Longitudinal assessment of oxidative stress markers and their relationship with exposure to PM2.5 and its bound metals in healthy participants.

OBJECTIVE: Exposure to ambient PM2.5 and its bound metals poses a risk to health and disease, via, in part, oxidative stress response. A variety of oxidative stress markers have been used as markers of response, but their relevance to environmental exposure remains to be established. We evaluated, longitudinally, a battery of oxidative stress markers and their relationship with the exposure of PM2.5 and its bound metals in a panel of healthy participants. MATERIAL AND METHODS: Levels of residence- and personal-based ambient air PM2.5 and its bound metals, as well as of lung function parameters, were assessed in a total of 58 questionnaire-administered healthy never smoker participants (male, 39.7%). Levels of urinary oxidative stress markers, including Nε-(hexanoyl)-lysine (HEL; an early lipid peroxidation product), 4-hydroxynonenal (4-HNE), N7-methylguanine (N7-meG), and 8-hydroxy-2-deoxyguanosine (8-OHdG), plasma antioxidants [superoxide dismutase (SOD) and glutathione peroxidase (GPx), and urinary metals were measured by ELISA, LC-MS, and ICP-MS, respectively. The results of three repeated measurements at two-month intervals were analyzed using the Generalized Estimating Equation (GEE). RESULTS: After adjusting for confounders, residence- and personal-based PM2.5 levels were positively associated with HEL (ß = 0.22 and 0.18) and N7-meG (ß = 0.39 and 0.13). Significant correlations were observed between personal air PM2.5-Pb and urinary Pb with HEL (ß = 0.08 and 0.26). While FVC, FEV1, FEV1/FVC, MMF, and PEFR predicted% were normal, a negative interaction (pollutant*time, P < 0.05) was noted for PM2.5-V, Mn, Co, Ni, Zn, As, and Pb. Additionally, a negative interaction was found for N7-meG (ß = -21.35, -18.77, -23.86) and SOD (ß = -26.56, -26.18, -16.48) with FEV1, FVC, and PEFR predicted%, respectively. CONCLUSION: These findings emphasize potential links between environmental exposure, internal dose, and health effects, thereby offering valuable markers for future research on metal exposure, oxidative stress, and health outcomes.

Exposure profiles of workers from indium tin oxide target manufacturing and recycling factories in Taiwan.

Indium tin oxide exposure poses a potential health risk, but the exposure assessment in occupational setting remains incomplete and continues to be a significant challenge. To this end, we investigated the association of work type, airborne indium concentration, respirable fraction of total indium, and cumulative indium exposure index (CEI) with the levels of plasma indium (P-In) and urinary indium (U-In) among 302 indium tin oxide target manufacturing and recycling workers in Taiwan. We observed that recycling-crushing produced the highest concentrations of total indium (area: 2084.8 µg/m3; personal: 3494.5 µg/m3) and respirable indium (area: 533.4 µg/m3; personal: 742.0 µg/m3). Powdering produced the highest respirable fraction of total indium (area: 58.6%; personal: 81.5%), where the workers had the highest levels of P-In (geometric mean: 2.0 µg/L) and U-In (1.0 µg/g creatinine). After adjusting for the confounder, the CEIs of powdering (ßPR = 0.78; ßPR = 0.44), bonding (ßPT = 0.61; ßPT = 0.37), and processing workers (ßPT = 0.43; ßPT = 0.28) showed significant associations with P-In and U-In, validating its utility in monitoring the exposure. Also, the respirable fraction of total indium significantly contributed to the increased levels of P-In and U-In among workers. The varying levels of relationship noted between indium exposure and the levels of P-In and U-In among workers with different work types suggested that setting the exposure limits among different work types is warranted.

The roles of lumbar load thresholds in cumulative lifting exposure to predict disk protrusion in an Asian population.

