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To determine demographic, reproductive, and maternal dietary factors that predict perfluoroalkyl substance (PFAS) concentrations in breast milk, we measured perfluorooctane sulfonic (PFOS) and perfluorooctanoic acid (PFOA) concentrations, using liquid chromatography-mass spectrometry, in 184 colostrum samples collected from women participating in a cohort study in Eastern Slovakia between 2002 and 2004. During their hospital delivery stay, mothers completed a food frequency questionnaire, and demographic and reproductive data were also collected. PFOS and PFOA predictors were identified by optimizing multiple linear regression models using Akaike's information criterion (AIC). The geometric mean concentration in colostrum was 35.3 pg/mL for PFOS and 32.8 pg/mL for PFOA. In multivariable models, parous women had 40% lower PFOS (95% CI: -56 to -17%) and 40% lower PFOA (95% CI: -54 to -23%) concentrations compared with nulliparous women. Moreover, fresh/frozen fish consumption, longer birth intervals, and Slovak ethnicity were associated with higher PFOS and PFOA concentrations in colostrum. These results will help guide the design of future epidemiologic studies examining milk PFAS concentrations in relation to health end points in children.

There are few HIV risk reduction interventions to meet the unique needs of women who experience intimate partner violence (IPV). This pilot study tested the feasibility, safety, and preliminary effects of an integrated IPV-sexual risk reduction intervention for abused women. Fifty-five women were randomized to the supporting positive and healthy relationships (SUPPORT) intervention (n = 27) or to a control group (n = 28). Assessments were conducted pre- and post-intervention and at 3-month follow-up. Post-intervention, SUPPORT participants showed a significant decrease in frequency of unprotected sex and an increase in safer sex communications with steady and other sexual partners. Compared to the control group, SUPPORT participants reported a higher number of safer sex conversations with their steady partner at the 3-month follow-up, and fewer episodes of IPV at both assessments in comparison to baseline. They showed improvements in sexual relationship power at both follow-ups and in several hypothesized antecedents of HIV-risk behavior. These encouraging preliminary findings suggest the need for a larger clinical trial.

Fish is the primary source of dietary omega-3 poly-unsaturated fatty acids EPA and DHA, which have been reported to reduce depressive symptoms in clinical trials. We assessed the association between fish consumption and depressive symptoms in a nationally representative sample of 10,480 adults from the 2005–2008 National Health and Nutrition Examination Survey. Depressive symptoms were classified by severity using the Patient Health Questionnaire. Fish meal consumption reported in 30-day food frequency questionnaires, and EPA+DHA intake computed from 24-h dietary recalls were evaluated in relation to depressive symptoms using multivariable ordinal logistic regression. Consumption of breaded fish showed an increased risk of greater depressive symptom severity, while all fish, non-breaded fish, and shell fish were not associated. Any EPA+DHA intake was significantly associated with fewer depressive symptoms. Exposure-response analyses revealed no clear patterns for any intake measures. Inconsistent patterns of associations in our study may be partially explained by exposure misclassification.

Objectives. We assessed the effects of a worksite multiple-component intervention addressing diet and physical activity on employees’ mean body mass index (BMI) and the percentage of employees who were overweight or obese. Methods. This group-randomized trial (n = 3799) was conducted at 10 worksites in the northeastern United States. Worksites were paired and allocated into intervention and control conditions. Within- and between-groups changes in mean BMIs and in the percentage of overweight or obese employees were examined in a volunteer sample. Results. Within-group mean BMIs decreased by 0.54 kilograms per meter squared (P = .02) and 0.12 kilograms per meter squared (P = .73) at the intervention and control worksites, respectively, resulting in a difference in differences (DID) decrease of 0.42 kilograms per meter squared (P = .33). The within-group percentage of overweight or obese employees decreased by 3.7% (P = .07) at the intervention worksites and increased by 4.9% (P = .1) at the control worksites, resulting in a DID decline of 8.6% (P = .02). Conclusions. Our findings support a worksite population strategy that might eventually reduce the prevalence of overweight and obesity by minimizing environmental exposures to calorically dense foods and increasing exposures to opportunities for energy expenditure within worksite settings.

