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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.A cross-sectional study.United States, national population-based survey.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.A total of 8133 adult participants over 20 years of age were used using NHANES 2009-2016.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.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.

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 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.

While surveys are a well-established instrument to capture 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 due to COVID-19, and anxiety and depression in seven major US cities utilizing Twitter data.We collected 18 million Tweets from January to September 2019 (baseline), and 2020 from seven US 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.Twitter depression and anxiety scores were consistently elevated above their 2019 baselines across all seven 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.Our study demonstrates 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.

BACKGROUND: Epidemiologic studies suggest cadmium exposure is associated with cardiovascular disease risk, including heart failure. However, prior findings may be influenced by tobacco smoking, a dominant source of cadmium exposure and risk factor for heart failure. The present study leverages up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to examine the relationship between urinary cadmium and incident heart failure among people who never smoked.METHODS: Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 men and 600 women and identified 958 incident heart failure cases occurring between baseline and 2015. Using a case-cohort approach, we estimated adjusted hazard ratios (aHR) for heart failure in Cox proportional hazards models with age as the time scale.RESULTS: Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median= 0.20; 25th, 75th= 0.13, 0.32 µg cadmium/g creatinine). In adjusted models, we found that higher urinary cadmium was associated with a higher rate of incident heart failure overall (aHR=1.1 per interquartile range difference; 95% CI= 1.0 - 1.2). In sex-stratified analyses the association seemed restricted to men (aHR= 1.5; 95% CI= 1.2 - 1.9).CONCLUSION: In this cohort of people who never smoked tobacco, environmental cadmium was positively associated with incident heart failure, especially among men.

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.

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.

Little is known about the characteristics and causes of early-onset cognitive impairment. Responders to the 2001 New York World Trade Center disaster represent an ageing population that was recently shown to have an excess prevalence of cognitive impairment. Neuroimaging and molecular data demonstrate that a subgroup of affected responders may have a unique form of parietal-dominant Alzheimer’s Disease. Recent neuropsychological testing and artificial intelligence approaches have emerged as methods that can be used to identify and monitor subtypes of cognitive impairment. We utilized data from World Trade Center responders participating in a health monitoring program and applied a deep learning approach to evaluate neuropsychological and neuroimaging data to generate a cortical atrophy risk score. We examined risk factors associated with the prevalence and incidence of high risk for brain atrophy in responders who are now at midlife. Training was conducted in a randomly selected two-thirds sample (N = 99) enrolled using of the results of a structural neuroimaging study. Testing accuracy was estimated for each training cycle in the remaining third subsample. After training was completed, the scoring methodology that was generated was applied to longitudinal data from 1441 World Trade Center responders. The artificial neural network provided accurate classifications of these responders in both the testing (Area Under the Receiver Operating Curve, 0.91) and validation samples (Area Under the Receiver Operating Curve, 0.87). At baseline and follow-up, responders identified as having a high risk of atrophy (n = 378) showed poorer cognitive functioning, most notably in domains that included memory, throughput, and variability as compared to their counterparts at low risk for atrophy (n = 1063). Factors associated with atrophy risk included older age [adjusted hazard ratio, 1.045 (95% confidence interval = 1.027–1.065)], increased duration of exposure at the WTC site [adjusted hazard ratio, 2.815 (1.781–4.449)], and a higher prevalence of post-traumatic stress disorder [aHR, 2.072 (1.408–3.050)]. High atrophy risk was associated with an increased risk of all-cause mortality [adjusted risk ratio, 3.19 (1.13–9.00)]. In sum, the high atrophy risk group displayed higher levels of previously identified risk factors and characteristics of cognitive impairment, including advanced age, symptoms of post-traumatic stress disorder, and prolonged duration of exposure to particulate matter. Thus, this study suggests that a high risk of brain atrophy may be accurately monitored using cognitive data., Dementia has a rising major impact on the health of ageing populations. World Trade Center responders are at increased risk for dementia, as characterized particularly by parietal-dominant cortical atrophy on neuroimaging. Clouston et al. used deep learning to predict the risk of developing cortical atrophy based on neuropsychological test results., Graphical abstract Graphical Abstract