BACKGROUND: The purpose of this study was to determine whether a specific threshold per lifting movement, the accumulation above which best predicts lumbar disk protrusion, exists or the total lifting load should be considered. METHODS: This was a retrospective study. Subjects with various lifting exposures were recruited. Disk protrusion was assessed by magnetic resonance imaging. The cumulative lifting load was defined as the sum of the time-weighed lumbar load for each job and was calculated using a biomechanical software system. The effectiveness of accumulation above different thresholds in predicting disk protrusion were compared using four statistical methods. RESULTS: A total of 252 men and 301 women were included in the final analysis. For the men, 3000 Newtons for each lifting task was the optimal threshold for predicting L4-S1 disk protrusion, whereas for the women, 2800 Newtons was optimal. CONCLUSIONS: Our findings suggested that for cumulative lifting exposure, including the total lifting load without defining a minimal exposure limit might not be the optimal method for predicting disk protrusion. The NIOSH 3400 Newton recommended limits do not appear to be the optimal thresholds for preventing disk protrusion. Different lifting thresholds might be needed for men and women in the workplace for their safety.

Longitudinal follow-up of health effects among workers handling engineered nanomaterials: a panel study.

BACKGROUND: Although no human illness to date is confirmed to be attributed to engineered nanoparticles, occupational epidemiological studies are needed to verify the health effects of nanoparticles. This study used a repeated measures design to explore the potential adverse health effects of workers handling nanomaterials. METHODS: Study population was 206 nanomaterial-handling workers and 108 unexposed controls, who were recruited from 14 nanotechnology plants. They were followed up no less than two times in four years. A questionnaire was used to collect potential confounders and detailed work conditions. Control banding was adopted to categorize risk level for each participant as a surrogate marker of exposure. Health hazard markers include cardiopulmonary dysfunction markers, inflammation and oxidative damage markers, antioxidant enzymes activity, and genotoxicity markers. The Generalized Estimating Equation model was applied to analyze repeated measurements. RESULTS: In comparison to the controls, a significant dose-dependent increase on risk levels for the change of superoxide dismutase (p<0.01) and a significant increase of glutathione peroxidase change in risk level 1 was found for nanomaterial-handling workers. However, the change of cardiovascular dysfunction, lung damages, inflammation, oxidative damages, neurobehavioral and genotoxic markers were not found to be significantly associated with nanomaterials handling in this panel study. CONCLUSIONS: This repeated measurement study suggests that there was no evidence of potential adverse health effects under the existing workplace exposure levels among nanomaterials handling workers, except for the increase of antioxidant enzymes.

Effects of nanoparticles exposure and PON1 genotype on heart rate variability.

OBJECTIVES: This study was to assess the association between different NPs exposure and PON1 genotype on Heart Rate Variability (HRV) parameters among workers. METHODS: This study included 235 non-CVD subjects handled to nanomaterials (NM) and 185 non-exposed controls without CVD from 14 NM plants. All participants completed short-term HRV measurements, and were collected blood specimens to measure PON1 activities and the genotype of the PON1 Q192R polymorphism. RESULTS: In a multivariate regression model, this study observed a positive relationship between nano-Ag exposure and HRV time-domain (RMSSD) and frequency-domain (HF). After adjusting for confounders, the results showed positive associations between RR homozygosity, PON1 paraoxonase/arylesterase activities with HRV, and was particularly noteworthy in RMSSD and HF. CONCLUSIONS: This study shows a significant increment of RMSSD and HF among workers who handled Nano-Ag materials. These results imply that Nano-Ag and PON1 Q192R genotype can trigger ANS reflexes and alter cardiac frequency and function.

Measurement of urinary arsenic profiles and DNA hypomethylation in a case-control study of urothelial carcinoma.

