Radon Exposure, Clonal Hematopoiesis, and Stroke Susceptibility in the Women's Health Initiative.

BACKGROUND AND OBJECTIVES: Studies suggest that clonal hematopoiesis of indeterminate potential (CHIP) may increase risk of hematologic malignancy and cardiovascular disease, including stroke. However, few studies have investigated plausible environmental risk factors for CHIP such as radon, despite the climate-related increases in and documented infrequency of testing for this common indoor air pollutant.The purpose of this study was to estimate the risk of CHIP related to radon, an established environmental mutagen. METHODS: We linked geocoded addresses of 10,799 Women's Health Initiative Trans-Omics for Precision Medicine (WHI TOPMed) participants to US Environmental Protection Agency-predicted, county-level, indoor average screening radon concentrations, categorized as follows: Zone 1 (>4 pCi/L), Zone 2 (2-4 pCi/L), and Zone 3 (<2 pCi/L). We defined CHIP as the presence of one or more leukemogenic driver mutations with variant allele frequency >0.02. We identified prevalent and incident ischemic and hemorrhagic strokes; subtyped ischemic stroke using Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria; and then estimated radon-related risk of CHIP as an odds ratio (OR) and 95% CI using multivariable-adjusted, design-weighted logistic regression stratified by age, race/ethnicity, smoking status, and stroke type/subtype. RESULTS: The percentages of participants with CHIP in Zones 1, 2, and 3 were 9.0%, 8.4%, and 7.7%, respectively (ptrend = 0.06). Among participants with ischemic stroke, Zones 2 and 1 were associated with higher estimated risks of CHIP relative to Zone 3: 1.39 (1.15-1.68) and 1.46 (1.15-1.87), but not among participants with hemorrhagic stroke: 0.98 (0.68-1.40) and 1.03 (0.70-1.52), or without stroke: 1.04 (0.74-1.46) and 0.95 (0.63-1.42), respectively (pinteraction = 0.03). Corresponding estimates were particularly high among TOAST-subtyped cardioembolism: 1.78 (1.30-2.47) and 1.88 (1.31-2.72), or other ischemic etiologies: 1.37 (1.06-1.78) and 1.50 (1.11-2.04), but not small vessel occlusion: 1.05 (0.74-1.49) and 1.00 (0.68-1.47), respectively (pinteraction = 0.10). Observed patterns of association among strata were insensitive to attrition weighting, ancestry adjustment, prevalent stroke exclusion, separate analysis of DNMT3A driver mutations, and substitution with 3 alternative estimates of radon exposure. DISCUSSION: The robust elevation of radon-related risk of CHIP among postmenopausal women who develop incident cardioembolic stroke is consistent with a potential role of somatic genomic mutation in this societally burdensome form of cerebrovascular disease, although the mechanism has yet to be confirmed.

Urine antimony and risk of cardiovascular disease - A prospective case-cohort study in Danish Non-Smokers.

BACKGROUND: Limited evidence suggests that antimony induces vascular inflammation and oxidative stress and may play a role in cardiovascular disease (CVD) risk. However, few studies have examined whether environmental antimony from sources other than tobacco smoking is related with CVD risk. The general population may be exposed through air, drinking water, and food that contains antimony from natural and anthropogenic sources, such as mining, coal combustion, and manufacturing. OBJECTIVES: To examine the association of urine antimony with incident acute myocardial infarction (AMI), heart failure, and stroke among people who never smoked tobacco. METHODS: Between 1993 and 1997, the Danish Diet, Cancer and Health (DCH) cohort enrolled participants (ages 50-64 years), including n = 19,394 participants who reported never smoking at baseline. Among these never smokers, we identified incident cases of AMI (N = 809), heart failure (N = 958), and stroke (N = 534) using the Danish National Patient Registry. We also randomly selected a subcohort of 600 men and 600 women. We quantified urine antimony concentrations in samples provided at enrollment. We used modified Cox proportional hazards models to estimate adjusted hazard ratios (HR) for each incident CVD outcome in relation to urine antimony, statistically adjusted for creatinine. We used a separate prospective cohort, the San Luis Valley Diabetes Study (SLVDS), to replicate these results. RESULTS: In the DCH cohort, urine antimony concentrations were positively associated with rates of AMI and heart failure (HR = 1.52; 95%CI = 1.12, 2.08 and HR = 1.58; 95% CI = 1.15, 2.18, respectively, comparing participants in the highest (>0.09 µg/L) with the lowest quartile (<0.02 µg/L) of antimony). In the SLVDS cohort, urinary antimony was positively associated with AMI, but not heart failure. DISCUSSION: Among this sample of Danish people who never smoked, we found that low levels of urine antimony are associated with incident CVD. These results were partially confirmed in a smaller US cohort.

