Associations between mercury exposure with blood pressure and lipid levels: A cross-sectional study of dental professionals.

Mercury (Hg) exposure is a public health problem worldwide that is now being addressed through the Minamata Convention on Mercury. Fish containing methylmercury and dental amalgam containing elemental Hg are the major sources of exposure for most populations. There is some evidence that methylmercury impacts cardiovascular and metabolic health, primarily in populations with high exposure levels. Studies of elemental Hg and these outcomes are relatively rare. We aimed to examine associations between Hg exposure (both elemental and methylmercury) and blood pressure, as well as cholesterol and triglyceride levels. In 2012, we recruited dental professionals attending the Health Screening Program at the American Dental Association (ADA) Annual Session in California. Total Hg levels in hair and blood samples were analyzed as indicators of methylmercury exposure and in urine as an indicator of primarily elemental Hg exposure (n = 386; mean ± sd age 55 ± 11 years). We measured blood pressure (systolic and diastolic) and lipid profiles (total cholesterol, high-density lipoprotein cholesterol [HDL], low-density lipoprotein cholesterol [LDL] and triglycerides). The geometric means (geometric standard deviations) for blood, hair, and urine Hg were 3.64 (2.39) µg/L, 0.60 (2.91) µg/g, and 1.30 (2.44) µg/L, respectively. For every one µg/L increase in specific gravity-adjusted urine Hg, LDL increased by 2.31 mg/dL (95% CI = 0.09, 4.54), in linear regression adjusting for BMI, race, sex, polyunsaturated fatty acid intake from fish consumption, smoking status, and use of cholesterol-lowering medication. No significant associations between Hg biomarkers and blood pressure or hair or blood Hg with lipid levels were observed. Results suggest that elemental Hg exposure may influence LDL concentrations in adults with low-level exposure, and this relationship merits further study in other populations.

Bayesian inference of dependent kappa for binary ratings.

In medical and social science research, reliability of testing methods measured through inter- and intraobserver agreement is critical in disease diagnosis. Often comparison of agreement across multiple testing methods is sought in situations where testing is carried out on the same experimental units rendering the outcomes to be correlated. In this article, we first developed a Bayesian method for comparing dependent agreement measures under a grouped data setting. Simulation studies showed that the proposed methodology outperforms the competing methods in terms of power, while maintaining a decent type I error rate. We further developed a Bayesian joint model for comparing dependent agreement measures adjusting for subject and rater-level heterogeneity. Simulation studies indicate that our model outperforms a competing method that is used in this context. The developed methodology was implemented on a key measure on a dichotomous rating scale from a study with six raters evaluating three classification methods for chest radiographs for pneumoconiosis developed by the International Labor Office.

Comparison of digital and film chest radiography for detection and medical surveillance of silicosis in a setting with a high burden of tuberculosis.

BACKGROUND: Continuing use of analog film and digital chest radiography for screening and surveillance for pneumoconiosis and tuberculosis in lower and middle income countries raises questions of equivalence of disease detection. This study compared analog to digital images for intra-rater agreement across formats and prevalence of changes related to silicosis and tuberculosis among South African gold miners using the International Labour Organization classification system. METHODS: Miners with diverse radiological presentations of silicosis and tuberculosis were recruited. Digital and film chest images on each subject were classified by four expert readers. RESULTS: Readings of film and soft copy digital images showed no significant differences in prevalence of tuberculosis or silicosis, and intra-rater agreement across formats was fair to good. Hard copy images yielded higher prevalences. CONCLUSION: Film and digital soft copy images show consistent prevalence of findings, and generally fair to good intra-rater agreement for findings related to silicosis and tuberculosis.

Bioaccessibility and bioavailability of methylmercury from seafood commonly consumed in North America: In vitro and epidemiological studies.

