Associations between long-term ambient PM2.5 exposure and the incidence of cardiopulmonary diseases and diabetes, attributable years lived with disability, and policy implication.

Long-term exposure to ambient PM2.5 is known associated with cardiovascular and respiratory health effects. However, the heterogeneous concentrationresponse function (CRF) between PM2.5 exposure across different concentration range and cardiopulmonary disease and diabetes mellitus (DM) incidence, and their implications on attributable years lived with disability (YLD) and regulation policy has not been well-studied. In this retrospective longitudinal cohort study, disease-free participants (approximately 170,000 individuals, aged ≥ 30 years) from the MJ Health Database were followed up (2007-2017) regarding incidents of coronary heart disease (CHD), ischemic stroke, chronic obstructive pulmonary disease (COPD), lower respiratory tract infections (LRIs), and DM. We used a time-dependent nonlinear weight-transformation Cox regression model for the CRF with an address-matched 3-year mean PM2.5 exposure estimate. Town/district-specific PM2.5-attributable YLD were calculated by multiplying the disease incidence rate, population attributable fraction, disability weight, and sex-age group specific subpopulation for each disease separately. The estimated CRFs for cardiopulmonary diseases were heterogeneously with the hazard ratios (HRs) increased rapidly for CHD and ischemic stroke at PM2.5 concentration lower than 10 µg/m3, whereas the HRs for DM (LRIs) increased with PM2.5 higher than 15 (20) µg/m3. Women had higher HRs for ischemic stroke and DM but not CHD. Relative to the lowest observed PM2.5 concentration of 6 µg/m3 of the study population, the PM2.5 level with an extra risk of 0.1 % (comparable to the disease incidence) for CHD, ischemic stroke, DM, and LRIs were 8.59, 11.85, 22.09, and 24.23 µg/m3, respectively. The associated attributable YLD decreased by 51.4 % with LRIs reduced most (83.6 %), followed by DM (63.7 %) as a result of PM2.5 concentration reduction from 26.10 to 16.82 µg/m3 during 2011-2019 in Taiwan. The proportion of YLD due to CHD and ischemic stroke remained dominant (56.4 %-69.9 %). The cost-benefit analysis for the tradeoff between avoidable YLD and mitigation cost suggested an optimal PM2.5 exposure level at 12 µg/m3. CRFs for cardiopulmonary diseases, attributable YLD, and regulation level, may vary depending on the national/regional background and spatial distribution of PM2.5 concentrations, as well as demographic characteristics.

Sex-specific interactive effect of melamine and DEHP on a marker of early kidney damage in Taiwanese adults: A national population-based study from the Taiwan Biobank.

Taiwan had the high incidence of chronic kidney disease (CKD) worldwide. Our objective was to examine associations between daily exposure of phthalates and melamine, two common nephrotoxins, and kidney damage risk in a well-established nationwide cohort. Study subjects were from Taiwan Biobank (TWB) with existing data of questionnaire and biochemical examinations. Average daily intake (ADI) levels of melamine and seven parental phthalates, including DEHP (di-2-ethylhexylphthalate), DiBP (Dibutyl phthalate), DnBP (Di-n-butyl phthalate), BBzP (Butyl benzyl phthalate), DEP (Diethyl phthalate), and DMP (Dimethyl phthalate) were estimated using a creatinine excretion-based model from urine melamine and 10 phthalate metabolites. Urine microalbumin to creatinine ratio (ACR) was used to represent for the outcome of kidney damage. Two statistical strategies were used: First, a weighted quantile sum (WQS) regression model to select the most important exposure variables of ADI levels of phthalates and melamine associated with ACR; Second, to examine effects of those most important exposure variables on ACR in multivariable linear regression models. In total, 1153 eligible adults were left for analyses. Of them, 591 (51.3%) and 562 (48.7%) were men and women, respectively, with a median age of 49 years old. By WQS, a significant and positive association was found between ADI of melamine and phthalates and ACR (ß = 0.14, p = 0.002). ADI levels of melamine had the highest weight (0.57), followed by DEHP (0.13). Next, examining the two most important exposures in association with ACR, we found that the higher the melamine and DEHP intakes, the higher the ACR levels were found. An interaction effect was also found between melamine and DEHP intakes on urine ACR (p = 0.015). This result was more prominent in men (p = 0.008) than in women (p = 0.651). Environmental co-exposure of melamine and DEHP can potentially affect ACR in the community-dwelling Taiwanese adult population.

