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BACKGROUND: Systemic inflammation has been associated with lower neurobehavioral performance in diverse populations, yet the evidence in adolescents remains lacking. Cytokines can alter neural network activity to induce neurocognitive changes. This work seeks to investigate the association between inflammation and neurobehavior in adolescents living in a rural region of Ecuador. METHODS: We examined 535 adolescents in rural communities of Ecuador (ESPINA study), 508 of which had neurobehavioral assessments (NEPSY-II) and circulating plasma levels of inflammatory markers (CRP, IL-6, TNF-⍺, sICAM-1, sVCAM-1, SAA, and sCD14). Associations between inflammatory biomarker concentrations and neurobehavioral scores were examined using adjusted bivariate semi-parametric models with generalized estimating equations. A partial least squares regression approach was used to create composite variables from multiple inflammation biomarkers and model their association with cognitive outcomes. RESULTS: Higher sCD14 and TNF-α concentrations were significantly associated with lower social perception scores, by -0.465 units (95% CI: -0.80, -0.13) and -0.418 units (-0.72, -0.12) for every 50% increase in inflammatory marker concentration, respectively. Similarly, every 50% increase in the inflammation summary score was associated with a significantly lower Social Perception score by -0.112 units (-0.19, -0.03). A greater inflammatory composite variable from seven markers was associated with lower scores in language (β = -0.11, p = 0.043), visuospatial processing (β = -0.15, p = 0.086), and social perception (β = -0.22, p = 0.005) domains. CONCLUSIONS: Higher levels of inflammation were associated with lower neurobehavioral performance in adolescents, especially with social perception. In addition, using a robust analytic method to examine an association between a composite inflammatory variable integrating seven markers led to additional findings, including the domains of language and visuospatial processing. A longitudinal follow-up of such investigations could unveil potential changes in inflammation-neurobehavior performance links through developmental stages and intervention opportunities.

BACKGROUND: Herbicides are the most used class of pesticides worldwide, and insect repellents are widely used globally. Yet, there is a dearth of studies characterizing the associations between these chemical groups and human neurobehavior. Experimental studies suggest that glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides can affect neurobehavior and the cholinergic and glutamatergic pathways in the brain. We aim to assess whether herbicides and insect repellents are associated with neurobehavioral performance in adolescents. METHODS: We assessed 519 participants (11-17 years of age) living in agricultural communities in Ecuador. We quantified urinary concentrations of glyphosate, 2,4-D, and two N,N-diethyl-meta-toluamide (DEET) insect repellent metabolites [3-(diethylcarbamoyl)benzoic acid (DCBA) and 3-(ethylcarbamoyl)benzoic acid (ECBA)] using isotope-dilution mass spectrometry. We assessed neurobehavioral performance using 9 subtests across 5 domains (attention/inhibitory control, memory/learning, language, visuospatial processing, and social perception). We characterized the associations using generalized estimating equations and multiple imputation for metabolites below detection limits. Models were adjusted for demographic and anthropometric characteristics, urinary creatinine, and sexual maturation. Mediation by salivary cortisol, dehydroepiandrosterone, 17β-estradiol, and testosterone was assessed using structural equation modeling. RESULTS: The mean of each neurobehavioral domain score was between 7.0 and 8.7 [standard deviation (SD) range: 2.0-2.3]. Glyphosate was detected in 98.3% of participants, 2,4-D in 66.2%, DCBA in 63.3%, and ECBA in 33.4%. 2,4-D was negatively associated with all neurobehavioral domains, but statistically significant associations were observed with attention/inhibition [score difference per 50% higher metabolite concentration (β)=-0.19 95% confidence interval (CI): -0.31, -0.07], language [β=-0.12 (95% CI: -0.23, -0.01)], and memory/learning [β=-0.11 (95% CI: -0.22, 0.01)]. Glyphosate had a statistically significant negative association only with social perception [β=-0.08 (95% CI: -0.14, -0.01)]. DEET metabolites were not associated with neurobehavioral performance. Mediation by gender and adrenal hormones was not observed. CONCLUSION: This study describes worse neurobehavioral performance associated with herbicide exposures in adolescents, particularly with 2,4-D. Replication of these findings among other pediatric and adult populations is needed. https://doi.org/10.1289/EHP11383.