Environmental exposure to arsenic may be involved in the disturbance of DNA hypomethylation. The aim of this study is the first to explore the effect of interactions of urinary total arsenic levels, arsenic methylation capacity, 8-hydroxy-2'-deoxyguanosine (8-OHdG), plasma folate, and global 5-methyl-2'-deoxycytidine (5-MedC) levels on the risk of urothelial carcinoma (UC). A hospital-based case-control study was constructed. The research involved the histological recruitment and pathological verification of 178 UC patients and 356 age-/sex-matched controls without prior history of cancer. Arsenic species were determined by high-performance liquid chromatography (HPLC)-hydride generation and atomic absorption. 5-MedC levels were detected by HPLC and triple-quadrupole mass spectrometry (MS). 8-OHdG was processed by an online solid-phase extraction LC-MS/MS. Plasma folate levels were measured using the chemiluminescent technology. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multiple logistic regression analysis. Results indicate that the high levels of total urinary arsenic, inorganic arsenic percentage, and 8-OHdG and the low levels of DMA % and plasma folate were independent factors of UC. In addition, global 5-MedC levels in the first quartile versus fifth quartile significantly increased the twofold OR of UC after potential factors were adjusted (95% CI:1.10-4.03). The interaction of 5-MedC level and high total arsenic level, insufficient arsenic capacity, high 8-OHdG, and low folate levels was insignificant. Results of stepwise logistic regression analysis indicate that high total urinary arsenic levels (Q3 versus Q1), low plasma folate level, and low global 5-MedC (Q4 versus Q5) significantly increased the ORs of UC. The above results suggest that high total arsenic, low plasma folate, and 5-MedC levels affect the ORs of UC independently.

Professional Driver's Job Stress and 8-year Risk of Cardiovascular Disease: The Taiwan Bus Driver Cohort Study.

BACKGROUND: Two main job stress models-the Demand-Control-Support (DC) model and the Effort-Reward Imbalance (ERI) model have been used to assess the impact of psychosocial work-related factors for cardiovascular disease (CVD). Limited evidence elaborates the independent and combined effects on CVD events, especially for professional drivers. This study assesses the independent and combined effects of DC and ERI models on an 8-year risk of CVD among professional drivers. METHODS: The Taiwan Bus Driver Cohort Study recruited 1650 professional drivers from a large bus company in 2005. The subjects were interviewed in person and completed the two job stress questionnaires. Researchers found 94 new cases of CVD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 390-459) from 2006 to 2012. A Cox proportional hazards model was performed to estimate the hazard ratio (HR) for CVD events. RESULTS: Occupational drivers with high overcommitment scores (thresholds of 15) had an elevated risk for CVD (HR = 1.71; 95% CI = 1.04, 2.82). Regarding target disease, overcommitment had an increased risk for CVD (not including hypertensive disease) (HR = 1.27; 95% CI = 1.05, 1.54) and ischemic heart disease (HR = 1.32; 95% CI = 1.05-1.65). CONCLUSION: Overcommitment, which is associated with job stress, appears to be associated with CVD risk in professional drivers.

Levels and temporal variations of urinary lead, cadmium, cobalt, and copper exposure in the general population of Taiwan.

Toxic metal contamination in food products and the environment is a public health concern. Therefore, understanding human exposure to cadmium (Cd), lead (Pb), cobalt (Co), and copper (Cu) levels in the general population of Taiwan is necessary and urgent. We aimed to establish the human biomonitoring data of urine toxic metals, exposure profile changes, and factors associated with metal levels in the general population of Taiwan. We randomly selected 1601 participants older than 7 years of age (36.9 ± 18.7 years (7-84 years)) from the Nutrition and Health Survey in Taiwan (NAHSIT) conducted during 1993-1996 (93-96) and 2005-2008 (05-08) periods and measured the levels of four metals in the participants' urine samples using inductively coupled plasma-mass spectrometry. The median (range) levels of urinary Cd, Pb, Co, and Cu in participants from the NAHSIT 93-96 (N = 821)/05-08 (N = 780) were 0.60 (ND-13.90)/0.72 (ND-7.44), 2.28 (ND-63.60)/1.09 (0.04-48.88), 0.91 (0.08-17.30)/1.05 (0.05-22.43), and 16.87 (2.62-158.28)/13.66 (1.67-189.70) µg/L, respectively. We found that the urinary median levels of Pb and Cu in our participants were significantly lower in the NAHSIT 05-08 (Pb 1.09 µg/L, Cu 13.66 µg/L) than in the NAHSIT 93-96 (Pb 2.28 µg/L, Cu 16.87 µg/L; P < 0.01), whereas those of Cd and Co were significantly higher in the NAHSIT 05-08 (Cd 0.72 µg/L, Co 1.05 µg/L; P < 0.01). Youths had higher exposure levels of Pb, Co, and Cu than adults. Participants with alcohol consumption, betel quid chewing, or cigarette smoking had significantly higher median levels of urinary Pb or Cu (P < 0.01) than those without. Principal components and cluster analysis revealed that sex had different exposure profiles of metals. We concluded that levels of urinary Cd, Pb, Co, and Cu exposure in the general Taiwanese varied by age, sex, and lifestyles.

