Determination of potential sources of heavy metals in patients with urothelial carcinoma in central Taiwan: a biomonitoring case-control study.

The clarification of possible exposure sources of multiple metals to identify associations between metal doses and urothelial carcinoma (UC) risk is currently limited in the literature. We sought to identify the exposure sources of 10 metals (Vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, cadmium, and lead) using principal component analysis (PCA) and then linked various principal component (PC) scores with environmental characteristics, including smoking-related indices, PM2.5, and distance to the nearest bus station. In addition, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and DNA hypomethylation markers (5-methyl-2'-deoxycytidine levels; %5-MedC) were investigated in combination with UC risks. We conducted this hospital-based case control study in 359 UC patients with histologically confirmed disease and 718 controls. All data were collected from face-to-face interviews and medical records. Approximately 6 mL blood was collected from participants for analysis of multiple heavy metal and DNA methylation in leukocyte DNA. Further, a 20 mL urine sample was collected to measure urinary cotinine and 8-OHdG levels. In addition, average values for PM2.5 for individual resident were calculated using the hybrid kriging/land-use regression model. In UC patients, significantly higher cobalt, nickel, copper, arsenic, and cadmium (µg/L) levels were observed in blood when compared with controls. Three PCs with eigenvalues > 1 accounted for 24.3, 15.8, and 10.7% of UC patients, and 26.9, 16.7, and 11.1% of controls, respectively. Environmental metal sources in major clusters were potentially associated with industrial activities and traffic emissions (PC1), smoking (PC2), and food consumption, including vitamin supplements (PC3). Multiple metal doses were linked with incremental urinary 8-OHdG and DNA hypomethylation biomarkers. For individuals with high PC1 and PC2 scores, both displayed an approximate 1.2-fold risk for UC with DNA hypomethylation.In conclusion, we provide a foundation for health education and risk communication strategies to limit metal exposure in environment, so that UC risks can be improved potentially.

Association of SGLT2 inhibitors with lower incidence of death in type 2 diabetes mellitus and causes of death analysis.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) potentially decrease all-cause and cardiovascular death, however, associations with non-cardiovascular death remain unclear. Therefore, we investigated SGLT2i associations with death and the cause of death. We used the Taiwanese National Health Institutes Research database linked to the National Register of Deaths (NRD). Incident type 2 diabetes mellitus (T2DM) patients and propensity score matched T2DM SGLT2i and Dipeptidyl peptidase 4 inhibitor (DPP4i) users were investigated. The index year was the SGLT2i or DPP4i prescription date from May 2016. Patients were followed-up until death or December 2018. Deaths verified by the NRD and grouped accordingly. Multiple Cox proportional hazards models were used. In total, 261,211 patients were included in the population; 47% of the patients were female and the average age was 62 years. The overall incidence of all-cause death was 8.67/1000 patient-years for SGLT2i and 12.41 for DPP4i users during follow-up. After adjusting for potential risk factors in the propensity score matched population, SGLT2i users were associated with lower risks of all-cause death, cardiovascular death, cancer death, and non-cancer, non-vascular death compared with DPP4i-users. For specific death causes, significantly lower death risks from heart disease, cerebrovascular disease, and accidents were associated with SGLT2i-use. SGLT2i benefits for T2DM patients were not different across subgroups. Compared with DPP4i-use, SGLT2i-use for T2DM was associated with lower disease and death risk.

Long-Term Exposure to Fine Particulate Matter and the Deterioration of Estimated Glomerular Filtration Rate: A Cohort Study in Patients With Pre-End-Stage Renal Disease.

