Association of the AhR, ARNT, and AhRR gene polymorphisms and cord blood AhR levels with elevated cord blood IgE susceptibility in Taiwan mother-infant pairs: a nested case-control study.

The roles of aryl hydrocarbon receptor (AhR), AhR-nuclear translocator (ARNT), and AhR repressor (AhRR) genes in the elevation of cord blood IgE (CbIgE) remained unclear. Our aims were to determine the polymorphisms of AhR, ARNT, and AhRR genes, cord blood AhR (CBAhR) level, and susceptibility to elevation of CbIgE. 206 infant-mother pairs with CbIgE>=0.35 IU/ml and 421 randomly selected controls recruited from our previous study. Genotyping was determined using TaqMan assays. Statistical analysis showed AhR rs2066853 (GG vs. AA+AG: adjusted OR (AOR)=1.5, 95%CI=1.10-2.31 and AOR=1.60, 95%CI=1.06-2.43, respectively) and the combination of AhR rs2066853 and maternal total IgE (mtIgE)>=100 IU/ml were significantly correlated with CbIgE>=0.35 IU/ml or CbIgE>=0.5 IU/ml. CBAhR in a random subsample and CbIgE levels were significantly higher in infants with rs2066853GG genotype. We suggest that infant AhR rs2066853 and their interactions with mtIgE>=100 IU/ml significantly correlate with elevated CbIgE, but AhRR and ARNT polymorphisms do not.

Toxicity prediction: An application of alternative testing and computational toxicology in contaminated groundwater sites in Taiwan.

Groundwater contamination remains a global threat due to its toxic effects to humans and the environment. The remediation of contaminated groundwater sites can be costly, thus, identifying the priority areas of concern is important to reduce money spent on resources. In this study, we aimed to identify and rank the priority groundwater sites in a contaminated petrochemical district by combining alternative, non-animal approaches - chemical analysis, cell-based high throughput screening (HTS), and Toxicological Priority Index (ToxPi) computational toxicology tool. Groundwater samples collected from ten different sites in a contaminated district showed pollutant levels below the detection limit, however, hepatotoxic bioactivity was demonstrated in human hepatoma HepaRG cells. Integrating the pollutants information (i.e., pollutant characteristics and concentration data) with the bioactivity data of the groundwater samples, an evidence-based ranking of the groundwater sites for future remediation was established using ToxPi analysis. The currently presented combinatorial approach of screening groundwater sites for remediation purposes can further be refined by including relevant parameters, which can boost the utility of this approach for groundwater screening and future remediation.

Aggregating exposures and toxicity equivalence approach into an integrated probabilistic dietary risk assessment for perchlorate, nitrate, and thiocyanate: Results from the National food monitoring study and National Food Consumption Database.

Perchlorate, nitrate, and thiocyanate, namely thyroid disrupting chemicals (TDCs), are found ubiquitously in the environment, leading to broad human exposure and primary uptake through the food web and drinking water. TDCs are all competitive inhibitors of thyroid iodide uptake activity, but limited studies have assessed the cumulative risk of dietary exposure to multiple TDCs. Thus, in this study, we analyzed the individual exposure risk from 310 food samples in 11 categories, and also assessed the cumulative health risks from TDCs for the Taiwanese population using a perchlorate equivalent concentration (PEC) approach. Consequently, this study not only demonstrated the non-carcinogenic health risks from individual exposure but also highlighted that the cumulative exposure to these TDCs may adversely affect human thyroid functioning. Vegetables, livestock, fruits, and dairy products are the most susceptible to PEC exposure. We highlighted nitrate as the main contributor to PEC exposure. Finally, controlling the overall TDC concentrations from vegetables, livestock, fruits, and dairy products is emphasized in this study. This is the first study to conduct a cumulative risk assessment of dietary exposure to TDCs using the PEC approach for the Taiwanese population through probabilistic and sensitivity analyses.

The Potential Biomarker of Di(2-ethylhexyl) Phthalate Exposure during Catheterization.