Benchmark dose in the presence of coexposure to melamine and diethylhexyl phthalate and urinary renal injury markers in pregnant women.

Environmental exposures to mixtures of toxic chemicals have potential interaction effects that may lead to hazard index values exceeding one. However, current regulation levels, such as tolerable daily intake (TDI), are mostly based on experimental studies conducted with a single chemical compound. In this study, we assessed the relationships between melamine and di-(2-ethylhexyl) phthalate (DEHP) exposure and their coexposure with the early renal injury markers N-acetyl -D-glucosaminidase (NAG), albumin/creatinine ratio (ACR), and microalbuminuria in 1236 pregnant women. Various generalized linear models with interaction terms and Bayesian kernel machine regression models were used for the (co-)exposure response associations. We derived the benchmark dose (BMD) and the corresponding one-sided 95% confidence bound BMDL based on the estimated (covariate-adjusted) average daily intake of melamine and DEHP metabolites measured in spot urine of the women collected during the third trimester. Given a benchmark response of 0.1, the BMDL level of melamine (DEHP) exposure on NAG (ACR, microalbuminuria) was 2.67 (11.20, 4.45) µg/kg_bw/day, and it decreased to as low as 1.46 (3.83, 2.73) µg/kg_bw/day when considering coexposure to DEHP (melamine) up to the 90th percentile. Both the exposure threshold levels of melamine and DEHP for early renal injuries in pregnant women were several-fold to one order lower than the current recommended TDIs by the WHO and the US FDA and EPA and were even lower considering coexposure. Because of concurrent exposures in real-world environments, more stringent regulation levels are recommended in susceptible populations, such as pregnant women, due to potential synergistic mixture effects.

Melamine and oxalate coexposure induces early kidney tubular injury through mitochondrial aberrations and oxidative stress.

Exposure to melamine, which is ubiquitous in daily life, is linked to adverse kidney outcomes. The melamine tolerable daily intake in humans is based on the no-observed-effect-level (NOEL) established in a single-toxicant murine model. However, humans are often simultaneously exposed to multiple environmental nephrotoxicants. The NOEL of melamine during coexposure with other toxicants needs to be evaluated. Oxalate is a potentially nephrotoxic terminal metabolite, and hyperoxaluria is reportedly associated with chronic kidney disease. We explored whether these two potential nephrotoxicants can interact and enhance kidney injury. We established a Sprague-Dawley rat model of coexposure to the melamine NOEL (63 mg/kg/day) and 2% hydroxy-L-proline (HLP, an oxalate precursor) in drinking water to simulate human environmental melamine exposure. Melamine/oxalate coexposure increased proximal tubular cell mitochondrial reactive oxygen species levels, lipid peroxidation and oxidative DNA damage. The degrees of mitochondrial damage, tubular cell apoptosis, tubular atrophy, and interstitial fibrosis were elevated in coexposed rat kidneys. The evidence indicated that exposure to the melamine NOEL can cause renal tubular injury via oxidative stress and that this effect may be enhanced via interaction of melamine with other environmental factors, such as oxalate. Thus, melamine risk assessment and toxicity prevention should be conducted carefully in different susceptible populations.

Phthalate exposure and prostate cancer in a population-based nested case-control study.

BACKGROUND: Phthalic acid esters are established as endocrine disruptors. The study aimed to evaluate the association between urinary phthalate metabolites and prostate cancer occurrence. METHODS: The study was based on the Taiwan Community-Based Cancer Screening Program, which was set up in 1991-1992 and followed periodically. By 2010, 80 incident prostate cancer cases were identified in the 12,020 men. For each case, 2 controls were randomly selected, matched by age (±3 years), urine collection date (±3 months), and residential township. Frequently used phthalate metabolites from the urine samples were quantified by liquid chromatography/electrospray ionization tandem mass spectrometry. Logistic regression was conducted to assess the association between the exposure levels and prostate cancer occurrence. RESULTS: Exposure to di (2-ethylhexyl), butyl-benzyl and di-isobutyl phthalates (DEHP, BBzP, DiBP) was positively associated with prostate cancer in men with waist circumference (WC) ≥90 cm but not in the leans. Odds ratio for the DEHP metabolite summary score (upper tertile compared to the rest) and prostate cancer were 7.76 (95% CI = 1.95-30.9) for WC ≥ 90 cm. CONCLUSIONS: DEHP, BBzP, and DiBP exposure were associated with prostate cancer occurrence in abdominally obese men. The main limitation remains the lack of mechanistic experiments and comparable toxicological data.