Depression and Anxiety on Twitter During the COVID-19 Stay-At-Home Period in 7 Major U.S. Cities.

Introduction: Although surveys are a well-established instrument to capture the population prevalence of mental health at a moment in time, public Twitter is a continuously available data source that can provide a broader window into population mental health. We characterized the relationship between COVID-19 case counts, stay-at-home orders because of COVID-19, and anxiety and depression in 7 major U.S. cities utilizing Twitter data. Methods: We collected 18 million Tweets from January to September 2019 (baseline) and 2020 from 7 U.S. cities with large populations and varied COVID-19 response protocols: Atlanta, Chicago, Houston, Los Angeles, Miami, New York, and Phoenix. We applied machine learning‒based language prediction models for depression and anxiety validated in previous work with Twitter data. As an alternative public big data source, we explored Google Trends data using search query frequencies. A qualitative evaluation of trends is presented. Results: Twitter depression and anxiety scores were consistently elevated above their 2019 baselines across all the 7 locations. Twitter depression scores increased during the early phase of the pandemic, with a peak in early summer and a subsequent decline in late summer. The pattern of depression trends was aligned with national COVID-19 case trends rather than with trends in individual states. Anxiety was consistently and steadily elevated throughout the pandemic. Google search trends data showed noisy and inconsistent results. Conclusions: Our study shows the feasibility of using Twitter to capture trends of depression and anxiety during the COVID-19 public health crisis and suggests that social media data can supplement survey data to monitor long-term mental health trends.

Antimony and sleep health outcomes: NHANES 2009-2016.

OBJECTIVES: Following an earlier National Health and Nutrition Examination Survey (NHANES) 2005-2008 analysis, we investigated the association between urine antimony and sleep health using more recent data, new measures of sleep health, and multiple measures of urine density adjustment in NHANES 2009-2016. DESIGN: A cross-sectional study. SETTING: United States, national population-based survey. MEASUREMENTS: Multinomial logistic regression (sleep duration) and a generalized linear model with log-binomial regression (OSA, daytime sleepiness, sleep problems) were used to analyze the association of urinary antimony with sleep health outcomes. Urine creatinine and osmolality were considered, combined with statistical adjustment and standardization to account for urine density. PARTICIPANTS: A total of 8133 adult participants over 20 years of age were used using NHANES 2009-2016. RESULTS: We did not observe associations between urine antimony and short sleep duration or sleep problems. We observed mixed results for long sleep duration; there was a negative association in NHANES 2015-2016 and no association in NHANES 2009-2014. For self-reported symptoms of OSA, which were only available in 2015-2016, we observed a positive association for upper quartile urine antimony compared with the first quartile (RR = 1.24; 95% CI: 1.03, 1.50) and a test for trend, P= .02. CONCLUSION: Urinary antimony was not consistently associated with short sleep duration, long sleep duration, or sleep problems, despite the findings from a relatively recent scientific article using earlier waves of NHANES. We observed a positive association between antimony and symptoms of OSA; this cross-sectional analysis requires confirmation.

The Impact of the COVID-19 Pandemic on Older Women in the Women's Health Initiative.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is a health crisis of which older adults are a high-risk group for severe illness and mortality. The objectives of this article are to describe the methods and responses to a COVID-19 survey administered by the Women's Health Initiative (WHI) to assess the impact of the pandemic on older women. METHODS: WHI is an ongoing prospective cohort study that recruited 161 808 postmenopausal women from 1993 to 1998. From June 2020 to October 2020, participants in active follow-up were surveyed by mail, phone, or online to assess health and well-being, living situations, lifestyle, health care, and self-reported COVID-19 testing, treatment, and preventive behaviors. RESULTS: Of 64 061 eligible participants, 49 695 (average age 83.6 years ± 5.6) completed the COVID-19 survey (response rate 77.6%). Many participants reported very good or good well-being (75.6%). Respondents reported being very concerned about the pandemic (51.1%; more common in urban compared to rural areas), with 6.9% reporting disruptions in living arrangements and 9.7% reporting changes in medication access. Participants (54.4%) reported physical activity levels were much less or somewhat less compared to levels before the pandemic, and this was more pronounced in urban areas versus rural areas (55.3% vs 44.4%). Participants engaged in preventive behaviors including wearing a face mask (93.2%). A total of 18.9% reported testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), among whom 3.5% (n = 311) reported testing positive. CONCLUSIONS: In this nationwide survey of older U.S. women, the COVID-19 pandemic was associated with impacts on health and well-being, living situations, lifestyle, health care access, and SARS-CoV-2 testing and preventive behaviors.

