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Previous U.S. population modeling studies have reported that urinary cadmium (Cd) excretion patterns differ with age, sex, and dietary exposure; associations between Cd exposures and health outcomes also have differed by age and sex. Therefore, it is important to test models used to estimate Cd exposures across an expanded Cd-exposure range. We estimated relative Cd exposures from both diet and smoking in low- and high-exposure scenarios to provide data for improving risk assessment calculations. We used a Cd toxicokinetic-based model to estimate Cd exposures based on urinary Cd levels measured for 399 persons in a low-exposure area (Bangkok) and 6,747 persons in a high-exposure area (Mae Sot) in Thailand. In Bangkok, we estimated dietary Cd exposures of 50-56 µg/day for males and 21-27 µg/day for females 20-59 years of age who never smoked. In Mae Sot, we estimated dietary Cd exposures of 188-224 µg/day for males and 99-113 µg/day for females 20-59 years of age who never smoked. In Bangkok, we estimated Cd exposures from smoking to be 5.5-20.4 µg/day for male smokers 20-59 years of age. In Mae Sot, we estimated Cd exposures from smoking to be 9.8-26 µg/day for male heavy smokers and 26 µg/day for female heavy smokers. This study provides estimates of Cd exposures from diet and smoking in low- and high-exposure scenarios. Our findings suggest a relatively small safety margin between the established tolerable Cd reference exposure of 62 µg/day and exposure levels previously associated with evidence of kidney and bone effects in Mae Sot residents, where dietary Cd exposures among women were only 1.6-2.1 times the reference value.

To elucidate the influence of cadmium exposure on bone metabolism, associations between urinary/blood cadmium and bone resorption/formation markers were investigated in older cadmium exposed men and women. Increased urinary cross-linked N-telopeptide of type I collagen (NTx), a bone resorption marker, was found to be associated with increased levels of parathyroid hormone, fractional excretion of calcium, and urinary/blood cadmium after adjusting for confounding factors in men. In women, urinary NTx was significantly associated with only urinary cadmium and a strong relationship with increased fractional excretion of calcium. Risk for bone metabolic disorders, indicated by high urinary NTx, significantly increased in men with blood cadmium ≥ 10 μg/L or urinary cadmium ≥ 10 μg/g creatinine. Increased osteocalcin level was significantly associated with increased blood cadmium in men. In conclusion, cadmium exposure appeared to have an influence on bone remodeling both bone resorption and formation in this population of older Thai men, and blood cadmium was more closely associated with bone metabolism than urinary cadmium.

Many microbial species have been recognized as enteropathogens for humans. Here, we predicted the causative agents of acute diarrhea using data from multiplex quantitative PCR (qPCR) assays targeting 19 enteropathogens. For this, a case-control study was conducted at eight hospitals in Thailand. Stool samples and clinical data were collected from 370 hospitalized patients with acute diarrhea and 370 non-diarrheal controls. Multiple enteropathogens were detected in 75.7% and 13.0% of diarrheal stool samples using multiplex qPCR and bacterial culture methods, respectively. Asymptomatic carriers of enteropathogens were found among 87.8% and 45.7% of individuals by qPCR and culture methods, respectively. These results suggested the complexity of identifying causative agents of diarrhea. An analysis using the quantification cut-off values for clinical relevance drastically reduced pathogen-positive stool samples in control subjects from 87.8% to 0.5%, whereas 48.9% of the diarrheal stool samples were positive for any of the 11 pathogens. Among others, rotavirus, norovirus GII, Shigella /EIEC, and Campylobacter were strongly associated with acute diarrhea ( P -value < 0.001). Characteristic clinical symptoms, epidemic periods, and age-related susceptibility to infection were observed for some enteropathogens. Investigations based on qPCR approaches covering a broad array of enteropathogens might thus improve our understanding of diarrheal disease etiology and epidemiological trends.