Study objectivesSleep-disordered breathing (SDB) is common in patients with congestive heart failure and has important implications regarding symptoms and prognosis. However, the burden of SDB on those with heart failure has not been well characterized in developing countries, including Mozambique in sub-Saharan Africa. Diagnosing SDB in individuals with congestive heart failure is important because treatment of SDB may improve outcomes.MethodsBetween September 2014 and April 2017, patients hospitalized in a specialized cardiology unit in Maputo, Mozambique with decompensated congestive heart failure were recruited using convenience sampling. We determined the prevalence of SDB and associated risk factors.ResultsA total of 165 patients were recruited, of which 145 had evaluable sleep study data. The overall prevalence of SDB in patients with decompensated congestive heart failure was 72%, and of these 46% had Cheyne-Stokes respirations. Male sex, higher body mass index, and lower left ventricular ejection fraction were all associated with a higher likelihood of SDB and more severe SDB. Cheyne-Stokes respirations were associated with male sex, lower ejection fraction, and larger left atrial size.ConclusionsWe conclude that in sub-Saharan Africa SDB is common in decompensated congestive heart failure and strongly predicted by demographic and echocardiographic parameters. This study highlights the need for the development of diagnostic tools and management strategies for patients with severe heart failure in resource-limited settings.CitationLo S, Mbanze I, Orr JE, et al. The prevalence of sleep-disordered breathing and associated risk factors in patients with decompensated congestive heart failure in Mozambique. J Clin Sleep Med. 2023;19(6):1103-1110.

ObjectiveTo characterize the association between residential environmental manganese (Mn) exposure and depression and anxiety, given prior associations among occupationally-exposed workers.MethodsWe administered the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) to 697 study participants in their preferred languages. These participants represented a population-based sample of residents aged ≥40 from two predominantly Black African communities in Gauteng province, South Africa: 605 in Meyerton, adjacent to a large Mn smelter, and 92 in Ethembalethu, a comparable non-exposed community. We investigated the associations between community (Meyerton vs. Ethembalethu) and severity of depression and anxiety, using linear regression, adjusting for age and sex. To document community-level differences in Mn exposure, we measured airborne PM2.5-Mn.ResultsMeyerton residents had BDI scores 5.63 points (95 % CI 3.07, 8.20) higher than Ethembalethu residents, with all questions contributing to this significant difference. STAI-state scores were marginally higher in Meyerton than Ethembalethu residents [2.12 (95 % CI -0.17, 4.41)], whereas STAI-trait scores were more similar between the communities [1.26 (95 % CI -0.82, 3.35)]. Mean PM2.5-Mn concentration was 203 ng/m3 at a long-term fixed site in Meyerton and 10 ng/m3 in Ethembalethu.ConclusionResidence near Mn emission sources may be associated with greater depression symptomatology, and possibly current, but not lifetime, anxiety.