Background: Di(2-ethylhexyl) phthalate (DEHP) may produce toxicity, posing a risk to human health. Medical devices composed of DEHP are frequently used in catheterization, but few studies have investigated DEHP exposure during catheterization. The aim of this prospective series was to characterize the exposure pattern of DEHP during catheterization. Methods: We enrolled 16 patients with congenital heart disease undergoing catheterization. Collection of urine was done to measure DEHP metabolites on hospitalization, before catheterization, after catheterization, and at discharge. The following DEHP metabolites were measured: mono-(2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and the ratio of MEHP to overall metabolites (MEHP%) was determined. DEHP exposure from polyvinyl chloride (PVC)-containing catheter and infusion systems were recorded in detail. Differences in DEHP levels before and after catheterization were analyzed. Results: Urinary levels of MEHP, MEHHP, and MEOHP significantly decreased from before catheterization to after catheterization (all p < 0.01), but did not change significantly from initial hospitalization to before catheterization. Urinary MEHP% significantly decreased from initial hospitalization to before catheterization (p < 0.001), then increased after catheterization (p < 0.001), and decreased gradually at discharge (p = 0.03). Urinary MEHP% after catheterization and at discharge was significantly positively related to the duration of using PVC-containing catheter systems. There was a significant positive correlation between urinary MEHP% and the duration of using PVC-containing infusion system before catheterization, and a borderline significant correlation at both post-catheterization time slots. Conclusions: Our results demonstrated that urinary MEHP% may be a potential biomarker of DEHP contamination from the use of PVC-containing catheters or infusion systems.

An Investigation of Pharmacists' Acceptance of NHI-PharmaCloud in Taiwan.

Taiwan's National Health Insurance (NHI) is one of the most successful insurance programs in the world. The National Health Insurance Administration (NHIA) established the NHI-PharmaCloud as a platform to reduce medication duplication and other medication errors among the NHI-contracted facilities. The NHI-PharmaCloud can help pharmacists access patient medication information from the preceding 3 months to improve drug safety. The use of NHI-PharmaCloud can improve the quality of healthcare, but improvements cannot occur if pharmacists are unwilling to use the platform. Therefore, the main objective of our study is to investigate the factors affecting pharmacists' adoption of the NHI-PharmaCloud. This study develops a research model using theories of technology adoption, self-efficacy, and perceived risk and uses randomly distributed survey questionnaires to collect data from local pharmacists. The results show that self-efficacy, perceived usefulness, and perceived psychological risk are 3 critical factors that could affect pharmacists' willingness to use the NHI-PharmaCloud. The research results may also help NHIA to effectively promote the usage of the NHI-PharmaCloud in Taiwan. In addition, governments in other countries may refer to the results of this study when implementing their own PharmaCloud-type systems to improve drug safety.

Association Between Dioxin and Metabolic Syndrome by Age and Sex in an Endemic Area of Exposure in Taiwan.

BACKGROUND: Some of the effects of dioxins seem to be different between men and women, and exposures starting at an early age seem to have more prominent effects. Therefore, we conducted a study in Taiwan to evaluate the associations between exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and metabolic syndrome (MetS) starting at different ages in both sexes. METHODS: We recruited participants from an area where residents were exposed to PCDD/Fs released from a factory and defined serum PCDD/Fs levels ≥20 pg WHO98-TEQDF/g lipid as high dioxin levels. MetS was defined as meeting three of the following criteria: fasting glucose ≥100 mg/dl or under treatment for diabetes, waist circumference ≥90 cm in men or ≥80 cm in women, triglycerides ≥150 mg/dl or under treatment for elevated triglycerides, high-density lipoprotein <40 mg/dl in men or <50 mg/dl in women, and blood pressures ≥130/85 mmHg or under treatment for hypertension. RESULTS: Of the 2758 participants, 785 patients with MetS were identified, and we observed positive associations between a high dioxin level and MetS. After adjusting for sex, age, and age at starting exposure, we found that a high dioxin level was an independent predictor for MetS (adjusted odds ratio =1.38; 95% confidence interval = 1.11, 1.72). When we stratified the participants by gender, we found that a high dioxin level remained an independent predictor of MetS in men, but not in women, regardless of the age at starting exposure. CONCLUSIONS: Exposure to PCDD/Fs was associated with MetS in men, independent of age and age at starting exposure.

Higher moisture content is associated with greater emissions of DEHP from PVC wallpaper.