Perinatal environmental exposures are potentially important contributors to the increase in autoimmune diseases. Yet, the mechanisms by which these exposures increase self-reactive immune responses later in life are poorly understood. Autoimmune diseases require CD4(+) T cells for initiation, progression, and/or clinical symptoms; thus, developmental exposures that cause durable changes in CD4(+) T cells may play a role. Early life activation of the aryl hydrocarbon receptor (AHR) causes persistent changes in the response of CD4(+) T cells to infection later in life but whether CD4(+) T cells are affected by developmental exposure in the context of an autoimmune disease is unknown. Gnaq(+/-) mice develop symptoms of autoimmune disease similar to those measured clinically, and therefore can be used to evaluate gene-environment interactions during development on disease progression. Herein, we examined the effect of AHR activation in utero and via lactation, or solely via lactation, on disease onset and severity in adult Gnaq(+/-) offspring. Developmental activation of the AHR-accelerated disease in Gnaq(+/-) mice, and this correlates with increases in effector CD4(+) T-cell populations. Increased symptom onset and cellular changes due to early life AHR activation were more evident in female Gnaq(+/-) mice compared with males. These observations suggest that developmental AHR activation by pollutants, and other exogenous ligands, may increase the likelihood that genetically predisposed individuals will develop clinical symptoms of autoimmune disease later in life.

To evaluate the quality and efficacy of the Ban Phaeo Mobile Eye Clinic (BPMEC) model in providing cataract surgery to rural Thailand.Retrospective review of 4-week postoperative visual acuity (VA) of 7040 patients receiving unilateral cataract surgery at 75 sites from October 2008 to March 2011. BPMEC conducted screening, surgery, and follow-up at partnering local hospitals that otherwise do not offer eye care. The primary outcome was achievement of VA ≥20/70, which was secondarily analyzed by cataract extraction method (phacoemulsification, phaco, or extracapsular cataract extraction, ECCE) and intraocular lens (IOL) type (foldable acrylic or rigid polymethylmethacrylate).Preoperatively, 249 eyes (4%) had uncorrected VA ≥20/70. Four weeks postoperatively, 5957 (85%) had VA ≥20/70, 3288 (47%) had VA ≥20/40, and 69 (1%) were lost to follow-up. Phaco was performed in 6324 eyes (90%), 1581 (25%) receiving foldable IOLs. A total of 1403 eyes (89%) undergoing phaco with a foldable IOL had postoperative VA ≥20/70, compared to 4058 (85%) and 496 (69%) of those undergoing phaco with a rigid IOL (p 0.05) and ECCE with a rigid IOL (p 0.001), respectively. Overall, 37 eyes were left aphakic. Reported intraocular complications included zonular dehiscence (37 eyes), retained lens fragment (2 eyes), wound leakage (1 eye), and posterior capsule tear (1 eye).The 4-week uncorrected postoperative VAs met the World Health Organization's quality target of VA ≥20/70 for eyes undergoing phaco and were comparable to those published by an urban hospital in Bangkok.

Background: Some experimental and human data suggest that exposure to polychlorinated biphenyls (PCBs) may induce ototoxicity, though results of previous epidemiologic studies are mixed and generally focus on either prenatal or postnatal PCB concentrations exclusively. Objectives: Our aim was to evaluate the association between pre- and postnatal PCB concentrations in relation to cochlear status, assessed by distortion product otoacoustic emissions (DPOAEs), and to further clarify the critical periods in development where cochlear status may be most susceptible to PCBs. Methods: A total of 351 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 months of age. Maternal pregnancy, cord, and child 6-, 16-, and 45-month blood samples were collected and analyzed for PCB concentrations. At 45 months of age, DPOAEs were assessed at 11 frequencies in both ears. Multivariate, generalized linear models were used to estimate the associations between PCB concentrations at different ages and DPOAEs, adjusting for potential confounders. Results: Maternal and cord PCB-153 concentrations were not associated with DPOAEs at 45 months. Higher postnatal PCB concentrations at 6-, 16-, and 45-months of age were associated with lower (poorer) DPOAE amplitudes. When all postnatal PCB exposures were considered as an area-under-the-curve metric, an increase in PCB-153 concentration from the 25th to the 75th percentile was associated with a 1.6-dB SPL (sound pressure level) decrease in DPOAE amplitude (95% CI: –2.6, –0.5; p = 0.003). Conclusions: In this study, postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic tests at age 45 months. Citation: Jusko TA, Sisto R, Iosif AM, Moleti A, Wimmerová S, Lancz K, Tihányi J, Šovčíková E, Drobná B, Palkovičová L, Jurečková D, Thevenet-Morrison K, Verner MA, Sonneborn D, Hertz-Picciotto I, Trnovec T. 2014. Prenatal and postnatal serum PCB concentrations and cochlear function in children at 45 months of age. Environ Health Perspect 122:1246–1252; http://dx.doi.org/10.1289/ehp.1307473

