The Use of the Kurtosis-Adjusted Cumulative Noise Exposure Metric in Evaluating the Hearing Loss Risk for Complex Noise.

OBJECTIVE: To test a kurtosis-adjusted cumulative noise exposure (CNE) metric for use in evaluating the risk of hearing loss among workers exposed to industrial noises. Specifically, to evaluate whether the kurtosis-adjusted CNE (1) provides a better association with observed industrial noise-induced hearing loss, and (2) provides a single metric applicable to both complex (non-Gaussian [non-G]) and continuous or steady state (Gaussian [G]) noise exposures for predicting noise-induced hearing loss (dose-response curves). DESIGN: Audiometric and noise exposure data were acquired on a population of screened workers (N = 341) from two steel manufacturing plants located in Zhejiang province and a textile manufacturing plant located in Henan province, China. All the subjects from the two steel manufacturing plants (N = 178) were exposed to complex noise, whereas the subjects from textile manufacturing plant (N = 163) were exposed to a G continuous noise. Each subject was given an otologic examination to determine their pure-tone HTL and had their personal 8-hr equivalent A-weighted noise exposure (LAeq) and full-shift noise kurtosis statistic (which is sensitive to the peaks and temporal characteristics of noise exposures) measured. For each subject, an unadjusted and kurtosis-adjusted CNE index for the years worked was created. Multiple linear regression analysis controlling for age was used to determine the relationship between CNE (unadjusted and kurtosis adjusted) and the mean HTL at 3, 4, and 6 kHz (HTL346) among the complex noise-exposed group. In addition, each subject's HTLs from 0.5 to 8.0 kHz were age and sex adjusted using Annex A (ISO-1999) to determine whether they had adjusted high-frequency noise-induced hearing loss (AHFNIHL), defined as an adjusted HTL shift of 30 dB or greater at 3.0, 4.0, or 6.0 kHz in either ear. Dose-response curves for AHFNIHL were developed separately for workers exposed to G and non-G noise using both unadjusted and adjusted CNE as the exposure matric. RESULTS: Multiple linear regression analysis among complex exposed workers demonstrated that the correlation between HTL3,4,6 and CNE controlling for age was improved when using the kurtosis-adjusted CNE compared with the unadjusted CNE (R = 0.386 versus 0.350) and that noise accounted for a greater proportion of hearing loss. In addition, although dose-response curves for AHFNIHL were distinctly different when using unadjusted CNE, they overlapped when using the kurtosis-adjusted CNE. CONCLUSIONS: For the same exposure level, the prevalence of NIHL is greater in workers exposed to complex noise environments than in workers exposed to a continuous noise. Kurtosis adjustment of CNE improved the correlation with NIHL and provided a single metric for dose-response effects across different types of noise. The kurtosis-adjusted CNE may be a reasonable candidate for use in NIHL risk assessment across a wide variety of noise environments.

Genetic polymorphisms of catechol-O-methyltransferase modify the neurobehavioral effects of mercury in children.

Mercury (Hg) is neurotoxic and children may be particularly susceptible to this effect. A current major challenge is identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. This study examined the hypothesis that genetic variants of catechol-O-methyltransferase (COMT) that are reported to alter neurobehavioral functions that are also affected by Hg in adults might modify the adverse neurobehavioral effects of Hg exposure in children. Five hundred and seven children, 8-12 yr of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings. Subjects were evaluated at baseline and at seven subsequent annual intervals for neurobehavioral performance and urinary Hg levels. Following the clinical trial, genotyping assays were performed for single-nucleotide polymorphisms (SNPs) of COMT rs4680, rs4633, rs4818, and rs6269 on biological samples provided by 330 of the trial participants. Regression-modeling strategies were employed to evaluate associations between allelic status, Hg exposure, and neurobehavioral test outcomes. Similar analysis was performed using haplotypes of COMT SNPs. Among girls, few interactions for Hg exposure and COMT variants were found. In contrast, among boys, numerous gene-Hg interactions were observed between individual COMT SNPs, as well as with a common COMT haplotype affecting multiple domains of neurobehavioral function. These findings suggest increased susceptibility to the adverse neurobehavioral effects of Hg among children with common genetic variants of COMT, and may have important implications for strategies aimed at protecting children from the potential health risks associated with Hg exposure.