Identification of osteopontin as a biomarker of human exposure to fine particulate matter.

Ambient particulate matter (PM) exposure is associated with pulmonary and cardiovascular diseases; however, there is scant research linking data on animal and human cells. The objective of this study was to investigate these associations. Vascular remodeling plays a crucial role in both pulmonary and cardiovascular diseases. Therefore, we conducted a transcriptomic analysis using vascular smooth muscle cells (VSMCs) to identify potential regulators or markers of PM exposure. We demonstrated that fine and coarse PM increased VSMC proliferation in mice. We conducted a genome-wide cDNA microarray analysis, followed by a pathway analysis of VSMCs treated with coarse PM for durations of 24, 48, and 72 h. Sixteen genes were discovered to be time-dependently upregulated and involved in VSMC proliferation. Osteopontin (OPN) is indicated as one of the regulators of these upregulated genes. Both fine and coarse PM from industrial and urban areas significantly increased OPN expression in VSMCs and macrophages. Moreover, oropharyngeal instillation of fine and coarse PM for 8 weeks increased the VSMCs in the pulmonary arteries of mice. OPN level was consistently increased in the lung tissues, bronchoalveolar lavage fluid, and serum of mice. Moreover, we analyzed the plasma OPN levels of 72 healthy participants recruited from the studied metropolitan area. Each participant wore a personal PM2.5 sampler to assess their PM2.5 exposure over a 24 h period. Our results indicate that personal exposure to fine PM is positively correlated with plasma OPN level in young adults. The data obtained in this study suggest that exposure to fine and coarse PM may cause pulmonary vascular lesions in humans and that OPN level may be a biomarker of PM exposure in humans.

Clustering of malignant pleural mesothelioma in asbestos factories: a subgroup analysis in a 29-year follow-up study to identify high-risk industries in Taiwan.

OBJECTIVE: Exposure to asbestos is the major cause for malignant pleural mesothelioma (MPM), but the causal link of individual cases is difficult to establish for lack of exposure information and long disease latency. METHODS: We established a retrospective cohort of workers employed in asbestos industries during the period of 1950-1989 and the occurrence of MPM during the period of 1980-2009 was examined with the Taiwan Cancer Registry. Estimated rate ratios (eRRs) were computed for each factory where any case of MPM was diagnosed by assuming Poisson distribution with a minimal latency of 20 years. RESULTS: A total of 18 MPM (17 males, 1 female) in eight factories were found. The incidence rate of MPM for the eight factories was 18.0 per million, ranging from 6.2 per million (military factory) to 268.2 per million (asbestos cement). We observed significantly increased risks for MPM in asbestos cement, thermal insulation and shipbuilding industries, with eRR (genders combined) of 113.6, 87.5 and 15.8, respectively. The sensitivity analyses considering latency showed similar findings in latency ≥30 years, and the shipbuilding industry presented a significant eRR given a latency ≥40 years. The gender-specific eRR showed similar results in men, but high eRR of 729.6 was observed in an asbestos cement factory where a female MPM was diagnosed. CONCLUSIONS: This nationwide study in Taiwan comprehensively shows that different asbestos manufacturing processes, including asbestos cement, thermal insulation and shipbuilding industries, were at significantly increased risks for MPM. We recommend to establish a medical screening programme for workers previously exposed to asbestos to identify MPM and other asbestos-related diseases at an earlier stage.

The impact of occupational psychological hazards and metabolic syndrome on the 8-year risk of cardiovascular diseases-A longitudinal study.