Water damage and moisture in buildings may become more prevalent due to the increasing frequency of extreme precipitation and flooding events resulting from climate change. However, the effects of moisture levels on phthalate emissions from building materials are still underreported. This study aims to evaluate the effect of moisture content (MC) on the level of di-(2ethylhexyl) phthalate (DEHP) emitted from plastic wallpaper (0.22wt% DEHP) within 15 days in a closed chamber. A scenario of short-term exposure to DEHP in buildings suffering from water damage was simulated. Experiments, controlled at 100% relative humidity (RH) of air and 28°C, were conducted under the following three conditions: (I) without wallpaper (control chamber), (II) dry wallpaper (MC at 3.57%) and (III) damp wallpaper (MC at 52.31%). Air and dust samples were collected at the elapsed time of 2, 4, 6, 8, 10, 13 and 15 days, and the wipe sample was collected on the last day. Higher DEHP concentrations were found to be emitted into the air and adsorbed on the dust for wallpapers with higher MC%. DEHP levels in the air exhibited an increasing trend with the length of the experiment. Overall, it was found that approximately 35.31% more total DEHP mass was released into the air, dust and wipe samples from damp wallpapers compared to dry wallpapers. It is concluded that DEHP emissions from plastic materials are affected by the inner moisture percentage.

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.

Discrimination of CD44 and Oct3/4 Expression in Pancreatic Adenocarcinoma from Benign Pancreatic Ducts in Small Biopsy Specimens.

Cluster of differentiation 44 (CD44) and octamer-binding transcription factor 3/4 (Oct3/4) are important factors influencing cancer stem cell (CSC) development, but their clinical applications on pancreatic cancer are still unknown. Here, we tested the hypothesis that expression of CD44 and Oct3/4 correlates with the clinicopathological parameters of pancreatic ductal adenocarcinomas (PDACs). Firstly, data on the mRNA expression levels in PDACs and normal pancreatic tissues were collected from Gene Expression Omnibus (GEO) repository datasets. Immunohistochemical analyses of CD44 and Oct3/4 were next performed in tissue microarrays of 80 surgical specimens derived from a Chinese population, which included 9 normal pancreatic ducts and 71 PDACs, amongst which 12 were well differentiated, 47 moderately differentiated, and 12 poorly differentiated. From the GEO results, mRNA expression levels of both CD44 and Oct3/4 were higher in PDACs than in normal pancreatic tissues. In addition, immunostaining scores of these biomarkers were higher in most PDACs than in non-neoplastic pancreatic ducts. The intensity of CD44 and Oct3/4 staining in normal pancreatic tissues was weak and limited to small areas. Although CD44 and Oct3/4 overexpression in PDACs tended to be associated with advanced histologic grades of PDACs, the correlation of CD44 and Oct3/4 expression with the American Joint Committee on Cancer (AJCC) pathological stage was not statistically significant. In conclusion, CD44 and Oct3/4 overexpression may imply malignant transformation of pancreatic ducts and could help pathologists make a more accurate diagnosis and decision on clear surgical margins.

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.

Emphysematous cholecystitis presenting as gas-forming liver abscess and pneumoperitoneum in a dialysis patient: a case report and review of the literature.

BACKGROUND: Emphysematous cholecystitis is a rare variant of acute cholecystitis with a high mortality rate. The combination of emphysematous cholecystitis, liver abscess and pneumoperitoneum are even rarer. Herein we present a case of emphysematous cholecystitis in a senile diabetic lady who had worsening hemodynamics while undergoing hemodialysis. CASE PRESENTATION: A 64-year-old woman with history of type 2 diabetes mellitus and end stage renal disease with regular hemodialysis presented to the emergency department with a 1-day history of sudden onset of lassitude and hypotension during hemodialysis. The result of a computed tomography (CT)-scan revealed air encircling the gallbladder, liver parenchymal and minimal pneumoperitoneal and liver abscess with no cholelithiasis. The patient had received empirical antibiotics with piperacillin-tazobactam 2.25 g intravenous route every 6 h for 14 days and cholecystectomy with surgical debridement and lead an uneventful postoperative hospital course. Escherichia coli was demonstrated as well as blood culture and peritoneal fluid culture. CONCLUSION: In a senile diabetic and dialysis patient, we should take emphysematous cholecystitis into consideration once vague abdominal pain occurrs. Empirical antibiotic therapy and adequate surgical intervention should take place as soon as possible.