BackgroundCholinesterase inhibitor pesticides, especially organophosphates, are endocrine disruptors and a few existing studies have linked self-reports of exposure with increased depression and anxiety. Some evidence suggests that associations may be stronger in women, but the mechanism of this gender difference is unclear. We assessed whether acetylcholinesterase (AChE) inhibition between 2 time points (reflecting greater cholinesterase inhibitor exposure) during different agricultural seasons in the year was associated with anxiety/depression symptoms.MethodsWe examined 300 adolescents (ages 11-17y, 51% female) living near agricultural settings in Ecuador (ESPINA study) twice in 2016: April and July-October. We assessed AChE activity (finger stick), estradiol, testosterone, dehydroepiandrosterone, cortisol (saliva) and anxiety and depression scales (CDI-2 and MASC-2).ResultsThe mean (SD) depression and anxiety scores were 52.8 (9.3) and 58.1 (9.6), respectively. The median (25th, 75th percentile) AChE change (July-October vs April) was -3.94% (-10.45%, 5.13%). For every 10% decrease in AChE activity, there was a 0.96 unit (95%CI: 0.01, 1.90) increase in depression symptoms and an OR of elevated depression score of 1.67 (1.04, 2.66). These associations were stronger in girls (OR=2.72 [1.23, 6.00]) than boys (1.18 [0.59, 2.37]). Adjustment for cortisol, testosterone and dehydroepiandrosterone reduced gender differences by 18-62%. No associations were observed with anxiety.DiscussionInhibition of AChE activity at 2 points in time during different pesticide spray periods was associated with greater depression symptoms, affecting girls more than boys. Gender differences may be partly explained by endocrine disruption. These findings suggest that AChE inhibition may transiently affect the mood of adolescents.

BACKGROUND: Off-target drift of pesticides from farms increases the risk of pesticide exposure of people living nearby. Cholinesterase inhibitors (i.e. organophosphates and carbamates) are frequently used in agriculture and inhibit acetylcholinesterase (AChE) activity. Greenhouse agriculture is an important production method, but it is unknown how far pesticide drift from greenhouses can extend and expose people living nearby. METHODS: This study included 1156 observations from 3 exams (2008, Apr, 2016 and Jul-Oct 2016) of 623 children aged 4-to-17 years living in agricultural communities in Ecuador. AChE, a physiological marker of cholinesterase inhibitor exposure, was measured in blood. Geographic positioning of greenhouses and homes were obtained using GPS receivers and satellite imagery. Distances between homes and the nearest greenhouse edge, and areas of greenhouse crops within various buffer zones around homes were calculated. Repeated-measures regression adjusted for hemoglobin and other covariates estimated change in AChE relative to distance from greenhouses. RESULTS: The pooled mean (SD) of AChE activity was 3.58 U/mL (0.60). The median (25th-75th %tile) residential distance to crops was 334 m (123, 648) and crop area within 500 m of homes (non-zero values only) was 18,482 m2 (7115, 61,841). Residential proximity to greenhouse crops was associated with lower AChE activity among children living within 275 m of crops (AChE difference per 100 m of proximity [95% CI] = -0.10 U/mL [-0.20, -0.006]). Lower AChE activity was associated with greater crop area within 500 m of homes (AChE difference per 1000 m2 [95% CI] = -0.026 U/mL [-0.040, -0.012]) and especially within 150 m (-0.037 U/mL [-0.065, -0.007]). CONCLUSIONS: Residential proximity to floricultural greenhouses, especially within 275 m, was associated with lower AChE activity among children, reflecting greater cholinesterase inhibitor exposure from pesticide drift. Analyses of residential proximity and crop areas near homes yielded complementary findings. Mitigation of off-target drift of pesticides from crops onto nearby homes is recommended.

Environ Health Perspect 131(10):107007 (2023), https://doi.org/10.1289/EHP11383 To provide a more reliable source of the same information, reference 62 has been changed from 'Kormorniczak M. Tanner Scale. Wikipedia' to 'Marshall WA, [...]

