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Journal of Parkinson's Disease 2024Parkinson's disease is the world's fastest growing brain disorder, and exposure to environmental toxicants is the principal reason. In this paper, we consider... (Review)
Review
Parkinson's disease is the world's fastest growing brain disorder, and exposure to environmental toxicants is the principal reason. In this paper, we consider alternative, but unsatisfactory, explanations for its rise, including improved diagnostic skills, aging populations, and genetic causes. We then detail three environmental toxicants that are likely among the main causes of Parkinson's disease- certain pesticides, the solvent trichloroethylene, and air pollution. All three environmental toxicants are ubiquitous, many affect mitochondrial functioning, and all can access humans via various routes, including inhalation and ingestion. We reach the hopeful conclusion that most of Parkinson's disease is thus preventable and that we can help to create a world where Parkinson's disease is increasingly rare.
Topics: Humans; Parkinson Disease; Trichloroethylene; Pesticides; Environmental Exposure
PubMed: 38217613
DOI: 10.3233/JPD-230357 -
JAMA Neurology Jul 2023An increased risk of Parkinson disease (PD) has been associated with exposure to the solvent trichloroethylene (TCE), but data are limited. Millions of people in the US...
IMPORTANCE
An increased risk of Parkinson disease (PD) has been associated with exposure to the solvent trichloroethylene (TCE), but data are limited. Millions of people in the US and worldwide are exposed to TCE in air, food, and water.
OBJECTIVE
To test whether the risk of PD is higher in veterans who served at Marine Corps Base Camp Lejeune, whose water supply was contaminated with TCE and other volatile organic compounds (VOCs), compared with veterans who did not serve on that base.
DESIGN, SETTING, AND PARTICIPANTS
This population-based cohort study examined the risk for PD among all Marines and Navy personnel who resided at Camp Lejeune, North Carolina (contaminated water) (n = 172 128), or Camp Pendleton, California (uncontaminated water) (n = 168 361), for at least 3 months between 1975 and 1985, with follow-up from January 1, 1997, until February 17, 2021. Veterans Health Administration and Medicare databases were searched for International Classification of Diseases diagnostic codes for PD or other forms of parkinsonism and related medications and for diagnostic codes indicative of prodromal disease. Parkinson disease diagnoses were confirmed by medical record review.
EXPOSURES
Water supplies at Camp Lejeune were contaminated with several VOCs. Levels were highest for TCE, with monthly median values greater than 70-fold the permissible amount.
MAIN OUTCOME AND MEASURES
Risk of PD in former residents of Camp Lejeune relative to residents of Camp Pendleton. In those without PD or another form of parkinsonism, the risk of being diagnosed with features of prodromal PD were assessed individually and cumulatively using likelihood ratio tests.
RESULTS
Health data were available for 158 122 veterans (46.4%). Demographic characteristics were similar between Camp Lejeune (5.3% women, 94.7% men; mean [SD] attained age of 59.64 [4.43] years; 29.7% Black, 6.0% Hispanic, 67.6% White; and 2.7% other race and ethnicity) and Camp Pendleton (3.8% women, 96.2% men; mean [SD] age, 59.80 [4.62] years; 23.4% Black, 9.4% Hispanic, 71.1% White, and 5.5% other race and ethnicity). A total of 430 veterans had PD, with 279 from Camp Lejeune (prevalence, 0.33%) and 151 from Camp Pendleton (prevalence, 0.21%). In multivariable models, Camp Lejeune veterans had a 70% higher risk of PD (odds ratio, 1.70; 95% CI, 1.39-2.07; P < .001). No excess risk was found for other forms of neurodegenerative parkinsonism. Camp Lejeune veterans also had a significantly increased risk of prodromal PD diagnoses, including tremor, anxiety, and erectile dysfunction, and higher cumulative prodromal risk scores.
CONCLUSIONS AND RELEVANCE
The study's findings suggest that the risk of PD is higher in persons exposed to TCE and other VOCs in water 4 decades ago. Millions worldwide have been and continue to be exposed to this ubiquitous environmental contaminant.
