Evelyn O. Talbott

Introduction: ALS is a neurodegenerative disorder with an unknown etiology for 90%–95% of cases. Several environmental and occupational exposures have been investigated although a prospective study examining the association of “ever living/working on a farm” (farming exposure) and insecticide exposure with risk of ALS mortality in women is lacking. Methods: Within the Women’s Health Initiative (WHI), a nested case-control study was conducted among 93,676 women (n = 151 ALS death cases, n = 1,496 matched controls) from the WHI Observational Study. This included a questionnaire about farming and insecticide exposure history 1 year after baseline. Conditional logistic regression models adjusted for education, smoking, and physical activity estimated risk of ALS death. Results: One-third of cases and 21% of controls reported farming exposure. Cases had higher odds of farming exposure than controls (adjusted odds ratio [aOR] = 1.59, 95% CI: 1.09–2.31) and was highest at durations of 15–19 (aOR = 1.81, 95% CI: 1.02–3.21) and ≥20 years (aOR = 2.32, 95% CI: 1.10–4.87) compared to no exposure. Tests for interaction revealed that women with farming and smoking exposure had higher odds of ALS death (aOR = 2.10, 95% CI: 1.26–3.51, p = 0.0045). Little evidence was noted for increased insecticide exposure and ALS mortality risk, although power was limited. Conclusion: Among post-menopausal women with 25+ years follow-up, a significant association was noted between farming exposure and risk of ALS death. This increased risk was highest among those who ever smoked. Future studies should include biomarkers of exposure and large cohorts of men and women with occupational and residential histories.

The rapid growth of unconventional natural gas development (UNGD), also known as hydraulic fracturing, has raised concerns of potential exposures to hazardous chemicals. Few studies have examined the risk of childhood cancer from exposure to UNGD. A case–control study included 498 children diagnosed with leukemia, lymphoma, central nervous system neoplasms, and malignant bone tumors during the period 2010–2019 identified through the Pennsylvania Cancer Registry. Cases were matched to controls using Pennsylvania birth records. For each subject, a new overall UNGD exposure metric was calculated which incorporates both spatial (proximity) and temporal (duration) aspects of well activity. Conditional logistic regression models were used to estimate the risk of combined and individual cancers by overall UNGD exposure, and well proximity. Children with a higher overall UNGD exposure (3rd/4th quartiles) had an increased risk for the four malignancies combined [OR] 1.69 (95% CI 1.01, 2.82) and 1.79 (95% CI 1.00, 3.19) compared to non-exposed children. Overall, individuals living within 0.5 miles of a UNGD site were 3.94 times (95% CI 1.66, 9.30) more likely to develop a malignancy compared to non-exposed children and the risk of lymphoma within 0.5 miles and 0.5–1 miles was also elevated [ORs of 5.05 (95% CI 1.09, 23.39) and 7.71 (95% CI 1.01, 59.00), respectively] compared to non-exposed. Our study found that overall UNGD cumulative activity as well as a proximity to UNGD wells were associated with an increased risk of childhood lymphoma and overall childhood cancers combined.

Objective: Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls. Methods: Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels. Results: 243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52). Conclusion: This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.

Cognitive impairment in older adults is a major public concern for Kazakhstan’s aging population. We aimed to (1) administer a neuropsychological test battery (NTB) in domains relevant to aging-associated cognitive impairment in a sample of adults aged 60+ without dementia in Almaty, Kazakhstan; (2) investigate the associations between demographic factors and test performance; and (3) provide information on the distribution of NTB scores as preliminary local normative data relevant for this population. A cross-sectional evaluation of 276 participants aged 60+ in Almaty, Kazakhstan, was conducted using cognitive instruments including tests of memory, attention, language, executive functions, visuospatial abilities, and processing speed. Multiple linear regression analyses were used to examine the association of demographic factors with neuropsychological test performance. The results from the regression analysis showed that those who are younger, have more years of education, are women, and are of Russian ethnicity had significantly better performance. The current study illustrated (1) the feasibility of administering the NTB to older adults in the general population in Kazakhstan; (2) the preliminary local normative neuropsychological measures; and (3) their independent associations with age, education, gender, and ethnicity. The findings are a platform for future research on dementia and cognitive impairment in older adults in Kazakhstan.