Cadmium is a widespread heavy metal pollutant that may act as an exogenous estrogenic hormone. Environmental cadmium exposure has been associated with risk of breast cancer in retrospective studies. We prospectively assessed the relationship between cadmium exposure, evaluated by creatinine-normalized urinary cadmium concentration, and invasive breast cancer among 12,701 postmenopausal women aged ≥50 years in a Women's Health Initiative study of bone mineral density. After a median of 13.2 years of follow-up (1993-2010), 508 cases of invasive breast cancer and 1,050 comparison women were identified for a case-cohort analysis. Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals. Risk of breast cancer was not associated with urinary cadmium parameterized either in quartiles (comparing highest quartile with lowest, hazard ratio = 0.80, 95% confidence interval: 0.56, 1.14; P for trend = 0.20) or as a log-transformed continuous variable (per 2-fold higher urinary cadmium concentration, hazard ratio = 0.94, 95% confidence interval: 0.86, 1.03). We did not observe an association between urinary cadmium and breast cancer risk in any subgroup examined, including never smokers and women with body mass index (weight (kg)/height (m)(2)) less than 25. Results were consistent in both estrogen receptor-positive and estrogen receptor-negative tumors. Our results do not support the hypothesis that environmental cadmium exposure is associated with risk of postmenopausal breast cancer.

Cadmium exposure has been associated with cardiovascular disease. Cigarette smoking is a key source of cadmium exposure and thus a potential confounder in observational studies of environmental cadmium and cardiovascular disease that include tobacco smokers. We leveraged up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to test the hypothesis that cadmium exposure is associated with acute myocardial infarction (AMI) among people who never smoked. Between 1993 and 1997, 19,394 never-smoking participants (ages 50–64 years) were enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 males and 600 females. We identified 809 AMI cases occurring between baseline and the end of 2015 using the Danish National Patient Registry. We quantified cadmium, creatinine, and osmolality in baseline urine samples. Using an unweighted case-cohort approach, we estimated adjusted hazard ratios (aHR) for AMI in Cox proportional hazards models with age as the time axis. Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 μg cadmium/g creatinine). We did not find strong evidence to support an association between higher urinary cadmium and AMI when comparing the highest versus lowest quartile (aHR = 1.16; 95% CI: 0.86 – 1.56) and per IQR increment in cadmium concentration (aHR = 1.02; 95% CI: 0.93 – 1.12). Results were not materially different across strata defined by sex. Results were generally similar using creatinine or osmolality to account for differences in urine dilution. While cadmium exposure has been identified as a risk factor for cardiovascular disease, we did not find strong evidence that urinary cadmium at relatively low-levels is associated with AMI among people who have never smoked.

Background Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking. Methods We conducted a nested case-control study within the Women’s Health Initiative (WHI) prospective cohort (n = 419 invasive case subjects and 838 control subjects). Control subjects were matched 2:1 to case subjects on age, enrollment date, follow-up time, and WHI study group. We quantified 13 phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk associated with each phthalate biomarker up to 19 years of follow-up. Results Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (eg, 4th vs 1st quartile of diethylhexyl phthalate, OR = 1.03, 95% CI = 0.91 to 1.17). Results were generally similar in analyses restricted to disease subtypes, to nonusers of postmenopausal hormone therapy, stratified by body mass index, or to case subjects diagnosed within three, five, or ten years. Conclusions In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer.

Context Phthalates are endocrine-disrupting chemicals that could disrupt normal physiologic function, triggering detrimental impacts on bone. Objective We evaluated associations between urinary phthalate biomarkers and BMD in postmenopausal women participating in the prospective Women’s Health Initiative (WHI). Methods We included WHI participants enrolled in the BMD substudy and selected for a nested case-control study of phthalates and breast cancer (N = 1255). We measured 13 phthalate biomarkers and creatinine in 2 to 3 urine samples per participant collected over 3 years, when all participants were cancer free. Total hip and femoral neck BMD were measured at baseline and year 3, concurrent with urine collection, via dual-energy x-ray absorptiometry. We fit multivariable generalized estimating equation models and linear mixed-effects models to estimate cross-sectional and longitudinal associations, respectively, with stratification on postmenopausal hormone therapy (HT) use. Results In cross-sectional analyses, mono-3-carboxypropyl phthalate and the sum of di-isobutyl phthalate metabolites were inversely associated with total hip BMD among HT nonusers, but not among HT users. Longitudinal analyses showed greater declines in total hip BMD among HT nonusers and with highest concentrations of mono-3-carboxyoctyl phthalate (–1.80%; 95% CI, –2.81% to –0.78%) or monocarboxynonyl phthalate (–1.84%; 95% CI, –2.80% to –0.89%); similar associations were observed with femoral neck BMD. Among HT users, phthalate biomarkers were not associated with total hip or femoral neck BMD change. Conclusion Certain phthalate biomarkers are associated with greater percentage decreases in total hip and femoral neck BMD. These findings suggest that phthalate exposure may have clinically important effects on BMD, and potentially fracture risk.

