Benchmark Dose of Melamine Exposure for a Renal Injury Marker Mediated by Oxidative Stress: Examples in Patients with Urolithiasis and Occupational Workers.

Establishing a safe exposure level from epidemiological studies while providing direct hazard characterization in humans often faces uncertainty in causality, especially cross-sectional data. With advances in molecular epidemiology, it is reasonable to integrate identified intermediate biomarkers into health risk assessment. In this study, by considering the mediation of the oxidative stress marker malondialdehyde (MDA), we explored the exposure threshold of melamine on the early renal injury marker N-acetyl-ß-D glucosaminidase (NAG). The benchmark dose (BMD) was derived from model averaging of the composite direct effect of melamine exposure and the indirect effect through the mediation of MDA on NAG levels. As illustrative examples, we analyzed 309 adult patients with calcium urolithiasis and 80 occupational workers for the corresponding exposure thresholds. The derived threshold was subpopulation-dependent, with the one-sided lower bound BMDL10 for the patients with urolithiasis with (without) the mediator MDA for the patients with kidney stones and the occupational workers being 0.88 (0.96) µg/kg_bw/day and 22.82 (18.09) µg/kg_bw/day, respectively. The derived threshold levels, considering the oxidative stress marker MDA, were consistent with those without adjusting for the mediation effect. However, the study outcomes were further supported by the suggested mechanism pathway. The threshold for the patients with urolithiasis was up to two orders lower than the current tolerable daily intake level of 200 µg/kg_bw/day recommended by the WHO (EFSA).

Elemental Characterization of Ambient Particulate Matter for a Globally Distributed Monitoring Network: Methodology and Implications.

Global ground-level measurements of elements in ambient particulate matter (PM) can provide valuable information to understand the distribution of dust and trace elements, assess health impacts, and investigate emission sources. We use X-ray fluorescence spectroscopy to characterize the elemental composition of PM samples collected from 27 globally distributed sites in the Surface PARTiculate mAtter Network (SPARTAN) over 2019-2023. Consistent protocols are applied to collect all samples and analyze them at one central laboratory, which facilitates comparison across different sites. Multiple quality assurance measures are performed, including applying reference materials that resemble typical PM samples, acceptance testing, and routine quality control. Method detection limits and uncertainties are estimated. Concentrations of dust and trace element oxides (TEO) are determined from the elemental dataset. In addition to sites in arid regions, a moderately high mean dust concentration (6 µg/m3) in PM2.5 is also found in Dhaka (Bangladesh) along with a high average TEO level (6 µg/m3). High carcinogenic risk (>1 cancer case per 100000 adults) from airborne arsenic is observed in Dhaka (Bangladesh), Kanpur (India), and Hanoi (Vietnam). Industries of informal lead-acid battery and e-waste recycling as well as coal-fired brick kilns likely contribute to the elevated trace element concentrations found in Dhaka.

Comparison of therapeutic outcomes in esophageal squamous cell carcinoma following neoadjuvant chemoradiotherapy: A prospective observational cohort study.

BACKGROUND: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) following neoadjuvant chemoradiotherapy (nCRT) may not always receive resection despite the possible achievement of a pathologic complete response (pCR) being associated with superior survival benefit. We aimed to compare outcomes among ESCC patients with or without pCR and those refusing surgery. METHODS: In total, 111 medically operable, non-cervical ESCC patients after the same protocol of nCRT (platinum/5-fluorouracil plus radiation 50Gy) were prospectively enrolled between 2011 and 2021. Eighty-three of them underwent esophagectomy comprising pCR (n = 32) and non-pCR (n = 51), while 28 operable patients declined surgery (refusal-of-surgery group). Predictors and survival data were analyzed. RESULTS: In terms of esophagectomy, 38.5% (32/83) patients achieved pCR. The pCR group exhibited better pretreatment performance status than the non-pCR group (adjusted odds ratio: 0.11, 95% confidence interval: 0.03-0.58; p = 0.01). Among pCR, non-pCR, and refusal-of-surgery groups, the 5-year overall survival (OS) rates were 56%, 29% and 50% (p = 0.08) and progression-free survival (PFS) rates were 52%, 28% and 36% (p = 0.07) respectively. The pCR group had significantly better OS and PFS than the non-PCR group (adjusted hazard ratio: 2.33 and 1.93, p = 0.02 and 0.049 respectively) but not the refusal-of-surgery group. CONCLUSION: Better pretreatment performance status is associated with higher chance of pCR. Consistent with previous studies, we found attainment of pCR confers the best OS and PFS. Suboptimal OS in the refusal-of-surgery group reflects some of them would have residual disease in addition to complete remission. Further studies are needed to identify prognostic factors of pCR to select candidates who could validly decline esophagectomy.

