Rotenone, Paraquat, and Parkinson's Disease Tanner, Caroline M.; Kamel, Freya; Ross, G. Webster ...
Environmental health perspectives,
06/2011, Volume:
119, Issue:
6
Journal Article
Peer reviewed
Open access
Background: Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson's disease (PD). Certain pesticides may ...affect these mechanisms, but no pesticide has been definitively associated with PD in humans. Objectives: Our goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans. Methods: We assessed lifetime use of pesticides selected by mechanism in a case–control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controlsrone case. Results: In 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.0-2.8 including rotenone (OR = 2.5; 95% CI, 1.3-4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2-3.6), including paraquat (OR = 2.5; 95% CI, 1.4-4.7). Conclusions: PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally—those that impair mitochondrial function and those that increase oxidative stress—supporting a role for these mechanisms in PD pathophysiology.
Most movements are not unitary, but are comprised of sequences. Although patients with cerebellar pathology display severe deficits in the execution and learning of sequences (Doyon et al., 1997; ...Shin and Ivry, 2003), most of our understanding of cerebellar mechanisms has come from analyses of single component movements. Eyelid conditioning is a cerebellar-mediated behavior that provides the ability to control and restrict inputs to the cerebellum through stimulation of mossy fibers. We utilized this advantage to test directly how the cerebellum can learn a sequence of inter-connected movement components in rabbits. We show that the feedback signals from one component are sufficient to serve as a cue for the next component in the sequence. In vivo recordings from Purkinje cells demonstrated that all components of the sequence were encoded similarly by cerebellar cortex. These results provide a simple yet general framework for how the cerebellum can use simple associate learning processes to chain together a sequence of appropriately timed responses.
Pesticide exposure may be positively associated with depression. Few previous studies have considered the episodic nature of depression or examined individual pesticides.
We evaluated associations ...between pesticide exposure and depression among male private pesticide applicators in the Agricultural Health Study.
We analyzed data for 10 pesticide classes and 50 specific pesticides used by 21,208 applicators enrolled in 1993-1997 who completed a follow-up telephone interview in 2005-2010. We divided applicators who reported a physician diagnosis of depression (n = 1,702; 8%) into those who reported a previous diagnosis of depression at enrollment but not follow-up (n = 474; 28%), at both enrollment and follow-up (n = 540; 32%), and at follow-up but not enrollment (n = 688; 40%) and used polytomous logistic regression to estimate odds ratios (ORs) and 95% CIs. We used inverse probability weighting to adjust for potential confounders and to account for the exclusion of 3,315 applicators with missing covariate data and 24,619 who did not complete the follow-up interview.
After weighting for potential confounders, missing covariate data, and dropout, ever-use of two pesticide classes, fumigants and organochlorine insecticides, and seven individual pesticides-the fumigants aluminum phosphide and ethylene dibromide; the phenoxy herbicide (2,4,5-trichlorophenoxy)acetic acid (2,4,5-T); the organochlorine insecticide dieldrin; and the organophosphate insecticides diazinon, malathion, and parathion-were all positively associated with depression in each case group, with ORs between 1.1 and 1.9.
Our study supports a positive association between pesticide exposure and depression, including associations with several specific pesticides.
Background Previous studies, mostly from Europe, suggest that early-life farming exposures protect against childhood asthma and allergy; few data exist on asthma and allergy in adults. Objective We ...sought to examine associations between early-life farming exposures and current asthma and atopy in an older adult US farming population. Methods We analyzed data from 1746 farmers and 1555 spouses (mean age, 63) from a case-control study nested within the Agricultural Health Study. Current asthma and early-life farming exposures were assessed via questionnaires. We defined atopy based on specific IgE > 0.70 IU/mL to at least 1 of 10 allergens measured in blood. We used logistic regression, adjusted for age, sex, race, state (Iowa or North Carolina), and smoking (pack years), to estimate associations between early-life exposures and asthma (1198 cases and 2031 noncases) or atopy (578 cases and 2526 noncases). Results Exposure to the farming environment in utero and in early childhood had little or no association with asthma but was associated with reduced odds of atopy. The strongest association was seen for having a mother who performed farm activities while pregnant (odds ratio, 0.60; 95% CI, 0.48-0.74) and remained significant in models with correlated early-life exposures including early childhood farm animal contact and raw milk consumption. Conclusions In a large US farming population, early-life farm exposures, particularly maternal farming activities while pregnant, were strongly associated with reduced risk of atopy in adults. These results extend previous work done primarily on childhood outcomes and suggest that protective associations of early-life farming exposures on atopy endure across the life course.
