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1.
Neuron ; 112(7): 1110-1116.e5, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38301647

RESUMEN

The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Knockdown of ε4 may provide a therapeutic strategy for AD, but the effect of APOE loss of function (LoF) on AD pathogenesis is unknown. We searched for APOE LoF variants in a large cohort of controls and patients with AD and identified seven heterozygote carriers of APOE LoF variants. Five carriers were controls (aged 71-90 years), one carrier was affected by progressive supranuclear palsy, and one carrier was affected by AD with an unremarkable age at onset of 75 years. Two APOE ε3/ε4 controls carried a stop-gain affecting ε4: one was cognitively normal at 90 years and had no neuritic plaques at autopsy; the other was cognitively healthy at 79 years, and lumbar puncture at 76 years showed normal levels of amyloid. These results suggest that ε4 drives AD risk through the gain of abnormal function and support ε4 knockdown as a viable therapeutic option.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Alelos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Genotipo , Longevidad/genética
2.
Nanotoxicology ; 17(10): 669-686, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38116948

RESUMEN

Thermal spray coating is a process in which molten metal is sprayed onto a surface. Little is known about the health effects associated with these aerosols. Sprague-Dawley rats were exposed to aerosols (25 mg/m3 × 4 hr/d × 4 d) generated during thermal spray coating using different consumables [i.e. stainless-steel wire (PMET731), Ni-based wire (PMET885), Zn-based wire (PMET540)]. Control animals received air. Bronchoalveolar lavage was performed at 4 and 30 d post-exposure to assess lung toxicity. The particles were chain-like agglomerates and similar in size (310-378 nm). Inhalation of PMET885 aerosol caused a significant increase in lung injury and inflammation at both time points. Inhalation of PMET540 aerosol caused a slight but significant increase in lung toxicity at 4 but not 30 d. Exposure to PMET731 aerosol had no effect on lung toxicity. Overall, the lung responses were in the order: PMET885≫PMET540 >PMT731. Following a shorter exposure (25 mg/m3 × 4 h/d × 1d), lung burdens of metals from the different aerosols were determined by ICP-AES at 0, 1, 4 and 30 d post-exposure. Zn was cleared from the lungs at the fastest rate with complete clearance by 4 d post-exposure. Ni, Cr, and Mn had similar rates of clearance as nearly half of the deposited metal was cleared by 4 d. A small but significant percentage of each of these metals persisted in the lungs at 30 d. The pulmonary clearance of Fe was difficult to assess because of inherently high levels of Fe in control lungs.


Asunto(s)
Pulmón , Aerosoles y Gotitas Respiratorias , Ratas , Animales , Ratas Sprague-Dawley , Administración por Inhalación , Metales/toxicidad , Aerosoles , Exposición por Inhalación , Líquido del Lavado Bronquioalveolar , Tamaño de la Partícula
3.
medRxiv ; 2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37547016

RESUMEN

The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer's Disease (AD). Knockdown of this allele may provide a therapeutic strategy for AD, but the effect of APOE loss-of-function (LoF) on AD pathogenesis is unknown. We searched for APOE LoF variants in a large cohort of older controls and patients with AD and identified six heterozygote carriers of APOE LoF variants. Five carriers were controls (ages 71-90) and one was an AD case with an unremarkable age-at-onset between 75-79. Two APOE ε3/ε4 controls (Subjects 1 and 2) carried a stop-gain affecting the ε4 allele. Subject 1 was cognitively normal at 90+ and had no neuritic plaques at autopsy. Subject 2 was cognitively healthy within the age range 75-79 and underwent lumbar puncture at between ages 75-79 with normal levels of amyloid. The results provide the strongest human genetics evidence yet available suggesting that ε4 drives AD risk through a gain of abnormal function and support knockdown of APOE ε4 or its protein product as a viable therapeutic option.