Topics: Aged; Male; Humans; Female; United States; Middle Aged; Child, Preschool; Military Personnel; Trichloroethylene; Parkinson Disease; Cohort Studies; Environmental Exposure; Medicare
PubMed: 37184848
DOI: 10.1001/jamaneurol.2023.1168 -
Seminars in Hematology Nov 2023As the most common non-Hodgkin lymphoma subtype, diffuse large B-cell lymphoma (DLBCL) incidence patterns generally parallel that for NHL overall. Globally, DLBCL...
As the most common non-Hodgkin lymphoma subtype, diffuse large B-cell lymphoma (DLBCL) incidence patterns generally parallel that for NHL overall. Globally, DLBCL accounts for a third of all NHLs, ranging between 20% and 50% by country. Based on United States (U.S.) cancer registry data, age-standardized incidence rate for DLBCL was 7.2 per 100,000. DLBCL incidence rises with age and is generally higher in males than females; in the U.S., incidence is highest among non-Hispanic whites (9.2/100,000). Like NHL incidence, DLBCL incidence rose in the first half of the 20th century but has largely plateaued. However, there is some evidence that incidence rates are rising in areas of historically low rates, such as Asia; there are also estimates for rising DLBCL incidence in the near future due to the changing demographics in developed countries whose aging population is growing. Established risk factors for DLBCL include those that result in severe immune deficiency such as HIV/AIDS, inherited immunodeficiency syndromes, and organ transplant recipients. Factors that lead to chronic immune dysregulations are also established risk factors, and include a number of autoimmune conditions (eg, Sjögren syndrome, systemic lupus erythematosus, rheumatoid arthritis), viral infections (eg, HIV, KSHV/HHV8, HCV, EBV), and obesity. Family history of NHL/DLBCL, personal history of cancer, and multiple genetic susceptibility loci are also well-established risk factors for DLBCL. There is strong evidence for multiple environmental exposures in DLBCL etiology, including exposure to trichloroethylene, benzene, and pesticides and herbicides, with recent associations noted with glyphosate. There is also strong evidence for associations with other viruses, such as HBV. Recent estimates suggest that obesity accounts for nearly a quarter of DLBCLs that develop, but despite recent gains in the understanding of DLBCL etiology, the majority of disease remain unexplained. An understanding of the host and environmental contributions to disease etiology, and concerted efforts to expand our understanding to multiple race/ethnic groups, will be essential for constructing clinically relevant risk prediction models and develop effective strategies for disease prevention.
Topics: Male; Female; Humans; United States; Aged; Lymphoma, Large B-Cell, Diffuse; Autoimmune Diseases; HIV Infections; Obesity
PubMed: 38242772
DOI: 10.1053/j.seminhematol.2023.11.004 -
Journal of Parkinson's Disease 2024The brain- and body-first models of Lewy body disorders predict that aggregated alpha-synuclein pathology usually begins in either the olfactory system or the enteric... (Review)
Review
The brain- and body-first models of Lewy body disorders predict that aggregated alpha-synuclein pathology usually begins in either the olfactory system or the enteric nervous system. In both scenarios the pathology seems to arise in structures that are closely connected to the outside world. Environmental toxicants, including certain pesticides, industrial chemicals, and air pollution are therefore plausible trigger mechanisms for Parkinson's disease and dementia with Lewy bodies. Here, we propose that toxicants inhaled through the nose can lead to pathological changes in alpha-synuclein in the olfactory system that subsequently spread and give rise to a brain-first subtype of Lewy body disease. Similarly, ingested toxicants can pass through the gut and cause alpha-synuclein pathology that then extends via parasympathetic and sympathetic pathways to ultimately produce a body-first subtype. The resulting spread can be tracked by the development of symptoms, clinical assessments, in vivo imaging, and ultimately pathological examination. The integration of environmental exposures into the brain-first and body-first models generates testable hypotheses, including on the prevalence of the clinical conditions, their future incidence, imaging patterns, and pathological signatures. The proposed link, though, has limitations and leaves many questions unanswered, such as the role of the skin, the influence of the microbiome, and the effects of ongoing exposures. Despite these limitations, the interaction of exogenous factors with the nose and the gut may explain many of the mysteries of Parkinson's disease and open the door toward the ultimate goal -prevention.