Phthalates might interfere with testicular function by reducing testosterone and insulin-like factor 3 levels.

STUDY QUESTION: Do phthalates create a male reproductive hormone imbalance by down-regulating the secretion of testosterone and insulin-like factor 3 (INSL3)? SUMMARY ANSWER: Our study suggests that exposure to phthalates is related to a reduction in the secretion of testosterone and INSL3 in adult males. WHAT IS KNOWN ALREADY: There is evidence that exposure to phthalates, an abundant group of industrial plasticizers, negatively affects testosterone biosynthesis, but little is known about the mechanism in men. The hypothesis that exposure to phthalates reduces the levels of testosterone and INSL3, a marker of Leydig cell function, is underexplored. STUDY DESIGN, SIZE, DURATION: This case-control study of 176 men ran from 2010 to 2012. Infertile men were recruited through infertility clinics in Taiwan, fertile men were recruited from childbirth preparation classes and all were categorized based on the World Health Organization definition of infertility and by the diagnoses of obstetricians. PARTICIPANTS/MATERIALS, SETTING, METHODS: Urinary concentrations of 11 phthalate metabolites were measured, along with serum levels of FSH, LH, total testosterone (TT), estradiol, sex hormone-binding globulin and Inhibin B. Androgen status indices including free testosterone (fT) and the free androgen index (FAI) were calculated. The circulating INSL3 level was evaluated using a radioimmunoassay. Non-parametric analyses, trend tests and linear regression models were used. MAIN RESULTS AND THE ROLE OF CHANCE: Urinary mono-n-butyl phthalate (MnBP), mono-(2-ethylhexyl) phthalate (MEHP) and mono-2-ethyl-5-carboxypentyl phthalate were significantly higher in infertile than in fertile men. Serum Inhibin B, the Inhibin B : FSH ratio, the TT : LH ratio and INSL3 were significantly lower in infertile men. In multiple regression models controlled for potential confounders, there is an inverse association between urinary levels of mono-methyl phthalate (MMP), mono-iso-butyl phthalate (MiBP), MEHP, MEHP% and serum TT (P = 0.001, 0.007, 0.042 and 0.012, respectively). The inverse associations were also found between urinary levels of MiBP, monobenzyl phthalate (MBzP), MEHP, MEHP% and serum fT (P = 0.028, 0.017, 0.045 and 0.027, respectively); between urinary levels of MMP, MEHP, MEHP% and the TT : LH ratio (P = 0.004, 0.029 and 0.039, respectively); between urinary levels of MMP, MiBP, MnBP, MBzP, MEHP and the FAI (P = 0.002, 0.008, 0.037, 0.028, 0.042 and 0.016, respectively). Urinary MBzP and MEHP% were negatively associated with a decrease in serum INSL3 (P = 0.049 and <0.001). We also observed a strong inverse relationship between MEHP% quartiles and serum TT, fT, the TT : LH ratio and INSL3 (Ptrend = 0.003, 0.080, 0.002 and 0.012, respectively). Serum INSL3, TT, fT and the TT : LH ratio were lower for men in the highest MEHP% quartile than in the reference group (P = 0.007, 0.002, 0.090 and 0.001, respectively). LIMITATIONS, REASONS FOR CAUTION: A potential limitation is using a single urine and blood sample to predict urinary phthalate metabolites and reproductive hormone status over long periods. However, there is evidence that a single measure provides a reliable result in population studies. WIDER IMPLICATIONS OF THE FINDINGS: Non-occupational exposure to phthalates, including di-2-ethylhexyl phthalate, might lead to adverse effects on testicular/Leydig cell function and be of concern owing to the ubiquitous multisource exposure to phthalates among the general population. Although our findings are in agreement with recent experimental data, more studies are required to draw firm conclusions on the relation of INSL3 to phthalate exposure or testicular/Leydig cell function.

Relationship between urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites and reproductive hormones in polyvinyl chloride production workers.