4.
Int J Mol Sci ; 24(13)2023 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-37445616

RESUMEN

The Apolipoprotein E (APOE) locus has garnered significant clinical interest because of its association with Alzheimer's disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either upregulated or downregulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Apolipoproteínas E/genética , Envejecimiento/genética , Envejecimiento/metabolismo , Genotipo , Mitocondrias/genética , Mitocondrias/metabolismo , Apolipoproteína E4/genética
5.
Ann Work Expo Health ; 67(3): 402-413, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36595023

RESUMEN

In practice, workers often handle the same chemical(s) of interest under different control measures (e.g. local ventilation, enclosed system) during a full shift. Stoffenmanager® allows users to predict either task-based or full-shift exposures. However, most previous studies evaluated the tool by comparing task-based exposures with measured exposures. Also, limited evaluation studies of the Advanced REACH Tool (ART) with the Bayesian approach (ART+B) are available, requiring additional evaluation studies. The performance of Stoffenmanager® and ART with and without the Bayesian approach was evaluated with measured full-shift exposures to volatile liquids in terms of accuracy, precision, and conservatism. Forty-two exposure situation scenarios (including 251 exposures), developed based on job tasks and chemicals handled during tasks from workplaces, were used to generate full-shift estimates. The estimates were then compared with measured exposures using various comparison methods. Overall, Stoffenmanager® appeared to be the most accurate among the testing tools, while ART+B was the most precise. The percentage of measured exposures exceeding the tools' 90th percentile estimates (%M>T) demonstrated that Stoffenmanager® (16%M>T) and ART+B (13%M>T) were more conservative than ART (41%M>T). When the 90% upper confidence limit of the 90th percentile estimate was considered, the level of conservatism changed from low (41%M>T) to medium (17%M>T) for ART and from medium (13%M>T) to high (0.8%M>T) for ART+B. The findings of this study indicate that no single tool would work for all ESs. Thus, it is recommended that users select a tool based on the performance results of three components (i.e. accuracy, precision, and conservatism), not depending on one or two components. The strength of this study is that the required tools' input parameters were obtained during the sample collection to minimize assumptions for many input parameters. In addition, unlike other previous studies, multiple subtasks, which happen often in workplaces, were incorporated in this study. Nevertheless, the present study did not cover all activities listed in the tools and was limited to volatile liquids, suggesting further studies cover other exposure categories (e.g. solid, metal) and diverse activities.


Asunto(s)
Exposición Profesional , Humanos , Exposición Profesional/análisis , Exposición por Inhalación/análisis , Teorema de Bayes , Medición de Riesgo/métodos , Monitoreo del Ambiente/métodos
6.
Arch Toxicol ; 96(12): 3201-3217, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35984461

RESUMEN

Thermal spray coating is an industrial process in which molten metal is sprayed at high velocity onto a surface as a protective coating. An automated electric arc wire thermal spray coating aerosol generator and inhalation exposure system was developed to simulate an occupational exposure and, using this system, male Sprague-Dawley rats were exposed to stainless steel PMET720 aerosols at 25 mg/m3 × 4 h/day × 9 day. Lung injury, inflammation, and cytokine alteration were determined. Resolution was assessed by evaluating these parameters at 1, 7, 14 and 28 d after exposure. The aerosols generated were also collected and characterized. Macrophages were exposed in vitro over a wide dose range (0-200 µg/ml) to determine cytotoxicity and to screen for known mechanisms of toxicity. Welding fumes were used as comparative particulate controls. In vivo lung damage, inflammation and alteration in cytokines were observed 1 day post exposure and this response resolved by day 7. Alveolar macrophages retained the particulates even after 28 day post-exposure. In line with the pulmonary toxicity findings, in vitro cytotoxicity and membrane damage in macrophages were observed only at the higher doses. Electron paramagnetic resonance showed in an acellular environment the particulate generated free radicals and a dose-dependent increase in intracellular oxidative stress and NF-kB/AP-1 activity was observed. PMET720 particles were internalized via clathrin and caveolar mediated endocytosis as well as actin-dependent pinocytosis/phagocytosis. The results suggest that compared to stainless steel welding fumes, the PMET 720 aerosols were not as overtly toxic, and the animals recovered from the acute pulmonary injury by 7 days.