Associations Between Changes in Loneliness and Social Connections, and Mental Health During the COVID-19 Pandemic: The Women's Health Initiative.

BACKGROUND: Older women have faced significant disruptions in social connections during the coronavirus disease 2019 pandemic. Whether loneliness increased or whether a change in loneliness from pre- to intrapandemic period was associated with mental health during the pandemic is unknown. METHODS: Older women (n = 27 479; mean age 83.2 [SD: 5.4] years) completed surveys in mid-2020, including questions about loneliness, living arrangements, changes in social connections, and mental health. Loneliness was also previously assessed in 2014-2016. We examined whether loneliness changed from the pre- to intrapandemic period and explored factors associated with this change. In multivariable models, we investigated the association of changes in loneliness and social connections with mental health. RESULTS: Loneliness increased from pre- to intrapandemic levels. Factors associated with worsening loneliness included older age, experiencing stressful life events, bereavement, histories of vascular disease and depression, and social connection disruptions. Factors associated with a decrease in loneliness included identifying as Black, engaging in more frequent physical activity, being optimistic, and having a higher purpose in life. A 3-point increase in loneliness scores was associated with higher perceived stress, higher depressive, and higher anxiety symptoms. Social connection disruptions showed modest or no associations with mental health. CONCLUSIONS: Loneliness increased during the pandemic in older women and was associated with higher stress, depressive, and anxiety symptoms. Our findings point to opportunities for interventions targeting lifestyle behaviors, well-being, disrupted social connections, and paying closer attention to those with specific medical and mental health histories that may reduce loneliness and improve mental health.

A wind speed threshold for increased outdoor transmission of coronavirus: an ecological study.

BACKGROUND: To examine whether outdoor transmission may contribute to the COVID-19 epidemic, we hypothesized that slower outdoor wind speed is associated with increased risk of transmission when individuals socialize outside. METHODS: Daily COVID-19 incidence reported in Suffolk County, NY, between March 16th and December 31st, 2020, was the outcome. Average wind speed and maximal daily temperature were collated by the National Oceanic and Atmospheric Administration. Negative binomial regression was used to model incidence rates while adjusting for susceptible population size. RESULTS: Cases were very high in the initial wave but diminished once lockdown procedures were enacted. Most days between May 1st, 2020, and October 24th, 2020, had temperatures 16-28 °C and wind speed diminished slowly over the year and began to increase again in December 2020. Unadjusted and multivariable-adjusted analyses revealed that days with temperatures ranging between 16 and 28 °C where wind speed was < 8.85 km per hour (KPH) had increased COVID-19 incidence (aIRR = 1.45, 95% C.I. = [1.28-1.64], P < 0.001) as compared to days with average wind speed ≥ 8.85 KPH. CONCLUSION: Throughout the U.S. epidemic, the role of outdoor shared spaces such as parks and beaches has been a topic of considerable interest. This study suggests that outdoor transmission of COVID-19 may occur by noting that the risk of transmission of COVID-19 in the summer was higher on days with low wind speed. Outdoor use of increased physical distance between individuals, improved air circulation, and use of masks may be helpful in some outdoor environments where airflow is limited.

Acute versus Chronic Exposures to Inhaled Particulate Matter and Neurocognitive Dysfunction: Pathways to Alzheimer's Disease or a Related Dementia.