Topics: Humans; Parkinson Disease; Environmental Exposure; Brain; Lewy Body Disease; alpha-Synuclein
PubMed: 38607765
DOI: 10.3233/JPD-240019 -
Materials (Basel, Switzerland) Nov 2023Groundwater contamination by trichloroethylene (TCE) presents a pressing environmental challenge with far-reaching consequences. Traditional remediation methods have... (Review)
Review
Groundwater contamination by trichloroethylene (TCE) presents a pressing environmental challenge with far-reaching consequences. Traditional remediation methods have shown limitations in effectively addressing TCE contamination. This study reviews the limitations of conventional remediation techniques and investigates the application of oxidant-based controlled-release materials, including encapsulated, loaded, and gel-based potassium permanganate since the year 2000. Additionally, it examines reductant controlled-release materials and electron donor-release materials such as tetrabutyl orthosilicate (TBOS) and polyhydroxybutyrate (PHB). The findings suggest that controlled-release materials offer a promising avenue for enhancing TCE degradation and promoting groundwater restoration. This study concludes by highlighting the future research directions and the potential of controlled-release materials in addressing TCE contamination challenges.
PubMed: 37959642
DOI: 10.3390/ma16217045 -
Frontiers in Immunology 2023As Systemic Sclerosis (SSc) is a connective tissue ailment that impacts various bodily systems. The study aims to clarify the molecular subtypes of SSc, with the...
BACKGROUND
As Systemic Sclerosis (SSc) is a connective tissue ailment that impacts various bodily systems. The study aims to clarify the molecular subtypes of SSc, with the ultimate objective of establishing a diagnostic model that can inform clinical treatment decisions.
METHODS
Five microarray datasets of SSc were retrieved from the GEO database. To eliminate batch effects, the combat algorithm was applied. Immune cell infiltration was evaluated using the xCell algorithm. The ConsensusClusterPlus algorithm was utilized to identify SSc subtypes. Limma was used to determine differential expression genes (DEGs). GSEA was used to determine pathway enrichment. A support vector machine (SVM), Random Forest(RF), Boruta and LASSO algorithm have been used to select the feature gene. Diagnostic models were developed using SVM, RF, and Logistic Regression (LR). A ROC curve was used to evaluate the performance of the model. The compound-gene relationship was obtained from the Comparative Toxicogenomics Database (CTD).
RESULTS
The identification of three immune subtypes in SSc samples was based on the expression profiles of immune cells. The utilization of 19 key intersectional DEGs among subtypes facilitated the classification of SSc patients into three robust subtypes (gene_ClusterA-C). Gene_ClusterA exhibited significant enrichment of B cells, while gene_ClusterC showed significant enrichment of monocytes. Moderate activation of various immune cells was observed in gene_ClusterB. We identified 8 feature genes. The SVM model demonstrating superior diagnostic performance. Furthermore, correlation analysis revealed a robust association between the feature genes and immune cells. Eight pertinent compounds, namely methotrexate, resveratrol, paclitaxel, trichloroethylene, formaldehyde, silicon dioxide, benzene, and tetrachloroethylene, were identified from the CTD.
CONCLUSION
The present study has effectively devised an innovative molecular subtyping methodology for patients with SSc and a diagnostic model based on machine learning to aid in clinical treatment. The study has identified potential molecular targets for therapy, thereby offering novel perspectives for the treatment and investigation of SSc.
Topics: Humans; Scleroderma, Systemic; Algorithms; B-Lymphocytes; Benzene; Databases, Factual
PubMed: 37849750
DOI: 10.3389/fimmu.2023.1257802 -
Neurobiology of Disease Jun 2024Idiopathic Parkinson's disease (PD) is epidemiologically linked with exposure to toxicants such as pesticides and solvents, which comprise a wide array of chemicals that...