Asunto(s)
Contaminantes Ocupacionales del Aire , Soldadura , Ratas , Animales , Masculino , Acero Inoxidable/toxicidad , Contaminantes Ocupacionales del Aire/toxicidad , FN-kappa B , Actinas , Factor de Transcripción AP-1 , Ratas Sprague-Dawley , Aerosoles y Gotitas Respiratorias , Soldadura/métodos , Exposición por Inhalación/efectos adversos , Pulmón , Polvo , Inflamación/patología , Citocinas , Clatrina/farmacología
7.
Toxicol Rep ; 9: 126-135, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35127456

RESUMEN

Thermal spray coating involves spraying a product (oftentimes metal) that is melted by extremely high temperatures and then applied under pressure onto a surface. Large amounts of a complex metal aerosol (e.g., Fe, Cr, Ni, Zn) are formed during the process, presenting a potentially serious risk to the operator. Information about the health effects associated with exposure to these aerosols is lacking. Even less is known about the chemical and physical properties of these aerosols. The goal was to develop and test an automated thermal spray coating aerosol generator and inhalation exposure system that would simulate workplace exposures. An electric arc wire-thermal spray coating aerosol generator and exposure system was designed and separated into two areas: (1) an enclosed room where the spray coating occurs; (2) an exposure chamber with different measurement devices and controllers. The physicochemical properties of aerosols generated during electric arc wire-thermal spray coating using five different consumable wires were examined. The metal composition of each was determined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES), including two stainless-steel wires [PMET720 (82 % Fe, 13 % Cr); PMET731(66 % Fe, 26 % Cr)], two Ni-based wires [PMET876 (55 % Ni, 17 % Cr); PMET885 (97 % Ni)], and one Zn-based wire [PMET540 (99 % Zn)]. The particles generated regardless of composition were poorly soluble, complex metal oxides and mostly arranged as chain-like agglomerates and similar in size distribution as determined by micro-orifice uniform deposit impactor (MOUDI) and electrical low-pressure impactor (ELPI). To allow for continuous, sequential spray coating during a 4-hr exposure period, a motor rotated the metal pipe to be coated in a circular and up-and-down direction. In a pilot animal study, male Sprague-Dawley rats were exposed to aerosols (25 mg/m3 × 4 h/d × 9 d) generated from electric arc wire- thermal spray coating using the stainless-steel PMET720 consumable wire. The targeted exposure chamber concentration was achieved and maintained during a 4-hr period. At 1 d after exposure, lung injury and inflammation were significantly elevated in the group exposed to the thermal spray coating aerosol compared to the air control group. The system was designed and constructed for future animal exposure studies to generate continuous metal spray coating aerosols at a targeted concentration for extended periods of time without interruption.

8.
Genes (Basel) ; 12(6)2021 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-34204109

RESUMEN

Increasing evidence suggests that the Translocase of Outer Mitochondria Membrane 40 (TOMM40) gene may contribute to the risk of Alzheimer's disease (AD). Currently, there is no consensus as to whether TOMM40 expression is up- or down-regulated in AD brains, hindering a clear interpretation of TOMM40's role in this disease. The aim of this study was to determine if TOMM40 RNA levels differ between AD and control brains. We applied RT-qPCR to study TOMM40 transcription in human postmortem brain (PMB) and assessed associations of these RNA levels with genetic variants in APOE and TOMM40. We also compared TOMM40 RNA levels with mitochondrial functions in human cell lines. Initially, we found that the human genome carries multiple TOMM40 pseudogenes capable of producing highly homologous RNAs that can obscure precise TOMM40 RNA measurements. To circumvent this obstacle, we developed a novel RNA expression assay targeting the primary transcript of TOMM40. Using this assay, we showed that TOMM40 RNA was upregulated in AD PMB. Additionally, elevated TOMM40 RNA levels were associated with decreases in mitochondrial DNA copy number and mitochondrial membrane potential in oxidative stress-challenged cells. Overall, differential transcription of TOMM40 RNA in the brain is associated with AD and could be an indicator of mitochondrial dysfunction.