Assays of urine biomarkers often use urine creatinine to account for urinary dilution, even though creatinine levels are influenced by underlying physiology and muscle catabolism. Urine osmolality—a measure of dissolved particles including ions, glucose, and urea—is thought to provide a more robust marker of urinary dilution but is seldom measured. The relationship between urine osmolality and creatinine is not well understood. We calculated correlation coefficients between urine creatinine and osmolality among 1375 members of a subcohort of the Danish Diet, Cancer, and Health Cohort, and within different subgroups. We used linear regression to relate creatinine with osmolality, and a lasso selection procedure to identify other variables that explain remaining variability in osmolality. Spearman correlation between urine creatinine and osmolality was strong overall (ρ = 0.90; 95% CI: 0.89–0.91) and in most subgroups. Linear regression showed that urine creatinine explained 60% of the variability in urine osmolality, with another 9% explained by urine thallium (Tl), cesium (Cs), and strontium (Sr). Urinary creatinine and osmolality are strongly correlated, although urine Tl, Cs, and Sr might help supplement urine creatinine for purposes of urine dilution adjustment when osmolality is not available.

Background Recent experimental work has shown that phthalates may increase inflammation. Prior research has not examined the role of exposure to phthalates in relation to inflammatory status among postmenopausal women who are at higher risk of developing inflammation-related chronic disorders. Objectives We aimed to examine the associations of urinary phthalate biomarker concentrations with circulating levels of c-reactive protein [CRP] and interleukin-6 [IL-6] among 443 postmenopausal women selected into a breast cancer case-control study nested within the Women's Health Initiative (WHI). Methods A total of 13 phthalate metabolites were measured in urine samples provided at WHI enrollment from 1993 to 1998. We also measured baseline levels of CRP and IL-6 in these women's serum or plasma samples. Multivariable linear models were used to investigate the role of each phthalate biomarker in relation to CRP and IL-6, adjusting for potential confounding factors and specifically evaluating the role of BMI. Results In adjusted models we observed positive associations of monocarboxynonyl phthalate (MCNP) with CRP (β = 0.092; 95% CI 0.026, 0.158) and IL-6 (β = 0.108; 95% CI 0.013, 0.204). These positive associations were attenuated and non-significant, however, after further adjustment for body mass index (BMI). In contrast, we observed inverse associations of monoethyl phthalate (MEP) (β = −0.019; 95% CI -0.036, −0.001) and monobenzyl phthalate (MBzP) (β = −0.034; 95% CI -0.058, −0.010) with CRP levels only after adjustment for BMI. Other phthalate biomarkers examined were not significantly associated with either CRP or IL-6 levels. Conclusions Overall, these results do not suggest an important role for phthalates in promoting an inflammatory response. Future prospective studies are warranted to improve understanding of these associations, particularly in clarifying the role of BMI.

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.

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.

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.

Background and aim Moderate fish consumption is recommended for prevention of coronary heart disease (CHD) as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have known beneficial effects on risk factors such as reducing blood pressure (BP) and increasing paraoxonase-1 (PON-1) activity. However concomitant methylmercury (MeHg) exposure from fish consumption may mitigate these benefits and the net effect on BP and PON-1 activity has not been extensively studied in western populations consuming diverse seafood types. We studied the correlation between EPA, DHA and Hg levels with BP and PON-1 activity in a population of avid seafood consumers. Methods Two hundred and eighty-eight avid seafood consumers from Long Island, NY had blood samples drawn for total blood mercury (THg), plasma EPA and DHA levels, and plasma PON-1 activity. Average systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were measured. Results Subjects’ mean EPA + DHA was 4.9% total fatty acids, mean THg was 7.6mcg/L. Mean SBP was 122.5 mmHg, mean DBP 70.3 mmHg, mean PP 52.2 mmHg and mean PON-1 activity 421.2U/L. THg was not associated with any of the BP measures in adjusted linear regression models; EPA + DHA was significantly inversely associated with PP (p = 0.02). THg was associated with a significant increase in PON-1 activity (p = 0.04), while EPA + DHA was associated with a significant decrease in PON-1 activity (p = 0.007); although the size of the effects was small. Conclusions Our findings suggest blood THg and serum DHA + EPA levels have limited relationship to BP and PON-1 activity, and may not be important modulators of these known CHD risk factors in this population of avid seafood consumers.