Background: Sedentary behaviors (SB) are activities associated with prolonged time periods of sitting, reclining, or laying down during waking hours. While the relation between SB and physical activity is complex, the common consensus is that SB is not the absence of physical activity and consists of its own determinants posing distinct health outcomes. These behaviors are of significant public health importance as the majority of Americans spend much of their days in SB and due to the increased risks of morbidity and mortality associated with SB. Adverse health outcomes associated with SB include cardiovascular disease, obesity, metabolic syndrome, hypertension and mortality. Television-viewing time and total sitting time have both been used widely to assess time spent in SB and therefore we hypothesize that TV-viewing time and total hours sitting will have high concordance and can be used interchangeably to represent sedentary behaviors. Methods: Using a sample (n = 2858) from the Images of a Healthy Worksite study, a group-randomized control trial involving nutrition and physical activity, the current study assessed how two different tools measured time spent in SB. Tertiles were created based upon the distribution of hours sitting and hours spent TV-vewing. Weighted Kappa statistics were used to measure concordance between hours of TV-viewing and total hours of time spent sitting for the entire sample and for subgroup analyses. Results: Weighted Kappa statistics for tertiles of hours sitting and tv hours were 0.0046, indicating little agreement on the television and the sitting items. Kappa w statistics for BMI categories also showed poor agreement (obese Kappa w = 0.02, overweight Kappa w = 0.002, and healthy subjects Kappa w = 0.006. The Kappa w statistics for males and females were -0.006 and 0.02, respectively. Kappa w statistics for the intervention group (Kappa w = 0.007) and for the control group (Kappa w = 0.0005) also showed little agreement. Conclusions: These results suggest that although commonly used, using television viewing time and total time spent sitting as interchangeable markers of SB, is not a valid assumption. We propose that total time spent sitting and hours spent television-viewing represent different domains within the construct of sedentary behavior. It is important for future researchers to use measures of sedentary behavior that capture the numerous domains involved in measuring SB to allow for the most sensitive measurement of this high-risk behavior.

The etiology of prostate cancer is uncertain, but intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs) may play a role. We evaluated prostate specific antigen (PSA) levels with fish consumption (the primary source of n-3 PUFAs) and calculated PUFA intake. Serum PSA concentrations were available from 6018 men who participated in the 2003–2010 National Health and Nutrition Examination Survey (NHANES). Fish consumption was calculated via 30-day Food Frequency Questionnaire data, whereas n-3 PUFA intake was calculated from 24-h dietary recalls. We employed multivariable logistic and linear regression models to evaluate the association of these exposure variables with PSA levels while controlling for relevant covariates. PSA levels were lower in men who ate more breaded fish, but no other types of fish consumption or n-3 PUFA intake were associated with PSA levels. Our findings provide little evidence for a role of fish or n-3 PUFA consumption in influencing PSA levels.