IntroductionThere is a lack of consistent study findings on associations between workplace exposures and the risk of Parkinson disease (PD) and a paucity of such data on women. We assessed PD risk among occupational groups to derive insights about potential occupation-specific exposures in a large cohort of women.MethodsThe Women's Health Initiative Observational Study (WHI-OS) is a prospective cohort that enrolled 91 627 postmenopausal women, 50 to 79 years of age, from 01 October 1993 through 31 December 1998, at 40 clinical centers across the United States, with average follow-up interval of 11 years. These women reported up to three paid jobs, held the longest since age 18; these jobs were coded and duration of employment calculated. We defined a case by self-report of doctor-diagnosed PD (at baseline or follow-up), death attributed to PD, or taking medication consistent with PD.ResultsAmong 2590 PD cases, we found evidence of excess risk among "counselors, social workers, and other community and social service specialists," and there was a suggestion of increased in risk among postsecondary teachers, and "building and grounds cleaning and maintenance" workers. There was also evidence of a deficit in risk among women who worked in sales. Results according to ever-employed and job duration were similar, except for evidence of excess risk among "health technologists and technicians" with more than 20 years of employment. Longer duration of life on a farm was associated with higher risk.ConclusionOur findings paint a largely reassuring picture of occupational risks for PD among US women.

Background Oral anticoagulants (OACs) are recommended for nonvalvular atrial fibrillation (NVAF) patients with moderate-to high-stroke risk. Objective To examine nationally reflective OAC usage in incident NVAF patients longitudinally. Design Three-year retrospective cohort analysis. Setting Medicare Part D recipients in the contiguous United States.Participants52,465 Medicare beneficiaries with incident NVAF in 2010 with two or more atrial fibrillation diagnoses seven or more days apart. Main outcome measure Stroke risk via congestive heart failure, hypertension, age greater than or equal to 75, diabetes, stroke, vascular disease, age 65-74, sex category (CHA2DS2-VASc) score. Primary outcome was proportion of patients receiving one or more OACs post-NVAF diagnoses. Results Of 48,980 high-risk patients, 32.7% received one or more OAC within 60 days of diagnosis. By close of 2011, 48% had one or more OAC. OAC use increased to 52.9% by close of 2012. Conclusions Fewer than 33% of high-risk NVAF patients received OACs within 60 days of diagnosis in 2010. Despite increased use over time, oral anticoagulation was below 53% at study end. Use of OACs declined with CHA2DS2-VASc greater than 6. Expanded efforts are warranted to augment OAC use in high stroke-risk patients.

Exposure to silica has been linked to excess risk of lung cancer and nonmalignant respiratory disease mortality. In this study we estimated risk for both these outcomes in relation to occupational silica exposure as well as the reduction in risk that would result from hypothetical interventions on exposure in a cohort of exposed workers. Analyses were carried out using data from an all-male study population consisting of 2,342 California diatomaceous earth workers regularly exposed to crystalline silica and followed between 1942 and 2011. We estimated subdistribution risk for each event under the natural course and interventions of interest using the parametric g-formula to adjust for healthy-worker survivor bias. The risk ratio for lung cancer mortality, comparing an intervention in which a theoretical maximum exposure limit was set at 0.05 mg/m3 (the current US regulatory limit) with the observed exposure concentrations, was 0.86 (95% confidence interval: 0.63, 1.22). The corresponding risk ratio for nonmalignant respiratory disease mortality was 0.69 (95% confidence interval: 0.52, 0.93). Our findings suggest that risks from both outcomes would have been considerably lower if historical silica exposures in this cohort had not exceeded current regulatory limits.

Prolonged exposures can have complex relationships with health outcomes, as timing, duration, and intensity of exposure are all potentially relevant. Summary measures such as cumulative exposure or average intensity of exposure may not fully capture these relationships. We applied penalized and unpenalized distributed-lag nonlinear models (DLNMs) with flexible exposure-response and lag-response functions in order to examine the association between crystalline silica exposure and mortality from lung cancer and nonmalignant respiratory disease in a cohort study of 2,342 California diatomaceous earth workers followed during 1942-2011. We also assessed associations using simple measures of cumulative exposure assuming linear exposure-response and constant lag-response. Measures of association from DLNMs were generally higher than those from simpler models. Rate ratios from penalized DLNMs corresponding to average daily exposures of 0.4 mg/m3 during lag years 31-50 prior to the age of observed cases were 1.47 (95% confidence interval (CI): 0.92, 2.35) for lung cancer mortality and 1.80 (95% CI: 1.14, 2.85) for nonmalignant respiratory disease mortality. Rate ratios from the simpler models for the same exposure scenario were 1.15 (95% CI: 0.89, 1.48) and 1.23 (95% CI: 1.03, 1.46), respectively. Longitudinal cohort studies of prolonged exposures and chronic health outcomes should explore methods allowing for flexibility and nonlinearities in the exposure-lag-response.