Linking metabolic syndrome with low bone mass through insights from BMI and health behaviors.

The objective of this study is to investigate the relationship between metabolic syndrome (MetS), and bone density in a 30- to 50-year-old Taiwanese population, and to explore the combined effects of BMI and health behaviors on this association. A total of 52,912 individuals aged 30-50 years from the Taiwan Biobank were included in this cross-sectional study. Bone density status was assessed using quantitative ultrasound (QUS). The joint effect was assessed by including an interaction term in the multi-logistic regression models to test the association between MetS, BMI, and bone density while controlling for potential confounders. MetS was associated with reduced bone density, with the risk of severe low bone density (SLBD) higher among BMI < 24 kg/m2 individuals with MetS (adjusted odds ratio [aOR] 1.5, 95% confidence interval [CI] 1.09-2.16), while the risk was not significant among BMI ≥ 24 kg/m2 individuals with MetS. Smoking, alcohol consumption, and lack of regular exercise among individuals with a BMI < 24 kg/m2 and MetS were associated with higher risk of severe low bone density (SLBD), the aORs (95%CI) were 2.9 (1.59-5.20), 2.1 (1.06-4.22), and 1.8 (1.24-2.54) respectively. Our study suggests that metabolic syndrome could increase the risk of severe low bone density, but this risk can be minimized through higher BMI, non-smoking, no alcohol consumption, and regular exercise. Conversely, smoking, alcohol consumption or lack of regular exercise may exacerbate the risk of severe low bone density. These findings highlight the importance of a multifactorial approach in managing bone healthcare.

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.

RepE: unsupervised representation learning for image enhancement in nonlinear optical microscopy.

We present an unsupervised learning denoising method, RepE (representation and enhancement), designed for nonlinear optical microscopy images, such as second harmonic generation (SHG) and two-photon fluorescence (TPEF). Addressing the challenge of effectively denoising images with various noise types, RepE employs an encoder network to learn noise-free representations and a reconstruction network to generate denoised images. It offers several key advantages, including its ability to (i) operate without restrictive statistic assumptions, (ii) eliminate the need for clean-noisy pairs, and (iii) requires only a few training images. Comparative evaluations on real-world SHG and TPEF images from esophageal cancer tissue slides (ESCC) demonstrate that our method outperforms existing techniques in image quality metrics. The proposed method provides a practical, robust solution for denoising nonlinear optical microscopy images, and it has the potential to be extended to other nonlinear optical microscopy modalities.

Rapid identification and monitoring of cooking oil fume-based toxic volatile organic aldehydes in lung tissue for predicting exposure level and cancer risks.

Cooking oil fumes (COFs) comprised of a mixture of cancer-causing volatile organic aldehydes (VOAs), particularly trans, trans-2,4-decadienal (t,t-DDE), 4-hydroxy-hexenal (4-HHE), and 4-hydroxy-nonenal (4-HNE). Monitoring toxic VOAs levels in people exposed to different cooking conditions is vital to predicting the cancer risk. For this purpose, we developed a fast tissue extraction (FaTEx) technique combined with UHPLC-MS/MS to monitor three toxic VOAs in mice lung tissue samples. FaTEx pre-treatment protocol was developed by combining two syringes for extraction and clean-up process. The various procedural steps affecting the FaTEx sample pre-treatment process were optimized to enhance the target VOAs' extraction efficiency from the sample matrix. Under the optimal experimental conditions, results exhibit good correlation coefficient values > 0.99, detection limits were between 0.5-3 ng/g, quantification limits were between 1-10 ng/g, and the matrix effect was <18.1%. Furthermore, the extraction recovery values of the spiked tissue exhibited between 88.9-109.6% with <8.6% of RSD. Cooking oil fume (containing t,t-DDE) treated mice at various time durations were sacrificed to validate the developed technique, and it was found that t,t-DDE concentrations were from 14.8 to 33.8 µg/g. The obtained results were found to be a fast, reliable, and semi-automated sample pre-treatment technique with good extraction efficiency, trace level detection limit, and less matrix effect. Therefore, this method can be applied as a potential analytical method to determine the VOAs in humans exposed to long-term cooking oil fumes.