Asunto(s)
Enfermedad de Alzheimer/genética , Encéfalo/metabolismo , Proteínas de Transporte de Membrana/genética , Mitocondrias/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Línea Celular , Células Cultivadas , Femenino , Dosificación de Gen , Humanos , Masculino , Potencial de la Membrana Mitocondrial , Proteínas de Transporte de Membrana/metabolismo , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales , Estrés Oxidativo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regulación hacia Arriba
9.
J Occup Environ Hyg ; 18(7): 295-304, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34129437

RESUMEN

This study investigated the effects of particle transfer to the covers of aerosol samplers during transportation of wood dust and welding fume samples. Wood dust samples were collected in a sanding chamber using four sampler types: closed-face cassettes (CFC), CFC with Accu-CAP inserts, disposable inhalable samplers (DIS), and Institute of Occupational Medicine (IOM). Welding fumes were collected in a walk-in chamber using the same samplers, with Solu-Sert replacing Accu-CAP. The samples were divided into two groups, with one group transported by air and the other by land. They were returned in the same manner and analyzed gravimetrically for wood dust and chemically for welding fumes. For wood dust, IOM showed a significantly higher percentage of particles transferred to the covers compared with the other samplers regardless of the transportation mode (p < 0.0001; 64% by air and 15% by land), while other samplers showed less than or close to 10% (3.5-12%). When the percentages of particle transfer to the covers were compared between the air and land transportation, both IOM and CFC samples showed differences between modes of transportation, while others did not. For welding fumes, most samples (61% of samples for copper [Cu] and 76% of samples for manganese [Mn]) showed nondetectable amounts of the analyte on the covers. For all samplers, the particle transfer to the covers for both transportation modes ranged from 0.2-33% for Cu and less than 4.5% for Mn. Overall, this study confirms that particle transfer to sampler covers during transport highly depends upon the transportation mode and sampler type for wood dust, whereas particle transfer seems minimal for welding fumes. The findings of this study are based on two materials and limited sample sizes. Further investigation considering different industry types and tasks, particle size ranges, and materials might be necessary. Nevertheless, occupational professionals should account for this transfer when handling and analyzing samples in practice.


Asunto(s)
Contaminantes Ocupacionales del Aire , Exposición Profesional , Aerosoles/análisis , Contaminantes Ocupacionales del Aire/análisis , Polvo/análisis , Monitoreo del Ambiente , Exposición por Inhalación/análisis , Exposición Profesional/análisis , Tamaño de la Partícula
10.
Front Public Health ; 9: 638082, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33748070

RESUMEN

Perchloroethylene (PERC) is the most common solvent used for dry cleaning in the United States. PERC is a reproductive toxicant, neurotoxicant, potential human carcinogen, and a persistent environmental pollutant. The Environmental Protection Agency is evaluating PERC under the Frank R. Lautenberg Chemical Safety for the 21st Century Act, which amended the Toxic Substances Control Act (amended TSCA), and has mandated that PERC dry cleaning machines be removed from residential buildings. Some local and state programs are also requiring or facilitating transitions to alternative cleaning technologies. However, the potential for these alternatives to harm human health and the environment is not well-understood. This review describes the issues surrounding the use of PERC and alternative solvents for dry cleaning while highlighting the lessons learned from a local government program that transitioned PERC dry cleaners to the safest current alternative: professional wet cleaning. Implications for future public health research and policy are discussed: (1) we must move away from PERC, (2) any transition must account for the economic instability and cultural aspects of the people who work in the industry, (3) legacy contamination must be addressed even after safer alternatives are adopted, and (4) evaluations of PERC alternatives are needed to determine their implications for the long-term health and sustainability of the people who work in the industry.


Asunto(s)
Tetracloroetileno , Carcinógenos , Humanos , Industrias , Solventes , Tetracloroetileno/efectos adversos
11.
Toxicol Ind Health ; 37(1): 47-58, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33305691

RESUMEN

Thermal spray coating is a process that applies a molten metal product under pressure onto a surface. Although thermal spray processes have been used for decades, exposure to aerosols formed during thermal spray coating is an emerging risk. Reports indicate that high concentrations of aerosols composed of toxic metals (e.g. chromium) are generated in the workplace. A knowledge gap exists related to the physicochemical properties of thermal spray coating aerosols as well as any potential associated health effects. The objective of this manuscript was to review thermal spray coating and previous studies that have examined the aerosols produced from this process. A thermal spray coating generator and exposure system is also described that has recently been developed to further evaluate the physical and chemical properties of aerosols formed during thermal spray coating as well as to assess the possible health effects of this process in an effort to mitigate potential occupational health hazards related to the industry.