There was little information concerning the combined effect of occupational psychosocial hazards such as long working hours, high job stress, and high fatigue on the risk of cardiovascular and cerebrovascular diseases (CVD). The aim of this study was to investigate the interaction among occupational psychosocial hazards and the impact of metabolic syndrome (MetS) on the risk of CVD among bus drivers. The Taiwan Bus Driver Cohort Study involving 1014 professional drivers was established in 2005 and comprehensively studied. The interactions among occupational psychosocial hazards and the impact of MetS on the risk of CVD were measured. A working pattern questionnaire, job stress questionnaires, the Swedish occupational fatigue inventory, the stress satisfaction offset score, biochemical measurements, and physical examinations were used to assess psychosocial hazards and the presence of metabolic syndrome. There were 707 eligible bus drivers with a mean age of 43.5years old. During the 8-years of follow-up, 77 drivers were diagnosed with CVD. Long working hours, high job stress, and high fatigue were associated with an increased risk of cardiovascular disease incidence in the multivariate analysis. There were synergistic effects among long working hours, high job stress, and high fatigue only in drivers with MetS. A combination of long working hours, high job stress, and high fatigue increased the risk of developing CVD in bus drivers with MetS.

Risk of Alzheimer's disease with metal concentrations in whole blood and urine: A case-control study using propensity score matching.

Environmental exposure to heavy metals is suspected to result in neuropathology damage and cognitive impairment. We aimed to explore the association of Alzheimer's disease (AD) risk with the internal dose of heavy metals by constructing a hospital-based case-control study and using propensity-score-matching methods. We investigated 170 patients with AD and 264 controls from the Department of Neurology and Family Medicine, China Medical University Hospital in Taiwan. All patients with AD received clinical neuropsychological examination and cognitive-function assessments, including the mini-mental status examination and clinical dementia rating scale. We also constructed a propensity-score-matched population of 82 patients with AD and 82 controls by matching age, gender, education, and AD-related comorbidity. Blood levels with cadmium, lead, mercury, selenium, and urinary arsenic profile were measured. Logistic regression models and 95% confidence intervals (CIs) were applied to estimate AD risk. After stratification by respective quartile cutoffs of heavy metals, the AD risk of study participants with high urinary inorganic arsenic (InAs%) or low dimethylarsinic acid (DMA%) significantly increased (p < 0.05), as similarly found in the propensity-score-matched population. In addition, people with a low median level of selenium and high median level of InAs%, or/and a low median level of DMA% had approximately two- to threefold significant AD risk. Urinary arsenic profiles may be associated with increased AD risk. Repeat measurements of heavy metals with large sample size and the surveying of potential exposure sources are recommended in future studies.

Feasibility of using urinary N7-(2-carbamoyl-2-hydroxyethyl) Guanine as a biomarker for acrylamide exposed workers.

Acrylamide (AA), a probable human carcinogen, is a widely-used industrial chemical but is also present in tobacco smoke and carbohydrate-rich foods processed at high temperatures. AA is metabolized to glycidamide (GA) to cause the formation of DNA adducts. N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GAG), the most abundant DNA adduct induced by GA, was recently detected in urine of smokers and non-smokers. In this study, we assessed the variability of AA exposure and biomarkers of AA exposure in urine samples repeatedly collected from AA-exposed workers and explored the half-life of N7-GAG. A total of 8 AA-exposed workers and 36 non-exposed workers were recruited. Pre-shift and post-shift urine samples were collected from the exposed group in parallel with personal sampling for eight consecutive days and from the control group on day 1 of the study. Urinary N7-GAG and the mercapturic acids of AA and GA, namely N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-(R,S)-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) were analyzed using on-line solid phase extraction-liquid chromatography-electrospray ionization/tandem mass spectrometry methods. We found that N7-GAG levels in urine were significantly higher in exposed workers than in controls and that N7-GAG level correlated positively with AAMA and GAMA levels. Results from this study showed that AAMA and GAMA possibly remain the more preferred biomarkers of AA exposure and that N7-GAG levels could be elevated by occupational exposures to AA and serve as a biomarker of AA-induced genotoxicity for epidemiological studies.

Exposure to fine particulate matter causes oxidative and methylated DNA damage in young adults: A longitudinal study.