Limited literature has explored the effect of air pollutants on chronic kidney disease (CKD) progression, especially for patients with pre-end-stage renal disease (pre-ESRD). In this study, we reported the linear and nonlinear relationships of air pollutants of particles with diameter <2.5 µm (PM2.5) and nitrogen dioxide (NO2) with estimated glomerular filtration rate (eGFR) deterioration after adjusting for smoking status and other traditional clinical factors. This study adopted a retrospective cohort of patients with stage 3b to stage 5 CKD (N = 11,479) from Taichung Veterans General Hospital during January 2006 to December 2020. The eGFR deterioration was defined as a decline in eGFR > 5 ml/min/1.73 m2/year. Hybrid kriging/land-use regression models were used to estimate the individual exposure levels of PM2.5 and NO2. The relationships of air pollutants with eGFR deterioration were evaluated using Cox proportional hazard models. After adjusting for smoking status, baseline eGFR stages, and other traditional clinical factors, the risk of eGFR deterioration was found to increase with increasing PM2.5 and NO2 level (p < 0.0001 and p = 0.041, respectively), especially for those exposed to PM2.5 ≥ 31.44 µg/m3 or NO2 ≥ 15.00 ppb. Similar results were also found in the two-pollutant models. Nonlinear dose-response relationships of eGFR deterioration were observed for concentrations of 26.11 µg/m3 for PM2.5 and 15.06 ppb for NO2. In conclusion, linear and nonlinear associations between PM2.5 and NO2 levels and the incidence risk of eGFR deterioration were observed in patients with pre-ESRD.

Relationships of multiple metals exposure, global DNA methylation, and urothelial carcinoma in central Taiwan.

The relationship between heavy metal exposure and human health has been investigated mostly for individual metals, failing to consider their potential interactions. In this study, we assessed the joint effects of multiple metals using generalized weighted quantile sum (WQS) regression on the risk of urothelial carcinoma (UC). Also, we performed mediation analysis to evaluate the mediator %5-MedC in DNA involved in the mechanism of urothelial carcinogenesis. We conducted a hospital-based case-control study of 355 UC patients and 710 controls, where diagnosis of UC was histologically confirmed. All data were collected from face-to-face interviews and medical records. Also, we measured six metals and 8-OHdG in urine samples along with %5-MedC in peripheral blood. Ni and Pb levels increased with UC risk in single-pollutant analysis using traditional logistic regression, and similar results were obtained in multi-pollutant analysis, where all metals analyzed were considered. In WQS analysis, the weights of Ni (27%), Pb (20%), Cr (18%), and Co (16%) predominated in the metal mixture index. WQS score and UC risk showed odds ratios of 1.65 (95%CI: 1.26, 2.15) and 1.43 (95%CI: 1.00, 2.05) for a linear and non-linear relationship, respectively. Finally, we did not observe a natural indirect effect of %5-MedC in DNA; however, a marginal effect of WQS score and natural direct effect were still found after considering a natural indirect effect. In conclusion, positive associations between WQS scores and increased risk of UC were observed. Interactions of multiple metals should be considered in assessing human health risk.

Integration of biomonitoring data and reverse dosimetry modeling to assess population risks of arsenic-induced chronic kidney disease and urinary cancer.

Chronic exposure to inorganic arsenic (iAs) is associated with chronic kidney disease (CKD) and urinary cancer, but the risks are poorly understood. Human biomonitoring can serve as a tool to better quantify human exposure and to conduct risk assessment. We aimed to assess the population risks of CKD and urinary cancer due to iAs intake based on the blood arsenic concentrations of 601 participants in Taiwan. A physiologically based pharmacokinetic modeling-based reverse dosimetry was conducted to estimate the daily intakes of iAs (DIiAs). We performed the benchmark dose (BMD) modeling for CKD using participants' estimated glomerular filtration rate (eGFR) and the estimated DIiAs to derive a point of departure (POD). Margin of exposure (MOE) was used to characterize the risks. The population with eGFR values of <60 mL/min/1.73 m2 had significantly higher DIiAs (median: 3.20 µg/kg/day, 2.5th-97.5th percentiles: 2.35-4.67 µg/kg/day) than those with normal renal function (1.99, 1.22-3.42 µg/kg/day). The POD for CKD was 1.557 µg/kg/day, which could serve as a possible reference value for CKD risk assessment. The MOEs indicated that the CKD risk due to iAs intake may potentially be a cause for high concern for the population with reduced renal function. The iAs-induced urinary cancer risk may be a cause for moderate-to-high concern.