Asunto(s)
Aerosoles/química , Contaminantes Ocupacionales del Aire/química , Exposición por Inhalación/análisis , Metales/química , Exposición Profesional/análisis , Humanos , Industrias , Tamaño de la Partícula
12.
Otolaryngol Head Neck Surg ; 163(3): 508-516, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32450780

RESUMEN

OBJECTIVES: To assess the exposure of surgical personnel to known carcinogens during pediatric tonsillectomy and adenoidectomy (T&A) and compare the efficacy of surgical smoke evacuation systems during T&A. STUDY DESIGN: Prospective, case series. SETTING: Tertiary children's hospital. SUBJECTS AND METHODS: The present study assessed operating room workers' exposure to chemical compounds and aerosolized particulates generated during T&A. We also investigated the effect of 3 different smoke-controlling methods: smoke-evacuator pencil cautery (SE), cautery with suction held by an assistant (SA), and cautery without suction (NS). RESULTS: Thirty cases were included: 12 in the SE group, 9 in SA, and 9 in NS. The chemical exposure levels were lower than or similar to baseline background concentrations, with the exception of methylene chloride and acetaldehyde. Within the surgical plume, none of the chemical compounds exceeded the corresponding occupational exposure limit (OEL). The mean particulate number concentration in the breathing zone during tonsillectomy was 508 particles/cm3 for SE compared to 1661 particles/cm3 for SA and 8208 particles/cm3 for NS cases. NS was significantly different compared to the other two methods (P = .0009). CONCLUSIONS: Although the exposure levels to chemicals were considerably lower than the OELs, continuous exposures to these chemicals could cause adverse health effects to surgical personnel. These findings suggest that the use of a smoke-evacuator pencil cautery or an attentive assistant with handheld suction would reduce exposure levels to the aerosolized particles during routine T&A, compared to the use of cautery without suction.


Asunto(s)
Adenoidectomía/instrumentación , Electrocoagulación/efectos adversos , Electrocoagulación/instrumentación , Exposición Profesional/prevención & control , Humo/efectos adversos , Tonsilectomía/instrumentación , Adenoidectomía/efectos adversos , Humanos , Quirófanos , Estudios Prospectivos , Tonsilectomía/efectos adversos
13.
Otolaryngol Head Neck Surg ; 162(6): 867-872, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32228131

RESUMEN

OBJECTIVES: To describe the effect of monopolar electrocautery (EC) settings on surgical plume particulate concentration during pediatric tonsillectomy. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary medical center. SUBJECTS AND METHODS: During total tonsillectomy exclusively performed with EC, air was sampled with a surgeon-worn portable particle counter. The airborne mean and maximum particle concentrations were compared for tonsillectomy performed with EC at 12 W vs 20 W, with smoke evacuation system (SES) and no smoke evacuation (NS). RESULTS: A total of 36 children were included in this analysis: 9 cases with EC at 12 W and SES (12SES), 9 cases with EC at 20 W and SES (20SES), 9 cases with EC at 12 W without SES (12NS), and 9 cases with EC at 20 W without SES (20NS). Mean particle number concentration in the breathing zone during tonsillectomy was 1661 particles/cm3 for 12SES, 5515 particles/cm3 for 20SES, 8208 particles/cm3 for 12NS, and 78,506 particles/cm3 for 20NS. There was a statistically significant difference in the particle number concentrations among the 4 groups. The correlation between the particle number concentration and EC time was either moderate (for 12SES) or negative (for remaining groups). CONCLUSION: Airborne particle concentrations during tonsillectomy are over 9.5 times higher when EC is set at 20 W vs 12 W with NS, which is mitigated to 3.3 times with SES. Applying lower EC settings with SES during pediatric tonsillectomy significantly reduces surgical plume exposure for patients, surgeons, and operating room personnel, which is a well-known occupational health hazard.