Previous studies have reported an increased risk of myocardial infarction (MI) associated with acute increases in PM concentration. Recently, we reported that MI/fine particle (PM2.5) associations may be limited to transmural infarctions. In this study, we retained data on hospital discharges with a primary diagnosis of acute myocardial infarction (using International Classification of Diseases ninth Revision [ICD-9] codes), for those admitted January 1, 2004 to December 31, 2006, who were ≥ 18 years of age, and were residents of New Jersey at the time of their MI. We excluded MI with a diagnosis of a previous MI and MI coded as a subendocardial infarction, leaving n = 1563 transmural infarctions available for analysis. We coupled these health data with PM2.5 species concentrations predicted by the Community Multiscale Air Quality chemical transport model, ambient PM2.5 concentrations, and used the same case-crossover methods to evaluate whether the relative odds of transmural MI associated with increased PM2.5 concentration is modified by the PM2.5 composition/mixture (i.e., mass fractions of sulfate, nitrate, elemental carbon, organic carbon, and ammonium). We found the largest relative odds estimates on the days with the highest tertile of sulfate mass fraction (OR = 1.13; 95% CI = 1.00, 1.27), nitrate mass fraction (OR = 1.18; 95% CI = 0.98, 1.35), and ammonium mass fraction (OR = 1.13; 95% CI = 1.00 1.28), and the lowest tertile of EC mass fraction (OR = 1.17; 95% CI = 1.03, 1.34). Air pollution mixtures on these days were enhanced in pollutants formed through atmospheric chemistry (i.e., secondary PM2.5) and depleted in primary pollutants (e.g., EC). When mixtures were laden with secondary PM species (sulfate, nitrate, and/or organics), we observed larger relative odds of myocardial infarction associated with increased PM2.5 concentrations. Further work is needed to confirm these findings and examine which secondary PM2.5 component(s) is/are responsible for an acute MI response.

Background: Lysophosphatidic acids (LPA) and lysophosphatidylcholines (LPC) are phospholipids, each containing one fatty acid, and have effects on atherogenic mechanisms. No data currently exist regarding the effects of aspirin and fish oil (FO) ingestion on these potent lipid mediators in humans with diabetes mellitus (DM). We hypothesized that ingestion of these agents alter LPA and LPC concentrations and that these effects correlate with platelet function. Methods: Using a sequential clinical trial approach, 30 adults with type 2 DM were treated with 81 mg/d of aspirin for 7 days, then with a 28-day regimen of FO (4g/day containing 1600 mg EPA and 800 mg DHA) after which they restarted 81 mg/d of aspirin for another 7 days. After the ingestion of a standard low-fat meal, phlebotomies were performed at baseline, 4 hours and 7 days after the ingestion of aspirin alone, 28 days after FO alone, and 4 hours and 7 days after aspirin and FO ingestion together. Eleven LPCs and 11 LPAs were analyzed using a modified Bligh and Dyer extract of plasma and infusion into an ABI QTrap 2000 via an Advion Nanomate robotic device. Platelet function was measured using whole blood aggregometry and via assays. Changes in concentrations of LPAs and LPCs compared to baseline were assessed using mixed models accounting for statin use, blood draw, BMI, presence of HTN, gender, race, smoking status, alcohol use, fish consumption, and education. Pearson’s correlations (r) were calculated for comparing LPAs and LPCs with platelet function. P-values less than 0.05 were considered statistically significant. Results: FO ingestion reduced concentrations of all 11 LPAs, including EPA (20:5n3) and DHA (22:6n3) species. EPA and DHA LPC concentrations significantly increased by FO alone and in combination with aspirin. Stearic acid (18:0) and alpha-linolenic acid (18:3n3) LPCs were significantly reduced by FO combined with aspirin after 4 hours and 7 days. Changes in 18:0 and oleic acid (18:1) LPAs after FO moderately correlated with the platelet aggregation agonist collagen (r=0.41, p=0.02 and r=0.39, p=0.03, respectively) whereas changes in EPA and DHA LPCs did not correlate with platelet aggregation or function. However, EPA changes with FO and aspirin moderately correlated with the platelet aggregation agonist ADP after 4 hours (r=0.46, p=0.01) but not 7 days (r=0.04, p=0.83). Conclusions: The ingestion of FO with and without aspirin has significant effects on plasma lysophospholipid levels in subjects with DM. Given the pleiotropic roles of lysophospholipids in platelet function and atherogenesis, these results suggest that the formation of potent lipid mediators- derived from ingested fats- may be more important than the simple ingestion of the fats. Our results should be used to generate new hypotheses applying different phospholipids in the evaluation of atherogenic mechanisms.