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

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.

Cadmium is a carcinogenic heavy metal. Urinary levels of cadmium are considered to be an indicator of long-term body burden, as cadmium accumulates in the kidneys and has a half-life of at least 10 years. However, the temporal stability of the biomarker in urine samples from a non-occupationally exposed population has not been rigorously established. We used repeated measurements of urinary cadmium (U-Cd) in spot urine samples and first morning voids from two separate cohorts, to assess the temporal stability of the samples. Urine samples from two cohorts including individuals of both sexes were measured for cadmium and creatinine. The first cohort (Home Observation of Perinatal Exposure (HOPE)) consisted of 21 never-smokers, who provided four first morning urine samples 2–5 days apart, and one additional sample roughly 1 month later. The second cohort (World Trade Center-Health Program (WTC-HP)) consisted of 78 individuals, including 52 never-smokers, 22 former smokers and 4 current smokers, who provided 2 spot urine samples 6 months apart, on average. Intra-class correlation was computed for groups of replicates from each individual to assess temporal variability. The median creatinine-adjusted U-Cd level (0.19 and 0.21 μg/g in the HOPE and WTC-HP, respectively) was similar to levels recorded in the United States by the National Health and Nutrition Examination Survey. The intra-class correlation (ICC) was high (0.76 and 0.78 for HOPE and WTC-HP, respectively) and similar between cohorts, irrespective of whether samples were collected days or months apart. Both single spot or first morning urine cadmium samples show good to excellent reproducibility in low-exposure populations.

Mechanisms of mercury (Hg) toxicity at low doses from seafood consumption, the most common exposure route, are not well understood. We tested the hypothesis that seafood Hg exposure is related to a shift in redox status, indicated by a decrease in the ratio of reduced to oxidized glutathione (GSH:GSSG) in blood, or increase in redox potential (Eh). We also examined whether key seafood nutrients (selenium (Se), omega-3 fatty acids) confound or modify this shift. We measured blood concentrations of total Hg, Se, GSH, GSSG, and the Omega-3 Index (% omega-3s of total fatty acids in red blood cell membranes) in seafood consumers in Long Island, NY. We examined relationships between Hg, GSH:GSSG ratio and Eh. Elevated blood Hg (> 5.8 μg L−1) was associated with lower GSH:GSSG (β = −116.73, p = 0.01), with no evidence of confounding by Se or Omega-3 Index. However, in models stratified by Omega-3 Index levels, Hg-GSH:GSSG associations were weakened among those with high Omega-3 Index levels (> 6% of fatty acids, β = −63.46, p = 0.28), and heightened among those with low Omega-3 Index (β = −182.53, p < 0.01). We observed comparable patterns for Eh in relation to Hg. These results support the hypothesis that Hg exposure from seafood is linked to a shift in redox status toward oxidative stress, modified by omega-3 fatty acids in this population. Further work should examine the role of different seafood nutrients and Hg-induced shifts in redox status in the diverse health effects associated with elevated Hg exposure.

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.

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.

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 &micro, g/L, which was nearly three times the Environmental Protection Agency (EPA) reference dose (5.8 &micro, g/L). The levels of the other metals were consistent with those in the general population: the mean Pb was 26.8 &micro, g/L, and the mean Cd was 0.43 &micro, g/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.

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 (β = 0.06, p = 0.23); Iowa (β = −0.07, p = 0.07); or Wisconsin (β = −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.

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 (β = 0.02, p = 0.96) and among those in counties with > 75% fluoridated (β = 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.

Cadmium, a heavy metal dispersed in the environment as a result of industrial and agricultural applications, has been implicated in several human diseases including renal disease, cancers, and compromised bone health. In the general population, the predominant sources of cadmium exposure are tobacco and diet. Urinary cadmium (uCd) reflects long-term exposure and has been frequently used to assess cadmium exposure in epidemiological studies; estimated dietary intake of cadmium (dCd) has also been used in several studies. The validity of dCd in comparison to uCd is unclear. This study aimed to compare dCd, estimated from food frequency questionnaires (FFQs), to uCd measured in spot urine samples from 1,002 participants of the Women’s Health Initiative. Using linear regression, we found that dCd was not statistically significantly associated with uCd (β=0.006, p-value=0.14). When stratified by smoking status, dCd was not significantly associated with uCd both in never smokers (β=0.006, p-value=0.09) and in ever smokers (β=0.003, p-value=0.0.67). Our results suggest that because of the lack of association between estimated dietary cadmium and measured urinary cadmium exposure, dietary estimation of cadmium exposure should be used with caution in epidemiologic studies.