Methylmercury (MeHg) is a global contaminant of concern and human exposures are largely realized via seafood consumption. While it is assumed that 95-100% of the ingested MeHg from seafood reaches systemic circulation, recent in vitro studies have yielded results to suggest otherwise. Of the published studies to have characterized the bioaccessibility or bioavailability of MeHg from seafood, only a handful of seafood species have been characterized, there exists tremendous variability in data within and across species, few species of relevance to North America have been studied, and none of the in vitro studies have adapted results to an epidemiology study. The objective of the current study was two-fold: (a) to characterize in vitro MeHg bioaccessibility and bioavailability from ten commonly consumed types of seafood in North America; and (b) to apply the bioaccessibility and bioavailability data from the in vitro study to an existing human MeHg exposure assessment study. Raw seafood samples (cod, crab, halibut, salmon, scallop, shrimp, tilapia, and three tuna types: canned light, canned white, fresh) were purchased in Montreal and their MeHg concentrations generally overlapped with values reported elsewhere. The bioaccessibility of MeHg from these samples ranged from 50.1±19.2 (canned white tuna) to 100% (shrimp and scallop) of the amount measured in the raw undigested sample. The bioavailability of MeHg from these samples ranged from 29.3±10.4 (crab) to 67.4±9.7% (salmon) of the value measured in the raw undigested sample. There were significant correlations between the initial MeHg concentration in seafood with the percent of that Hg that was bioaccessible (r=-0.476) and bioavailable (r=-0.294). When the in vitro data were applied to an existing MeHg exposure assessment study, the estimated amount of MeHg absorbed into systemic circulation decreased by 25% and 42% when considering bioaccessibility and bioavailability, respectively. When the in vitro data were integrated into a regression model relating dietary MeHg intake from seafood with hair and blood Hg biomarkers, there were no differences in key model parameters when comparing the default model (that assumes 100% bioavailability) with models adjusted for the in vitro bioaccessibility and bioavailability data. In conclusion this work adds to a growing number of studies that together suggest that MeHg bioavailability from seafood may be less than 100%, but also documents the challenges when integrating such in vitro data into human exposure and risk assessments.

Genetic polymorphisms are associated with hair, blood, and urine mercury levels in the American Dental Association (ADA) study participants.

BACKGROUND/AIMS: Mercury (Hg) is a potent toxicant of concern to the general public. Recent studies suggest that several genes that mediate Hg metabolism are polymorphic. We hypothesize that single nucleotide polymorphisms (SNPs) in such genes may underline inter-individual differences in exposure biomarker concentrations. METHODS: Dental professionals were recruited during the American Dental Association (ADA) 2012 Annual Meeting. Samples of hair, blood, and urine were collected for quantifying Hg levels and genotyping (88 SNPs in classes relevant to Hg toxicokinetics including glutathione metabolism, selenoproteins, metallothioneins, and xenobiotic transporters). Questionnaires were administrated to obtain information on demographics and sources of Hg exposure (e.g., fish consumption and use of dental amalgam). Here, we report results for 380 participants with complete genotype and Hg biomarker datasets. ANOVA and linear regressions were used for statistical analysis. RESULTS: Mean (geometric) Hg levels in hair (hHg), blood (bHg), urine (uHg), and the average estimated Hg intake from fish were 0.62µg/g, 3.75µg/L, 1.32µg/L, and 0.12µg/kg body weight/day, respectively. Out of 88 SNPs successfully genotyped, Hg biomarker levels differed by genotype for 25 SNPs, one of which remained significant following Bonferroni correction in ANOVA. When the associations between sources of Hg exposure and SNPs were analyzed with respect to Hg biomarker concentrations, 38 SNPs had significant main effects and/or gene-Hg exposure source interactions. Twenty-five, 23, and four SNPs showed significant main effects and/or interactions for hHg, bHg, and uHg levels, respectively (p<0.05), and six SNPs (in GCLC, MT1M, MT4, ATP7B, and BDNF) remained significant following Bonferroni correction. CONCLUSION: The findings suggest that polymorphisms in environmentally-responsive genes can influence Hg biomarker levels. Hence, consideration of such gene-environment factors may improve the ability to assess the health risks of Hg more precisely.