Idiopathic Parkinson's disease (PD) is epidemiologically linked with exposure to toxicants such as pesticides and solvents, which comprise a wide array of chemicals that pollute our environment. While most are structurally distinct, a common cellular target for their toxicity is mitochondrial dysfunction, a key pathological trigger involved in the selective vulnerability of dopaminergic neurons. We and others have shown that environmental mitochondrial toxicants such as the pesticides rotenone and paraquat, and the organic solvent trichloroethylene (TCE) appear to be influenced by the protein LRRK2, a genetic risk factor for PD. As LRRK2 mediates vesicular trafficking and influences endolysosomal function, we postulated that LRRK2 kinase activity may inhibit the autophagic removal of toxicant damaged mitochondria, resulting in elevated oxidative stress. Conversely, we suspected that inhibition of LRRK2, which has been shown to be protective against dopaminergic neurodegeneration caused by mitochondrial toxicants, would reduce the intracellular production of reactive oxygen species (ROS) and prevent mitochondrial toxicity from inducing cell death. To do this, we tested in vitro if genetic or pharmacologic inhibition of LRRK2 (MLi2) protected against ROS caused by four toxicants associated with PD risk - rotenone, paraquat, TCE, and tetrachloroethylene (PERC). In parallel, we assessed if LRRK2 inhibition with MLi2 could protect against TCE-induced toxicity in vivo, in a follow up study from our observation that TCE elevated LRRK2 kinase activity in the nigrostriatal tract of rats prior to dopaminergic neurodegeneration. We found that LRRK2 inhibition blocked toxicant-induced ROS and promoted mitophagy in vitro, and protected against dopaminergic neurodegeneration, neuroinflammation, and mitochondrial damage caused by TCE in vivo. We also found that cells with the LRRK2 G2019S mutation displayed exacerbated levels of toxicant induced ROS, but this was ameliorated by LRRK2 inhibition with MLi2. Collectively, these data support a role for LRRK2 in toxicant-induced mitochondrial dysfunction linked to PD risk through oxidative stress and the autophagic removal of damaged mitochondria.
Topics: Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Animals; Reactive Oxygen Species; Rats; Trichloroethylene; Mitochondria; Rotenone; Parkinson Disease; Paraquat; Dopaminergic Neurons; Oxidative Stress; Humans; Environmental Pollutants; Rats, Sprague-Dawley
PubMed: 38705492
DOI: 10.1016/j.nbd.2024.106522 -
BMC Public Health Dec 2023The laundry and dry cleaning industries are critical for maintaining cleanliness and hygiene in our daily lives. However, they have also been identified as sources of... (Review)
Review
BACKGROUND
The laundry and dry cleaning industries are critical for maintaining cleanliness and hygiene in our daily lives. However, they have also been identified as sources of hazardous chemical exposure for workers, leading to potentially severe health implications. Despite mounting evidence that solvents like perchloroethylene and trichloroethylene are carcinogenic, they remain commonly used in the industry. Additionally, while alternative solvents are increasingly being utilized in response to indications of adverse health and environmental effects, there remains a significant gap in our understanding of the potential risks associated with exposure to these new agents.
METHODS
This study aims to identify gaps in the literature concerning worker exposure to contemporary toxic chemicals in the laundry and dry cleaning industry and their associated carcinogenic risks. A scoping review of peer-reviewed publications from 2012 to 2022 was conducted to achieve this objective, focusing on studies that detailed chemical exposures, sampling methods, and workers within the laundry and dry cleaning sector.
RESULTS
In this scoping review, 12 relevant papers were assessed. A majority (66%) examined perchloroethylene exposure, with one notable finding revealing that biomarkers from dry cleaners had significant micronuclei frequency and DNA damage, even when exposed to PCE at levels below occupational exposure limits. Similarly, another study supported these results, finding an increase in early DNA damage among exposed workers. Separate studies on TCE and benzene presented varied exposure levels and health risks, raising concern due to their IARC Group 1 carcinogen classification. Information on alternative solvents was limited, highlighting gaps in health outcome data, exposure guidelines, and carcinogenic classifications.
CONCLUSION
Research on health outcomes, specifically carcinogenicity from solvent exposure in dry cleaning, is limited, with 66% of studies not monitoring health implications, particularly for emerging solvents. Further, findings indicated potential DNA damage from perchloroethylene, even below set occupational limits, emphasizing the need to reevaluate safety limits. As alternative solvents like butylal and high-flashpoint hydrocarbons become more prevalent, investigations into the effects of their exposure are necessary to safeguard workers' health. This scoping review is registered with the Open Science Framework, registration DOI: https://doi.org/10.17605/OSF.IO/Q8FR3 .