High-Field Asymmetric Waveform Ion Mobility Spectrometry Analysis of Carcinogenic Aromatic Amines in Tobacco Smoke with an Orbitrap Tribrid Mass Spectrometer.

Smoking is a risk factor for bladder cancer (BC), although the specific chemicals responsible for BC remain uncertain. Considerable research has focused on aromatic amines (AAs), including o-toluidine (o-tol), o-anisidine (o-anis), 2-naphthylamine (2-NA), and 4-aminobiphenyl (4-ABP), which are linked to human BC based on elevated BC incidence in occupationally exposed factory workers. These AAs arise at nanogram levels per combusted cigarette. The unambiguous identification of AAs, particularly low-molecular-weight monocyclic AAs in tobacco smoke extracts, by liquid chromatography-mass spectrometry (LC-MS) is challenging due to their poor performance on reversed-phase columns and co-elution with isobaric interferences from the complex tobacco smoke matrix. We employed a tandem liquid-liquid and solid-phase extraction method to isolate AAs from the basic fraction of tobacco smoke condensate (TSC) and utilized high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to high-resolution accurate mass (HRAM) Orbitrap LC-MS2 to assay AAs in TSC. The employment of FAIMS greatly reduced sample complexity by removing precursor co-isolation interfering species at the MS1 scan stage, resulting in dramatically improved signal-to-noise of the precursor ions and cleaner, high-quality MS2 spectra for unambiguous identification and quantification of AAs in TSC. We demonstrate the power of LC/FAIMS/MS2 by characterizing and quantifying two low-molecular-weight carcinogenic AAs, o-tol and o-anis, in TSC, using stable isotopically labeled internal standards. These results demonstrate the power of FAIMS in trace-level analyses of AA carcinogens in the complex tobacco smoke matrix.

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.

Simultaneous biomonitoring of volatile organic compounds' metabolites in human urine samples using a novel in-syringe based fast urinary metabolites extraction (FaUMEx) technique coupled with UHPLC-MS/MS analysis.

Assessing the impact of human exposure to environmental toxicants is often crucial to biomonitoring the exposed dose. In this work, we report a novel fast urinary metabolites extraction (FaUMEx) technique coupled with UHPLC-MS/MS analysis for the highly sensitive and simultaneous biomonitoring of the five major urinary metabolites (thiodiglycolic acid, s-phenylmercapturic acid, t,t-muconic acid, mandelic acid, and phenyl glyoxylic acid) of common volatile organic compounds' (VOCs) exposure (vinyl chloride, benzene, styrene, and ethylbenzene) in human. FaUMEx technique comprises of two-steps, liquid-liquid microextraction was performed first in an extraction syringe using 1 mL of methanol (pH 3) as an extraction solvent and then, the extractant was passed through a clean-up syringe (pre-packed-with various sorbents including 500 mg anhydrous MgSO4, 50 mg C18, and 50 mg SiO2) to obtain the high order of matrice clean-up and preconcentration efficiency. The developed method displayed excellent linearity, and the correlation coefficients were >0.998 for all the target metabolites with detection and quantification limits of 0.02-0.24 ng mL-1 and 0.05-0.72 ng mL-1, respectively. Furthermore, the matrix effects were < ±5%, and inter and intra-day precision were <9%. Moreover, the presented method was applied and validated to real sample analysis for biomonitoring of VOC's exposure levels. The results showed that the developed FaUMEx-UHPLC-MS/MS method is fast, simple, low-cost, low-solvent consumption, high sensitivity with good accuracy and precision for five targeted urinary VOCs' metabolites. Therefore, the presented dual-syringe mode FaUMEx strategy with UHPLC-MS/MS technique can be applied to biomonitoring of various urinary metabolites to assess human exposure to environmental toxicants.

Rapid Identification and Analysis of Ochratoxin-A in Food and Agricultural Soil Samples Using a Novel Semi-Automated In-Syringe Based Fast Mycotoxin Extraction (FaMEx) Technique Coupled with UHPLC-MS/MS.