An estimated 92% of the world's population live in regions where people are regularly exposed to high levels of anthropogenic air pollution. Historically, research on the effects of air pollution have focused extensively on cardiovascular and pulmonary health. However, emerging evidence from animal and human studies has suggested that chronic exposures to air pollution detrimentally change the functioning of the central nervous system with the result being proteinopathy, neurocognitive impairment, and neurodegenerative disease. Case analyses of aging World Trade Center responders suggests that a single severe exposure may also induce a neuropathologic response. The goal of this report was to explore the neuroscientific support for the hypothesis that inhaled particulate matter might cause an Alzheimer's-like neurodegenerative disease, in order to consider proposed mechanisms and latency periods linking inhaled particulate matter and neurodegeneration, and to propose new directions in this line of research.

Incidence of brain and spinal cord cancer and county-level radon levels in New Jersey, Wisconsin, Minnesota, Pennsylvania, and Iowa, USA.

Ionizing radiation at diagnostic and therapeutic doses is a known contributor to the development of brain and spinal cord (CNS) cancer. However, little is known about risk from exposure to radon, a natural radiation source which the general population is exposed to residentially and environmentally. This study investigated correlations between mean county radon levels and CNS cancer incidence in five highly populated and radon-enriched US states (Minnesota, mean radon level 4.6 pCi/L; Wisconsin, 5.7 pCi/L; Pennsylvania, 8.6 pCi/L; Iowa, 6.1 pCi/L; and New Jersey, 4.4 pCi/L). Mean radon levels per county were accessed through AirChek, which provides publicly available radon data measured in residences and workplaces. CNS cancer incidence data were accessed through the states' health department websites and span differing amounts of time due to the publicly accessible nature of the data, though all time spans were over 10 years. Negative binomial regressions were run to assess correlations between mean radon and CNS cancer incidence per county. Quantile maps were constructed and Moran's I was calculated to assess spatial autocorrelation in residuals; no spatial autocorrelation was evident. Iowa was the only state with a significant positive association between radon and CNS incidence; no associations were detected in other states, and a negative association was observed in the 5 states combined. This study does not provide evidence that radon is a risk factor for CNS cancer; however, the possibility of an association cannot be ruled out due to limitations of the study, principally its ecologic nature and lack of individual-level exposure data.

Urinary concentrations of phthalate biomarkers and weight change among postmenopausal women: a prospective cohort study.

BACKGROUND: Some phthalates are endocrine disrupting chemicals used as plasticizers in consumer products, and have been associated with obesity in cross-sectional studies, yet prospective evaluations of weight change are lacking. Our objective was to evaluate associations between phthalate biomarker concentrations and weight and weight change among postmenopausal women. METHODS: We performed cross-sectional (N = 997) and longitudinal analyses (N = 660) among postmenopausal Women's Health Initiative participants. We measured 13 phthalate metabolites and creatinine in spot urine samples provided at baseline. Participants' weight and height measured at in-person clinic visits at baseline, year 3, and year 6 were used to calculate body mass index (BMI). We fit multivariable multinomial logistic regression models to explore cross-sectional associations between each phthalate biomarker and baseline BMI category. We evaluated longitudinal associations between each biomarker and weight change using mixed effects linear regression models. RESULTS: In cross-sectional analyses, urinary concentrations of some biomarkers were positively associated with obesity prevalence (e.g. sum of di (2-ethylhexyl) phthalate metabolites [ΣDEHP] 4th vs 1st quartile OR = 3.29, 95% CI 1.80-6.03 [p trend< 0.001] vs normal). In longitudinal analyses, positive trends with weight gain between baseline and year 3 were observed for mono-(2-ethyl-5-oxohexyl) phthalate, monoethyl phthalate (MEP), mono-hydroxybutyl phthalate, and mono-hydroxyisobutyl phthalate (e.g. + 2.32 kg [95% CI 0.93-3.72] for 4th vs 1st quartile of MEP; p trend < 0.001). No statistically significant associations were observed between biomarkers and weight gain over 6 years. CONCLUSIONS: Certain phthalates may contribute to short-term weight gain among postmenopausal women.

Geographic patterns of prescription opioids and opioid overdose deaths in New York State, 2013-2015.