Effect of cigarette smoking on noise-induced hearing loss in workers exposed to occupational noise in China.

Excessive exposure to high noise level environments has the potential to cause noise-induced hearing loss (NIHL), and cigarette smoking has also been shown to have a potential adverse effect on hearing. The aim of this study was to determine whether smoking interacts with noise in the development of hearing loss, and if so, the extent of the contribution from smoking on NIHL. A cross-sectional study was designed to assess the effect of smoking on NIHL in 517 male workers (non-smokers: N = 199; smokers: N = 318) exposed to a high-level industrial noise environment in China. Shift-long temporal waveforms of the noise that workers were exposed to for evaluation of noise exposures, and audiometric threshold measures were obtained on all selected subjects. The subjects used hearing protection devices only within the last 1-2 years. The results suggest that smoking has an adverse effect on NIHL in workers exposed to high level industrial noise, i.e., the median high frequency hearing thresholds were significantly greater in smokers than non-smokers exposed to noise for more than 10 years. This effect was observed at 4.0 and 6.0 kHz. Smoking did not have an adverse effect on NIHL in workers exposed to noise less than 10 years. Multivariate regression analysis revealed that the odds ratio (OR) for high frequency hearing loss (i.e., hearing threshold greater than 40 dB at 4.0 kHz) were 1.94 for smokers in comparison to non-smokers. The results suggest that: (1) smokers have a higher risk of developing high frequency hearing loss than non-smokers with a similar occupational noise exposure, and (2) the interaction between cigarette smoking and high-level noise exposure may be additive. There is a need to develop and analyze a larger database of workers with well-documented exposures and smoking histories for better understanding of the effect of smoking on NIHL incurred from high-level industrial noise exposures. A better understanding of the role of smoking may lead to its incorporation into hearing risk assessment for noise exposure.

The use of the kurtosis metric in the evaluation of occupational hearing loss in workers in China: implications for hearing risk assessment.

This study examined: (1) the value of using the statistical metric, kurtosis [ß(t)], along with an energy metric to determine the hazard to hearing from high level industrial noise environments, and (2) the accuracy of the International Standard Organization (ISO-1999:1990) model for median noise-induced permanent threshold shift (NIPTS) estimates with actual recent epidemiological data obtained on 240 highly screened workers exposed to high-level industrial noise in China. A cross-sectional approach was used in this study. Shift-long temporal waveforms of the noise that workers were exposed to for evaluation of noise exposures and audiometric threshold measures were obtained on all selected subjects. The subjects were exposed to only one occupational noise exposure without the use of hearing protection devices. The results suggest that: (1) the kurtosis metric is an important variable in determining the hazards to hearing posed by a high-level industrial noise environment for hearing conservation purposes, i.e., the kurtosis differentiated between the hazardous effects produced by Gaussian and non-Gaussian noise environments, (2) the ISO-1999 predictive model does not accurately estimate the degree of median NIPTS incurred to high level kurtosis industrial noise, and (3) the inherent large variability in NIPTS among subjects emphasize the need to develop and analyze a larger database of workers with well-documented exposures to better understand the effect of kurtosis on NIPTS incurred from high level industrial noise exposures. A better understanding of the role of the kurtosis metric may lead to its incorporation into a new generation of more predictive hearing risk assessment for occupational noise exposure.

Use of historical data and a novel metric in the evaluation of the effectiveness of hearing conservation program components.