In this work, a fast mycotoxin extraction (FaMEx) technique was developed for the rapid identification and quantification of carcinogenic ochratoxin-A (OTA) in food (coffee and tea) and agricultural soil samples using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) detection. The FaMEx technique advancement is based on two plastic syringes integrated setup for rapid extraction and its subsequent controlled clean-up process. In the extraction process, a 0.25-g sample and extraction solvent were added to the first syringe barrel for the vortex-based extraction. Then, the extraction syringe was connected to a clean-up syringe (pre-packed with C18, activated carbon, and MgSO4) with a syringe filter. Afterward, the whole set-up was placed in an automated programmable mechanical set-up for controlled elution. To enhance FaMEx technology performance, the various influencing sample pretreatment parameters were optimized. Furthermore, the developed FaMEx method indicated excellent linearity (0.9998 and 0.9996 for coffee/tea and soil) with highly sensitive detection (0.30 and 0.29 ng/mL for coffee/tea and soil) and quantification limits (1.0 and 0.96 for coffee/tea and soil), which is lower than the toxicity limit compliant with the European Union regulation for OTA (5 ng/g). The method showed acceptable relative recovery (84.48 to 100.59%) with <7.34% of relative standard deviation for evaluated real samples, and the matrix effects were calculated as <-13.77% for coffee/tea and -9.7 for soil samples. The obtained results revealed that the developed semi-automated FaMEx/UHPLC-MS/MS technique is easy, fast, low-cost, sensitive, and precise for mycotoxin detection in food and environmental samples.

Change in PD-L1 and CD8 Expression after Chemoradiotherapy for Esophageal Squamous Cell Carcinoma.

Esophageal cancer has a dismal prognosis with a five-year survival rate below 20%. Recently, immunotherapy has become a new standard of care for this cancer; therefore, we aimed to examine the programmed death ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) tissues before and after concurrent chemoradiation therapy (CCRT). In total, 64 patients with pre-CCRT ESCC specimens were examined for PD-L1 expression, with twenty-three of them having a partial response (N = 23) or stable disease (N = 1) after CCRT while post-CCRT tissue specimens were collected. All of them were tested for PD-L1 and 15 of them also had CD8 expression in the paired ESCC samples. The prevalence of PD-L1 positivity was 54.7% and we found a trend of decreased PD-L1 expression and increased CD8 positive signal after CCRT. High pre-CCRT PD-L1 H-score in tumors was related to poor prognosis (adjusted hazard ratio = 2.81; p = 0.02), although CD8 signal was not associated with overall survival either in pre- or post-CCRT treatment. In conclusion, we found that PD-L1 expression tended to decrease in CCRT responders and our result supports PD-L1 expression in tumor as a predictor of ESCC prognosis.

Breast Cancer Incidence among Female Workers by Different Occupations and Industries: A Longitudinal Population-Based Matched Case-Control Study in Taiwan.

BACKGROUND: Breast cancer is the leading cause of cancer incidence worldwide and in Taiwan. The relationship between breast cancer and occupational types remains unclear. This study aimed to investigate lifetime breast cancer incidence by different occupational industries among female workers in Taiwan. METHODS: A population-based retrospective case-control study was conducted using three nationwide population-based databases. Matched case and control groups were identified with 1-to-4 exact matching among 103,047 female workers with breast cancer diagnosed in 2008-2017 and those without breast cancer. Their lifetime labor enrollment records were tracked using the National Labor Insurance Database, 1950-2017. Conditional logistic regression was used to analyze the association between types of occupational industries and risk of incident breast cancer. RESULTS: Our study found slightly significant breast cancer risk among the following major occupational classifications: manufacturing (OR: 1.027, 95% CI: 1.011-1.043); wholesale and retail trade (OR: 1.068, 95% CI: 1.052-1.084); information and communication (OR: 1.074, 95% CI: 1.043-1.105); financial and insurance activities (OR: 1.109, 95% CI: 1.086-1.133); real estate activities (OR: 1.050, 95% CI: 1.016-1.085); professional, scientific, and technical activities (OR: 1.118, 95% CI: 1.091-1.145); public administration, defense, and social security (OR: 1.054, 95% CI: 1.023-1.087), education (OR: 1.199, 95% CI: 1.168-1.230); and human health and social work activities (OR: 1.125, 95% CI: 1.096-1.156). CONCLUSIONS: Greater percentages of industrial occupations (i.e., manufacturing, wholesale and retail, or health professionals) were associated with slightly increased breast cancer risk. Further studies should investigate the possible risk factors among female workers in those industries with slightly higher incidence of breast cancer.