Asunto(s)
Polvo/análisis , Electrocoagulación/métodos , Exposición Profesional , Quirófanos/normas , Tonsilectomía/métodos , Niño , Estudios Transversales , Humanos
14.
Ann Work Expo Health ; 64(5): 547-557, 2020 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-32155240

RESUMEN

Selecting a proper respirator requires determining the ratio of an employee's maximum use concentration (MUC) divided by the occupational exposure limit of a chemical. Current industrial hygiene practice often is to obtain a percentile estimate (e.g. 95th) of the measured exposure distribution to apply as the MUC. However, practitioners who are not yet familiar with statistical or mathematical approaches may choose the highest exposure data point as the MUC, a method that is still considered appropriate by the Occupational Safety and Health Administration. Nonetheless, choosing a respirator using the highest exposure data point when only limited data are available may result in not always providing the most adequate respirator. Because some practitioners are not familiar with exposure assessment tools, our primary goal in this study was to demonstrate the best process when selecting respiratory protection by using a combination of exposure data and assessment tools. Three user-friendly tools, IHDataAnalyst, Advanced REACH Tool, and IHSTAT, were selected to demonstrate how to use different types of tool outputs when choosing a respirator. A decision logic was developed to help users navigate the combining of different data inputs. Personal full-shift exposure data collected in four different workplaces were used to describe four different outcomes generated when the maximum exposure data point and the tool's output are compared with the exposure limit of the chemical. Outcomes varied, from determinations of 'high confidence' (or final decision) to 'low confidence' (or indicating more data are needed) in the selection of a respirator recommendation. In conclusion, systematically adopting the combination of exposure data and assessment tools could increase practitioners' confidence in decision-making when choosing respirators from a limited exposure data set. These suggested guidelines will lead practitioners toward good industrial hygiene practices.


Asunto(s)
Exposición Profesional , Salud Laboral , Dispositivos de Protección Respiratoria , Humanos , Exposición Profesional/análisis , Lugar de Trabajo
15.
J Expo Sci Environ Epidemiol ; 30(3): 554-566, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32015431

RESUMEN

In Europe, several occupational exposure models have been developed and are recommended for regulatory exposure assessment. Only some information on the substance of interest (e.g., vapor pressure) and the workplace conditions (e.g., ventilation rate) is required in these models to predict an exposure value that will be later used to characterize the risk. However, it has been shown that models may differ in their predictions and that usually, one of the models best fits a given set of exposure conditions. Unfortunately, there are no clear rules on how to select the best model. In this study, we developed a new modeling approach that together uses the three most popular models, Advanced REACH Tool, Stoffenmanger, and ECETOC TRAv3, to obtain a unique exposure prediction. This approach is an extension of the TREXMO tool, and is called TREXMO+. TREXMO+ applies a machine-learning technique on a set of exposure data with the measured values to split them into smaller subsets, corresponding to exposure conditions sharing similar characteristics. For each subset, TREXMO+ then establishes a regression model with the three REACH tools used as the exposure predictors. The performance of the new model was tested and a comparison was made between the results obtained by TREXMO+ and those obtained by conventional tools. TREXMO+ model was found to be less biased and more accurate than the REACH models. Its prediction differs generally from measurements by a factor of 2-3 from measurements, whereas conventional models were found to differ by a factor 2-14. However, as the available test dataset is limited, its results will need to be confirmed by larger-scale tests.