Immunization is a core component of the human right to health. However, accessibility to the Expanded Program on Immunization (EPI) might be difficult among migrant children. This study aims to assess the vaccination coverage of migrant children under a mobile immunization program, initiated by the Thai government in 2014. A cross-sectional, mixed-methods study was conducted in five districts along the Thailand–Myanmar border during July–December 2018. The immunization history during their first year of life was obtained. Focus group discussions were conducted among stakeholders to explore their satisfaction toward the immunization service. Mothers/guardians of 1707 migrant children participated in the survey, with a 71% response rate. The vaccination coverage increased during 2014–2017. The highest vaccination coverage was observed for Bacillus Calmette-Guérin vaccine, with 83.2% coverage in 2017. The vaccination coverage of three doses of diphtheria-tetanus-pertussis vaccine and Hepatitis B vaccine and oral polio vaccine increased from 34.8% in 2014 to 56.3% in 2017. For measles-containing vaccine, the vaccination coverage increased from 32.4% in 2014 to 54.6% in 2017. Overall, all stakeholders were satisfied with the immunization service. Increased workload and communication barriers were the main factors that influenced the satisfaction toward the immunization program.

First, the urinary metabolic profiling by gas chromatography-mass spectrometry (GC-MS), was performed to compare ten cadmium (Cd) toxicosis cases from a Cd-polluted area in Mae Sot (Thailand) with gender-matched healthy controls. Orthogonal partial list square-discrimination analysis was used to identify new biomarker candidates in highly Cd exposed toxicosis cases with remarkable renal tubular dysfunction. The results of the first step of this study showed that urinary citrate was a negative marker and myo-inositol was a positive marker for Cd toxicosis in Thailand. In the second step, we measured urinary citrate in the residents (168 Cd-exposed subjects and 100 controls) and found significantly lower levels of urinary citrate and higher ratios of calcium/citrate and magnesium/citrate, which are risk factors for nephrolithiasis, in highly Cd-exposed residents. Additionally, this inverse association of urinary citrate with urinary Cd was observed after adjustment for age, smoking and renal tubular dysfunction, suggesting a direct effect of Cd on citrate metabolism. These results indicate that urinary citrate is a useful biomarker for the adverse health effects of Cd exposure in a Thai population with a high prevalence of nephrolithiasis.

Cadmium (Cd) has been found as an environmental pollutant in Mae Sot district, Tak province, Thailand. Prolong exposure to high levels of Cd of the resident increases high risk of Cd toxicity especially to kidney which is the primary target of Cd. In order to investigate the early effect of Cd induced renal dysfunction, a kidney injury molecule-1 (KIM-1), a novel biomarker of renal tubular dysfunction, was measured using an enzyme linked immunosorbent assay (ELISA). The method was validated and used to quantify the KIM-1 concentrations in the urine of 700 subjects (260 men, 440 women) who lived in the Cd contaminated area. The KIM-1 concentrations were compared to the concentrations of two conventional renal tubular dysfunction biomarkers, N-acetyl-β-D-glucosaminidase (NAG) and β 2 -microglobulin (β 2 -MG). Urinary KIM-1 was correlated with urinary and blood Cd as well as NAG. After adjustment of age and smoking, urinary KIM-1 was correlated with blood Cd more than urinary NAG did. Clear dose response relationships of urinary KIM-1 with urinary Cd were shown in both men and women. These results indicate that the urinary KIM-1 might be more sensitive biomarker than urinary NAG and β 2 -MG for an early detection of renal tubular dysfunction. It is useful as a tool to detect renal effect of toxicity due to chronic Cd exposure at high level.

DNA methylation changes with age, and may serve as a biomarker of aging. Cadmium (Cd) modifies cellular processes that promote aging and disrupts methylation globally. Whether Cd modifies aging processes by influencing establishment of age-associated methylation marks is currently unknown. In this pilot study, we characterized methylation profiles in > 450 000 CpG sites in 40 non-smoking women (age 40–80) differentially exposed to environmental Cd from Thailand. Based on specific gravity adjusted urinary Cd, we classified them as high (HE) and low (LE) exposed and age-matched within 5 years. Urinary Cd was defined as below 2 µg/l in the LE group. We predicted epigenetic age (DNAm-age) using two published methods by Horvath and Hannum and examined the difference between epigenetic age and chronologic age (Δage). We assessed differences by Cd exposure using linear mixed models adjusted for estimated white blood cell proportions, BMI, and urinary creatinine. We identified 213 age-associated CpG sites in our population (P < 10−4). Counterintuitively, the mean Δage was smaller in HE vs. LE (Hannum: 3.6 vs. 7.6 years, P = 0.0093; Horvath: 2.4 vs. 4.5 years, P = 0.1308). The Cd exposed group was associated with changes in methylation (P < 0.05) at 12, 8, and 20 age-associated sites identified in our population, Hannum, and Horvath. From the results of this pilot study, elevated Cd exposure is associated with methylation changes at age-associated sites and smaller differences between DNAm-age and chronologic age, in contrast to expected age-accelerating effects. Cd may modify epigenetic aging, and biomarkers of aging warrant further investigation when examining Cd and its relationship with chronic disease and mortality.