Topics: Humans; Tetrachloroethylene; Occupational Exposure; Solvents; Hydrocarbons; Trichloroethylene; Neoplasms
PubMed: 38129859
DOI: 10.1186/s12889-023-17306-y -
Ecotoxicology and Environmental Safety Jul 2023More and more clinical evidence shows that occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) patients often present immune kidney damage....
More and more clinical evidence shows that occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) patients often present immune kidney damage. However, the exact mechanisms of cell-to-cell transmission in TCE-induced immune kidney damage remain poorly understood. The present study aimed to explore the role of high mobility group box-1 (HMGB 1) in glomerular endothelial cell-podocyte transmission. 17 OMDT patients and 34 controls were enrolled in this study. We observed that OMDT patients had renal function injury, endothelial cell activation and podocyte injury, and these indicators were associated with serum HMGB 1. To gain mechanistic insight, a TCE-sensitized BALB/c mouse model was established under the interventions of sirtuin 1 (SIRT 1) activator SRT 1720 (0.1 ml, 5 mg/kg) and receptor for advanced glycation end products (RAGE) inhibitor FPS-ZM 1 (0.1 ml, 1.5 mg/kg). We identified HMGB 1 acetylation and its endothelial cytoplasmic translocation following TCE sensitization, but SRT 1720 abolished the process. RAGE was located on podocytes and co-precipitated with extracellular acetylated HMGB 1, promoting podocyte injury, while SRT 1720 and FPS-ZM 1 both alleviated podocyte injury. The results demonstrate that interventions to upstream and downstream pathways of HMGB 1 may weaken glomerular endothelial cell-podocyte transmission, thereby alleviating TCE-induced immune renal injury.
Topics: Animals; Mice; Acetylation; Endothelial Cells; HMGB Proteins; Kidney; Kidney Diseases; Mice, Inbred BALB C; Podocytes; Trichloroethylene; Cell Communication
PubMed: 37216866
DOI: 10.1016/j.ecoenv.2023.115042 -
ACS Environmental Au Jul 2023Products and starting materials containing volatile organic compounds (VOCs) can easily be found in a variety of businesses, making them a common source of occupational...
Products and starting materials containing volatile organic compounds (VOCs) can easily be found in a variety of businesses, making them a common source of occupational exposure. To prevent negative impacts on employee health, field industrial hygienists must conduct regular sampling to ensure exposures remain below the regulatory limits set by governmental and professional associations. As such, the need for sensitive and reliable exposure assessment techniques becomes evident. Over the preceding decade, the industrial hygiene research group at the University of Alabama at Birmingham (UAB) has been working on the development of an emerging, preanalytical technique known as photothermal desorption (PTD) to improve upon the analytical sensitivity of currently employed methods. PTD's novel design uses pulses of high-energy light to desorb analytes from thermally conductive, carbonaceous sorbents, to be delivered to downstream analytical detectors. Since PTD's conception, the theoretical framework and advances in sorbent fabrication have been investigated; however, further work is needed to produce a field-ready sampling device for use with PTD. As such, objectives of the present work were to design a PTD-compatible diffusive sampler prototype and characterize the prototype's sampling efficiencies for toluene, -hexane, trichloroethylene, and isopropyl alcohol. In pursuit of these objectives, the study empirically quantified the sampled masses of toluene, -hexane, trichloroethylene, and isopropyl alcohol, at occupationally relevant air concentrations, to be 12.17 ± 0.06, 8.2 ± 0.1, 3.97 ± 0.06, and 8.0 ± 0.1 mg, respectively. Moreover, the analyte sampling efficiencies were found to be 2.2 ± 0.1, 1.7 ± 0.1, 1.2 ± 0.1, and 0.51 ± 0.05 (unitless) when comparing empirically (i.e., laboratory observed) sample mass values to theoretically predicted values. The sampling efficiencies and collected sample masses reported herein demonstrate the promising design of PTD-compatible diffusive samplers. When used in conjunction with the PTD method, the prototype samplers present strong evidence for improving analytical sensitivity in exposure assessments of VOCs in the workplace.
PubMed: 37483304
DOI: 10.1021/acsenvironau.2c00071