OBJECTIVES: To evaluate the effectiveness of hearing conservation programs (HCP) and their specific components in reducing noise-induced hearing loss (NIHL). METHODS: This retrospective cohort study was conducted at one food-processing plant and two automotive plants. Audiometric and work-history databases were combined with historical noise monitoring data to develop a time-dependent exposure matrix for each plant. Historical changes in production and HCP implementation were collected from company records, employee interviews and focus groups. These data were used to develop time-dependent quality assessments for various HCP components. 5478 male (30,427 observations) and 1005 female (5816 observations) subjects were included in the analysis. RESULTS: Analyses were conducted separately for males and females. Females tended to have less NIHL at given exposure levels than males. Duration of noise exposure stratified by intensity (dBA) was a better predictor of NIHL than the standard equivalent continuous noise level (L(eq)) based upon a 3-dBA exchange. Within this cohort, efficient dBA strata for males were <95 versus ≥ 95, and for females <90 versus ≥ 90. The reported enforced use of hearing protection devices (HPDs) significantly reduced NIHL. The data did not have sufficient within-plant variation to determine the effectiveness of noise monitoring or worker training. An association between increased audiometric testing and NIHL was believed to be an artifact of increased participation in screening. CONCLUSIONS: Historical audiometric data combined with noise monitoring data can be used to better understand the effectiveness of HCPs. Regular collection and maintenance of quality data should be encouraged and used to monitor the effectiveness of these interventions.

The association between serotonin transporter gene promotor polymorphism (5-HTTLPR) and elemental mercury exposure on mood and behavior in humans.

A functional polymorphism in the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) is reported to affect mood and behavior in humans. In this study, the effects of 5-HTTLPR polymorphism on neurobehavioral and mood domains that are known to be affected by elemental mercury (Hg degrees ) exposure in human subjects were examined. The Behavioral Evaluation for Epidemiologic Studies (BEES) test battery was administered concurrently with urine and buccal-cell collections for 164 male dentists (DD) and 101 female dental assistants (DA) with occupational exposure to Hg degrees for an average of 19 and 10 yr, respectively. Geometric mean urinary mercury (Hg) levels in DD and DA were 2.52 (2.22) microg/L and 1.98 (1.98) microg/L, respectively. Corresponding indices of chronic occupational Hg degrees exposure, weighted for historical exposure, were 1212 (1877) and 316 (429). 5-HTTLPR status was 40% and 20% wild type, 40% and 56% single allelic substitution, and 20% and 24% double allelic substitution for the two genders. DD and DA were evaluated separately. Regression analyses controlled for age, premorbid intelligence, frequency of alcohol per week, and education. 5-HTTLPR polymorphism was associated with 5 behavioral measures in DD and with 12 behavioral measures in DA. Mood scores were more consistently associated with the variant in both groups. The strongest evidence for an additive effect for urinary Hg and 5-HTTLPR polymorphism in both groups was for tests of Finger Tap(Alternate) and Hand Steadiness(Factor1). Other significant additive effects that were less consistent across groups were also observed. These results add to the growing evidence of genetic determinants of mood and behavior that potentially increase susceptibility to Hg toxicity in humans.

Catechol O-methyltransferase (COMT) VAL158MET functional polymorphism, dental mercury exposure, and self-reported symptoms and mood.

Associations were evaluated between a functional single nucleotide polymorphism (Val158Met) in the gene encoding the catecholamine catabolic enzyme catechol O-methyltransferase (COMT), dental mercury exposure, and self-reported symptoms and mood among 183 male dentists and 213 female dental assistants. Self-reported symptoms, mood, and detailed work histories were obtained by computerized questionnaire. Spot urine samples were collected and analyzed for mercury concentrations to evaluate recent exposures, whereas a chronic mercury exposure index for all subjects was created from the work histories. COMT polymorphism status was determined using a polymerase chain reaction (PCR)-based assay. Scores for current, recent, and chronic self-reported symptom groups and six self-reported mood factors were evaluated with respect to recent and chronic mercury exposure and COMT polymorphism status. Multiple regression analysis controlled for age, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Separate evaluations were conducted for dentists and dental assistants. No consistent patterns of association between either urinary mercury concentration or the chronic index of mercury exposure and any category of symptoms were observed. However, consistent and significant associations were found between increased symptoms and the COMT polymorphism involving the double allelic substitution (full mutation) compared to subjects with no substitutions. Associations with mood were limited to polymorphism status among female dental assistants, and were observed for four of six mood factors and overall mood score. These findings extend evidence of genetic factors potentially affecting human susceptibility to the toxic effects of mercury and other environmental chemicals.