An increased understanding is needed of the physiological effects and plausible biological mechanisms that link PM2.5 (particulate matter with an aerodynamic diameter below 2.5µm) exposure to mortality and morbidities such as atherosclerosis and respiratory disease. PM2.5 causes carcinogenic health effects. Biomonitoring in humans has suggested that 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxodG) and N7-methylguanine (N7-MeG) are correlated with oxidative and methylated DNA damage. Thus, it is meaningful to explore the mechanisms of mutagenesis and carcinogenesis associated with oxidative and methylated DNA damage by simultaneously measuring these two markers. We recruited 72 participants from 2 areas (residential and commercial as well as residential and industrial) in the greater Taipei metropolitan area at baseline. Personal samplers were used to collect 24-hour PM2.5-integrated samples. All participants completed an interview, and blood and urine samples were collected the next morning. All collection procedures were repeated twice after a two-month follow-up period. Urinary 8-oxodG and N7-MeG were assayed as biomarkers of oxidative and methylated DNA damage, respectively. Plasma superoxide dismutase (SOD) and glutathione peroxidase-1 (GPX-1) were measured as biomarkers of antioxidants. Urinary 1-hydroxypyrene (1-OHP) was used as a biomarker of exposure to polycyclic aromatic hydrocarbons (PAHs). The mean PM2.5 level was 37.3µg/m3 at baseline. PM2.5 concentrations were higher during winter than during spring and summer. After adjusting for confounds through a generalized estimating equation (GEE) analysis, N7-MeG was significantly increased by 8.1% (ß=0.034, 95% CIs=0.001-0.068) per 10µg/m3 increment in PM2.5. 8-oxodG levels were positively correlated with N7-MeG according to both cross-sectional and longitudinal analyses, and 1-OHP was significantly associated with increasing 8-oxodG and N7-MeG concentrations. Exposure to PM2.5 increases methylated DNA damage. The mean level of urinary N7-MeG was 1000-fold higher than that of 8-oxodG.

Global DNA methylation and oxidative stress biomarkers in workers exposed to metal oxide nanoparticles.

This is the first study to assess global methylation, oxidative DNA damage, and lipid peroxidation in workers with occupational exposure to metal oxide nanomaterials (NMs). Urinary and white blood cell (WBC) 8-hydroxydeoxyguanosine (8-OHdG), and exhaled breath condensate (EBC) 8-isoprostane were measured as oxidative stress biomarkers. WBC global methylation was measured as an epigenetic alteration. Exposure to TiO2, SiO2, and indium tin oxide (ITO) resulted in significantly higher oxidative biomarkers such as urinary 8-OHdG and EBC 8-isoprostane. However, significantly higher WBC 8-OHdG and lower global methylation were only observed in ITO handling workers. Significant positive correlations were noted between WBC and urinary 8-OHdG (Spearman correlation r=0.256, p=0.003). Furthermore, a significant negative correlation was found between WBC 8-OHdG and global methylation (r=-0.272, p=0.002). These results suggest that exposure to metal oxide NMs may lead to global methylation, DNA oxidative damage, and lipid peroxidation.

Usefulness of overnight pulse oximeter as the sleep assessment tool to assess the 6-year risk of road traffic collision: evidence from the Taiwan Bus Driver Cohort Study.