Although the benefits of fish consumption are widely recognized, seafood may also be a source of exposure to heavy metals such as cadmium. Many types of seafood are rich in cadmium, but bioavailability and potential for toxicity after consumption is less clear. This study investigates the relationship between seafood intake and the level of cadmium (Cd) in the blood in a 252 person cohort of avid seafood consumers in the Long Island Study of Seafood Consumption (New York). Blood cadmium is an established biomarker of cadmium exposure, reflecting both recent and decade-long exposure. Data on the amounts and frequency of eating various types of seafood were self-reported by avid seafood consumers recruited in 2011–2012. After adjusting for age, BMI, sex, current smoking status, and income in a linear regression model, we found no association between regular seafood intake ( β = −0.01; p = 0.11) but did identify an association between salmon intake in cups/week (ln transformed) ( β = 0.20; p = 0.001) and blood cadmium. After accounting for salmon, no other types of seafood were meaningfully associated with blood cadmium. No association was found between rice intake, blood zinc, or dietary iron or calcium and blood cadmium. Results suggest that seafood is not a major source of cadmium exposure, but that salmon intake does marginally increase blood cadmium levels. Given that cadmium levels in salmon are not higher than those in many other seafood species, the association with salmon intake is likely attributed to higher consumption of salmon in this population.

We examined the association between seafood consumption, mercury concentration, polyunsaturated fatty acids, selenium, and Vitamin D in relation to C-reactive protein using the cross-sectional US National Health and Nutrition Examination Survey 2005-2006. We hypothesized that seafood consumption and fatty acids will be negatively associated, and mercury will be positively associated with C-reactive protein, and that statistical adjustment for these factors will alleviate confounding thereby making these associations more apparent. The study sample included 1217 participants (706 males, 511 females) aged 16-49. Sex-stratified sample weighted multiple linear regression models revealed no associations of mercury, polyunsaturated fatty acids, fish intake, selenium, or vitamin D with serum C-reactive protein. However, when all variables were included together in one model, fish intake was associated with lower levels of CRP in females suggesting confounding in models that do not mutually adjust for seafood contaminants and nutrients. Prospective studies are needed to confirm these findings.

Background: Cadmium is a human lung carcinogen, and recent evidence suggests it may play a role in hormone-related cancers because of its estrogenic activity. Case-control studies consistently show higher cadmium concentrations in urine from women diagnosed with breast cancer compared with control women. Our aim was to investigate the association between urinary cadmiumand breast cancer in a prospective design.Methods: We conducted a case-cohort study using the population-based Danish Diet Cancer and Health Cohort. Women age 50 to 64 years were recruited in 1993-1997 and provided urine for analysis. We identified 900 incident case patients in the Danish Cancer Registry and compared with 898 individuals in a subcohort. Urine samples collected at enrollment into the cohort were analyzed for cadmium and creatinine. We estimated incidence rate ratios (IRRs) for breast cancer in Cox proportional hazards models with age as time axis and calculated 95% confidence intervals (CIs).Results: The linear analysis showed no association between urinary cadmiumand risk for breast cancer (IRR = 1.00, 95% CI = 0.81 to 1.24 per ng Cd/mL urine). The categorical analyses showed a slightly higher risk for breast cancer for the second (IRR = 1.10, 95% CI = 0.86 to 1.42) and third (IRR = 1.14, 95% CI = 0.83 to 1.55) exposure tertiles compared with the lowest tertile. Results were similar in analyses of breast cancer subtypes defined by estrogen and progesterone receptor status and by histology, and analyses stratified by years from baseline to diagnosis.Conclusions: This large prospective study showed no association between urinary concentration of cadmium and subsequent risk for development of postmenopausal breast cancer.

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-1β, 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.