Introduction Many diabetics are insensitive to aspirin's platelet anti-aggregation effects. The possible modulating effects of co-administration of aspirin and fish oil in subjects with diabetes are poorly characterized. Participants and methods Thirty adults with type 2 diabetes mellitus were treated with aspirin 81 mg/d for 7 days, then with fish oil 4 g/day for 28 days, then the combination of fish oil and aspirin for another 7 days. Results Aspirin alone and in combination with fish oil reduced platelet aggregation in most participants. Five of 7 participants classified as aspirin insensitive 1 week after daily aspirin ingestion were sensitive after the combination. Although some platelet aggregation measures correlated positively after aspirin and fish oil ingestion alone and (in combination) in all individuals, correlation was only observed in those who were aspirin insensitive after ingestion of the combination. Conclusions Co-administration of aspirin and fish oil may reduce platelet aggregation more than aspirin alone in adults with diabetes mellitus.

Cost Effectiveness of MADIT-CRT. Background: The Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) trial demonstrated that cardiac resynchronization therapy (CRT) when added to the implantable cardiac defibrillator (ICD) reduces risk of heart failure or death in minimally symptomatic patients with reduced cardiac ejection fraction and wide QRS complex. Objectives: To evaluate 4-year cost-effectiveness of CRT-ICD compared to ICD alone using MADIT-CRT data. Research Design: Patients enrolled in the trial were randomized to implantation of either ICD or CRT-ICD in a 2:3 ratio, with up to 4-year follow-up period. Cost-effectiveness analyses were conducted, and sensitivity analyses by age, gender, and left bundle branch block (LBBB) conduction pattern were performed. Subjects: A total of 1,271 patients with ICD or CRT-ICD (US centers only) who reported healthcare utilization and health-related quality of life data. Measures: We used the EQ-5D (US weights) to assess patient HRQOL and translated utilization data to costs using national Medicare reimbursement rates. Results: Average 4-year healthcare expenditures in CRT-ICD patients were higher than costs of ICD patients ($62,600 vs 57,050, P = 0.015), mainly due to the device and implant-related costs. The incremental cost-effectiveness ratio of CRT-ICD compared to ICD was $58,330/quality-adjusted life years (QALY) saved. The cost effectiveness improved with longer time horizon and for the LBBB subgroup ($7,320/QALY), with no cost-effectiveness benefit being evident in the non-LBBB group. Conclusions: In minimally symptomatic patients with low ejection fraction and LBBB, CRT-ICD is cost effective within 4-year horizon when compared to ICD-only. (J Cardiovasc Electrophysiol, Vol. 24, pp. 66-74, January 2013)

Using a case-crossover study design and conditional logistic regression, we compared the relative odds of transmural (full-wall) myocardial infarction (MI) calculated using exposure surrogates that account for human activity patterns and the indoor transport of ambient PM(2.5) with those calculated using central-site PM(2.5) concentrations to estimate exposure to PM(2.5) of outdoor origin (exposure to ambient PM(2.5)). Because variability in human activity and indoor PM(2.5) transport contributes exposure error in epidemiologic analyses when central-site concentrations are used as exposure surrogates, we refer to surrogates that account for this variability as "refined" surrogates. As an alternative analysis, we evaluated whether the relative odds of transmural MI associated with increases in ambient PM(2.5) is modified by residential air exchange rate (AER), a variable that influences the fraction of ambient PM(2.5) that penetrates and persists indoors. Use of refined exposure surrogates did not result in larger health effect estimates (ORs=1.10-1.11 with each interquartile range (IQR) increase), narrower confidence intervals, or better model fits compared with the analysis that used central-site PM(2.5). We did observe evidence for heterogeneity in the relative odds of transmural MI with residential AER (effect-modification), with residents of homes with higher AERs having larger ORs than homes in lower AER tertiles. For the level of exposure-estimate refinement considered here, our findings add support to the use of central-site PM(2.5) concentrations for epidemiological studies that use similar case-crossover study designs. In such designs, each subject serves as his or her own matched control. Thus, exposure error related to factors that vary spatially or across subjects should only minimally impact effect estimates. These findings also illustrate that variability in factors that influence the fraction of ambient PM(2.5) in indoor air (e.g., AER) could possibly bias health effect estimates in study designs for which a spatiotemporal comparison of exposure effects across subjects is conducted.