BACKGROUND:Studies suggesting a protective effect of estrogen in neurodegenerative diseases prompted us to investigate this relationship in progressive supranuclear palsy (PSP). METHODS:This case-control study evaluated the self-reported reproductive characteristics and estrogen of 150 women with PSP and 150 age-matched female controls who participated in the Environmental Genetic-PSP study. Conditional logistic regression models were generated to examine associations of PSP with estrogen. RESULTS:There was no association between years of estrogen exposure duration and PSP. There was a suggestion of an inverse association between composite estrogen score and PSP that did not reach statistical significance (P = .06). Any exposure to estrogen replacement therapy halved the risk of PSP (odds ratio = 0.52; 95% confidence interval = 0.30-0.92; P = .03). Among PSP cases, earlier age at menarche was associated with better performance on Hoehn and Yahr stage (β = -0.60; SE = 0.26; P = .02) and Unified Parkinson's Disease Rating Scale II score (β = -5.19; SE = 2.48; P = .04) at clinical examination. CONCLUSIONS:This case-control study suggests a protective role of lifetime estrogen exposure in PSP. Future studies will be needed to confirm this association. © 2018 International Parkinson and Movement Disorder Society.

PurposeMother's Day (May) is a holiday with substantial demand for flowers, associated with heightened flower production and escalated pesticide use. The effect of spray seasons on pesticide exposures of children living in agricultural communities but who do not work in agriculture is poorly understood. In this study, we estimated the association of time after Mother's Day harvest with children's acetylcholinesterase (AChE) activity. AChE is a physiological marker of organophosphate/carbamate pesticide exposures that may take up to 3 months to normalize after its inhibition.MethodsWe examined 308 children, aged 4-9 years, in Ecuadorian agricultural communities during a low flower-production season but within 63-100 days (mean: 81.5 days, SD: 10.9) after Mother's Day harvest. We quantified AChE activity (mean: 3.14 U/mL, SD: 0.49) from a single finger-stick sample.ResultsWe observed positive linear associations between time after the harvest and AChE among participants living near plantations. The associations were strongest among participants living within 233 m [(0.15 U/mL (95% CI 0.02, 0.28)], slightly weaker among participants living within 234-532 m [0.11 U/mL (0.00, 0.23)], and not associated among participants at greater distances. Similar findings were observed across categories of areas of flower plantations within 500 m of homes.ConclusionsThese cross-sectional findings suggest that a peak pesticide-use period can decrease AChE activity of children living near plantations. These seasonal pesticide exposures could induce short- and long-term developmental alterations in children. Studies assessing exposures at multiple times in relation to pesticide spray seasons among children who do not work in agriculture are needed.

Background: Progressive supranuclear palsy (PSP) is a tauopathy that has a multifactorial etiology. Numerous studies that have investigated lead exposure and traumatic brain injury (TBI) as risk factors for other tauopathies, such as Alzheimer's disease, but not for PSP. Objective: We sought to investigate the role of firearm usage, as a possible indicator of lead exposure, and TBI as risk factors for PSP in a population of military veterans. Methods: We included participants from a larger case-control study who reported previous military service. Our sample included 67 PSP cases and 68 controls. Participants were administered a questionnaire to characterize firearm use in the military and occurrence of TBI. Results: Cases were significantly less educated than controls. In unadjusted analyses, the proportion of PSP cases (80.6%) and controls (64.7%) who reported use of firearms as part of their military job was positively associated with PSP, odds ratio (OR) 2.2 (95% CI: 1-5.0). There were no significant case-control differences in mean service duration. There was only a weak association with history of TBI, OR 1.6 (95% CI: 0.8-3.4). In multivariate models, firearm usage (OR 3.7, 95% CI: 1.5, 9.8) remained significantly associated with PSP. Conclusions: Our findings show a positive association between firearm usage and PSP and an inverse association between education and PSP. The former suggests a possible etiologic role of lead. Further studies are needed to confirm the potential etiologic effects of metals on PSP. The study was registered in clinicaltrials.gov. ClinicalTrials.gov Identifier: NCT00431301.