Long-term symptomatic, functional, and work outcomes of carpal tunnel syndrome among construction workers.

BACKGROUND: The long-term outcomes of carpal tunnel syndrome (CTS) including symptoms, functional status, work disability, and economic impact are unknown. METHODS: We conducted a retrospective study of 234 active construction workers with medical claims for CTS and 249 workers without CTS claims; non-cases were matched on age, trade, and insurance eligibility. We conducted telephone interviews with cases and non-cases and collected administrative data on work hours. RESULTS: Compared to non-cases, CTS cases were more likely to report recurrent hand symptoms, decreased work productivity/quality, decreased performance of physical work demands, and greater functional limitations. Surgical cases showed larger improvements on multiple outcomes than non-surgical cases. Minimal differences in paid work hours were seen between cases and non-cases in the years preceding and following CTS claims. CONCLUSIONS: Persistent symptoms and functional impairments were present several years after CTS diagnosis. Long-term functional limitations shown by this and other studies indicate the need for improved prevention and treatment.

Self-reported physical work exposures and incident carpal tunnel syndrome.

BACKGROUND: To prospectively evaluate associations between self-reported physical work exposures and incident carpal tunnel syndrome (CTS). METHODS: Newly employed workers (n = 1,107) underwent repeated nerve conduction studies (NCS), and periodic surveys on hand symptoms and physical work exposures including average daily duration of wrist bending, forearm rotation, finger pinching, using vibrating tools, finger/thumb pressing, forceful gripping, and lifting >2 pounds. Multiple logistic regression models examined relationships between peak, most recent, and time-weighted average exposures and incident CTS, adjusting for age, gender, and body mass index. RESULTS: 710 subjects (64.1%) completed follow-up NCS; 31 incident cases of CTS occurred over 3-year follow-up. All models describing lifting or forceful gripping exposures predicted future CTS. Vibrating tool use was predictive in some models. CONCLUSIONS: Self-reported exposures showed consistent risks across different exposure models in this prospective study. Workers' self-reported job demands can provide useful information for targeting work interventions.

New insight into biomarkers of human mercury exposure using naturally occurring mercury stable isotopes.

Human exposure to methylmercury (MeHg) and elemental mercury vapor (Hg(0)(g)) are often estimated using total Hg concentrations in hair and urine, respectively. We investigated whether Hg stable isotopes could be used to better distinguish between exposure to Hg(0)(g) versus MeHg. We found that hair from North American dental professionals was characterized by high positive Δ(199)Hg values (mean = 1.86‰, 1 SD = 0.12‰, n = 11). This confirms that among people who regularly consume fish, total Hg concentrations in hair reflect exposure to MeHg. In contrast, we found that urine from the same individuals was characterized by a range of Δ(199)Hg values (0.29 to 1.77‰, 2 SD = 0.06‰, n = 12) that were significantly correlated to the number of dental amalgams in each individual's mouth. We hypothesize that fish-derived MeHg is demethylated within the body, causing mass-dependent fractionation and the excretion of inorganic Hg in urine. Mercury in urine therefore represents a mixture of demethylated fish-derived MeHg and amalgam-derived inorganic Hg. We estimate that the majority (>70%) of Hg in urine from individuals with <10 dental amalgams is derived from ingestion of MeHg in fish. These data suggest that within populations that consume fish, urine total Hg concentrations may overestimate Hg exposure from personal dental amalgams.

Associations of blood and urinary mercury with hypertension in U.S. adults: the NHANES 2003-2006.