OBJECTIVES: To examine the relationship between prescription opioid rates and prescription opioid overdose deaths using spatial cluster and regression analyses. METHODS: Publicly available county-level data were obtained from the New York State Health Department and the Centers for Disease Control and Prevention, 2013-2015. Kulldorff's spatial scan statistic was used to investigate spatial clustering of New York State opioid prescription overdose death rates, as well as opioid prescription rates. A Poisson regression was used to analyze opioid prescriptions as a predictor of mortality accounting for spatial autocorrelation in the residuals. RESULTS: We report 1440 overdose mortalities and 26.8 million opioid prescriptions throughout New York State in 2013-2015. Multiple significant clusters were found for both opioid prescription mortalities as well as prescriptions, although the locations of the elevated rates did not strongly overlap. Poisson regression showed a significant, small, negative relationship between prescriptions and opioid mortalities, wherein for every 10,000 prescriptions increased, the number of opioid mortalities decreased approximately 0.12%; therefore, essentially a null relationship. CONCLUSIONS: Simply reducing the number of prescriptions may not be effective in reducing prescription related mortality; although opioid prescription dosing information should be made available to engender a better evaluation of the epidemic. Geographical differences in opioid mortalities exist above and beyond what can be explained by prescription rate data; identifying these locations may help inform and guide public health interventions. Despite the recent reduction in opioid prescription rates, the overall population is still inundated with prescriptions.

Temporal stability of urinary cadmium in samples collected several years apart in a population of older persons.

OBJECTIVES: There is growing evidence that urine cadmium is a temporally stable biomarker indicative of long-term cadmium exposure; however questions remain with regard to generalizability to older persons, the impact of changes in smoking behavior, and the degree of temporal stability when repeat sample collection spans years instead of weeks or months. METHODS: Using archived samples from cohorts of older men (Osteoporotic Fractures in Men (MrOS-US)) and women (Study of Osteoporotic Fractures (SOF)) (mean age = 80 at study visit 2), we analyzed two morning urine samples each from 39 men and 18 women with a diverse self-reported smoking history. For MrOS, samples were collected approximately 6 years apart, and 4 years apart for SOF. Intra-class correlations were computed to assess temporal stability, and adjusted for age and body mass index. RESULTS: The median creatinine-adjusted urinary cadmium levels (0.39 µg/g for men, 0.89 µg/g for women) were similar to levels expected for these age/sex groups in the US according to the National Health and Nutrition Examination Survey. The overall intra-class correlation was high (ICC = 0.85; 95% CI: 0.76-0.91) and similar between cohorts (MrOS: ICC = 0.74; 95% CI: 0.58-0.86; SOF: ICC = 0.81; 95% CI: 0.59-0.93), but slightly lower among those who stopped smoking between visits of sample collection (ICC = 0.64; 95% CI: 0.31-0.87) or among former smokers who quit prior to the first sample collection (ICC = 0.68; 95% CI: 0.25-0.93). CONCLUSIONS: We report good-to-excellent reproducibility of urine cadmium using morning urine samples collected 4-6 years apart from older men and women, but slightly lower correlations among those with a history of smoking. Single measures of urine cadmium are a reliable biomarker in older men and women.

Fluoridation and county-level secondary bone cancer among cancer patients 18 years or older in New York State.

The decision whether to fluoridate drinking water continues to be controversial in some communities. Dental and skeletal fluorosis in response to chronic fluoride overexposure are cited as reasons to avoid community water fluoridation in spite of evidence of the oral and skeletal health benefits fluoridation confers. Community fluoridation of ~ 1 mg/L fluoride has not been found to be associated with primary bone cancer but is associated with improved bone strength. No studies have examined fluoride exposure and secondary bone cancer, a common metastasis with significant morbidity. We hypothesize that fluoridation could diminish the likelihood of secondary bone cancer due to its role in bone fortification. We examined the association between community water fluoridation category and prevalence of secondary bone cancer from 2008 to 2010 among cancer patients of 18 years of age or older in counties in New York State. Relative to counties with less than 25% of the water supply fluoridated, we report no association between secondary bone cancer among cancer patients in counties with 25-75% of the water supply fluoridated (ß = 0.02, p = 0.96) and among those in counties with > 75% fluoridated (ß = 0.02, p = 0.97). We found no evidence of an association between community water fluoridation category and secondary bone cancer from 2008 to 2010 at the county level in New York State.

Expression of Genes Involved in Stress, Toxicity, Inflammation, and Autoimmunity in Relation to Cadmium, Mercury, and Lead in Human Blood: A Pilot Study.