Asunto(s)
Exposición Profesional/estadística & datos numéricos , Europa (Continente) , Humanos , Aprendizaje , Medición de Riesgo/métodos
16.
PLoS One ; 15(1): e0227667, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31978088

RESUMEN

The apolipoprotein E gene (APOE) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), yet the expression of APOE is not clearly understood. For example, it is unclear whether AD patients have elevated or decreased APOE expression or why the correlation levels of APOE RNA and the ApoE protein differ across studies. Likewise, APOE has a single CpG island (CGI) that overlaps with its 3'-exon, and this CGI's effect is unknown. We previously reported that the APOE CGI is highly methylated in human postmortem brain (PMB) and that this methylation is altered in AD frontal lobe. In this study, we comprehensively characterized APOE RNA transcripts and correlated levels of RNA expression with DNA methylation levels across the APOE CGI. We discovered the presence of APOE circular RNA (circRNA) and found that circRNA and full-length mRNA each constitute approximately one third of the total APOE RNA, with truncated mRNAs likely constituting some of the missing fraction. All APOE RNA species demonstrated significantly higher expression in AD frontal lobe than in control frontal lobe. Furthermore, we observed a negative correlation between the levels of total APOE RNA and DNA methylation at the APOE CGI in the frontal lobe. When stratified by disease status, this correlation was strengthened in controls but not in AD. Our findings suggest a possible modified mechanism of gene action for APOE in AD that involves not only the protein isoforms but also an epigenetically regulated transcriptional program driven by DNA methylation in the APOE CGI.


Asunto(s)
Enfermedad de Alzheimer/genética , Apolipoproteínas E/genética , Encéfalo/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Apolipoproteínas E/metabolismo , Autopsia , Estudios de Casos y Controles , Cerebelo/metabolismo , Islas de CpG , Metilación de ADN , Femenino , Lóbulo Frontal/metabolismo , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Masculino , Polimorfismo de Nucleótido Simple , ARN Circular/genética , ARN Circular/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo
17.
Environ Sci Nano ; 7: 1539-1553, 2020 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-37205161

RESUMEN

Manufacturing, processing, use, and disposal of nanoclay-enabled composites potentially lead to the release of nanoclay particles from the polymer matrix in which they are embedded; however, exposures to airborne particles are poorly understood. The present study was conducted to characterize airborne particles released during sanding of nanoclay-enabled thermoplastic composites. Two types of nanoclay, Cloisite® 25A and Cloisite® 93A, were dispersed in polypropylene at 0%, 1%, and 4% loading by weight. Zirconium aluminum oxide (P100/P180 grits) and silicon carbide (P120/P320 grits) sandpapers were used to abrade composites in controlled experiments followed by real-time and offline particle analyses. Overall, sanding the virgin polypropylene with zirconium aluminum oxide sandpaper released more particles compared to silicon carbide sandpaper, with the later exhibiting similar or lower concentrations than that of polypropylene. Thus, a further investigation was performed for the samples collected using the zirconium aluminum oxide sandpaper. The 1% 25A, 1% 93A, and 4% 93A composites generated substantially higher particle number concentrations (1.3-2.6 times) and respirable mass concentrations (1.2-2.3 times) relative to the virgin polypropylene, while the 4% 25A composite produced comparable results, regardless of sandpaper type. It was observed that the majority of the inhalable particles were originated from composite materials with a significant number of protrusions of nanoclay (18-59%). These findings indicate that the percent loading and dispersion of nanoclay in the polypropylene modified the mechanical properties and thus, along with sandpaper type, affected the number of particles released during sanding, implicating the cause of potential adverse health effects.

18.
Ann Work Expo Health ; 64(1): 96-105, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31786604

RESUMEN

This study experimentally evaluates the performance of different sorbent tubes for sampling acetone vapor in workplace air. A dynamic atmosphere system produced an acetone alone and a mixture with other analytes containing ~73, 483, and 1898 µg acetone mass loading at 25, 50, and 75% relative humidity (RH) at 25°C. Sorbent samples were analyzed in accordance with OSHA Method 69 (Carbosieve S-III) and NMAM 1501, modified to use Anasorb 747 sorbent. Both methods were modified to include the additional analytes. Additional extraction procedures with and without 1% dimethylformamide and anhydrous magnesium sulfate were included in the modified NMAM 1501 using Anasorb 747. Silica gel sorbent tubes analyzed according to NMAM 2027 were included. There were significant reductions in the recovery of acetone from both Anasorb 747 and Carbosieve S-III collected from air at 75% RH, relative to collection at 25 or 50% RH at very low loading compared with that of samples collected at mid to high loading. Silica gel provided a consistent recovery of acetone at all RHs and in the presence of other chemical interferences at 75% RH. The likely cause of mass dependence may arise from the humidity effect on acetone adsorption onto both beaded active carbon and carbon molecular sieve either in sampling or in analysis. The present study confirms not only previous observations but also adds to the literature showing carbonaceous sorbents are not well suited for sampling ketones at high humidity and low concentration.


