How Generalizable Are Findings from a Community-Based Prospective Cohort Study? Extending Estimates from the Adult Changes in Thought Study to Its Source Population.

Background: The Adult Changes in Thought (ACT) study is a cohort of Kaiser Permanente Washington members ages 65+ that began in 1994. Objective: We wanted to know how well ACT participants represented all older adults in the region, and how well ACT findings on eye disease and its relationship with Alzheimer's disease generalized to all older adults in the Seattle Metropolitan Region. Methods: We used participation weights derived from pooling ACT and Behavioral Risk Factor Surveillance System (BRFSS) data to estimate prevalences of common eye diseases and their associations with Alzheimer's disease incidence. Cox proportional hazards models accounted for age, education, smoking, sex, and APOE genotype. Confidence intervals for weighted analyses were bootstrapped to account for error in estimating the weights. Results: ACT participants were fairly similar to older adults in the region. The largest differences were more self-reported current cholesterol medication use in BRFSS and higher proportions with low education in ACT. Incorporating the weights had little impact on prevalence estimates for age-related macular degeneration or glaucoma. Weighted estimates were slightly higher for diabetic retinopathy (weighted 5.7% (95% Confidence Interval 4.3, 7.1); unweighted 4.1% (3.6, 4.6)) and cataract history (weighted 51.8% (49.6, 54.3); unweighted 48.6% (47.3, 49.9)). The weighted hazard ratio for recent diabetic retinopathy diagnosis and Alzheimer's disease was 1.84 (0.34, 4.29), versus 1.32 (0.87, 2.00) in unweighted ACT. Conclusions: Most, but not all, associations were similar after participation weighting. Even in community-based cohorts, extending inferences to broader populations may benefit from evaluation with participation weights.

Association between Adverse Childhood Experiences and Multiple Sclerosis in Icelandic Women-A Population-Based Cohort Study.

BACKGROUND: A growing literature, mostly based on selected populations, indicates that traumas may be associated with autoimmune diseases, yet few studies exist on adverse childhood experiences (ACEs) and multiple sclerosis (MS) in the general population. OBJECTIVE: We assessed cross-sectional associations between self-reported ACEs and MS among Icelandic women in the population-based Stress-And-Gene-Analysis (SAGA) cohort. METHODS: Participants (n = 27,870; mean age 44.9 years) answered a web-based survey that included the ACE-International Questionnaire and a question about MS diagnosis. Log-linear Poisson regression models estimated MS prevalence ratios and 95% confidence intervals for ACEs adjusted for covariates. RESULTS: 214 women reported having been diagnosed with MS (crude prevalence = 7.7 per 1000). Compared to women without MS, women with MS reported more fatigue, body pain and bladder problems. The average cumulative number of ACEs was 2.1. After adjustment for age, education, childhood deprivation, smoking and depressive symptoms, MS prevalence did not increase with increasing ACEs exposure (PR = 1.00, 95% CI = 0.92, 1.09). Thirteen ACE categories, including abuse, neglect, household dysfunction and violence were not individually or independently associated with MS. CONCLUSION: Limited by self-reported data and cross-sectional design, results do not consistently support associations between ACEs in the development of MS among adult Icelandic women.

Farming, Pesticides, and Brain Cancer: A 20-Year Updated Systematic Literature Review and Meta-Analysis.

Twenty additional years of epidemiologic literature have become available since the publication of two meta-analyses on farming and brain cancer in 1998. The current systematic literature review and meta-analysis extends previous research and harmonizes findings. A random effects model was used to calculate meta-effect estimates from 52 studies (51 articles or reports), including 11 additional studies since 1998. Forty of the 52 studies reported positive associations between farming and brain cancer with effect estimates ranging from 1.03 to 6.53. The overall meta-risk estimate was 1.13 (95% CI = 1.06, 1.21), suggesting that farming is associated with a 13% increase in risk of brain cancer morbidity or mortality. Farming among white populations was associated with a higher risk of brain cancer than among non-white populations. Livestock farming (meta-RR = 1.34; 95% CI = 1.18, 1.53) was associated with a greater risk compared with crop farming (meta-RR = 1.13; 95% CI = 0.97, 1.30). Farmers with documented exposure to pesticides had greater than a 20% elevated risk of brain cancer. Despite heterogeneity among studies, we conclude that the synthesis of evidence from 40 years of epidemiologic literature supports an association between brain cancer and farming with its potential for exposure to chemical pesticides.