DNA Damage and Oxidative Stress of Tobacco Smoke Condensate in Human Bladder Epithelial Cells.

Smoking is a major risk factor for bladder cancer (BC), with up to 50% of BC cases being attributed to smoking. There are 70 known carcinogens in tobacco smoke; however, the principal chemicals responsible for BC remain uncertain. The aromatic amines 4-aminobiphenyl (4-ABP) and 2-naphthylamine (2-NA) are implicated in BC pathogenesis of smokers on the basis of the elevated BC risk in factory workers exposed to these chemicals. However, 4-ABP and 2-NA only occur at several nanograms per cigarette and may be insufficient to induce BC. In contrast, other genotoxicants, including acrolein, occur at 1000-fold or higher levels in tobacco smoke. There is limited data on the toxicological effects of tobacco smoke in human bladder cells. We have assessed the cytotoxicity, oxidative stress, and DNA damage of tobacco smoke condensate (TSC) in human RT4 bladder cells. TSC was fractionated by liquid-liquid extraction into an acid-neutral fraction (NF), containing polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, phenols, and aldehydes, and a basic fraction (BF) containing aromatic amines, heterocyclic aromatic amines, and N-nitroso compounds. The TSC and NF induced a time- and concentration-dependent cytotoxicity associated with oxidative stress, lipid peroxide formation, glutathione (GSH) depletion, and apurinic/apyrimidinic (AP) site formation, while the BF showed weak effects. LC/MS-based metabolomic approaches showed that TSC and NF altered GSH biosynthesis pathways and induced more than 40 GSH conjugates. GSH conjugates of several hydroquinones were among the most abundant conjugates. RT4 cell treatment with synthetic hydroquinones and cresol mixtures at levels present in tobacco smoke accounted for most of the TSC-induced cytotoxicity and the AP sites formed. GSH conjugates of acrolein, methyl vinyl ketone, and crotonaldehyde levels also increased owing to TSC-induced oxidative stress. Thus, TSC is a potent toxicant and DNA-damaging agent, inducing deleterious effects in human bladder cells at concentrations of <1% of a cigarette in cell culture media.

Design of a Lab-On-Chip for Cancer Cell Detection through Impedance and Photoelectrochemical Response Analysis.

In this study, a biochip was fabricated using a light-absorbing layer of a silicon solar element combined with serrated, interdigitated electrodes and used to identify four different types of cancer cells: CE81T esophageal cancer, OE21 esophageal cancer, A549 lung adenocarcinoma, and TSGH-8301 bladder cancer cells. A string of pearls was formed from dielectrophoretic aggregated cancer cells because of the serrated interdigitated electrodes. Thus, cancer cells were identified in different parts, and electron-hole pairs were separated by photo-excited carriers through the light-absorbing layer of the solar element. The concentration catalysis mechanism of GSH and GSSG was used to conduct photocurrent response and identification, which provides the fast, label-free measurement of cancer cells. The total time taken for this analysis was 13 min. Changes in the impedance value and photocurrent response of each cancer cell were linearly related to the number of cells, and the slope of the admittance value was used to distinguish the location of the cancerous lesion, the slope of the photocurrent response, and the severity of the cancerous lesion. The results show that the number of cancerous cells was directly proportional to the admittance value and the photocurrent response for all four different types of cancer cells. Additionally, different types of cancer cells could easily be differentiated using the slope value of the photocurrent response and the admittance value.

Breast cancer incidence in a national cohort of female workers exposed to special health hazards in Taiwan: a retrospective case-cohort study of ~ 300,000 occupational records spanning 20 years.