There is growing evidence of immunotoxicity related to exposure to toxic trace metals, and an examination of gene expression patterns in peripheral blood samples may provide insights into the potential development of these outcomes. This pilot study aimed to correlate the blood levels of three heavy metals (mercury, cadmium, and lead) with differences in gene expression in 24 participants from the Long Island Study of Seafood Consumption. We measured the peripheral blood mRNA expression of 98 genes that are implicated in stress, toxicity, inflammation, and autoimmunity. We fit multiple linear regression models with multiple testing correction to correlate exposure biomarkers with mRNA abundance. The mean blood Hg in this cohort was 16.1 µg/L, which was nearly three times the Environmental Protection Agency (EPA) reference dose (5.8 µg/L). The levels of the other metals were consistent with those in the general population: the mean Pb was 26.8 µg/L, and the mean Cd was 0.43 µg/L. The expression of three genes was associated with mercury, four were associated with cadmium, and five were associated with lead, although none were significant after multiple testing correction. Little evidence was found to associate metal exposure with mRNA abundance for the tested genes that were associated with stress, toxicity, inflammation, or autoimmunity. Future work should provide a more complete picture of physiological reactions to heavy metal exposure.

Predictors of Urinary Arsenic Levels among Postmenopausal Danish Women.

Arsenic is a risk factor for several noncommunicable diseases, even at low doses. Urinary arsenic (UAs) concentration is a good biomarker for internal dose, and demographic, dietary, and lifestyle factors are proposed predictors in nonoccupationally exposed populations. However, most predictor studies are limited in terms of size and number of predictors. We investigated demographic, dietary, and lifestyle determinants of UAs concentrations in 744 postmenopausal Danish women who had UAs measurements and questionnaire data on potential predictors. UAs concentrations were determined using mass spectrometry (ICP-MS), and determinants of the concentration were investigated using univariate and multivariate regression models. We used a forward selection procedure for model optimization. In all models, fish, alcohol, and poultry intake were associated with higher UAs concentration, and tap water, fruit, potato, and dairy intake with lower concentration. A forward regression model explained 35% (R²) of the variation in concentrations. Age, smoking, education, and area of residence did not predict concentration. The results were relatively robust across sensitivity analyses. The study suggested that UAs concentration in postmenopausal women was primarily determined by dietary factors, with fish consumption showing the strongest direct association. However, the majority of variation in UAs concentration in this study population is still unexplained.

County-Level Radon and Incidence of Female Thyroid Cancer in Iowa, New Jersey, and Wisconsin, USA.

BACKGROUND: Few studies have investigated the association between radon and thyroid cancer despite the sensitivity of the thyroid gland to radiation. Our goal is to investigate the association between county-level radon and incidence of female thyroid cancer in the US States of Iowa, New Jersey, and Wisconsin. METHODS: Thyroid cancer incidence data were provided by individual state cancer registries and span 1990-2013. Radon data come from a publicly available third-party database, AirChek, accessed in 2017. We tabulated the percent of radon above four picocuries per liter and the female thyroid cancer incidence rate in each county. Quantile maps were constructed, and an ordinary least-squares regression model was run using Geoda 1.10.0.8 (Chicago, IL, USA). RESULTS: No association was observed between county-level radon and incidence of female thyroid cancer in any of the States: New Jersey (ß = 0.06, p = 0.23); Iowa (ß = -0.07, p = 0.07); or Wisconsin (ß = -0.01, p = 0.78). A spatial regression model was considered, but the Moran's I of the residuals from each of the models was not significant, so no spatial term was required. DISCUSSION: In this county-level ecological study across three different States in the US, we did not find an association between elevated radon and thyroid cancer incidence in women. While this ecologic study reports null findings, due to the ecologic fallacy, individual-level studies of this association may still be warranted.

Mercury, omega-3 fatty acids, and seafood intake are not associated with heart rate variability or QT interval.

Mercury (Hg), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) concentrations differ across seafood types. Our aim was to investigate the association of Hg, EPA, and DHA, as well as avid consumption of diverse seafood types, with cardiovascular variables heart rate variability (HRV) and QT interval duration (QTc) in a contemporary population. We measured HRV and QTc by Holter monitor, EPA and DHA in plasma, total Hg in whole blood, and possible confounders in 94 avid seafood consumers from Long Island, NY. Participants had mean Hg of 8.4 mcg/L, mean EPA of 1.2%, and mean DHA of 3.7% of total fatty acids. Adjusted for possible confounders, EPA+DHA, Hg, and total seafood consumption were not associated with HRV or QTc. Associations with consumption of specific seafood types were suggested (eg, tuna steak with QTc and anchovies with HRV) but require verification.