Background: In order to support health service organizations in arranging a system for prevention of road traffic collisions (RTC), it is important to study the usefulness of sleep assessment tools. A cohort study was used to evaluate the effectiveness of subjective and objective sleep assessment tools to assess for the 6-year risk of both first RTC event only and recurrent RTC events. Methods: The Taiwan Bus Driver Cohort Study (TBDCS) recruited 1650 professional drivers from a large bus company in Taiwan in 2005. The subjects were interviewed in person, completed the sleep assessment questionnaires and had an overnight pulse oximeter survey. Moreover, this cohort of drivers was linked to the National Traffic Accident Database (NTAD) and researchers found 139 new RTC events from 2005 to 2010. Primary outcomes were traffic collisions from NTAD, nocturnal oxygen desaturation index (ODI) from pulse oximeter, Pittsburg sleeping quality score, Epworth daytime sleepiness score, Snore Outcomes Survey score and working patterns from questionnaires. A Cox proportional hazards model and an extended Cox regression model for repeated events were performed to estimate the hazard ratio for RTC. Results: The RTC drivers had increased ODI4 levels (5.77 ± 4.72 vs 4.99 ± 6.68 events/h; P = 0.008) and ODI3 levels (8.68 ± 6.79 vs 7.42 ± 7.94 events/h; P = 0.007) in comparison with non-RTC drivers. These results were consistent regardless of whether ODI was evaluated as a continuous or a categorical variable. ODI4 and ODI3 levels increased the 6-year RTC risks among professional drivers even after adjusting for age, education, history of cardiovascular disease, caffeine intake, sleeping pills used, bus driving experience and shift modes. Moreover, there was an increased trend for ODI between the stratification of the number of RTCs in comparison with the non-RTC group. In the extended Cox regression models for repeated RTC events with the Anderson and Gill intensity model and Prentice-Williams-Petersen model, measurement of ODI increased hazards of the subsequent RTC events. Conclusion: This study showed that an increase in the 6-year risk of RTC was associated with objective measurement of ODI for a sign of sleep-disordered breathing (SDB), but was not associated with self-reported sleeping quality or daytime sleepiness. Therefore, the overnight pulse oximeter is an effective sleep assessment tool for assessing the risk of RTC. Further research should be conducted regarding measures to prevent against SDB among professional drivers.

Effect of CYP3A4 genetic polymorphisms on the genotoxicity of 4,4'-methylene-bis(2-chloroaniline)-exposed workers.

OBJECTIVES: We investigated the relationship between 4,4'-methylene-bis(2-chloroaniline) (MBOCA) exposure and micronucleus (MN) frequency, and how this association was affected by genetic polymorphism of the cytochrome P450 enzyme (CYP3A4). METHODS: We divided the study population into an exposed group (n=44 with total urine MBOCA ≥20 µg/g creatinine) and a control group (n=47 with total urine MBOCA <20 µg/g creatinine). Lymphocyte MN frequency (MNF) and micronucleated cell (MNC) frequency were measured by the cytokinesis-block MN assay method. MNF reported as the number of micronuclei in binucleated cells per 1000 cells, and MNC reported as the number of binucleated cells with the presence of MN per 1000 cells. CYP3A4 alleles were measured by PCR-based restriction fragment length polymorphism (PCR-RFLP). RESULTS: The mean MNF (6.11 vs 4.46 MN/1000 cells, p<0.001) and MNC (5.75 vs 4.15 MN/1000 cells, p<0.001) in the exposed workers was significantly higher than that in the controls. The CYP3A4 polymorphism A/A+A/G influenced the difference in the mean MNF (5.97 vs 4.38 MN/1000 cells, p<0.001) and MNC (5.60 vs 4.15 MN/1000 cells, p<0.001) between the MBOCA-exposed and control groups. After adjusting risk factors, the MNF level in the MBOCA-exposed workers was 0.520 MN cells/1000 cells (p<0.001) higher than the control group among the CYP3A4 A/A+A/G genotype. Similarly, the MNC level in the MBOCA-exposed workers was 0.593 MN/1000 cells (p<0.001) higher than the control group among the CYP3A4 A/A+A/G genotype. However, the difference in adjusted MNF and MNC between the exposed and control groups was not significant for the CYP3A4 polymorphism with the G/G genotype. CONCLUSIONS: We recommend that lymphocytes MNF and MNC are good indicators to evaluate MBOCA genotoxicity. Individuals with the CYP3A4 polymorphism A/A and A/G genotypes appear to be more susceptible to MBOCA genotoxicity.

Relationships among DNA hypomethylation, Cd, and Pb exposure and risk of cigarette smoking-related urothelial carcinoma.

