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Purpose: To assess whether polymorphisms of haptoglobin (Hp) modify the relationship between dietary iron and the risk of gestational iron-deficiency anemia (IDA). Methods: This study analyzed 1430 singleton pregnant women aged 20 ~ ≤ 48 years from the 2017–2019 National Nutrition and Health Survey of Pregnant Women in Taiwan. Sociodemographic, blood biochemical, Hp phenotype, and 24-h dietary recall data were collected. Erythropoiesis-related total prenatal supplementation was defined as the reported use of multivitamins and minerals, vitamin B complex, folate, and iron. Results: Distributions of the Hp 1-1, Hp 2-1, and Hp 2-2 phenotypes were 13.6, 39.8, and 46.5%, respectively. Women with the Hp 1-1 phenotype had the lowest mean levels of serum ferritin (p-trend = 0.017), the highest prevalence of gestational ID (p-trend = 0.033) as well as the highest prevalence of gestational IDA (did not reach statistical differences, p-trend = 0.086). A gene–diet interaction on serum ferritin was observed between the Hp 1 and Hp 2 (2-1/2-2) alleles (p < 0.001). An adjusted multivariate logistic regression showed that compared to those with a normal blood iron status and who reported using erythropoiesis-related total prenatal supplements, those who did not had a 4.05-fold [odds ratio (OR) = 4.05 (95% confidence interval (CI) 2.63–6.24), p < 0.001] increased risk of gestational IDA. The corresponding ORs for carriers of the Hp 1 and Hp 2 alleles were 4.78 (95% CI 1.43–15.99) and 3.79 (95% CI 2.37–6.06), respectively. Conclusion: Pregnant women who are Hp 1 carriers are at increased risk for developing IDA if they do not meet the recommended dietary allowance for iron or use erythropoiesis-related prenatal supplements. [ABSTRACT FROM AUTHOR]

Objective: The coexistence of underweight (UW) and overweight (OW)/obese (OB) at the population level is known to affect iron deficiency (ID) anaemia (IDA), but how the weight status affects erythropoiesis during pregnancy is less clear at a population scale. This study investigated associations between the pre-pregnancy BMI (pBMI) and erythropoiesis-related nutritional deficiencies. Design: Anthropometry, blood biochemistry and 24-h dietary recall data were collected during prenatal care visits. The weight status was defined based on the pBMI. Mild nutrition deficiency-related erythropoiesis was defined if individuals had an ID, folate depletion or a vitamin B12 deficiency. Setting: The Nationwide Nutrition and Health Survey in Taiwan (Pregnant NAHSIT 2017–2019). Participants: We included 1456 women aged 20 to 45 years with singleton pregnancies. Results: Among these pregnant women, 9·6 % were UW, and 29·2 % were either OW (15·8 %) or OB (13·4 %). A U-shaped association between the pBMI and IDA was observed, with decreased odds (OR; 95 % CI) for OW subjects (0·6; 95 % CI (0·4, 0·9)) but increased odds for UW (1·2; 95 % CI (0·8, 2·0)) and OB subjects (1·2; 95 % CI (0·8, 1·8)). The pBMI was positively correlated with the prevalence of a mild nutritional deficiency. Compared to normal weight, OB pregnant women had 3·4-fold (3·4; 95 % CI (1·4, 8·1)) higher odds for multiple mild nutritional deficiencies, while UW individuals had lowest odds (0·3; 95 % CI (0·1, 1·2)). A dietary analysis showed negative relationships of pBMI with energy, carbohydrates, protein, Fe and folate intakes, but positive relationship with fat intakes. Conclusion: The pre-pregnancy weight status can possibly serve as a good nutritional screening tool for preventing IDA during pregnancy. [ABSTRACT FROM AUTHOR]

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are related to cognitive dysfunction and mental disability. These genes, along with folate and vitamin B12 levels, are regulators of one-carbon metabolism, which synthesizes S-adenosylmethionine (SAM) as a methyl donor for arsenic methylation. The aim of this study was to explore whether polymorphisms of MTHFR and MTR influence arsenic methylation capacity and plasma folate and vitamin B12 levels and if these influences cause developmental delay in preschool children. A total of 178 children with developmental delay and 88 without developmental delay were recruited from August 2010 to March 2014. A high-performance liquid chromatography–hydride generator and atomic absorption spectrometer were used to determine urinary arsenic species. Plasma folate and vitamin B12 concentrations were measured by SimulTRAC-SNB radioassay. Polymorphisms of MTHFR C677T, MTHFR A1298C, and MTR A2756G were examined by polymerase chain reaction and restriction fragment length variation. The results show that MTHFR C677T C/T and T/T genotypes had a lower risk of developmental delay than the C/C genotype (odds ratio [OR] = 0.47; 95% confidence interval, 0.26–0.85). Subjects with the MTHFR C677T C/C genotype had significantly lower plasma folate and vitamin B12 levels than those with the MTHFR C677T C/T and T/T genotype. The MTHFR C677T C/C genotype combined with high total urinary arsenic and poor arsenic methylation capacity indices significantly increased the OR of developmental delay in a dose–response manner. This is the first study to show the combined effect of MTHFR C677T genotype and poor arsenic methylation capacity on developmental delay. [ABSTRACT FROM AUTHOR]