A probabilistic approach for benchmark dose of melamine exposure for a marker of early renal dysfunction in patients with calcium urolithiasis.

Environmental exposure to melamine has been associated with early renal injury in urolithiasis patients even when urinary concentrations of melamine are low. The aim of this study was to derive a benchmark dose (BMD) for melamine for urolithiasis patients. To do this, one-spot urine sample from 309 participants was obtained to measure urinary melamine and N-acetyl ß-D-glucosaminidase (NAG), an early renal damage biomarker. The participants were then classified into four exposure groups based on the outcomes of melamine tableware usage questionnaire. A beta distribution of urinary excretion fraction for each group was assumed to estimate their average daily intakes (AvDIs) of melamine. The BMD and the corresponding one-sided 95% lower bound (BMDL) was then derived based on Bayesian model averaging of alternative regression models between the participants' NAG levels and their estimated AvDIs, adjusting for age, gender, and other covariates. Bayesian Markov chain Monte Carlo simulations were used for all the estimates. With a benchmark response of 0.10, the simulated BMDL of 4.89 µg/kg-bw/day for melamine exposure threshold was much lower than the WHO's current recommended tolerable daily intake of 200 µg/kg_bw/day and the US FDA's 63 µg/kg_bw/day. The current regulation level of melamine might not safeguard urolithiasis patients from further deterioration of renal function.

Intellectual evaluation of children exposed to phthalate-tainted products after the 2011 Taiwan phthalate episode.

INTRODUCTION: Phthalate exposure may reduce intellectual development in young children. In 2011, numerous Taiwanese children had been reported to have consumed phthalate-tainted products. We investigated the effects of phthalate exposure on the intellectual development of these children after the 2011 Taiwan di-2-ethylhexyl phthalate (DEHP) episode. METHODS: We recruited 204 children, aged 3-12 y, from 3 hospitals in Taiwan between 2012 and 2013. First-morning urine samples were collected for analyzing 5 phthalate metabolites. We applied a Bayesian model to estimate the past DEHP exposure (estDEHPADD) of each participant before the 2011 DEHP episode. Demographic information, consumption of phthalate-tainted products, and maternal education, of each participant were obtained using a questionnaire. We used the Wechsler intelligence evaluation tools for assessing the children's and maternal intelligence quotient. RESULTS AND DISCUSSION: The median levels of mono-2-ethylhexyl phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-n-butyl phthalate, and mono-iso-butyl phthalate in the children were 9.97, 45.8, 32.2, 46.2, and 24.3µg/g creatinine, respectively. Using the aforementioned urinary phthalate metabolites, we found that the children's verbal comprehension index (N =98) was significantly negatively associated with urinary log10 MEOHP (ß, -11.92; SE, 5.33; 95%CI, -22.52~ -1.33; P=0.028) and log10 ΣDBP metabolites (ß, -10.95; SE, 4.93; 95%CI, -20.74~ -1.16; P=0.029) after adjustment for age, gender, maternal IQ and education, passive smoking, estDEHPADD, active and passive smoking during pregnancy. Through a tolerable daily intake-based approach, we only found a significant negative association between past estimate DEHPADD and VIQ≥3-<6 in preschool children whereas no correlation was observed between current DEHP exposure and IQ≥3-<6 score with/ without estimate DEHPADD adjustment. It revealed that the effect of past high-DEHP exposure on verbal-related neurodevelopment of younger child are more sensitive. CONCLUSION: Our results are consistent with the hypothesis that exposure to DEHP and DnBP affects intellectual development in preschool and school-aged children, particularly their language learning or expression ability.