Environmental Carcinogens and Cancer Risk.

The year 2022 will mark the 60th anniversary of the 1962 publication of Rachel Carson's seminar work Silent Spring  [...].

Cooking and Gardening Behaviors and Improvements in Dietary Intake in Hispanic/Latino Youth.

Background: School gardening interventions typically include cooking and gardening (CG) components; however, few studies have examined associations between CG psychosocial behaviors (attitudes, self-efficacy, and motivation), dietary intake, and obesity parameters. This study assessed the association between changes in CG behaviors with changes in dietary intake and obesity in participants of the LA Sprouts study, an after-school, 12-week, randomized controlled CG intervention conducted in four inner-city elementary schools in Los Angeles. Methods: Process analysis using data from 290 low-income, primarily Hispanic/Latino third through fifth-grade students who were randomized to either the LA Sprouts intervention (n = 160) or control group (n = 130). Height, weight, waist circumference, dietary intake via questionnaire, and CG behaviors were collected at baseline and postintervention. Linear regressions determined whether changes in CG behaviors predicted changes in dietary intake and obesity outcomes. Results: There were no differences in changes in CG psychosocial behaviors between intervention and control groups, therefore groups were combined. Participants were 49% male, 87% Hispanic/Latino, and an average age of nine. Increases in cooking behaviors significantly predicted increases in dietary fiber intake (p = 0.004) and increases in vegetable intake (p = 0.03). Increases in gardening behaviors significantly predicted increased intake of dietary fiber (p = 0.02). Changes in CG behaviors were not associated with changes in BMI z-score or waist circumference. Conclusions: Results from this study suggest that school-based interventions should incorporate CG components, despite their potentially costly and time-intensive nature, as these behaviors may be responsible for improvements in dietary intake of high-risk minority youth.

Iron Accumulation Is Not Homogenous among Patients with Parkinson's Disease.

Background. Iron is considered to lead to neurodegeneration and has been hypothesized as a possible cause of Parkinson's disease (PD). Susceptibility-weighted imaging (SWI) is a powerful tool to measure phase related iron content of brain. Methods. Twelve de novo patients with PD were recruited from the Movement Disorders Clinic, Department of Neurology, Loma Linda University. Twelve age- and sex-matched non-PD subjects were recruited from neurology clinic as controls. Using SWI, the phase related iron content was estimated from different brain regions of interest (ROIs). Results. There was a trend between increasing age and iron accumulation in the globus pallidus and putamen in all subjects. Iron accumulation was not significant in different ROIs in PD patients compared to controls after adjustment for age. Our data revealed heterogeneity of phase values in different brain ROIs among all subjects with an exaggerated trend at SN in PD patients. Conclusions. Our data suggest a nonhomogeneous pattern of iron accumulation in different brain regions among PD patients. Further studies are needed to explore whether this may correlate to the progression of PD. To our knowledge, this is the first study demonstrating the heterogeneity of iron accumulation in the brain, among patients with PD.

Vitamin D receptor gene polymorphisms and Parkinson's disease in a population with high ultraviolet radiation exposure.

INTRODUCTION: A high prevalence of vitamin D deficiency has been reported in Parkinson's disease (PD). Epidemiologic studies examining variability in genes involved in vitamin D metabolism have not taken into account level of exposure to ultraviolet radiation (UVR). We examined whether exposure to UVR (as a surrogate for vitamin D levels) and variations in the vitamin D receptor gene (VDR) are associated with PD. METHODS: Within a geographical information system (GIS) we linked participants' geocoded residential address data to ground level UV data to estimate historical exposure to UVR. Six SNPs in VDR were genotyped in non-Hispanic Caucasian subjects. RESULTS: Average lifetime UVR exposure levels were >5000 Wh/m(2), which was higher than levels for populations in previous studies, and UVR exposure did not differ between cases and controls. Homozygotes for the rs731236 TT (major allele) genotype had a 31% lower risk of PD risk (OR=0.69; 95% CI=0.49, 0.98; p=0.04 for TT vs. TC+CC). The rs7975232 GG (minor allele) genotype was also associated with decreased risk of PD (OR=0.63; 95% CI=0.42, 0.93; p=0.02 for GG vs. TG+TT). The association between PD risk and a third locus, rs1544410 (BsmI), was not statistically significant after adjustment for covariates, although there was a trend for lower risk with the GG genotype. CONCLUSIONS: This study provides initial evidence that VDR polymorphisms may modulate risk of PD in a population highly exposed to UVR throughout lifetime.