Relationships among cigarette smoking, urinary biomarkers, and urothelial carcinoma risk: a case-control study.

Cigarette smoke is a known risk factor for urothelial carcinoma (UC). However, there is limited information about the distributions and effects of volatile organic compounds (VOCs) on smoking-related UC risk. With this hospital-based case-control study, we explored the associations between urinary levels of cotinine and VOC metabolites (acrylamide, 1,3-butadiene, and benzene) and the risk of UC. Urological examinations and pathological verifications were used to confirm the diagnoses of UC. All study participants provided smoking-related information via questionnaires and face-to-face interviews; they also provided urine samples for the measurement of VOC metabolites, cotinine, and 8-hydroxydeoxyguanosine (8-OHdG), which was used as an indicator of oxidative stress. We applied multiple logistic regression analysis to estimate the risk of UC, and we found that levels of urinary cotinine and 8-OHdG were higher in the UC group than in the control group. Furthermore, urinary levels of VOC metabolites, including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine-3, trans,trans-muconic acid (t,t-MA), and S-phenylmercapturic acid (SPMA), increased with increasing levels of urinary cotinine. After adjusting for potential risk factors, dose-response relationships were observed between UC risk and urinary levels of AAMA, t,t-MA, SPMA, and 8-OHdG. Participants with high urinary levels of cotinine, AAMA, t,t-MA, SPMA, and 8-OHdG had risks of UC that were 3.5- to 6-fold higher than those of participants with lower levels. Future, large-scale investigations of the risks of UC should be explored, and repeated measurement of VOC metabolites should be assessed.

Effect of Implementing Electronic Toll Collection in Reducing Highway Particulate Matter Pollution.

Highway vehicle emissions can result in adverse health problems to nearby residents and workers, especially during traffic congestion. In response, the policy to implement electronic toll collection (ETC) has helped alleviate traffic congestion, as compared to manual toll collection (MTC) and has led to reduced air pollution and improved public health. However, the effect of ETC in reducing particulate matter polluting the air is not well understood, especially in the ultrafine particle (UFP) range (particle diameter <100 nm). To the best of our knowledge, this is the first study to investigate how ETC affects the traffic pattern and air quality, especially UFP and PM2.5. We selected a site in Tainan, Taiwan, and measured UFP and PM2.5 concentrations before and after the construction of the ETC system. The computed traffic volumes during peak travel periods (7:00 AM to 9:00 AM and 4:00 PM to 6:00 PM) respectively, accounted for approximately 23-25% and 14-18% before and after the implementation of ETC, indicating that peak traffic volumes were more homogeneous after ETC. Moreover, the results indicate that the full implementation of ETC can help reduce UFP number concentrations and PM2.5 mass concentrations in the highway downwind area by 4 × 103 #/cm3 and 20.5 µg/m3, respectively. After the full implementation of the ETC, significant reductions in both the UFP number concentration and PM2.5 mass concentration were seen. Furthermore, excessive lifetime cancer risks (ELCR) from exposure to PM2.5 and UFP together were reduced 49.3% after the implementation of the ETC. Accordingly, ETC not only helps alleviate traffic congestion but also reduces traffic emissions and lifetime cancer risk for people living or working near highways.

PM2.5 components and outpatient visits for asthma: A time-stratified case-crossover study in a suburban area.