Effects of high di(2-ethylhexyl) phthalate (DEHP) exposure due to tainted food intake on pre-pubertal growth characteristics in a Taiwanese population.

On May 23, 2011, a major scandal involving the illegal use of phthalates as clouding agents in food products was reported. Specifically, di(2-ethylhexyl) phthalate (DEHP) was purposefully added to foods as a substitute emulsifier. The purpose of this study was to examine the effects of DEHP exposure on the growth characteristics of the child victims of this scandal. Eighty-eight victims, originating from northern, central, and southern Taiwan and ranging in age from 6.0 to 10.5 years, were invited to participate in this study during clinic visits. The participants underwent follow-up health examinations from August 2012 to February 2013. We collected information on each participant's history of exposure to tainted food products using a questionnaire, and we analyzed their urinary concentrations of DEHP metabolites using high-performance liquid chromatography/tandem mass spectrometry. These data were then used to estimate their daily DEHP intake (DIAll) during the scandal. We also measured physical development parameters (height, weight, and bone age) and hormone levels (thyroid, sex and growth hormones) to evaluate their overall growth characteristics. The average (SD) duration of DEHP intake from tainted nutrition supplements was 1.39 (1.01) years. The median DIAll values were 19.93 and 20.69µg/kg bw/day for boys and girls, respectively. Among the enrolled children, the DIAll values of 46.9% of boys and 51.3% of girls exceeded the reference dose (RfD) of 20µg/kg bw/day established by the US Environmental Protection Agency. Our results demonstrate that DIAll is negatively associated with the height percentile, weight percentile, bone age/chronological age, and insulin-like growth factor 1 (IGF-1) levels but not with IGF binding protein 3 (IGF-BP3) level, IGF-1/IGF-BP3, sex hormones, or thyroid hormone levels. The DEHP DIAll value exceeded the RfD at high rates among children of both genders. Our results suggest that high levels of DEHP exposure due to the consumption of tainted food products are negatively associated with body weight, height, bone age, and IGF-1 levels in children. The likelihood of delayed puberty among the affected children is therefore a reasonable concern, and further follow-up is required.

Long-term results of a phase II trial with frontline concurrent chemoradiotherapy followed by consolidation chemotherapy for localized nasal natural killer/T-cell lymphoma.

PURPOSE: A phase II trial was conducted to evaluate the therapeutic efficacy and safety profiles of frontline concurrent chemoradiotherapy (CCRT) plus consolidation chemotherapy for patients with stage I/II nasal natural killer/T-cell lymphoma (NKTCL). PATIENTS AND METHODS: Patients with newly diagnosed, measurable stage I/II nasal NKTCL were eligible. The CCRT included two cycles of the DEP regimen (dexamethasone, etoposide, and cisplatin) every 4 wk with concurrent 5040 cGy radiation in 28 fractions for 5 wk. Patients without disease progression after CCRT were subjected to two cycles of DVIP consisted of dexamethasone, etoposide, ifosphamide, mesna, and cisplatin every 4 wk. The primary endpoint was tumor response rate, and secondary endpoints were survival and toxicities. This phase II study has been registered in the ClinicalTrials.gov (NCT00292695). RESULTS: Thirty-three patients received CCRT, and 29 patients received two cycles of consolidation DVIP after CCRT. Among the 32 evaluable patients, 20 achieved complete response and 6 achieved partial response. The overall and complete response rate was 81% (95% CI, 68-95%) and 63% (95% CI, 46-79%), respectively. The 2-yr and 5-yr progression-free survival rate for intention-to-treat population was 64% (95% CI, 47-80%) and 60% (95% CI, 39-73%), respectively; while the corresponding overall survival rate was 73% (95% CI, 57-88%) and 66% (95% CI, 50-83%), respectively. The most common treatment-related grade 3/4 adverse event was leukopenia (85%). CONCLUSION: Frontline CCRT plus consolidation chemotherapy is feasible and effective for treating localized nasal NKTCL.

Modeling horizontal and vertical variation in intraurban exposure to PM2.5 concentrations and compositions.