The association between serotonin transporter gene promoter polymorphism (5-HTTLPR), self-reported symptoms, and dental mercury exposure.

The associations between a polymorphism of the serotonin transporter gene (5-HTTLPR), dental mercury exposure, and self-reported symptoms were evaluated among 157 male dentists and 84 female dental assistants. Self-reported symptoms and detailed work histories were obtained by computerized questionnaire. Spot urine samples were collected and analyzed for mercury concentrations to evaluate recent exposures, whereas a chronic mercury exposure index was created from the work histories. 5-HTTLPR polymorphism status was determined using a polymerase chain reaction (PCR)-based assay. Scores for current, recent, and chronic self-reported symptom groups were evaluated with respect to recent and chronic mercury exposure and 5-HTTLPR polymorphism status. Multiple regression analysis controlled for age, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Analyses were restricted to Caucasian subjects due to the highly skewed distribution of the 5-HTTLPR polymorphism. Separate evaluations were conducted for dentists and dental assistants. In contrast to previous reports, no consistent associations were found between either urinary mercury concentration or the chronic index of mercury exposure and any category of symptoms. However, both significant and consistent associations were observed between increased symptoms and the 5-HTTLPR polymorphism involving two copies of the short or "s" allele (full mutation), but not with the polymorphism involving only one copy (heterozygous), demonstrating a gene-dose relationship for symptom reporting. These findings suggest that within this restricted population increased symptoms of depression, anxiety, and memory are associated with the 5-HTTLPR polymorphism among both males and females.

Rates and risk factors for human cutaneous anthrax in the country of Georgia: National surveillance data, 2008-2015.

INTRODUCTION: Anthrax is endemic in the country of Georgia. The most common cutaneous anthrax form accounts for 95% of anthrax cases and often is self-resolving. Humans are infected from processing contaminated animal products, contacting sick animals, or by insect bites. OBJECTIVE: We aimed to describe the burden of human cutaneous anthrax and associated risk factors using the national surveillance data. METHODS: We extracted all human cutaneous anthrax cases from Electronic Integrated Disease Surveillance System (EIDSS) from 1 January 2008 to 31 December 2015. We conducted descriptive analyses to characterize the number of confirmed, probable and suspected cases by age groups, gender, ethnicity, year and geographic area. RESULTS: Out of 911 reported cutaneous anthrax cases, 299 (33%) were rejected. Out of remaining 612 cases, 437 (71%), 172 (28%), and 3 (<0.004%) were classified as confirmed, probable and suspected cases of cutaneous Anthrax, respectively; 467 (76.3%) were male. Georgians accounted for 56% (343/612) of cutaneous anthrax cases. Handling animal products (aOR 4.36, 95% CI 2.61-7.26) and living near pastoralist routes (aOR 2.74, 95%CI 1.57-4.76) were associated with cutaneous anthrax. CONCLUSIONS: This study provides eight-year trends for cutaneous anthrax in humans in the country of Georgia. A comprehensive explanation for the observed rise and fall of the incidence rates of human cutaneous anthrax in 2008-2015 remains to be clarified but is likely associated with discontinuation of mandatory national livestock vaccination in 2008 coupled with weakened human and animal national health systems which were disrupted after the Soviet Union collapsed. Our analysis identifies living near pastoralist routes, handling animal products and travel to endemic areas within two weeks before the disease onset as risk factors for cutaneous anthrax. The evidence underscores the importance of One Health recommendations to activate anthrax awareness campaigns, supervise the destruction of known anthrax carcasses, record global position system coordinates of sites and disinfect infected soils and introduce a participatory health education tool on anthrax.

Correction: Rates and risk factors for human cutaneous anthrax in the country of Georgia: National surveillance data, 2008-2015.

[This corrects the article DOI: 10.1371/journal.pone.0192031.].