OBJECTIVE: Breast cancer is the most common cancer among women worldwide. In Taiwan, workers exposed to any of 31 hazardous chemicals or carcinogens in the work environment are designated as especially exposed workers (EEWs) by Taiwan's Ministry of Labor. We assessed the risk of breast cancer in this nationwide female EEW cohort. METHODS: We conducted a nationwide retrospective study of 4,774,295 workers combining data collected from Taiwan's Ministry of Labor's EEW database between 1997 and 2018 and Taiwan's Cancer Registry between 1997 and 2016. Standardized incidence ratios (SIRs) for women exposed to different hazards and breast cancer incidence rate ratios (IRRs) were calculated by Poisson regression, adjusting for age and duration of exposure. RESULTS: 3248 female workers with breast cancer and 331,967 without breast cancer were included. The SIRs and adjusted IRRs were 1.27 (95% CI 1.18-1.35) and 1.31 (95% CI 1.21-1.42) for lead, 1.74 (95% CI 1.23-2.24) and 1.52 (95% CI 1.13-2.04) for 1,1,2,2-tetrachloroethane, 1.47 (95% CI 1.12-1.82) and 1.42 (95% CI 1.12-1.81) for trichloroethylene/tetrachloroethylene), 1.40 (95% CI 1.23-1.57) and 1.38 (95% CI 1.22-1.57) for benzene, and 2.07 (95% CI 1.06-3.09) and 1.80 (95% CI 1.10-2.94) for asbestos. The results remained similar when factoring in a 2- or 5-year latency period. CONCLUSION: This study found possible correlations between occupational exposure to lead, chlorinated solvents (such as 1,1,2,2-tetrachloroethane, trichloroethylene, and tetrachloroethylene), benzene, and asbestos with breast cancer risk among female EEW, suggesting a need for regular screening for breast cancer for employees exposed to these special workplace hazards.

Rapid green analytical methodology for simultaneous biomonitoring of five toxic areca nut alkaloids using UHPLC-MS/MS for predicting health hazardous risks.

Areca nut (AN) is a fundamental component of betel quid (BQ), an addictive and carcinogenic mixture chewed by hundreds of millions of people in India-Asia-Pacific. Chewing of BQ is associated with oral cancers due to specific carcinogenic alkaloids (arecaidine, guvacine, guvacoline, arecoline, N-Nitrosoguvacoline) in AN. To predict the hazardous health risks of short and long-term chewing of BQ, it is crucial to identify five toxic AN alkaloids in saliva and urine of BQ chewers. This study reports a green analytical methodology comprising in-syringe assisted vortex-induced salt-enhanced liquid-liquid microextraction coupled with ultra-HPLC-MS/MS for simultaneous biomonitoring of five AN alkaloids in saliva and urine. The analytical method validation results exhibited good linearities between 0.05 and 1000 ng mL-1 with r2 > 0.9930. The detection and quantification limits were between 0.01 and 1.5 and 0.05-5 ng mL-1. Relative recoveries ranged between 87.9% and 110.1% with RSD < 9.1% for saliva samples, 81.5-115.1% with RSD < 9.7% for urine samples. The results indicated the successful identification and real-time monitoring of concentrations of five target AN alkaloids in saliva and urine of BQ chewers and demonstrated the utility of this technique as an efficient analytical protocol for routine biomonitoring of levels of toxic AN alkaloids from BQ chewers and to predict the exposure level and its harmful health risk.

Association Between Prenatal Exposure to Metals and Atopic Dermatitis Among Children Aged 4 Years in Taiwan.