Land use regression (LUR) models are increasingly used to evaluate intraurban variability in population exposure to fine particulate matter (PM2.5). However, most of these models lack information on PM2.5 elemental compositions and vertically distributed samples. The purpose of this study was to evaluate intraurban exposure to PM2.5 concentrations and compositions for populations in an Asian city using LUR models, with special emphasis on examining the effects of having measurements on different building stories. PM2.5 samples were collected at 20 sampling sites below the third story (low-level sites). Additional vertically stratified sampling sites were set up on the fourth to sixth (mid-level sites, n=5) and seventh to ninth (high-level sites, n=5) stories. LUR models were built for PM2.5, copper (Cu), iron (Fe), potassium (K), manganese (Mn), nickel (Ni), sulfur (S), silicon (Si), and zinc (Zn). The explained concentration variance (R(2)) of the PM2.5 model was 65%. R(2) values were >69% in the Cu, Fe, Mn, Ni, Si, and Zn models and <44% in the K and S models. Sampling height from ground level was a significant predictor in the PM2.5 and Si models. This finding stresses the importance of collecting vertically stratified information on PM2.5 mass concentrations to reduce potential exposure misclassification in future health studies. In addition to traffic variables, some models identified gravel-plant, industrial, and port variables with large buffer zones as important predictors, indicating that PM from these sources had significant effects at distant places.

Benchmark dose calculation for ordered categorical responses.

The use of benchmark dose (BMD) calculations for dichotomous or continuous responses is well established in the risk assessment of cancer and noncancer endpoints. In some cases, responses to exposure are categorized in terms of ordinal severity effects such as none, mild, adverse, and severe. Such responses can be assessed using categorical regression (CATREG) analysis. However, while CATREG has been employed to compare the benchmark approach and the no-adverse-effect-level (NOAEL) approach in determining a reference dose, the utility of CATREG for risk assessment remains unclear. This study proposes a CATREG model to extend the BMD approach to ordered categorical responses by modeling severity levels as censored interval limits of a standard normal distribution. The BMD is calculated as a weighted average of the BMDs obtained at dichotomous cutoffs for each adverse severity level above the critical effect, with the weights being proportional to the reciprocal of the expected loss at the cutoff under the normal probability model. This approach provides a link between the current BMD procedures for dichotomous and continuous data. We estimate the CATREG parameters using a Markov chain Monte Carlo simulation procedure. The proposed method is demonstrated using examples of aldicarb and urethane, each with several categories of severity levels. Simulation studies comparing the BMD and BMDL (lower confidence bound on the BMD) using the proposed method to the correspondent estimates using the existing methods for dichotomous and continuous data are quite compatible; the difference is mainly dependent on the choice of cutoffs for the severity levels.

Consumption of bovine spongiform encephalopathy (BSE) contaminated beef and the risk of variant Creutzfeldt-Jakob disease.

To date, the variant Creutzfeldt-Jakob disease (vCJD) risk assessments that have been performed have primarily focused on predicting future vCJD cases in the United Kingdom, which underwent a bovine spongiform encephalopathy (BSE) epidemic between 1980 and 1996. Surveillance of potential BSE cases was also used to assess vCJD risk, especially in other BSE-prevalent EU countries. However, little is known about the vCJD risk for uninfected individuals who accidentally consume BSE-contaminated meat products in or imported from a country with prevalent BSE. In this article, taking into account the biological mechanism of abnormal prion PrP(res) aggregation in the brain, the probability of exposure, and the expected amount of ingested infectivity, we establish a stochastic mean exponential growth model of lifetime exposure through dietary intake. Given the findings that BSE agents behave similarly in humans and macaques, we obtained parameter estimates from experimental macaque data. We then estimated the accumulation of abnormal prions to assess lifetime risk of developing clinical signs of vCJD. Based on the observed number of vCJD cases and the estimated number of exposed individuals during the BSE epidemic period from 1980 to 1996 in the United Kingdom, an exposure threshold hypothesis is proposed. Given the age-specific risk of infection, the hypothesis explains the observations very well from an extreme-value distribution fitting of the estimated BSE infectivity exposure. The current BSE statistics in the United Kingdom are provided as an example.

Burden of cardiovascular disease attributable to long-term exposure to ambient PM2.5 concentration and the cost-benefit analysis for the optimal control level.