Background The aim of the present study was to estimate the benchmark doses (BMD) for renal effects for health risk assessment of residents living in Cd-polluted and non-polluted areas in a Thai population. Methods The study participants consisted of inhabitants aged 40 years or older who lived in a non-polluted area (40 men and 41 women) and in the environmentally polluted Mae Sot District (230 men and 370 women) located in northwestern Thailand. We measured urinary and blood cadmium (Cd) as markers of long-term exposure and urinary β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) as renal tubular effect markers. An updated hybrid approach was applied to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) of urinary and blood Cd for Cd-induced renal effects in these subjects. BMD and BMDL corresponding to an additional risk (BMR) of 5% were calculated with the background risk at zero exposure set to 5% after adjusting for age and smoking status. Results The estimated BMDLs of urinary Cd for renal effect markers were 6.9 for urinary β2-MG and 4.4 for NAG in men and 8.1 for β2-MG and 6.1 for NAG μg/g creatinine (Creat) in women. These BMDLs of urinary Cd (μg/g Creat) for NAG were less than the geometric mean urinary Cd in the polluted area (6.5 in men and 7.1 in women). The estimated BMDLs of blood Cd (μg/L) were 6.2 for urinary β2-MG and 5.0 for NAG in men and 5.9 for β2-MG and 5.8 for NAG in women. The calculated BMDLs were similar or less compared with the geometric mean blood Cd (μg/L) in the polluted Thai area (6.9 in men and 5.2 in women). Conclusion The BMDLs of urinary and blood Cd for renal effects were estimated to be 4.4 - 8.1 μg/g Creat and 4.4 - 6.2 μg/L in the Thai population aged ≥ 40 years old, suggesting that more than 40% of the residents were at risk of adverse renal effects induced by Cd exposure in Thailand.

The cadmium (Cd) contaminated rice fields in Mae Sot District, Tak Province, Thailand has been one of the major environmental problems in Thailand for the last 10 years. We used disability adjusted life years (DALYs) to estimate the burden of disease attributable to Cd in terms of additional DALYs of Mae Sot residents. Cd exposure data included Cd and β2–microglobulin (β2-MG) in urine (as an internal exposure dose) and estimated cadmium daily intake (as an external exposure dose). Compared to the general Thai population, Mae Sot residents gained 10%–86% DALYs from nephrosis/nephritis, heart diseases, osteoporosis and cancer depending on their Cd exposure type and exposure level. The results for urinary Cd and dietary Cd intake varied according to the studies used for risk estimation. The ceiling effect was observed in results using dietary Cd intake because of the high Cd content in rice grown in the Mae Sot area. The results from β2-MG were more robust with additional DALYs ranging from 36%–86% for heart failure, cerebral infraction, and nephrosis/nephritis. Additional DALYs is a useful approach for assessing the magnitude of environmental Cd exposure. The Mae Sot population lost more healthy life compared to populations living in a non- or less Cd polluted area. This method should be applicable to various types of environmental contamination problems if exposure assessment information is available.

Environmental cadmium contamination is present in some rural villages of Mae Sot District, Tak Province, northwestern Thailand. We compared the health of 751 persons aged ≥ 35 years living in 3 contaminated villages with 682 people from 3 non-contaminated villages with similar socio-demographic and lifestyle characteristics in the same district. All the subjects were screened for urinary cadmium (a biomarker for long-term cadmium exposure), renal function, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, urinary tract stone disease and bone mineral density in 2012. The study renal functions included urinary excretion of β2-microglobulin (early tubular effect), total urine protein and glomerular filtration rate (glomerular effects). The geometric mean of urinary cadmium level was significantly higher among persons living in the contaminated areas (2.96 μg/g creatinine) than those in the non-contaminated areas (0.60 μg/g creatinine). Persons living in contaminated areas had a significantly higher prevalence of renal dysfunction, bone mineral loss, hypertension and urinary stones than those living in non-contaminated areas. There were no significant differences between the 2 groups in the prevalence of diabetes, hypercholesterolemia and hypertriglyceridemia. This study shows health effects due to environmental cadmium exposure. The prevalences of diabetes, hypercholesterolemia, and hypertriglyceridemia were not associated with cadmium exposure.