Asunto(s)
Acetona/análisis , Contaminantes Ocupacionales del Aire/análisis , Humedad , Exposición Profesional/análisis , Lugar de Trabajo , Adsorción
19.
Ann Work Expo Health ; 63(7): 814-820, 2019 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-31120098

RESUMEN

Within the framework of Registration, Evaluation, Authorization, and restriction of CHemicals (REACH), occupational exposure models are often used to predict the levels of exposure at a workplace. Poor inter-assessor agreement with their use poses a concern that may lead to different and dangerous risk conclusions. TREXMO (v1, 2016), a web tool providing parameter translations between six exposure models under REACH, is expected to improve the inter-assessor agreement. In this study, 18 assessors performed exposure assessment for six exposure situations within and outside the framework of this translation tool. In more than half of the evaluated cases, the results showed better agreement between assessors selecting the exposure parameters within the framework of TREXMO than when manually coding. The most affected were the parameters related to activity (such as "handling types" of Stoffenmanager) and exposure control (such as local controls). Furthermore, the agreement between the estimates calculated by different assessors was also improved when performing the translations between the models. For Stoffenmanager, for example, the relative standard deviation of 70-121%, obtained for vapors without applying the translation system, was 29-94% with the translations from ART. These findings showed a potential of TREXMO to impact the inter-assessor agreement. Because the study was limited to 18 assessors and only six exposure situations were assessed, further investigations are suggested.


Asunto(s)
Monitoreo del Ambiente/normas , Modelos Estadísticos , Exposición Profesional/estadística & datos numéricos , Medición de Riesgo/métodos , Algoritmos , Monitoreo del Ambiente/métodos , Humanos , Internet , Exposición Profesional/análisis
20.
J Occup Environ Hyg ; 16(3): 250-257, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30640589

RESUMEN

This study evaluates the performance of the disposable inhalable aerosol sampler (DIAS), a new sampler developed to be more cost-effective than the traditional inhalable particle samplers and comparable to the inhalable particle sampling convention. Forty-eight pairs of the DIAS prototype and the IOM sampler were utilized to collect copper exposure measurements (23 personal and 25 area) at an electrorefinery facility. The geometric mean (GM) value of ratios of exposure data (DIAS/IOM) was 1.1, while the GM of ratios (DIAS/IOM) was 1.6 for the area exposure data, revealing 84% of the ratios were greater than one. For both personal and area exposure data, the concordance correlation coefficient tests revealed significant disagreements between the two types of samplers and suggested precision as the source of the disagreement. The estimated mean concentration was higher for the DIAS compared that for the IOM for the area exposure data (p < 0.05), while the results were comparable for the personal exposure data (p = 0.49). Overall, the DIAS generated higher exposure results compared to the IOM sampler for the area exposures. For the personal exposures, the findings were inconclusive due to inconsistent results of factors aforementioned. This study is limited to one metal component (copper) of the dust at a worksite. To date, this is the first field evaluation using personal exposure data to test the performance of the DIAS and the second evaluation using area exposure data. Thus, it will be necessary to conduct additional field evaluations with various elements to further evaluate the performance of the DIAS. In addition, particle migration to the internal walls of the cap was observed during the transportation of collected samples to a laboratory for both sampler types (6.4% for the DIAS and 7.4% for the IOM). Occupational health and safety professionals should be aware of potential errors caused from transferring samples from a field to a laboratory and should be careful not to exclude particles collected on the caps.


Asunto(s)
Aerosoles/análisis , Contaminantes Ocupacionales del Aire/análisis , Cobre , Polvo/análisis , Monitoreo del Ambiente/instrumentación , Exposición por Inhalación/análisis , Exposición Profesional/análisis , Equipos Desechables , Monitoreo del Ambiente/métodos , Diseño de Equipo , Humanos
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