Environmental exposure to fine particulate matter PM2.5 is known to be associated with many hazardous health effects, including cardiovascular diseases (CVDs). To reduce the related health burden, it is crucial that policy-makers throughout the world set regulation levels according to their own evidence-based study outcomes. However, there appears to be a lack of decision-making methods for the control level of PM2.5 based on the burden of disease. In this study, 117,882 CVD-free participants (≥30-years-old) of the MJ Health Database were followed-up (for a median of 9 years) between 2007 and 2017. Each participant's residential address was matched to the 3× 3 km grid PM2.5 concentration estimates with a 5-year average for long-term exposure. We used a time-dependent nonlinear weight-transformation Cox regression model for the concentration-response function (CRF) between exposure to PM2.5 and CVD incidence. Town/district-specific PM2.5-attributable years of life in disability (YLDs) in CVD incidence were calculated by using the relative risk (RR) of the PM2.5 concentration level relative to the reference level. A cost-benefit analysis was proposed by assessing the trade-off between the gain in avoidable YLDs (given a reference level at u and considering mitigation cost) versus the loss in unavoidable YLDs by not setting at the lowest observed health effect level u0. The CRF varied across different areas with dissimilar PM2.5 exposure ranges. Areas with low PM2.5 concentrations and population sizes provided crucial information for the CVD health effect at the lower end. Additionally, women and older participants were more susceptible. The avoided town/district-specific YLDs in CVD incidence due to lower RRs ranged from 0 to 3000 person-years comparing the PM2.5 concentration levels in 2019 with the levels in 2011. Based on the cost-benefit analysis, an annual PM2.5 concentration of 13 µg/m3 would be optimal, which provides a guideline for the updated regulation level (currently at 15 µg/m3). The proposed cost-benefit analysis method may be applied to other countries/regions for regulation levels that are most suitable for their air pollution status and population health.

Elafin as a Prognostic Marker in Esophageal Squamous Cell Carcinoma: A Pilot Study Using Three-Dimensional Imaging and Genomic Profiling.

Esophageal cancers are globally the sixth deadliest malignancy, with limited curative options. The association of high serum elafin levels, a molecule produced by epithelial cells, with esophageal squamous cell carcinoma (ESCC) risk is established, but its link to poor ESCC prognosis remains unclear. To explore this question, we first used three-dimensional confocal imaging to create a model of the spatial distribution of elafin inside locoregional ESCC tissues. Then, after analyzing data obtained from whole-genome microarrays for ESCC cell lines and their more invasive sublines, we performed in vitro experiments using RNA sequencing to identify possible elafin-related pathways. Three-dimensional tissue imaging showed elafin distributed as an interweaved-like fibrous structure in the stroma of tissue obtained from patients with high serum levels of elafin and poorer prognoses. By contrast, the signal was confined inside or around the tumor nest in patients who had lower serum levels and better survival. The analysis of a TCGA dataset revealed that higher levels of elafin mRNA in stage I-IIIA ESCC patients were associated with shorter survival. The in vitro studies revealed that elafin promoted ESCC cell proliferation, migration, and invasion via the epithelial-mesenchymal transition pathway. Thus, elafin inhibition could potentially be used therapeutically to improve survival in patients with locoregional ESCC.

Environmental melamine exposure and adverse kidney outcomes in patients with type 2 diabetes mellitus.

The impact of melamine exposure on kidney outcomes in type 2 diabetes mellitus (T2D) patients remains unclear. In this prospective cohort study, 561 T2D patients during October 2016 and June 2020 were enrolled and followed until December 2021. Baseline one-spot urinary corrected melamine levels were measured by LC-MS/MS. Average daily intake (ADI) of melamine represented environmental melamine exposure in daily life, and was estimated using urinary corrected melamine level by creatinine excretion (CE)-based model. Primary kidney outcomes were defined as doubling of serum creatinine levels or end stage kidney disease (ESKD), and secondary kidney outcomes included rapid decline in kidney function as estimated glomerular filtration rate (eGFR) decline >5 ml/min/1.73 m2/year. Baseline median urinary corrected melamine levels and estimated DI of melamine were 0.8 µg/mmol and 0.3 µg/kg/day in 561 T2D patients. During 3.7 years of follow-up, urinary corrected melamine level was positively correlated with reaching composite outcomes of either doubling of serum creation levels or ESKD and rapid decline in kidney function. Those with the highest quartile of urinary corrected melamine had 2.96-fold risk of composite outcomes of either doubling of serum creation levels or ESKD and 2.47-fold risk of eGFR decline >5 ml/min/1.73 m2/year. Estimated ADI of melamine also had significant correlation with adverse kidney outcomes. Furthermore, the positive relationship between melamine exposure and rapid decline in kidney function was only found in T2D patients with male, baseline eGFR ≥60 ml/min/1.73 m2 or glycated hemoglobin ≤7%. In conclusion, melamine exposure is significantly associated with adverse kidney outcomes in T2D patients, especially in those with male, well sugar control or good baseline kidney function.