BACKGROUND: Few studies have examined the association between hypertension and mercury exposure in the general population. We examined cross-sectional associations between blood (mainly methylmercury) or urinary mercury (mainly inorganic mercury) and hypertension in representative U.S. adults and effect modifications by dietary omega-3 fatty acids and serum selenium. METHODS: We examined 6607 adults aged 20 years or older, using the National Health and Nutrition Examination Survey (NHANES) from 2003/2004 to 2005/2006 (2201 adults were available for urinary mercury from NHANES 2003-2006; 2117 available for serum selenium from NHANES 2003-2004 aged 40 years or older). The average of omega-3 fatty acids from two 24-h recalls was calculated. RESULTS: The weighted prevalence of hypertension was 32.2%. The geometric means (95% confidence intervals) of blood total and urinary mercury were 1.03 (0.95, 1.11)µg/L and 0.51 (0.47, 0.54)µg/L, respectively. The adjusted odds ratios for a doubling increase in blood mercury and urinary mercury were 0.94 (0.87 to 1.01) and 0.87 (0.78 to 0.99), respectively, after adjusting for potential confounders. The associations remained similar, even after adjusting for either omega-3 fatty acids or selenium or both. No significant effect modification by either omega-3 fatty acids or selenium was observed. CONCLUSIONS: In this cross-sectional study of the U.S. general population, we found no association of hypertension with blood mercury but a suggestive inverse association with urinary mercury. Future prospective studies are warranted to confirm these findings.

Natural history and predictors of long-term pain and function among workers with hand symptoms.

OBJECTIVE: To evaluate predictors of hand symptoms and functional impairment after 3 years of follow-up among workers with different types of hand symptoms including carpal tunnel syndrome (CTS). Functional status and job limitations were also analyzed as key secondary objectives. DESIGN: Cohort design of 3 years duration. SETTING: Working population-based study. PARTICIPANTS: Newly employed workers without a preexisting diagnosis of CTS (N=1107). Subjects were categorized into 4 groups at baseline examination: no hand symptoms, any hand symptoms but not CTS (recurring symptoms in hands, wrist, or fingers without neuropathic symptoms), any hand symptoms of CTS (neuropathic symptoms in the fingers and normal nerve conduction study), or confirmed CTS (CTS symptoms and abnormal nerve conduction study). Among workers with hand pain at baseline, subject and job characteristics were assessed as prognostic factors for outcomes, using bivariate and multivariate regression models. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The primary outcome assessed by questionnaire at 3 years was "severe hand pain" in the past 30 days. RESULTS: At baseline, 155 workers (17.5% of 888 followed workers) reported hand symptoms, of which 21 had confirmed CTS. Presence of hand pain at baseline was a strong predictor of future hand pain and job impairment. Subjects with confirmed CTS at baseline were more likely than workers with other hand pain to report severe hand pain (adjusted prevalence ratios 1.98 [95% confidence interval 1.11-3.52]) and functional status impairment (adjusted prevalence ratios 3.37 [95% confidence interval 1.01-11.29]). Among subjects meeting our case definition for CTS at baseline, only 4 (19.1%) reported seeing a physician in the 3-year period. CONCLUSIONS: Hand symptoms persisted among many workers after 3-year follow-up, especially among those with CTS, yet few symptomatic workers had seen a physician.

Use of hand diagrams in screening for ulnar neuropathy: comparison with electrodiagnostic studies.

INTRODUCTION: The objective of this study was to determine whether a hand diagram could be used to predict ulnar mononeuropathy. METHODS: This was a prospective study of 117 consecutive patients referred for hand symptoms. Each subject filled out a hand diagram of symptoms and had median and ulnar sensory and motor nerve conduction studies, including ulnar conduction across the elbow. RESULTS: The best model for predicting an ulnar mononeuropathy included hand diagram scores of definite or possible. The model had a sensitivity of 50% and specificity of 93% with an ROC area of 0.90. CONCLUSIONS: The ulnar hand diagram scoring system can be useful as a screening tool in the electrodiagnostic laboratory or for epidemiologic studies.

Agreement between clinical screening procedures for neuropathy in the feet.