OBJECTIVES: We investigated the relationship between urinary metabolites of di(2-ethylhexyl) phthalate (DEHP) and reproductive hormones in workers of polyvinyl chloride (PVC) production plants. After exposure, most of the DEHP is rapidly metabolised to mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), which may be associated with reproductive hormone interruption and testicular toxicity. Some studies report that urinary concentrations of phthalate metabolites for plastics workers are significantly higher than for the general population. However, little is known about the disruption of reproductive hormones for DEHP exposure workers. METHODS: This cross-sectional study of 82 male workers measured the biomarkers for their reproductive hormones and their exposure to DEHP. Relationships between urinary concentrations of DEHP metabolites were estimated using multivariate linear regression and quartile analysis models. RESULTS: The geometric means of urinary creatinine-adjusted (µg/g-Cre) concentrations of MEHP, MEOHP and MEHHP during the post-shift period were 23.9, 66.9 and 84.6, respectively. In multiple regression models adjusted for potential confounders, there were significant positive associations between urinary concentrations of DEHP metabolites and estradiol (E2) (p<0.01), and in the ratio of E2 to testosterone (p<0.05). Moreover, quartile analysis showed significant positive relationships between the total urinary concentration of DEHP metabolites and E2 (ptrend=0.024), and in the ratio of E2 to testosterone (ptrend=0.031). CONCLUSIONS: Relationships between reproductive hormones and the total urinary concentration of DEHP metabolites in male PVC production workers were significantly positive. This indicated that aromatase activity had increased in male workers exposed to DEHP, which is consistent with animal studies.

Urinary metabolites of di(2-ethylhexyl) phthalate relation to sperm motility, reactive oxygen species generation, and apoptosis in polyvinyl chloride workers.

PURPOSE: To measure the concentrations of urinary di(2-ethylhexyl) phthalate (DEHP) metabolites in polyvinyl chloride (PVC) workers and a control group for determining the relationship of DEHP exposure to semen quality, sperm reactive oxygen species (ROS) generation, and sperm apoptosis. METHODS: We assessed the metabolites of DEHP, namely urinary mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and semen quality, such as sperm concentration, motility, morphology, ROS generation, and DNA damage by using terminal deoxynucleotidyl transferase-mediated nick end labeling assay obtained from 47 workers employed within two PVC pellet plants and 15 graduate students in Taiwan. RESULTS: Sperm concentration and motility were significantly affected in the high-exposure group. The percentage and intensity of sperm ROS generation were higher in the high-exposure group than those in the control group. After adjustment for age, smoking status, and coffee consumption, the decrease in sperm motility was inversely associated with the concentration of MEHP (ß = -0.549, p = 0.0085), MEHHP (ß = -0.155, p = 0.0074), and MEOHP (ß = -0.201, p = 0.0041). Moreover, sperm apoptosis and ROS generation were positively associated with MEHHP and MEOHP concentration, respectively. CONCLUSIONS: This was the first study to explore the associations between levels of DEHP exposure, sperm motility, ROS generation, and apoptosis. The results suggested that urinary MEHHP and MEOHP were sensitive biomarkers for reflecting the relationship between DEHP exposure and semen quality.

Hyperuricemia after exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans near a highly contaminated area.

BACKGROUND: Hyperuricemia (too much uric acid in the blood) is the predisposing condition for gout and is associated with hypertriglyceridemia, diabetes mellitus, and coronary artery disease. Polychlorinated dibenzo-p-dioxins and dibenzo-furans (PCDD/Fs) cause renal toxicity and elevate uric acid. The aim of this analysis was to investigate and clarify the effect of moderate-to-high PCDD/F exposure on hyperuricemia risk. METHODS: In this cross-sectional study, we recruited 1531 healthy participants living near a deserted pentachlorophenol factory. We measured serum levels of 17 2,3,7,8-substituted PCDD/Fs, and then examined associations between the main predictor variable, serum TEQ(DF-2005) (total PCDD/Fs 2005 World Health Organization [WHO] toxic equivalency [TEQ]), and dependent variables such as uric acid, glomerular filtration rates, and hyperuricemia risk. RESULTS: We observed a strong monotonic inverse relationship between serum TEQ(DF-2005) quartiles and the estimated glomerular filtration rate after adjusting for confounding factors (Men: ß were 0, -4.7, -6.2, and -14.8; Women: ß were 0, -6.7, -12.9, and -21.5). In addition, we observed a suggestive positive trend between serum TEQDF-2005 quartiles and uric acid only in men after adjusting for confounding factors (Men: ß were 0, 0.40, 0.36, and 0.59; P for trend <0.05). Men with serum TEQ(DF-2005) higher than the reference group's (<7.4 pg WHO(2005)-TEQ(DF/g) lipid) had a higher hyperuricemia risk after adjusting for confounding factors (25th to <50th percentile, adjusted odds ratio [AOR] = 2.20 [95% confidence interval {CI} = 1.30-3.73]; 50th to <75th percentile, AOR = 1.86 [95% CI = 1.08-3.22]; ≥ 75th percentile, AOR = 3.00 [95% CI = 1.69-5.31]). CONCLUSIONS: We conclude that serum TEQ(DF-2005) is an important determinant of serum uric acid levels and heightens the risk of hyperuricemia in general populations.