In response to the limited supply of personal protective equipment during the pandemic caused by SARS-CoV-2, recent studies demonstrate that gaseous H.sub.2 O.sub.2 is an effective decontaminant of ...N95 filtering facepiece respirators to enable reuse of these items in a clinical setting. This paper evaluates the efficacy of the Arca Aerosolized Hydrogen Peroxide Decontamination System (Arca), a novel aerosolized H.sub.2 O.sub.2 decontamination system, using biologic indicator testing. The Arca produces and circulates H.sub.2 O.sub.2 aerosol inside of a sealed stainless steel chamber. The Arca's decontamination efficacy was evaluated in 8 decontamination trials with 2 H.sub.2 O.sub.2 concentrations (3% and 12%) and 4 decontamination cycle durations (45, 60, 90, and 120 minutes). Efficacy was evaluated by testing: 1) the concentration in parts per million (ppm) of H.sub.2 O.sub.2 produced inside the chamber and the concentration in ppm of H.sub.2 O.sub.2 vented from the chamber, and 2) the decontamination of Mesa Biologic Indicator filter strips (BI) inoculated with Geobacillus Stearothermophilus. Control tests were conducted by submerging BI strips in 3mL of 3% and 12% H.sub.2 O.sub.2 for 120 minutes (negative controls) and by not exposing one BI strip to H.sub.2 O.sub.2 (positive control). Greater than 5000 ppm of H.sub.2 O.sub.2 was detected on the concentration strips inside the chamber for each of the eight decontamination trials. No vented H.sub.2 O.sub.2 was detected on the external concentration strips after any decontamination trial. No growth was observed for any of the negative controls after seven days. The positive control was positive for growth. The Arca Aerosolized Hydrogen Peroxide Decontamination System is effective at decontaminating bacterial G. Stearothermophilus at a cycle time of 45 minutes utilizing 6mL of 3% H.sub.2 O.sub.2 solution.
The prevalence of chronic kidney disease and its risk factors is increasing worldwide, and the rapid rise in global need for end-stage kidney disease care is a major challenge for health systems, ...particularly in low- and middle-income countries. Countries are responding to the challenge of end-stage kidney disease in different ways, with variable provision of the components of a kidney care strategy, including effective prevention, detection, conservative care, kidney transplantation, and an appropriate mix of dialysis modalities. This collection of case studies is from 15 countries from around the world and offers valuable learning examples from a variety of contexts. The variability in approaches may be explained by country differences in burden of disease, available human or financial resources, income status, and cost structures. In addition, cultural considerations, political context, and competing interests from other stakeholders must be considered. Although the approaches taken have often varied substantially, a common theme is the potential benefits of multistakeholder engagement aimed at improving the availability and scope of integrated kidney care.
Abstract Background Chronic exposure to microorganisms inside homes can impact respiratory health. Few studies have used advanced sequencing methods to examine adult respiratory outcomes, especially ...continuous measures. We aimed to identify metagenomic profiles in house dust related to the quantitative traits of pulmonary function and airway inflammation in adults. Microbial communities, 1264 species (389 genera), in vacuumed bedroom dust from 779 homes in a US cohort were characterized by whole metagenome shotgun sequencing. We examined two overall microbial diversity measures: richness (the number of individual microbial species) and Shannon index (reflecting both richness and relative abundance). To identify specific differentially abundant genera, we applied the Lasso estimator with high-dimensional inference methods, a novel framework for analyzing microbiome data in relation to continuous traits after accounting for all taxa examined together. Results Pulmonary function measures (forced expiratory volume in one second (FEV 1 ), forced vital capacity (FVC), and FEV 1 /FVC ratio) were not associated with overall dust microbial diversity. However, many individual microbial genera were differentially abundant ( p -value < 0.05 controlling for all other microbial taxa examined) in relation to FEV 1 , FVC, or FEV 1 /FVC. Similarly, fractional exhaled nitric oxide (FeNO), a marker of airway inflammation, was unrelated to overall microbial diversity but associated with differential abundance for many individual genera. Several genera, including Limosilactobacillus , were associated with a pulmonary function measure and FeNO, while others, including Moraxella to FEV 1 /FVC and Stenotrophomonas to FeNO, were associated with a single trait. Conclusions Using state-of-the-art metagenomic sequencing, we identified specific microorganisms in indoor dust related to pulmonary function and airway inflammation. Some were previously associated with respiratory conditions; others were novel, suggesting specific environmental microbial components contribute to various respiratory outcomes. The methods used are applicable to studying microbiome in relation to other continuous outcomes.
In epidemiologic studies where physician-based case adjudication is not feasible, Parkinson's disease (PD) case ascertainment is often limited to self-reports which may not be accurate. We evaluated ...strategies to identify PD cases in the Agricultural Health Study (AHS).
Doctor-diagnosed PD was self-reported on all cohort-wide surveys; potential cases were also identified from death certificates. Follow-up surveys asked about PD-related motor and non-motor symptoms. For PD confirmation, we collected additional diagnosis, symptom, and treatment data from 510 potential PD cases or their proxy (65% of those contacted) in a supplemental screener and obtained medical records for a subset (n = 65). We classified PD cases using established criteria and screener data.
Of 510 potential PD cases, 75% were considered "probable" or "possible"; this proportion increased among participants diagnosed by a specialist (81.2%), taking PD medication (85.2%), or reporting ≥5 motor symptoms (86.8%) in a regular AHS survey. Of those with medical records, 93% (57 of 61) of probable or possible PD was confirmed. Never-smoking and non-motor and motor symptoms reported in prior AHS surveys were more common with probable/possible PD than unconfirmed PD.
In this retrospective PD case ascertainment effort, we found that PD self-report with information on motor symptoms or medications may be a reasonable alternative for identifying PD cases when physician exam is not feasible. Because of intervening mortality, screeners could not be obtained from about one-third of those contacted. Thus, findings warrant replication.
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