INTRODUCTION: The correlation between monofilament testing, symptom surveys, and electrodiagnostic studies for the diagnosis of axonal polyneuropathy has not been well studied. This investigation was done to assess the agreement between these procedures in a non-random sample of volunteers. METHODS: The procedures evaluated included electrodiagnostic tests of the sural nerve, monofilament testing of the great toe, a symptom survey, and a body diagram. Kappa coefficients and sensitivity and specificity, using nerve conduction as a "gold standard," were used to determine the agreement between various combinations of procedures. RESULTS: Poor agreement (kappa values -0.12-0.44) and sensitivity (sensitivity <30%) were found for all combinations of symptoms and monofilament results in comparison with sural peak latency and amplitude. CONCLUSIONS: Overall, the results demonstrated a low discriminatory power for the screening procedures for identifying persons with impaired sural nerve function. The results highlight the need for further development and evaluation of screening methods for distal neuropathy in population-based studies.

Differential aging of median and ulnar sensory nerve parameters.

INTRODUCTION: Nerve conduction velocity slows and amplitude declines with aging. METHODS: Median and ulnar sensory nerves were tested at the annual meetings of the American Dental Association. Seven hundred four subjects had at least two observations. The rate of change in the nerve parameters was estimated while controlling for gender, age, change in hand temperature, baseline body mass index (BMI), and change in BMI. RESULTS: Amplitudes of the median sensory nerve action potentials decreased by 0.58 µV per year, whereas conduction velocity decreased at a rate of 0.41 m/s per year. Corresponding values for the ulnar nerve were 0.89 µV and 0.29 m/s per year. The rates of change in amplitudes did not differ, but the median nerve demonstrated a more rapid loss of conduction velocity. CONCLUSIONS: The rate of change for the median conduction velocity was higher than previously reported. The rate of change of median conduction velocity was significantly greater than for the ulnar nerve.

Performance of simplified scoring systems for hand diagrams in carpal tunnel syndrome screening.

PURPOSE: Katz et al have published a standardized scoring system of hand diagrams for carpal tunnel syndrome. The purpose of this study was to quantitatively evaluate an alternative scoring of the hand diagram for detection of carpal tunnel syndrome. METHODS: In a prospective study of 1,107 workers, 221 workers with hand symptoms completed hand diagrams and electrodiagnostic testing for carpal tunnel syndrome. Scoring algorithms for the hand diagrams included the Katz rating; a median nerve digit score (0-2) with a maximum of 2 symptomatic digits of thumb, index, and long fingers; and isolated digit scores (0-1) of thumb, index, or long finger. Intraclass correlation coefficients quantified inter-rater reliability. Sensitivity, specificity, and logistic regression analyses evaluated the scoring systems' ability to predict abnormal median nerve conduction. RESULTS: One hundred ten subjects illustrated symptoms within the median nerve distribution. All scoring systems demonstrated substantial inter-rater reliability. "Classic" or "probable" Katz scores, median nerve digit score of 2, and positive long finger scores were significantly associated with abnormal median nerve distal sensory latency and median-ulnar difference. Abnormal distal motor latency was significantly associated with the median nerve digit score of 2 and positive long finger scores. Increasing Katz scores from "possible" to "probable" and "classic" were not associated with greater odds of electrodiagnostic abnormality. Positive long finger scores performed at least as well as the most rigorous scoring by Katz. CONCLUSIONS: Symptoms diagrammed within the median nerve distribution are associated with abnormal nerve conduction among workers. The median nerve digit score and the long finger score offer increased ease of use compared to the Katz method, while maintaining similar performance characteristics. The long finger appears best suited for isolated digit scoring to predict abnormal median nerve conduction in a working population. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

Monitoring SARS-CoV-2 in air and on surfaces and estimating infection risk in buildings and buses on a university campus.