Breastfeeding benefits both infant and maternal health. Use of epidural anesthesia during labor is increasingly common and may interfere with breastfeeding. Studies analyzing epidural anesthesia's association with breastfeeding outcomes show mixed results; many have methodological flaws. We analyzed potential associations between epidural anesthesia and overall breast-feeding cessation within 30 days postpartum while adjusting for standard and novel covariates and uniquely accounting for labor induction. A pooled analysis using Kaplan-Meier curves and modified Cox Proportional Hazard models included 772 breastfeeding mothers from upstate New York who had vaginal term births of healthy singleton infants. Subjects were drawn from two cohort studies (recruited postpartum between 2005 and 2008) and included maternal self-report and maternal and infant medical record data. Analyses of potential associations between epidural anesthesia and overall breastfeeding cessation within 1 month included additional covariates and uniquely accounted for labor induction. After adjusting for standard demographics and intrapartum factors, epidural anesthesia significantly predicted breastfeeding cessation (hazard ratio 1.26 [95% confidence interval 1.10, 1.44], p < 0.01) as did hospital type, maternal age, income, education, planned breastfeeding goal, and breastfeeding confidence. In post hoc analyses stratified by Baby Friendly Hospital (BFH) status, epidural anesthesia significantly predicted breastfeeding cessation (BFH: 1.19 [1.01, 1.41], p < 0.04; non-BFH: 1.65 [1.31, 2.08], p < 0.01). A relationship between epidural anesthesia and breastfeeding was found but is complex and involves institutional, clinical, maternal and infant factors. These findings have implications for clinical care and hospital policies and point to the need for prospective studies.

Although ionizing radiation is a known carcinogen, the long-term risk from relatively higher-dose diagnostic procedures during childhood is less well known. We evaluated this risk indirectly by assessing thyroid cancer incidence in a cohort treated with "lower-dose" chest radiotherapy more than 55 years ago. Between 2004 and 2008, we re-surveyed a population-based cohort of subjects treated with radiation for an enlarged thymus during infancy between 1926 and 1957 and their unexposed siblings. Thyroid cancer occurred in 50 irradiated subjects (mean thyroid dose, 1.29 Gy) and in 13 nonirradiated siblings during 334,347 person-years of follow-up. After adjusting for attained age, Jewish religion, sex and history of goiter, the rate ratio for thyroid cancer was 5.6 (95% CI: 3.1-10.8). The adjusted excess relative risk per gray was 3.2 (95% CI: 1.5-6.6). The adjusted excess absolute risk per gray was 2.2 cases (95% CI: 1.4-3.2) per 10,000 person-years. Cumulative thyroid cancer incidence remains elevated in this cohort after a median 57.5 years of follow-up and is dose-dependent. Although the incidence appeared to decrease after 40 years, increased risk remains a lifelong concern in those exposed to lower doses of medical radiation during early childhood.

Objective To quantify optimal minimum durations of exclusive breastfeeding associated with maintenance of any breastfeeding at 15 time points during the first year of life. Study design Mothers (n = 1189) from the prospective Infant Feeding Practices Study II cohort who initiated exclusive breastfeeding with healthy term infants were included. In a 80:20 split-sample validation study, receiver operating characteristic curves estimated optimal minimum durations of exclusive breastfeeding needed to predict maintenance of any breastfeeding at 15 time points during the first year (n = 951). Logistic regression estimated the predictive performance of the identified thresholds adjusted for maternal age, race, education, parity, support system, and return-to-work status. Results were validated in the remaining 20% (n = 238). Results Optimal minimum durations ranged from 4.0-17.1 weeks of exclusive breastfeeding associated with maintenance of any breastfeeding at 15 time points. All estimated threshold durations were statistically significant after adjustment. Conclusions Using a methodological approach unique to breastfeeding duration research, the authors report optimal durations of exclusive breastfeeding associated with duration of any breastfeeding at time points throughout the first year. Perinatal clinicians, pediatricians, lactation professionals, policymakers, researchers, and families might apply these findings to achieve desirable collective breastfeeding duration outcomes.