Low levels of lead and glutathione markers of redox status in human blood.

Exposure to lead (Pb) is implicated in a plethora of health threats in both adults and children. Increased exposure levels are associated with oxidative stress in the blood of workers exposed at occupational levels. However, it is not known whether lower Pb exposure levels are related to a shift toward a more oxidized state. To assess the association between blood lead level (BLL) and glutathione (GSH) redox biomarkers in a population of healthy adults, BLL and four GSH markers (GSH, GSSG, GSH/GSSG ratio and redox potential E h ) were measured in the blood of a cross-sectional cohort of 282 avid seafood-eating healthy adults living on Long Island (NY). Additionally, blood levels of two other metals known to affect GSH redox status, selenium (Se) and mercury (Hg), and omega-3 index were tested for effect modification. Regression models were further adjusted for demographic and smoking status. Increasing exposure to Pb, measured in blood, was not associated with GSSG, but was associated with lower levels of GSH/GSSG ratio and more positive GSH redox potential E h , driven by its association with GSH. No effect modification was observed in analyses stratified by Hg, Se, omega-3 index, sex, age, or smoking. Blood Pb is associated with lower levels of GSH and the GSH/GSSG ratio in this cross-sectional study of healthy adults.

Blood cadmium and depressive symptoms: Confounded by cigarette smoking.

Our aim was to explore the association between blood cadmium (BCd) and depressive symptoms, adjusting for pack years and blood cotinine, and also stratifying by smoking status. Using data from the US National Health and Nutrition Examination Survey (NHANES) 2005-2012, we categorized depressive symptoms using the PHQ-9 (Patient Health Questionnaire-9) survey and modeled depressive symptoms in relation to BCd adjusted for blood cotinine, pack years of smoking, and other covariates. We also stratified by self-reported smoking status (current, former, never). There were 11,209 subjects from 2005 to 2012, age ≥ 18 with PHQ-9, smoking, and blood cadmium data available. 876 (7.8%) met criteria for depressive symptoms. Depressive symptoms were associated with BCd levels in a crude model and with adjustment for pack years and cotinine. The association disappeared when analyzed among current, former, or never smokers. Consistent with the literature, we found an association between BCd and depressive symptoms; however, that association disappears in analyses stratified by smoking status. This suggests residual confounding may be present. It is important to stratify by smoking status when investigating health outcomes associated with BCd.

Mercury exposure, serum antinuclear antibodies, and serum cytokine levels in the Long Island Study of Seafood Consumption: A cross-sectional study in NY, USA.

Mercury (Hg) is a well-known neurotoxin, and has been more recently studied specifically as an immunotoxin. In experimental and a few epidemiologic studies, Hg has been associated with distinct cytokine profiles and antinuclear antibody (ANA) positivity, though patterns at lower levels of exposure, typical of seafood consumers with a western diet, are not well characterized. Seafood consumers (n=287) recruited on Long Island, NY completed food frequency and health questionnaires and provided blood for analysis of Hg, poly-unsaturated fatty acids (omega-3 and omega-6 fatty acids), selenium (Se), ANA, and several cytokines (IL-1ß, IL-4, IL-10, TNF-α, IL-17, IFN-γ, and IL-1ra). Logistic and linear regression analyses were conducted to evaluate associations between serum Hg and cytokines and ANA. Adjusted models accounted for gender, age, ethnicity, income, education, smoking, BMI, selenium, omega-3 fatty acids, omega-6 fatty acids, omega-6/omega-3 ratio, and fish intake. Sex-stratified models were also generated with the expectation that immune profiles would differ between women and men. Median blood Hg was 4.58µg/L with 90th %ile =19.8µg/L. Nine individuals displayed ANA positivity at serum titers above 1:80; many of the cytokines were below detection limits, and the ability to detect was used in the logistic regression analyses. In linear and logistic regression analyses, Hg was not significantly associated with any of the seven investigated cytokines or with ANA-positivity. Therefore, Hg was not associated with altered immune profiles in this population of seafood consumers.