BACKGROUND: Evidence is needed on the presence of SARS-CoV-2 in various types of environmental samples and on the estimated transmission risks in non-healthcare settings on campus. OBJECTIVES: The objective of this research was to collect data on SARS-CoV-2 viral load and to examine potential infection risks of people exposed to the virus in publicly accessible non-healthcare environments on a university campus. METHODS: Air and surface samples were collected using wetted wall cyclone bioaerosol samplers and swab kits, respectively, in a longitudinal environmental surveillance program from August 2020 until April 2021 on the University of Michigan Ann Arbor campus. Quantitative rRT-PCR with primers and probes targeting gene N1 were used for SARS-CoV-2 RNA quantification. The RNA concentrations were used to estimate the probability of infection by quantitative microbial risk assessment modeling and Monte-Carlo simulation. RESULTS: In total, 256 air samples and 517 surface samples were collected during the study period, among which positive rates were 1.6% and 1.4%, respectively. Point-biserial correlation showed that the total case number on campus was significantly higher in weeks with positive environmental samples than in non-positive weeks (p = 0.001). The estimated probability of infection was about 1 per 100 exposures to SARS-CoV-2-laden aerosols through inhalation and as high as 1 per 100,000 exposures from contacting contaminated surfaces in simulated scenarios. SIGNIFICANCE: Viral shedding was demonstrated by the detection of viral RNA in multiple air and surface samples on a university campus. The low overall positivity rate indicated that the risk of exposure to SARS-CoV-2 at monitored locations was low. Risk modeling results suggest that inhalation is the predominant route of exposure compared to surface contact, which emphasizes the importance of protecting individuals from airborne transmission of SARS-CoV-2 and potentially other respiratory infectious diseases. IMPACT: Given the reoccurring epidemics caused by highly infectious respiratory viruses in recent years, our manuscript reinforces the importance of monitoring environmental transmission by the simultaneous sampling and integration of multiple environmental surveillance matrices for modeling and risk assessment.

Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals.

Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione S-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n=515), and total mercury content was measured. Average urine (1.06±1.24 microg/L) and hair mercury levels (0.49±0.63 microg/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5'), or both (SEPP1 3'UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption).

Physical examination has a low yield in screening for carpal tunnel syndrome.

BACKGROUND: physical examination is often used to screen workers for carpal tunnel syndrome (CTS). In a population of newly hired workers, we evaluated the yield of such screening. METHODS: our study population included 1,108 newly hired workers in diverse industries. Baseline data included a symptom questionnaire, physical exam, and bilateral nerve conduction testing of the median and ulnar nerves; individual results were not shared with the employer. We tested three outcomes: symptoms of CTS, abnormal median nerve conduction, and a case definition of CTS that required both symptoms and median neuropathy. RESULTS: of the exam measures used, only Semmes-Weinstein sensory testing had a sensitivity value above 31%. Positive predictive values were low, and likelihood ratios were all under 5.0 for positive testing and over 0.2 for negative testing. CONCLUSION: physical examination maneuvers have a low yield for the diagnosis of CTS in workplace surveillance programs and in post-offer, pre-placement screening programs.

Lifetime exposure to arsenic in drinking water and bladder cancer: a population-based case-control study in Michigan, USA.

OBJECTIVE: Arsenic in drinking water has been linked with the risk of urinary bladder cancer, but the dose-response relationships for arsenic exposures below 100 microg/L remain equivocal. We conducted a population-based case-control study in southeastern Michigan, USA, where approximately 230,000 people were exposed to arsenic concentrations between 10 and 100 microg/L. METHODS: This study included 411 bladder cancer cases diagnosed between 2000 and 2004, and 566 controls recruited during the same period. Individual lifetime exposure profiles were reconstructed, and residential water source histories, water consumption practices, and water arsenic measurements or modeled estimates were determined at all residences. Arsenic exposure was estimated for 99% of participants' person-years. RESULTS: Overall, an increase in bladder cancer risk was not found for time-weighted average lifetime arsenic exposure >10 microg/L when compared with a reference group exposed to <1 microg/L (odds ratio (OR) = 1.10; 95% confidence interval (CI): 0.65, 1.86). Among ever-smokers, risks from arsenic exposure >10 microg/L were similarly not elevated when compared to the reference group (OR = 0.94; 95% CI: 0.50, 1.78). CONCLUSIONS: We did not find persuasive evidence of an association between low-level arsenic exposure and bladder cancer. Selecting the appropriate exposure metric needs to be thoughtfully considered when investigating risk from low-level arsenic exposure.