Phthalates may promote female puberty by increasing kisspeptin activity.

STUDY QUESTION: Is there an association between exposure to phthalates and the timing of female puberty? SUMMARY ANSWER: Our study suggests that the early onset of puberty is related to increased kisspeptin secretion. WHAT IS KNOWN ALREADY: Girls are maturing earlier than in past decades and the quantity of phthalates used in consumer products has concurrently risen. The hypothesis that exposure to phthalates may increase kisspeptin secretion and thereby cause early-onset puberty is unexplored. STUDY DESIGN, SIZE, DURATION: This case-control study ran from 2006 to 2009. We enrolled 104 girls. Girls in the central precocious puberty (CPP) (case) group were recruited from a pediatric endocrinology policlinic in Taiwan; prepubescent controls were recruited from local elementary schools and all were categorized based on a pediatrician's diagnosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: The physical characteristics of puberty were assessed and levels of LH, FSH estradiol and kisspeptin-54 in blood samples were evaluated using radioimmunoassay. Reversed-phase high-performance liquid chromatography-tandem mass spectrometry was used to analyze seven urinary phthalate metabolites. Non-parametric analyses, trend tests and linear regressions were performed on the data. MAIN RESULTS AND THE ROLE OF CHANCE: All seven urinary phthalate metabolites in the CPP group were significantly (P < 0.05) higher than in prepubescent controls. Serum kisspeptin-54 levels were higher (P = 0.022) in the CPP group than controls and were still significantly higher after adjusting for age (P = 0.03). There was a significant increasing trend (P(trend) = 0.005) between levels of kisspeptin and the stages of puberty. The concentration of kisspeptin-54 did not change in girls treated with leuprorelin acetate. There was a significant positive correlation between kisspeptin-54 and urinary mono-n-butyl phthalate (ng/ml: R(2) = 0.251, P < 0.001; µg/g-creatinine: R(2) = 0.109, P = 0.024). LIMITATIONS, REASONS FOR CAUTION: The study duration was short and the sample size relatively small; therefore, we were unable to collect sufficient evidence to support the temporality between exposure to phthalates and the subsequent occurrence of PP. WIDER IMPLICATIONS OF THE FINDINGS: Kisspeptin may promote the onset of puberty in girls who are exposed to a high level of phthalates, especially di-n-butyl phthalate. These data suggest that developing a kisspeptin antagonist might be an alternative strategy for treating PP. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants NSC 96-2621-Z-006-013 and NSC 97-2621-M-006-001 from the Taiwan National Science Council. The authors have no conflicts of interest to disclose.

Simultaneous determination of 24 congeners of 2- and 3-monochloropropanediol esters and 7 congeners of glycidyl esters using direct multi-residue analytical LC-MS/MS methods in various food matrices.

Glycidyl esters (GEs) and 2- and 3-monochloropropanediol esters (MCPDEs) are emerging process-generated food contaminants known as possible carcinogens. Herein, a direct method is developed and validated for the first time to simultaneously quantify seven GEs and twenty-four MCPDE congeners of processed foods using liquid chromatography-tandem mass spectrometry in a single sequence without ester cleavage or derivatisation, thereby allowing for the simultaneous analysis of numerous food matrices with high accuracy and precision. Our results show levels of GEs varying from

Chemical decontamination of foods using non-thermal plasma-activated water.