The association of ambient air pollution with airway inflammation in schoolchildren.

The biologic mechanisms involved in airway inflammatory response to air pollution are not clearly understood. The authors conducted a longitudinal study to investigate whether exposure to ambient air pollutants affected inflammatory cells and mediators from nasal lavage in schoolchildren. Study participants were 100 elementary and middle-school students in New Taipei City, Taiwan. A structured respiratory health questionnaire was administered in September 2007, followed by monthly measurement of nasal inflammation from October 2007 to November 2009. During the study period, daily concentrations of air pollutants were obtained from the Environmental Protection Administration monitoring station and the Aerosol Supersite. Mixed-effects models were applied to examine the association between air pollution and nasal inflammatory cells and mediators, including percentages of neutrophils, eosinophils, and monocytes in lavaged cells and interleukin-8. A total of 824 measurements were obtained from 100 participants over a period of 10 months. The level of particulate matter with an aerodynamic diameter of 2.5 µm or less (PM(2.5)) was found to be associated with percentage of neutrophils (ß = 3.45%, 95% confidence interval: 0.89, 6.01) and interleukin-8 level (ß = 29.98 pg/mL, 95% confidence interval: 3.26, 56.69) in the nasal lavage on the day of exposure. In this longitudinal cohort study of schoolchildren, results indicated that exposure to PM(2.5) might induce nasal inflammation.

Age- and gender-specific population attributable risks of metabolic disorders on all-cause and cardiovascular mortality in Taiwan.

BACKGROUND: The extent of attributable risks of metabolic syndrome (MetS) and its components on mortality remains unclear, especially with respect to age and gender. We aimed to assess the age- and gender-specific population attributable risks (PARs) for cardiovascular disease (CVD)-related mortality and all-cause mortality for public health planning. METHODS: A total of 2,092 men and 2,197 women 30 years of age and older, who were included in the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), were linked to national death certificates acquired through December 31, 2009. Cox proportional hazard models were used to calculate adjusted hazard ratios and PARs for mortality, with a median follow-up of 7.7 years. RESULTS: The respective PAR percentages of MetS for all-cause and CVD-related mortality were 11.6 and 39.2 in men, respectively, and 18.6 and 44.4 in women, respectively. Central obesity had the highest PAR for CVD mortality in women (57.5%), whereas arterial hypertension had the highest PAR in men (57.5%). For all-cause mortality, younger men and post-menopausal women had higher PARs related to Mets and its components; for CVD mortality, post-menopausal women had higher overall PARs than their pre-menopausal counterparts. CONCLUSIONS: MetS has a limited application to the PAR for all-cause mortality, especially in men; its PAR for CVD mortality is more evident. For CVD mortality, MetS components have higher PARs than MetS itself, especially hypertension in men and waist circumference in post-menopausal women. In addition, PARs for diabetes mellitus and low HDL-cholesterol may exceed 20%. We suggest differential control of risk factors in different subpopulation as a strategy to prevent CVD-related mortality.

Avatar-like body imaging of dermal exposure to melamine in factory workers analyzed by ambient mass spectrometry.