BackgroundExposures to cholinesterase inhibitor pesticides (e.g. organophosphates) have been associated with children's neurobehavioral alterations, including attention deficit and impulsivity. Animal studies have observed transient alterations in neurobehavioral performance in relation to cholinesterase inhibitor pesticide exposures; however, limited evidence exists regarding transient effects in humans.MethodsWe estimated the associations between neurobehavioral performance and time after Mother's Day flower harvest (the end of a heightened pesticide usage period) among 308 4-to 9-year-old children living in floricultural communities in Ecuador in 2008 who participated in the ESPINA study. Children's neurobehavior was examined once (NEPSY-II: 11 subtests covering 5 domains), between 63 and 100days (SD: 10.8days) after Mother's Day harvest (blood acetylcholinesterase activity levels can take 82days to normalize after irreversible inhibition with organophosphates).ResultsThe mean (SD) neurobehavioral scaled scores across domains ranged from 6.6 (2.4) to 9.9 (3.3); higher values reflect greater performance. Children examined sooner after Mother's Day had lower neurobehavioral scores than children examined later, in the domains of (score difference per 10.8days, 95%CI): Attention/Inhibitory Control (0.38, 0.10-0.65), Visuospatial Processing (0.60, 0.25-0.95) and Sensorimotor (0.43, 0.10-0.77). Scores were higher with longer time post-harvest among girls (vs. boys) in Attention/Inhibitory Control.ConclusionsOur findings, although cross-sectional, are among the first in non-worker children to suggest that a peak pesticide use period may transiently affect neurobehavioral performance, as children examined sooner after the flower harvest had lower neurobehavioral performance than children examined later. Studies assessing pre- and post-exposure measures are needed.

Hormone therapy (HT) is a class of medications widely prescribed to women in the Western world. Evidence from animal models and in vitro studies suggests that estrogen may protect against nigrostriatal system injury and increase dopamine synthesis, metabolism, and transport. Existing epidemiologic research indicates a possible reduced risk of Parkinson's disease (PD) associated with HT use. The objective of this study was to evaluate PD risk associated with specific HT formulations. Neurologist-confirmed cases and age-matched controls were identified from Group Health Cooperative (GHC) of Washington State. Final analysis included 137 female cases and 227 controls. Hormone therapy use was ascertained from the GHC pharmacy database, further classified as conjugated estrogens, esterified estrogens, and progestin. Ever use of HT formulation demonstrated a suggested elevated risk with esterified estrogen use (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.0-9.8), and no risk associated with conjugated estrogen use (OR, 0.6; 95% CI, 0.6-1.3). Restricting this analysis to prescriptions that included progestin further elevated the risk associated with esterified estrogen use (OR, 6.9; 95% CI, 2.1-22.9); again, no risk was associated with conjugated estrogen use (OR, 1.7; 95% CI, 0.6-5.0). The findings from this study suggest an increase in PD risk associated with esterified estrogen use combined with progestin, and no risk associated with conjugated estrogen with progestin. These findings could have important implications for choice of HT in clinical practice.