Cigarette smoking and environmental exposure to heavy metals are important global health issues, especially for urothelial carcinoma (UC). However, the effects of cadmium and lead exposure, as well as the levels of DNA hypomethylation, on UC risk are limited. We evaluated the possible exposure sources of Cd and Pb and the relationship among DNA hypomethylation, urinary Cd and Pb levels, and UC risk. We recruited 209 patients with UC and 417 control patients for a hospital-based case-control study between June 2011 and August 2014. We collected environmental exposure-related information with questionnaires. Blood and urine samples were analyzed to measure the Cd and Pb exposure and 5-methyl-2'-deoxycytidine levels as a proxy for DNA methylation. Multivariate logistic regression and 95% confidence intervals were applied to estimate the risk for UC. Study participants with high Cd and Pb exposure in blood or urine had significantly increased risk of UC, especially among the smokers. After adjusting for age and gender, the possible connections of individual cumulative cigarette smoking or herb medicine exposure with the increased levels of Cd and Pb were observed in the controls. Participants with 8.66%-12.39% of DNA hypomethylation had significantly increased risk of UC compared with those with ≥12.39% of DNA hypomethylation. Environmental factors including cigarette smoking and herb medicine may contribute to the internal dose of heavy metals levels. Repeat measurements of heavy metals with different study design, detailed dietary information, and types of herb medicine should be recommended for exploring UC carcinogenesis in future studies.

Utility of overnight pulse oximeter as a screening tool for sleep apnea to assess the 8-year risk of cardiovascular disease: Data from a large-scale bus driver cohort study.

BACKGROUND: Professional drivers' work under conditions predisposes them for development of sleep-disordered breathing (SDB) and cardiovascular disease (CVD). However, the effect of SDB on CVD risk among professional drivers has never been investigated. A cohort study was used to evaluate the effectiveness of overnight pulse oximeter as a sleep apnea screening tool to assess the 8-year risk of CVD events. METHODS: The Taiwan Bus Driver Cohort Study (TBDCS) recruited 1014 professional drivers in Taiwan since 2005. The subjects completed questionnaire interview and overnight pulse oximeter survey. This cohort was linked to the National Health Insurance Research Dataset (NHIRD). Researchers found 192 CVD cases from 2005 to 2012. Cox proportional hazards model was performed to estimate the hazard ratio for CVD. The statistical analysis was performed using SAS software in 2015. RESULTS: ODI4 and ODI3 levels increased the 8-year CVD risk, even adjusting for CVD risk factors (HR: 1.36, 95% CI: 1.05 to 1.78; p=0.022, and HR: 1.40, 95% CI: 1.03 to 1.90; p=0.033). ODI4 and ODI3 thresholds of 6.5 and 10events/h revealed differences of CVD risks (HR: 1.72, 95% CI: 1.00 to 2.95; p=0.048, and HR: 1.76, 95% CI: 1.03 to 3.03; p=0.041). Moreover, the ODI levels had an increased risk for hypertensive disease (not including essential hypertension). CONCLUSIONS: This study concludes that ODI for a sign of SDB is an independent predictor of elevated risk of CVD. Further research should be conducted regarding measures to prevent against SDB in order to reduce CVD risk in professional drivers.

The relationship between plasma and urinary 8-hydroxy-2-deoxyguanosine biomarkers measured by liquid chromatography tandem mass spectrometry.

Although 8-hydroxy-2-deoxyguanosine (8-OHdG) is a widely used promising biomarker of DNA damage, there are concerns about which tissues or body fluids should be sampled. The objective of this study is to evaluate the correlation of DNA oxidative damage biomarkers, 8-OHdG, between blood and urine and risk factors associated with 8OHdG. The study population was recruited from a baseline survey of a worksite lifestyle study including 92 office workers aged 23 to 60 years. A self-administered questionnaire was used to collect information on personal characteristics. The plasma and urinary 8-OHdG was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). In linear regression, a positive relation was found (p < 0.01) between the log-transformed plasma and urinary 8-OHdG levels adjusted for gender, age, BMI, and smoking status. Our findings showed that age, gender and smoking were significantly associated with plasma 8-OHdG, but not with urinary 8-OHdG. Our results suggest that there is a positive relation between the biomarkers of plasma (steady state DNA damage) and urinary 8-OHdG (total DNA damage). However, the plasma 8-OHdG is more sensitive than urinary 8-OHdG to detect increased oxidative damages induced by risk factors.