Importance: The prevalence of atopic dermatitis has substantially increased in recent decades, and atopic dermatitis could lead to allergic airway inflammation later in life. A previous study found that inorganic arsenic exposure was associated with allergic airway inflammation in children aged 8 to 14 years. However, the association between prenatal exposure to arsenic and other metals and the risk of atopic dermatitis among young children remains unknown. Objective: To assess the association between prenatal exposure to arsenic and other metals and the occurrence of atopic dermatitis in children at age 4 years. Design, Setting, and Participants: In total, 1152 pregnant women were enrolled in the original Taiwan Maternal and Infant Cohort Study (TMICS), a multicenter birth cohort study conducted at 9 hospitals in northern, central, southern, and eastern Taiwan from October 2012 to May 2015. Of those, 586 mothers and children aged 4 years participated in follow-up questionnaire interviews from August 2016 to January 2019. After excluding 216 participants with missing data, the final statistical analysis of follow-up data included 370 mother and child pairs from the central and eastern regions of Taiwan. Data were analyzed from February 2 to August 12, 2021. Exposures: Arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc during pregnancy. Main Outcomes and Measures: The outcome was parent-reported atopic dermatitis history among children aged 4 years. The presence of atopic dermatitis was defined as a positive response to the question, "Has your child ever had atopic dermatitis diagnosed by a physician?" During the initial TMICS study period, concentrations of arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc were measured in maternal urine during the third trimester of pregnancy using an inductively coupled plasma mass spectrometer. Estimated total inorganic arsenic exposure was calculated using a model that included data on both total arsenic and arsenic species (arsenite, arsenate, monomethylarsonate, and dimethylarsenate) obtained from a previous TMICS cohort. Results: Among 370 children included in the analysis, the mean (SD) age was 3.94 (0.59) years; 208 children (56.2%) were male, and 267 children (72.2%) were from the central region of Taiwan. A total of 110 children (29.7%) had atopic dermatitis at age 4 years. Maternal estimated total inorganic arsenic exposure during pregnancy was associated with increased odds of atopic dermatitis among children at age 4 years (odds ratio [OR], 2.42 [95% CI, 1.33-4.39] for every doubled increase of total inorganic arsenic) after adjusting for parental allergies, child's sex, geographic area, maternal educational level, and exposure to tobacco smoke. Every increased unit in the weighted quantile sum index of maternal metal exposure was significantly associated with atopic dermatitis (OR, 1.63; 95% CI, 1.28-2.07). Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal mixture index. Conclusions and Relevance: This cohort study found that prenatal exposure to inorganic arsenic and coexposure to inorganic arsenic and cadmium were associated with a higher risk of atopic dermatitis in young children. These findings suggest that prevention of exposure to inorganic arsenic and cadmium during pregnancy may be helpful for the control of atopic dermatitis and other potential allergies in children.

Breast Cancer Risk Among Female Health Professionals: A 35-Year Population-Based Longitudinal Cohort Study in Taiwan.

INTRODUCTION: Breast cancer is the most frequently diagnosed cancer among women worldwide. Previous studies have found a higher risk in nurses but no clear relationship among other health professionals. This study aims to investigate the risks of incident breast cancer among female health professionals compared with that among nonhealth professionals in Taiwan. METHODS: This longitudinal observational cohort study included >35 years (1979-2016) of data from 4 nationwide population-based databases in Taiwan and identified matched cohorts with 1-to-2 propensity score matching between 277,543 health professionals and 555,086 nonhealth professionals. This study calculated total person-years for study subjects and compared breast cancer incidence between matched health and nonhealth professionals. Multivariable Cox proportional hazards and competing risk analyses were used, stratified by birth age, job tenure categories, and types of health professional license. Statistical analyses were conducted in 2019-2020. RESULTS: Health professionals had a significantly higher risk of breast cancer (hazard ratio=1.34, 95% CI=1.28-1.41; subdistribution hazard ratio=1.36, 95% CI=1.30, 1.42). Elevated risk of breast cancer incidence was associated with birth age, job tenure, and several health professional license types, including physician, pharmacist, registered nurse, midwife, medical technologist, and psychologist. CONCLUSIONS: Elevated breast cancer risk was found overall in female health professionals. Regular ultrasonography for younger women and mammography for those aged >45 years may be necessary in the annual labor physical examination for female health professionals.

Association of Particulate Matter from Cooking Oil Fumes with Heart Rate Variability and Oxidative Stress.

Many studies have reported various cardiovascular autonomic responses to ambient particulate matter (PM) pollution, but few have reported such responses to occupational PM exposures. Even fewer have demonstrated a relationship between PM pollution and oxidative stress in humans. This panel study evaluates the association between occupational exposure to PM in cooking oil fumes (COFs), and changes in both heart rate variability (HRV) and oxidative stress responses in 54 male Chinese cooks. Linear mixed-effects regression models were adopted to estimate the strength of the association between PM and HRV. Participants' pre- and post-workshift urine samples were analyzed for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). Exposure to PM in COFs from 15 min to 2 h were associated with a decrease in HRV and an increase in heart rate among cooks. The urinary 8-OHdG levels of cooks were significantly elevated after workshift exposure to COFs. The levels of PM2.5, PM1.0, and particulate benzo(a)pyrene in COFs were all positively correlated with cross-workshift urinary 8-OHdG levels. Furthermore, the levels of benzo(a)pyrene in COFs were positively correlated with cross-workshift urinary MDA levels. The effects of COFs on HRV were independent of cross-workshift urinary 8-OHdG levels. Exposure to COFs leads to disturbed autonomic function and an increased risk of oxidative DNA injury among cooks in Chinese restaurants.