BackgroundApolipoprotein (APOE) e4 allele status has been linked to clinical presentation and progression in Alzheimer's disease; however, evidence for a role of APOE e4 in Parkinson's disease (PD) remains largely inconclusive. In this analysis we explored potential significant associations between APOE e4 allele status and characteristics of clinical presentation in patients with PD.MethodsData came from 424 subjects evaluated using the Uniform Data Set (UDS) assessment collected by the National Alzheimer's Coordinating Center. Subjects had a known year of diagnosis of PD and experienced change in motor function prior to any change in cognition. Linear and logistic regression were used to model the association between APOE e4 carrier status and clinical characteristics including measures of cognitive decline and motor and neuropsychiatric symptoms. Amyloid burden was also evaluated for a subset of patients who died and consented to autopsy.ResultsOdds of dementia were higher in APOE e4 carriers (OR = 5.15), and, on average, APOE e4 carriers scored two points worse on tests of episodic memory and the Clinical Dementia Rating Sum of Boxes assessment. There was little evidence to support an association between e4 carrier status and severity of motor features, and, of the four neuropsychiatric symptoms evaluated, only presence of hallucinations was significantly associated with APOE e4 carrier status (OR = 5.29). Neuropathology data revealed higher frequencies of neuritic and diffuse amyloid plaques in APOE e4 carriers compared to non-carriers.ConclusionsAPOE e4 allele status is associated with dementia and severity of Alzheimer's disease pathologic features in PD.

BackgroundPrevious studies indicate that as many as six genes within the PARK10 region (RNF11, UQCRH, HIVEP3, EIF2B3, USP24, ELAVL4) might modify susceptibility or age at onset in Parkinson's disease (PD).MethodsWe sought to identify new PD susceptibility genes and to validate previously nominated candidate genes within the PARK10 region using a two-stage design. We used data from a large, publicly-available genome-wide association study (GWAS) in the discovery stage (n = 2000 cases and 1986 controls) and data from three independent studies for the replication stage (total n = 2113 cases and 2095 controls). Marker density was increased by imputation using HapMap 3 and 1000 Genomes reference panels, and over 40,000 single nucleotide polymorphisms (SNPs) were used in the final analysis. The association between each SNP and PD was modeled using logistic regression with an additive allele dosage effect and adjusted for sex, age, and axes of geographical variation.ResultsAlthough the discovery stage yielded promising findings for SNPs in several novel genes, including DAB1, none of the results were validated in the replication stage. Furthermore, in meta-analyses across all datasets no genes within PARK10 reached significance after accounting for multiple testing.ConclusionOur results suggest that common variation in the PARK10 region is not associated with PD risk. However, additional studies are needed to assess the role of PARK10 in modifying age at onset and to determine whether rare variants in this region might affect PD susceptibility.

BackgroundLittle is known about the effects of organic solvents on male reproductive health. To assess fertility and reproductive endocrine function in solvent-exposed men, we investigated time-to-pregnancy using a retrospective cohort design and cross-sectionally measured reproductive hormone concentrations in painters and millwrights compared to a reference group of carpenters.MethodsDetailed occupational, exposure, medical, and time-to-pregnancy histories were obtained by telephone interview. Plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone concentrations were determined by immunoassay. Exposure indices, which summarized working life exposure to total solvents, chlorinated solvents, aromatic solvents, and thinners, degreasers, varnishes, and adhesives as a category were calculated from exposure histories.ResultsFSH concentrations increased significantly with increasing exposure indices for all solvents and for chlorinated solvents. There were no significant associations of solvent exposure indices with LH or testosterone levels. LH, FSH, and testosterone concentrations also did not differ by job title. Using Cox regression, time-to-pregnancy was non-significantly longer in the painters and millwrights than the carpenters. There was no significant association between time-to-pregnancy and any of the solvent exposure indices; however, it should be noted that some of the pregnancies occurred more than 20 years previously, potentially reducing the reliability of the retrospectively collected pregnancy and exposure data.ConclusionsThe significant associations between FSH levels and solvent exposure indices suggest the potential for adverse effects of solvent exposures on reproductive function in men.