, modeled the hazard of each outcome (starting at 20 years of age) as a function of retrospective serum PFOA concentration estimates (generated through fate, transport and exposure modeling), controlling for sex, race, education, smoking, alcohol use, body mass index, and diabetes.Results: Among 32,254 participants (28,541 community; 3,713 worker), 12,325 reported hypertension with medication, 9,909 reported hypercholesterolemia with medication, and 3,147 reported coronary artery disease (2,550 validated). Hypercholesterolemia incidence increased with increasing cumulative PFOA exposure (sum of yearly serum concentration estimates), most notably among males 40–60 years of age. Compared with the lowest exposure quintile (< 142 ng/mL-years), hazard ratios for subsequent quintiles (ng/mL-years: 142 to < 234; 234 to < 630; 630 to < 3,579; ≥ 3,579) were 1.24, 1.17, 1.19, and 1.19 overall and 1.38, 1.32, 1.31, and 1.44 among men 40–60 years of age. There was no apparent association between PFOA exposure and hypertension or coronary artery disease incidence.Conclusions: Higher PFOA exposure was associated with incident hypercholesterolemia with medication, but not with hypertension or coronary artery disease.Citation: Winquist A, Steenland K. 2014. Modeled PFOA exposure and coronary artery disease, hypertension, and high cholesterol in community and worker cohorts. Environ Health Perspect 122:1299–1305; http://dx.doi.org/10.1289/ehp.1307943     

Survey of County-Level Heat Preparedness and Response to the 2011 Summer Heat in 30 U.S. States

Background: Adapting to extreme heat is becoming more critical as our climate changes. Previous research reveals that very few communities in the United States have programs to sufficiently prevent health problems during hot weather.Objective: Our goal was to examine county-level local heat preparedness and response in 30 U.S. states following the unusually hot summer of 2011.Methods: Using a multimodal survey approach, we invited local health and emergency response departments from 586 counties to participate in the largest survey to date of heat preparedness and response in the United States. County-level responses were pooled into national and regional-level summaries. Logistic regressions modeled associations between heat planning/response and county characteristics, including population, poverty rates, typical summer weather, and 2011 summer weather.Results: Of 586 counties, 190 (32%) responded to the survey. Only 40% of these counties had existing heat plans. The most common heat responses were communication about heat, outreach, and collaborations with other organizations. Both heat preparedness and heat response were, on average, more extensive in counties with higher populations, lower poverty rates, and lower percentages of older people. Heat response was generally more extensive in counties with heat plans.Conclusions: Most responding counties were underprepared for extreme heat in 2011 and lacked a formal response plan. Because counties with heat plans were more likely to act to prevent adverse heat impacts to residents, local health departments should consider adopting such plans, especially because increased extreme heat is anticipated with further climate change.Citation: White-Newsome JL, Ekwurzel B, Baer-Schultz M, Ebi KL, O’Neill MS, Anderson GB. 2014. Survey of county-level heat preparedness and response to the 2011 summer heat in 30 U.S. States. Environ Health Perspect 122:573–579; http://dx.doi.org/10.1289/ehp.1306693     

Development of a whole cell pneumococcal vaccine: BPL inactivation,cGMP production,and stability

Pneumococcal infections impose a large burden of disease on the human population, mainly in developing countries, and the current pneumococcal vaccines offer serotype-specific protection, but do not cover all pathogenic strains, leaving populations vulnerable to disease caused by non-vaccine serotypes. The pneumococcal whole cell vaccine is a low-cost strategy based on non-capsular antigens common to all strains, inducing serotype-independent immunity. Therefore, we developed the process for the cGMP production of this cellular vaccine. Initially, three engineering runs and two cGMP runs were performed in 60-L bioreactors, demonstrating the consistency of the production process, as evaluated by the growth curves, glucose consumption and metabolite formation (lactate and acetate). Cell recovery by tangential filtration was 92 ± 13%. We optimized the conditions for beta-propiolactone (BPL) inactivation of the bacterial suspensions, establishing a maximum cell density of OD₆₀₀ between 27 and 30, with a BPL concentration of 1:4000 (v/v) at 150 rpm and 4 °C for 30 h. BPL was hydrolyzed by heating for 2 h at 37 °C. The criteria and methods for quality control were defined using the engineering runs and the cGMP Lots passed all specifications. cGMP vaccine Lots displayed high potency, inducing between 80 and 90% survival in immunized mice when challenged with virulent pneumococci. Sera from mice immunized with the cGMP Lots recognized several pneumococcal proteins in the extract of encapsulated strains by Western blot. The cGMP whole cell antigen bulk and whole cell vaccine product lots were shown to be stable for up to 12 and 18 months, respectively, based upon survival assays following i.p. challenge. Our results show the consistency and stability of the cGMP whole cell pneumococcal vaccine lots and demonstrate the feasibility of production in a developing country setting.     

Strong protection induced by an experimental DIVA subunit vaccine against bluetongue virus serotype 8 in cattle

Bluetongue virus (BTV) infections in ruminants pose a permanent agricultural threat since new serotypes are constantly emerging in new locations. Clinical disease is mainly observed in sheep, but cattle were unusually affected during an outbreak of BTV seroype 8 (BTV-8) in Europe. We previously developed an experimental vaccine based on recombinant viral protein 2 (VP2) of BTV-8 and non-structural proteins 1 (NS1) and NS2 of BTV-2, mixed with an immunostimulating complex (ISCOM)–matrix adjuvant. We demonstrated that bovine immune responses induced by this vaccine were as good or superior to those induced by a classic commercial inactivated vaccine. In this study, we evaluated the protective efficacy of the experimental vaccine in cattle and, based on the detection of VP7 antibodies, assessed its DIVA compliancy following virus challenge. Two groups of BTV-seronegative calves were subcutaneously immunized twice at a 3-week interval with the subunit vaccine (n = 6) or with adjuvant alone (n = 6). Following BTV-8 challenge 3 weeks after second immunization, controls developed viremia and fever associated with other mild clinical signs of bluetongue disease, whereas vaccinated animals were clinically and virologically protected. The vaccine-induced protection was likely mediated by high virus-neutralizing antibody titers directed against VP2 and perhaps by cellular responses to NS1 and NS2. T lymphocyte responses were cross-reactive between BTV-2 and BTV-8, suggesting that NS1 and NS2 may provide the basis of an adaptable vaccine that can be varied by using VP2 of different serotypes. The detection of different levels of VP7 antibodies in vaccinated animals and controls after challenge suggested a compliancy between the vaccine and the DIVA companion test. This BTV subunit vaccine is a promising candidate that should be further evaluated and developed to protect against different serotypes.     

Erratum to: Race,ethnicity, and the duration of untreated psychosis: a systematic review

Social Psychiatry and Psychiatric Epidemiology -