The presence of chemical contaminants in foods and agricultural products is one of the major safety issues worldwide, posing a serious concern to human health. Nonthermal plasma (NTP) containing richly reactive oxygen and nitrogen species (RONS) has been trialed as a potential decontamination method. Yet, this technology comes with multiple downsides, including adverse effects on the quality of treated foods and limited exposure to entire surfaces on samples with hard-to-reach spots, further hindering real-life applications. Therefore, plasma-activated water (PAW) has been recently developed to facilitate the interactions between RONS and contaminant molecules in the liquid phase, allowing a whole surface treatment with efficient chemical degradation. Here, we review the recent advances in PAW utilized as a chemical decontamination agent in foods. The reaction mechanisms and the main RONS contributors involved in the PAW-assisted removal of chemical contaminants are briefly outlined. Also, the comprehensive effects of these treatments on food qualities (chemical and physical characteristics) and toxicological evaluation of PAW (in vitro and in vivo) are thoroughly discussed. Ultimately, we identified some current challenges and provided relevant suggestions, which can further promote PAW research for real-life applications in the future.

Sequential therapy achieves a higher eradication rate than standard triple therapy in Taiwan.

BACKGROUND AND AIMS: Most clinical trials concerning sequential therapy have been conducted in Italy. The efficacy of sequential therapy for Helicobacter pylori (H. pylori) eradication in Asia remains unclear. The aim of this study was to compare the efficacy of sequential therapy with standard triple therapy in Taiwan. METHODS: From January 2005 to December 2009, 233 H. pylori-infected patients receiving either a 10-day sequential therapy (40 mg pantoprazole and 1 g amoxicillin, twice daily, for the initial 5 days, followed by 40 mg pantoprazole, 500 mg clarithromycin, and 500 mg metronidazole, twice daily, for the subsequent 5 days, n = 118) or a 7-day standard triple therapy (40 mg pantoprazole, 500 mg clarithromycin, and 1 g amoxicillin twice daily for 7 days, n = 115) were included in the retrospective study. All the patients underwent a follow-up endoscopy with a rapid urease test and histological examination or a urea breath test at 8 weeks after the end of anti-H. pylori therapy to assess H. pylori status. RESULT: Intention-to-treat analysis demonstrated a significantly higher eradication rate for the sequential group than for the triple group (93% vs 80%, respectively, P = 0.003). Per-protocol analysis also showed similar results (93% vs 80%, P = 0.005). Both groups had similar frequencies of adverse events (29% vs 22%) and drug compliance (98% vs 97%). CONCLUSION: Sequential therapy achieves a higher eradication rate than standard triple therapy in Taiwan. The novel treatment can be used as a first-line therapy for H. pylori infection for Taiwanese.

Insights into the long-term fates and impacts of polybrominated diphenyl ethers in sediment samples in Taiwan: The national project for background monitoring of the environmental distribution of chemical substances (BMECs).

This study aimed to evaluate the impact factors and effectiveness of management policies on the presence of polybrominated diphenyl ethers (PBDEs) in sediment samples in Taiwan from the last 10 years. Twenty-four PBDE congeners were detected in 838 sediment samples collected from 4 stages (2006-2019) in 30 principal rivers, based on the national project for background monitoring of the environmental distribution of chemical substances. The ΣPBDE concentrations in the 4 stages ranged from 30.00 to 147.10 ng/g dw, 6.03-15.30 ng/g dw, 4.99-7.00 ng/g dw, and 1.20-2.10 ng/g dw in the northern, southern, central, and eastern areas, respectively. The concentrations of PBDEs (e.g., penta-BDE and octa-BDE) in sediment samples notably decreased (-6 to -73%) as the Taiwan Environmental Protection Administration implemented policies banning PBDEs (except deca-BDE). The PBDEs levels of the sediment samples collected in the dry season were higher than those collected in the wet season. The levels of ΣPBDEs in sediment samples were affected by season, the amount of general waste present, and nearby PBDE-related factories and e-waste recycling facilities. Reducing the release of PBDEs, especially deca-BDE, through sound waste management and recycling practices is still needed to improve environmental sustainability in Taiwan.