Application of the U.S. EPA mode of action Framework for purposes of guiding future research: a case study involving the oral carcinogenicity of hexavalent chromium.

Mode of action (MOA) analysis provides a systematic description of key events leading to adverse health effects in animal bioassays for the purpose of informing human health risk assessment. Uncertainties and data gaps identified in the MOA analysis may also be used to guide future research to improve understanding of the MOAs underlying a specific toxic response and foster development of toxicokinetic and toxicodynamic models. An MOA analysis, consistent with approaches outlined in the MOA Framework as described in the Guidelines for Carcinogen Risk Assessment, was conducted to evaluate small intestinal tumors observed in mice chronically exposed to relatively high concentrations of hexavalent chromium (Cr(VI)) in drinking water. Based on review of the literature, key events in the MOA are hypothesized to include saturation of the reductive capacity of the upper gastrointestinal tract, absorption of Cr(VI) into the intestinal epithelium, oxidative stress and inflammation, cell proliferation, direct and/or indirect DNA modification, and mutagenesis. Although available data generally support the plausibility of these key events, several unresolved questions and data gaps were identified, highlighting the need for obtaining critical toxicokinetic and toxicodynamic data in the target tissue and in the low-dose range. Experimental assays that can address these data gaps are discussed along with strategies for comparisons between responsive and nonresponsive tissues and species. This analysis provides a practical application of MOA Framework guidance and is instructive for the design of studies to improve upon the information available for quantitative risk assessment.

Outdoor work and risk for Parkinson's disease: a population-based case-control study.

OBJECTIVES: Sunlight is the main contributor to vitamin D in humans. Since inadequate levels of vitamin D have been linked to increased risks for neurodegenerative diseases, we examined whether outdoor work is associated with a reduced risk for Parkinson's disease in a population-based case-control study of Danish men. METHODS: We identified 3819 men with a primary diagnosis of Parkinson's disease in the period 1995-2006 in the Danish National Hospital Register and selected 19,282 age- and sex-matched population controls at random from the Central Population Register. Information on work history was ascertained from the Danish Supplementary Pension Fund and the Central Population Register. Based on trade grouping codes and job titles, we evaluated the extent of outdoor work of study subjects as a proxy of exposure to sunlight. RESULTS: Relying on trade grouping codes, we estimated ORs for study subjects with moderate, frequent and maximal outdoor work compared with exclusive indoor work of 0.90 (95% CI 0.78 to 1.02), 0.86 (95% CI 0.75 to 0.99) and 0.72 (95% CI 0.63 to 0.82), respectively, for Parkinson's disease. Reduced risks were also found for Parkinson's disease among outdoor workers based on study subjects' job titles. CONCLUSIONS: Our findings suggest that men working outdoors have a lower risk for Parkinson's disease. Further studies of measured vitamin D levels in outdoor workers are warranted to clarify a potential inverse association between vitamin D and the risk for Parkinson's disease.

α-Synuclein gene may interact with environmental factors in increasing risk of Parkinson's disease.

BACKGROUND: Although of great interest and suggested in prior reports, possible α-synuclein (SNCA) gene-environment interactions have not been well investigated in humans. METHODS: We used a population-based approach to examine whether the risk of Parkinson's disease (PD) depended on the combined presence of SNCA variations and two important environmental factors, pesticide exposures and smoking. RESULTS/CONCLUSIONS: Similar to recent meta- and pooled analyses, our data suggest a lower PD risk in subjects who were either homozygous or heterozygous for the SNCA REP1 259 genotype, and a higher risk in subjects who were either homozygous or heterozygous for the REP1 263 genotype, especially among subjects with an age of onset ≤68 years. More importantly, while analyses of interactions were limited by small cell sizes, risk due to SNCA variations seemed to vary with pesticide exposure and smoking, especially in younger onset cases, suggesting an age-of-onset effect.

Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: a meta-analysis.

INTRODUCTION: We conducted a systematic literature review and meta-analysis of oral cavity, esophageal, stomach, small intestine, colon, and rectal cancers among workers occupationally exposed to Cr(VI). METHODS: Using PubMed, studies published from 1950 to 2009 evaluating the relationship between Cr(VI) exposure and GI cancers were identified. Measures of effect and variability were extracted from 32 studies meeting specific inclusion criteria, and meta-analysis summary relative risk measures were calculated using random effects models and inverse variance weighting methods. RESULTS: Meta-standardized mortality ratios (SMRs) were, for cancer of the: oral cavity [1.02 (95% CI=0.77-1.34)]; esophagus [1.17 (95% CI=0.90-1.51)]; stomach [1.09 (95% CI=0.93-1.28)]; colon [0.89 (95% CI=0.70-1.12)]; and rectum [1.17 (95% CI=0.98-1.39)]. Analyses of more highly exposed subgroups included in the studies or subgroups based on geographic region or by industry with recognized Cr(VI) exposures (welding, chrome plating, chromate production, and pigment production) did not result in elevated meta-SMRs except for esophageal cancer among US cohorts [meta-SMR=1.49 (95% CI=1.06-2.09)]. However, that finding was based on a subgroup of only four studies, one of which was a PMR study. Potential confounding by socioeconomic status (SES), diet and/or smoking, or limitations due to the healthy-worker effect (HWE) were evaluated, and while smoking, diet and SES may be important factors that may have upwardly biased the meta-SMRs, HWE is not likely to have significantly affected the summary results. None of three studies reporting small intestine cancers observed a statistically significant increased risk. DISCUSSION: These meta-analyses and literature review indicate that Cr(VI)-exposed workers are not at a greater risk of GI cancers than the general population.

Measured posterior annuloplasty for repair of non-ischemic mitral regurgitation. A single unit follow-up.

UNLABELLED: The aim of this report is to evaluate short- and long-term outcomes of annuloplasty method of our choice: measured posterior annuloplasty (MPA). MPA is a piece of a Duran ring cut to the length of free-edge of anterior mitral leaflet (AML) and anchored with multiple pledgeted U-sutures from trigone to trigone into the posterior annulus. MATERIAL AND METHODS: From 1988 to 2000, 103 consecutive patients with non-ischemic mitral regurgitation were scheduled preoperatively to be repaired by MPA. RESULTS: Preoperative mitral valve regurgitation (MR) grade was 3.8+/-0.5 and decreased to 0.1+/-0.3 (P<0.0001) after repair. One patient was converted to insertion of mechanical prosthesis after grade 3 MR persisted after septal myectomy and MPA. Three patients needed instant revision of the repair one due to SAM and two due to stenosis. No patient had a stenosis or unacceptable (>1) MR after the procedure. There was one operative death (1.0%) and 3 hospital/30-day deaths (2.9%). Sixteen patients (16.3%) expired during the follow-up to 91 months (mean 57.4+/-19.5, median 60 months) none due to failure of MPA. There were no reoperations due to failure of MPA. Three patients had a reoperation, one for dehiscence of reconstruction after P2 resection and two patients due to progression of anterior leaflet degeneration and calcification with 4+ MR. New York Heart Association (NYHA) functional classification decreased from 2.3+/-0.8 to 1.4+/-0.6 (P<0.0001) and only one patient had an increase from II to III. Eighty-eight patients (96.7%) were in NYHA class I-II. Ten patients had an increase of MR from 0 to trace or 1 and one from 0 to 2. Two patients were diagnosed with mild stenosis without need of reoperation. CONCLUSIONS: MPA is a durable and stable alternative for repair of non-ischemic mitral regurgitation of different etiologies. The technique gives an objective measure of the length of the band and no patient is left with a significant MR or mitral valve stenosis (MS). First-time success rate is very high and instant repairs few and minor. Freedom of MPA related reoperations is 100%.

Mildly elevated TSH and cognition in middle-aged and older adults.