Few investigations of health event clustering have evaluated residential mobility, though causative exposures for chronic diseases such as cancer often occur long before diagnosis. Recently developed Q-statistics incorporate human mobility into disease cluster investigations by quantifying space- and time-dependent nearest neighbor relationships. Using residential histories from two cancer case-control studies, we created simulated clusters to examine Q-statistic performance. Results suggest the intersection of cases with significant clustering over their life course, Q(i), with cases who are constituents of significant local clusters at given times, Q(it), yielded the best performance, which improved with increasing cluster size. Upon comparison, a larger proportion of true positives were detected with Kulldorf's spatial scan method if the time of clustering was provided. We recommend using Q-statistics to identify when and where clustering may have occurred, followed by the scan method to localize the candidate clusters. Future work should investigate the generalizability of these findings.

Environmental toxins, pathogens and host susceptibility cofactors may interact to contribute to disease. In vitro mercury exposure inhibited antiviral cytokines in human cells; however, little is known about the relationship between mercury and viruses in children. Children are susceptible to mercury toxicity; lower vitamin B-12 and folate levels and higher homocysteine levels may represent susceptibility cofactors. This study aimed to evaluate associations between total blood mercury (Hg) and measles antibodies in children, and the influence of these susceptibility cofactors.Cross-sectional data on serum measles antibodies, Hg, homocysteine, methylmalonic acid (MMA, indicator of B-12 deficiency), and folate were obtained from the 2003-2004 NHANES for children aged 6-11 years with measles seropositivity (n=692). We used linear regression to evaluate relationships between measles antibodies and Hg, stratified by sex, MMA ≥, folate, and homocysteine≥sample medians, adjusted for demographic, nutritional and environmental cofactors.Hg (range: 0.10-19.10μg/L) was inversely associated with measles antibodies (range: 1.00-28.24 units) in non-stratified analysis (n=692), yet positively associated among the subset of boys with higher MMA and lower folate (n=98). Among this subset with higher homocysteine levels (n=61), correlations were positive across all Hg quartiles relative to Q1 (Hg≤0.20μg/L): Q2:β=6.60 (3.02, 10.19); Q3:β=8.49 (6.17, 10.81); Q4 (Hg0.80μg/L):β=4.90 (2.12, 7.67) (p(trend)=0.077).Stratification by susceptibility cofactors revealed opposing directionality for correlations between Hg and measles antibodies, with positive effect estimates at lowest exposures only among boys with higher MMA, lower folate and higher homocysteine levels.

Familial aggregation of testicular cancer has been reported consistently, but it is less clear if there is any association between risk of testicular cancer and other cancers in the family. We conducted a population-based case-control study to examine the relationship between risk of testicular cancer and 22 different cancers in first-degree relatives. We included 3,297 cases of testicular cancer notified to the Danish Cancer Registry between 1991 and 2003. A total of 6,594 matched controls were selected from the Danish Civil Registration System, which also provided the identity of 40,104 first-degree relatives of case and controls. Familial cancer was identified by linkage to the Danish Cancer Registry, and we used conditional logistic regression to analyze whether cancer among first-degree relatives was associated with higher risk of testicular cancer. Rate ratio for testicular cancer was 4.63 (95% CI: 2.41-8.87) when a father, 8.30 (95% CI: 3.81-18.10) when a brother and 5.23 (95% CI: 1.35-20.26) when a son had testicular cancer compared to no familial testicular cancer. Results were similar when analyses were stratified by histologic subtypes of testicular cancer. Familial non-Hodgkin lymphoma and esophageal cancer were associated with testicular cancer; however, these may be chance findings. The familial aggregation of testicular and possibly other cancers may be explained by shared genes and/or shared environmental factors, but the mutual importance of each of these is difficult to determine.

Cadmium is a naturally-occurring element, and humans are exposed from cigarettes, food, and industrial sources. Following exposure, cadmium accumulates in the kidney and is slowly released into the urine, usually proportionally to the levels found in the kidneys. Cadmium levels in a single spot urine sample have been considered indicative of long-term exposure to cadmium; however, such a potentially exceptional biomarker requires careful scrutiny. In this review, we report good to excellent temporal stability of urinary cadmium (intraclass correlation coefficient 0.66–0.81) regardless of spot urine or first morning void sampling. Factors such as changes in smoking habits and diseases characterized by increased excretion of proteins may produce short-term changes in urinary cadmium levels. We recommend that epidemiologists use this powerful biomarker in prospective studies stratified by smoking status, along with thoughtful consideration of additional factors that can influence renal physiology and cadmium excretion.