Ambient mass spectrometry thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) can rapidly identify chemicals without pretreatment of biological samples. This study used a rapid semi-quantitative TD-ESI/MS screening technique for the probe skin sampling of melamine workers occupationally exposed to different ambient melamine concentrations to create avatar-like body images, which were then used to study temporal and dynamic changes in nephrotoxic melamine exposure. We enrolled four voluntary melamine workers from one factory, each from one of four worksites. Melamine exposure was highest in manufacturing and molding, followed by grinding and polishing, packing, and administration, the lowest. Skin samples were collected Friday (end-of-shift) and Monday (pre-shift). Early morning one-spot urine samples were also collected right after skin sampling. 2198 probe skin samples were collected and subjected to semi-quantitative TD-ESI/MS analyses of melamine chemical within 40 h. After normalization, converted body image scores revealed exposure to be highest in the manufacturing worker on Friday and lowest in the administrative worker on Monday. The absolute differences (Friday minus Monday) of normalized body image scores were all significantly positive in each individual worker and across all four workers (permutation test, all p-values < 0.002). The slope estimates of the linear regression line between body image scores and urinary melamine levels were 0.81 (p-value = 0.008). We concluded that this fast and non-invasive technique can potentially be used to study temporal and dynamic changes in exposure to occupational hazards. A future study of developing an automatic and reproducible TD-ESI/MS sampling platform is needed.

Identifying low-PM2.5 exposure commuting routes for cyclists through modeling with the random forest algorithm based on low-cost sensor measurements in three Asian cities.

Cyclists can be easily exposed to traffic-related pollutants due to riding on or close to the road during commuting in cities. PM2.5 has been identified as one of the major pollutants emitted by vehicles and associated with cardiopulmonary and respiratory diseases. As routing has been suggested to reduce the exposures for cyclists, in this study, PM2.5 was monitored with low-cost sensors during commuting periods to develop models for identifying low exposure routes in three Asian cities: Taipei, Osaka, and Seoul. The models for mapping the PM2.5 in the cities were developed by employing the random forest algorithm in a two-stage modeling approach. The land use features to explain spatial variation of PM2.5 were obtained from the open-source land use database, OpenStreetMap. The total length of the monitoring routes ranged from 101.36 to 148.22 km and the average PM2.5 ranged from 13.51 to 15.40 µg/m³ among the cities. The two-stage models had the standard k-fold cross-validation (CV) R2 of 0.93, 0.74, and 0.84 in Taipei, Osaka, and Seoul, respectively. To address spatial autocorrelation, a spatial cross-validation approach applying a distance restriction of 100 m between the model training and testing data was employed. The over-optimistic estimates on the predictions were thus prevented, showing model CV-R2 of 0.91, 0.67, and 0.78 respectively in Taipei, Osaka, and Seoul. The comparisons between the shortest-distance and lowest-exposure routes showed that the largest percentage of reduced averaged PM2.5 exposure could reach 32.1% with the distance increases by 37.8%. Given the findings in this study, routing behavior should be encouraged. With the daily commuting trips expanded, the cumulative effect may become significant on the chronic exposures over time. Therefore, a route planning tool for reducing the exposures shall be developed and promoted to the public.

Genetic Polymorphisms of MnSOD Modify the Impacts of Environmental Melamine on Oxidative Stress and Early Kidney Injury in Calcium Urolithiasis Patients.

Environmental melamine exposure increases the risks of oxidative stress and early kidney injury. Manganese superoxide dismutase (MnSOD), glutathione peroxidase, and catalase can protect the kidneys against oxidative stress and maintain normal function. We evaluated whether their single-nucleotide polymorphisms (SNPs) could modify melamine's effects. A total of 302 patients diagnosed with calcium urolithiasis were enrolled. All patients provided one-spot overnight urine samples to measure their melamine levels, urinary biomarkers of oxidative stress and renal tubular injury. Median values were used to dichotomize levels into high and low. Subjects carrying the T allele of rs4880 and high melamine levels had 3.60 times greater risk of high malondialdehyde levels than those carrying the C allele of rs4880 and low melamine levels after adjustment. Subjects carrying the G allele of rs5746136 and high melamine levels had 1.73 times greater risk of high N-Acetyl-ß-d-glucosaminidase levels than those carrying the A allele of rs5746136 and low melamine levels. In conclusion, the SNPs of MnSOD, rs4880 and rs5746136, influence the risk of oxidative stress and renal tubular injury, respectively, in calcium urolithiasis patients. In the context of high urinary melamine levels, their effects on oxidative stress and renal tubular injury were further increased.