The effects of fine particles (PM2.5) on asthma have been widely confirmed by epidemiological research studies. However, a limited number of studies have investigated the relationship between exposure to different PM2.5 components and asthma. We characterized the PM2.5 components in a suburban site of central Taiwan and conducted a time-stratified case-crossover study to elaborate the effects of daily concentration of each PM2.5 component on asthma outpatient visits. We retrieved asthma outpatient claims for individuals less than 20 years old with a residential address in the Shalu district, Taiwan, from the National Health Insurance Research Database during 2000-2010. Multiple linear regression models were used to back extrapolate the historic concentration of individual components of PM2.5 from 2000 through to 2010, including black carbon (BC) and eight ions, namely, sulfate, nitrate (NO3-), ammonium, chloride, potassium (K+), magnesium, calcium, sodium. The odds ratio (OR) with a 95% confidence interval (CI) of individual PM2.5 components on asthma was estimated by conditional logistic regression. A total of 887 asthma outpatient visits with individuals who have an average age of 7.96±3.88 years were selected. After adjusting for confounders, we found an interquartile range (IQR) increase in BC level, an IQR increase in NO3- level, and an IQR increase in K+ level that were all associated with the increased risk of asthma outpatient visits from the current day (OR = 1.18, 95% CI: 1.05-1.34; OR = 1.11, 95% CI: 1.01-1.21; and OR = 1.16, 95% CI: 1.04-1.30, respectively). The effects of these components on asthma were stronger in the cold season than in the warm season. However, we did not find any lagging effects. The results suggest that exposure to NO3-, BC, and K+ derived from industry-related combustion or motor vehicles emission sources may increase the risk of asthma outpatient visits, particularly during the cold season.

Kinetics for the distribution of acrylamide in French fries, fried oil and vapour during frying of potatoes.

Kinetic analysis for the formation of acrylamide in heated foods has been typically performed using only measured data of acrylamide in foods; however, its possible loss caused by release from heated foods into fried oil and air has seldom been considered. The results obtained from the monitoring of acrylamide by frying French fries indicated that acrylamide is distributed in three phases: French fries, frying oil, and air. From the evolved gas analysis of acrylamide and the measured concentration profile of the total acrylamide amount present in these phases, the kinetic behaviour for acrylamide formation does not obey the commonly used model of two-step consecutive reactions during frying, while a lumped kinetic model was proposed for the total acrylamide amount. Moreover, a high acrylamide level in air was observed, implying that, apart from consumers of French fries, fast-food restaurant workers are potentially subject to occupational hazards from acrylamide inhalation.

Association between levels of urinary heavy metals and increased risk of urothelial carcinoma.

OBJECTIVES: To evaluate possible sources of exposure to heavy metals in the general population, and to determine the association between urinary heavy metals and urothelial carcinoma risk. METHODS: We recruited 205 patients with urothelial carcinoma and 406 control participants for a case-control study between June 2011 and December 2013. The control participants were frequency-matched with cases according to sex and age. We measured the urinary levels of arsenic, cadmium, chromium, nickel and lead by using inductively coupled plasma mass spectrometry. We collected environmental exposure-related information through questionnaires. Multivariate logistic regression and 95% confidence intervals were applied to estimate the urothelial carcinoma risk and potential effects of urothelial carcinoma-related risk factors on the levels of urinary heavy metals. RESULTS: Patients with urothelial carcinoma showed higher urinary levels of arsenic, cadmium, chromium, nickel and lead than the controls. After considering other potential risk factors, a significantly increased risk for urothelial carcinoma was observed in patients with increased urinary levels of cadmium, chromium, nickel and lead. Smokers showed a high urinary cadmium level. In addition to cadmium, a high urinary lead level was associated with cumulative cigarette smoking and herbal medicine use. CONCLUSION: Environmental factors might contribute to higher urinary levels of heavy metals and ultimately result in urothelial carcinoma carcinogenesis. These findings can promote proper environmental surveillance of exposure to heavy metals in the general population.

A statistical regression model for the estimation of acrylamide concentrations in French fries for excess lifetime cancer risk assessment.

Human exposure to acrylamide (AA) through consumption of French fries and other foods has been recognized as a potential health concern. Here, we used a statistical non-linear regression model, based on the two most influential factors, cooking temperature and time, to estimate AA concentrations in French fries. The R(2) of the predictive model is 0.83, suggesting the developed model was significant and valid. Based on French fry intake survey data conducted in this study and eight frying temperature-time schemes which can produce tasty and visually appealing French fries, the Monte Carlo simulation results showed that if AA concentration is higher than 168 ppb, the estimated cancer risk for adolescents aged 13-18 years in Taichung City would be already higher than the target excess lifetime cancer risk (ELCR), and that by taking into account this limited life span only. In order to reduce the cancer risk associated with AA intake, the AA levels in French fries might have to be reduced even further if the epidemiological observations are valid. Our mathematical model can serve as basis for further investigations on ELCR including different life stages and behavior and population groups.