Asthma affects millions of people globally and is especially concerning in populations living with poor air quality. This study examines the association of ambient outdoor air pollutants on asthma-related emergency department (ED) visits in children and adults throughout the Pittsburgh region. A time-stratified case-crossover design is used to analyze the lagged effects of fine particulate matter (PM_2.5) and gaseous pollutants, e.g., ozone (O₃), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and carbon monoxide (CO) on asthma-related ED visits (n = 6682). Single-, double-, and multi-pollutant models are adjusted for temperature and analyzed using conditional logistic regression. In children, all models show an association between O₃ and increased ED visits at lag day 1 (OR: 1.12, 95% CI, 1.03–1.22, p < 0.05) for the double-pollutant model (OR: 1.10, 95% CI: 1.01-1.20, p < 0.01). In adults, the single-pollutant model shows associations between CO and increased ED visits at lag day 5 (OR: 1.13, 95% CI, 1.00–1.28, p < 0.05) and average lag days 0–5 (OR: 1.22, 95% CI: 1.00–1.49, p < 0.05), and for NO₂ at lag day 5 (OR: 1.04, 95% CI: 1.00–1.07, p < 0.05). These results show an association between air pollution and asthma morbidity in the Pittsburgh region and underscore the need for mitigation efforts to improve public health outcomes.

Objective: This article aims to examine the association between long-term ambient air pollution and progression of subclinical atherosclerosis with 2-year follow-up among midlife women from the Study of Women's Health Across the Nation (SWAN). Materials and Methods: Carotid duplex ultrasonography was performed in participants from a SWAN ancillary study carried out at the Pittsburgh and Chicago sites. Mean and maximum carotid intima-media thickness (CIMT) and plaque burden were assessed throughout the common, bulb, and internal carotid artery. The yearly mean exposure to PM_2.5 (particulate matter) and ozone was generated based on monitors within 20 km of the participants' home. The effect of air pollutants during follow-up on progression of CIMT was estimated using linear mixed-effects models, and the effect on progression of plaque presence and plaque index, a measure of extent of plaque, was evaluated using logistic regression. Results: This study included 417 (257 White and 160 Black) women with a mean age of 51 years at baseline. A 1 μg/m³ higher yearly mean exposure to PM_2.5 during follow-up was associated with a 4.28 (95% confidence interval [CI]: 0.02–8.54) μm/year increase in maximum CIMT, after adjusting for socioeconomic and traditional cardiovascular disease (CVD) risk factors. Exposure to PM_2.5 contributed to a 30% (95% CI: 3%–65%) higher odds of plaque index progression adjusting for socioeconomic factors only. Conclusions: PM_2.5 independently contributed to progression of subclinical atherosclerosis, among women transitioning through menopause, a time of increasing CVD risk. Yet no significant associations between ozone and subclinical atherosclerosis were observed.

Infants and children are particularly vulnerable to in utero and early-life exposures. Thus, a mother’s exposures before and during pregnancy could have important consequences for her child’s health, including cancer development. We examined whether birth certificate–derived maternal anthropometric characteristics were associated with increased risk of subsequent childhood cancer development, accounting for established maternal and infant risk factors. Pennsylvania birth and cancer registry files were linked by the state Department of Health, yielding a virtual cohort of births and childhood cancers from 2003 through 2016. The analysis included 1,827,875 infants (13,785,309 person-years at risk), with 2,352 children diagnosed with any cancer and 747 with leukemia before age 14 years. Children born to mothers with a body mass index (weight (kg)/height (m)²) of ≥40 had a 57% (95% confidence interval: 12, 120) higher leukemia risk. Newborn size of ≥30% higher than expected was associated with 2.2-fold and 1.8-fold hazard ratios for total childhood cancer and leukemia, respectively, relative to those with expected size. Being P for curvilinearity < 0.0001). Newborn size did not mediate the association between maternal obesity and childhood cancer. The results suggest a significant role of early-life exposure to maternal obesity- and fetal growth–related factors in childhood cancer development.

Objective To assess whether prediagnostic levels of plasma branched-chain amino acids (BCAAs) are associated with amyotrophic lateral sclerosis (ALS) risk. Methods We included participants from 5 large cohort studies—The Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition, the Multiethnic Cohort Study, and the Women's Health Initiative—and identified 275 individuals who developed ALS during follow-up. Two controls were randomly selected for each case, matched on cohort, age, sex, fasting status, and time of blood draw. We measured metabolites using liquid chromatography–mass spectrometry and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for the association of individual BCAAs with ALS risk. Results None of the 3 BCAAs was associated with a higher ALS risk. The risk estimates were similar for leucine (RR top vs bottom quartile: 0.87, 95% CI 0.57–1.33), isoleucine (RR top vs bottom quartile: 0.81, 95% CI 0.52–1.24), and valine (RR top vs bottom quartile: 0.80, 95% CI 0.52–1.23) in a multivariable analysis adjusted for body mass index, smoking, level of education, and physical activity. The estimates did not vary significantly by sex, fasting status, or time interval between blood draw and disease onset. Conclusion The results from this study do not support the hypothesis that BCAAs are risk factors for ALS.