BACKGROUND: It is accepted that markedly elevated thyroid-stimulating hormone (TSH) levels are associated with impaired cognitive function. However, the findings regarding the association between mildly elevated TSH levels and cognition are equivocal. The objective of this study was to assess the relation between TSH levels in the normal to mildly elevated range (0.3-10.0 mIU/L) and several domains of cognitive function. METHODS: A healthy, community-based sample of 489 men and women (40-88 years old, mean = 60.5 years) enrolled in the B-Vitamin Atherosclerosis Intervention Trial were studied. A neuropsychological test battery was used to assess a broad array of cognitive functions. Four uncorrelated neuropsychological factors were extracted by principal component analysis. Using multivariable linear regression, performance on each factor was examined in relation to TSH levels, controlling for age, gender, race-ethnicity, education, homocysteine levels, low-density lipoprotein cholesterol levels, and smoking status. RESULTS: TSH levels were not associated with any of the four factor scores in the total sample or in younger (age < 60) or older (age >or= 60) subjects, although there was a trend for older subjects with higher levels of TSH to do more poorly on paragraph recall (p = 0.06). Gender-stratified analyses showed that TSH was positively associated with scores on word list learning for females only (p = 0.003). CONCLUSIONS: In this community-based sample of middle-aged to older individuals, increasing TSH levels were not associated with significantly reduced cognitive performance in any domain. Further exploration of the effects of gender on the association between TSH and cognition is warranted.

Mode-of-action framework for evaluating the relevance of rodent forestomach tumors in cancer risk assessment.

Studies have shown that a majority of known human carcinogens also cause cancer in laboratory animals. The converse, however, is not as well established-known animal carcinogens are not equally predictive of human carcinogenicity. A particularly controversial aspect of interspecies extrapolation is application of rodent forestomach tumor data for predicting cancer risk in humans, given that a human counterpart for the rodent forestomach does not exist. Proliferative lesions in the rodent forestomach may result from a combination of factors related to route-specific tissue irritation and/or unnatural dosing regimens and are less likely to be relevant in evaluating human carcinogenic potential, particularly when tumors are exclusive to the forestomach. We review the comparative functional anatomy, physiology, tumor biology, tissue concordance, and historical regulatory practices in the use of forestomach tumors for cancer risk assessment, examining specific chemical examples. We also propose a standardized mode-of-action approach that combines multiple risk characterization criteria, including relevance to human exposure conditions, physiologically based toxicokinetics, genotoxicity, and comparative/mechanistic toxicology. Forestomach tumors associated with chronic irritation of the forestomach epithelium, particularly those induced by repeated oral gavage dosing, should not form the basis for carcinogenic classification or quantitative cancer potency estimates for humans. Genotoxic chemicals and those that cause tumors at multiple sites, at doses at or below the maximum tolerated dose, and in the absence of forestomach irritation, are more likely to be relevant human carcinogens. Cancer risk assessment that utilizes forestomach tumor data should consider relevant human exposures, systemic bioavailability, tissue dosimetry and concordance.

Serum organochlorines and breast cancer: a case-control study among African-American women.

This population-based case-control study of African-American women (355 breast cancer case patients, 327 controls) examined the association between breast cancer and circulating levels of PCBs and dichlorodiphenyldichloroethene (DDE), a metabolite of DDT. Case patients were diagnosed with invasive breast carcinoma and interviewed between June 1995 and July 1998, and control subjects were identified by random digit dialing methods. Serum levels of DDE and total PCBs were adjusted for total lipid content. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable unconditional logistic regression methods. Effect modification by tumor receptor status and cancer treatment was investigated. Breast cancer risk was not associated with increasing quintiles of lipid-adjusted PCBs or DDE (highest versus lowest quintile adjusted for age, body mass index (BMI) and breastfeeding for DDE: OR = 1.02, 95% CI = (0.61, 1.72), p-trend = 0.74; for PCBs: OR = 1.01, 95% CI = (0.63, 1.63), p-trend = 0.56). Risk did not differ by strata of BMI, breastfeeding, parity, menopausal status or tumor receptor status. This study, the largest study of African-American women to date, does not support a role of DDE and total PCBs in breast cancer risk at the levels measured.