Urinary levels of 1-hydroxypyrene in children residing near a coal-fired power plant.

BACKGROUND: The effects of emissions from coal-fired power plants on children's exposure to polycyclic aromatic hydrocarbons (PAHs) are not well understood. OBJECTIVES: This study aimed to evaluate the sources and the urinary levels of 1-hydroxypyrene, a biomarker of exposure to PAHs, among children living in proximity to a coal-fired power plant. METHODS: Study areas consisted of two high exposure and two low exposure communities, at different distances and directions from a large coal-fired power plant in central Taiwan. Study subjects included 369 children aged 1-13 years and randomly selected from each community. Each child's urinary 1-hydroxypyrene concentration was measured by a high-performance liquid chromatography-fluorescence detector method. Samples of ambient air were analyzed for PAHs using a gas chromatography-mass spectrometry method. Information on important factors was collected by an interview using a structured questionnaire. Multiple regression analysis was used to assess factors significantly associated with urinary 1-hydroxypyrene levels. RESULTS: Levels of PAHs in ambient air in the high exposure communities were higher than those in the low exposure communities. Children living in high exposure communities had higher mean urinary 1-hydroxypyrene concentrations than those in low exposure communities (0.186 and 0.194 vs. 0.113 and 0.122 µmol/mol-creatinine, respectively). The difference in urinary 1-hydroxypyrene levels between the high exposure communities and one low exposure community remained significant after adjusting for age, gender, environmental tobacco smoke, dietary exposure, and traffic. CONCLUSIONS: Children living in communities downwind of and in proximity to the coal-fired power plant had significantly increased urinary 1-hydroxypyrene levels.

Development of a multi-pathway probabilistic health risk assessment model for swimmers exposed to chloroform in indoor swimming pools.

For swimmers, exposure to chloroform, a probable carcinogen, in indoor swimming pools can be through different pathways such as ingestion, dermal absorption, inhalation during swimming, and inhalation during resting. In order to evaluate health risk results from excessive exposure to chloroform, concentrations of chloroform in pool water were first collected and analyzed. Then, a two-layer model is used, which is capable of estimating the concentrations of chloroform in the boundary layer adjacent to the water surface and the concentrations of chloroform in indoor swimming pool air. The use of stratification model is important for estimating the risks for swimmers since they are exposed to these kinds of situations while performing swimming and resting in indoor swimming pools environment. The incremental lifetime cancer risk (ILCR) was then estimated using the multi-pathway exposure model. The results showed that the 95th percentile of ILCRs calculated for male and female swimmers were 2.80 × 10(-4) and 2.47 × 10(-4), respectively. The major exposure routes were found to be inhalation during swimming which contributes to more than 99% of the total health risk. Our study suggested that to protect swimmers from excessive exposure to chloroform, alternative methods or processes of disinfection should be considered for swimming pool managers.

Health risk of consuming heavy metals in farmed tilapia in central Taiwan.

Taiwan is a small island nation, and many aquaculture sites are located near industrial parks. Anthropogenic activities may contaminate fish ponds. Therefore, we investigated the concentrations of eight metal elements in tilapia tissues (muscle and scale) at two fisheries. We compared the difference in metal content in tilapia at these two fisheries with that in non-contaminated fish at the Fisheries Research Institute. Probabilistic risk analysis was carried out to assess the health risk for people who eat contaminated tilapia. The predicted 95th percentiles of the hazard quotient and excess lifetime cancer risk for residents consuming contaminated tilapia were found to be in the range of 3.1-9.2 and 1.03 x 10(-5)-1.85 x 10(-5), respectively.