Developmental delay has been associated with inefficient arsenic methylation capacity in preschool children. Folate and vitamin B12 are important nutrients that produce s-adenosylmethionine during single-carbon metabolism and provide methyl groups for arsenic methylation. The aim of the present study was to explore whether plasma folate and vitamin B12 levels influence arsenic methylation capacity and in turn are related to developmental delay in preschool children. A case–control study was conducted in 178 children with developmental delay and 88 normal children, who were recruited from Shin Kong Wu Ho-Su Memorial Teaching Hospital from August 2010 to March 2014. Arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) in the urine was determined by high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Plasma folate and vitamin B12 levels were measured using a SimulTRAC-SNB radioassay. The results show that the combination of high plasma folate and high vitamin B12 levels were correlated with efficient arsenic methylation capacity (low MMAV %, low InAs %, and high DMAV %). High MMAV % significantly increased and high DMAV % and secondary methylation index decreased the odds ratio (OR) of developmental delay in a dose-dependent manner in both low plasma folate and low vitamin B12 (low/low) groups; the multivariate OR and 95% confidence interval were 5.01 (0.83–30.06), 0.21 (0.04–1.23), and 0.20 (0.03–1.20), respectively. This is the first study to show that the combination of high plasma folate and high vitamin B12 levels increases arsenic methylation capacity and indirectly decreases the OR of developmental delay in preschool children. [ABSTRACT FROM AUTHOR]

Background: Previous studies have stressed the importance of tobacco exposure for the mood disorders of depression and anxiety. Although a few studies have focused on perinatal women, none have specifically considered the effects of smoking and secondhand smoke exposure on perinatal suicidal ideation. Thus, this study aimed to investigate the relationships of smoking/secondhand smoke exposure status with suicidal ideation, depression, and anxiety from the first trimester to the first month post partum.Methods: This cross-sectional study based on self-reported data was conducted at five hospitals in Taipei, Taiwan from July 2011 to June 2014. The questionnaire inquired about women's pregnancy history, sociodemographic information, and pre-pregnancy smoking and secondhand smoke exposure status, and assessed their suicidal ideation, depression, and anxiety symptoms. Logistic regression models were used for analysis.Results: In the 3867 women in the study, secondhand smoke exposure was positively associated with perinatal depression and suicidal ideation. Compared with women without perinatal secondhand smoke exposure, women exposed to secondhand smoke independently exhibited higher risks for suicidal ideation during the second trimester (odds ratio (OR) = 7.63; 95 % confidence interval (CI) = 3.25-17.93) and third trimester (OR = 4.03; 95 % CI = 1.76-9.23). Women exposed to secondhand smoke had an increased risk of depression, especially those aged 26-35 years (OR = 1.71; 95 % CI = 1.27-2.29).Conclusions: Secondhand smoke exposure also considerably contributes to adverse mental health for women in perinatal periods, especially for the severe outcome of suicidal ideation. Our results strongly support the importance of propagating smoke-free environments to protect the health of perinatal women. [ABSTRACT FROM AUTHOR]

Background: To examine the changes in the maternal mortality ratio (MMR) and causes of maternal death in Taiwan based on nationwide linked data sets. Methods: We linked four population-based data sets (birth registration, birth notification, National Health Insurance inpatient claims, and cause of death mortality data) to identify maternal deaths for 2004–2011. Subsequently, we calculated the MMR (deaths per 100,000 live births) and the proportion of direct and indirect causes of maternal death by maternal age and year. Findings: Based on the linked data sets, we identified 236 maternal death cases, of which only 102 were reported in officially published mortality data, with an underreporting rate of 57% [(236−102) × 100 / 236]. The age-adjusted MMR was 18.4 in 2004–2005 and decreased to 12.5 in 2008–2009; however, the MMR leveled off at 12.6 in 2010–2011. The MMR increased from 5.2 in 2008–2009 to 7.1 in 2010–2011 for patients aged 15–29 years. Women aged 15–29 years had relatively lower proportion in dying from direct causes (amniotic fluid embolism and obstetric hemorrhage) compared with their counterpart older women. Conclusions: Approximately two-thirds of maternal deaths were not reported in officially published mortality data. Routine surveillance of maternal mortality by using enhanced methods is necessary to monitor the health status of reproductive-age women. Furthermore, a comprehensive maternal death review is necessary to explore the preventability of these maternal deaths. [ABSTRACT FROM AUTHOR]

Abstract: Environmental exposure to lead or mercury can cause neurodevelopmental damage. Arsenic is another neurotoxicant that can affect intellectual function in children. This study was designed to explore the difference of arsenic methylation capacity indices between with and without developmental delay in preschool children. We also aimed to identify whether blood levels of lead or mercury modify the effect of arsenic methylation capacity indices. A cross sectional study was conducted from August 2010 to March 2012. All participants recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In all, 63 children with developmental delay and 35 children without developmental delay were recruited. Urinary arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) were measured with a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Lead and mercury levels of red blood cells were measured by inductively coupled mass spectrometry. All participants underwent developmental assessments to confirm developmental delays, including evaluations of gross motor, fine motor, speech-language, cognition, social, and emotional domains. Urinary total arsenic and MMAV percentage were significantly positively associated and DMAV percentage was negatively associated with the risk of developmental delay in a dose-dependent manner after adjustment for blood lead or mercury levels and other risk factors. A multivariate regression analysis indicated that blood lead level and arsenic methylation capacity each independently contributed to the risk of developmental delay. This is the first study to show that arsenic methylation capacity is associated with developmental delay, even without obvious environmental arsenic exposure. [Copyright &y& Elsevier]

Background: The risk of venous thromboembolism (VTE) and the development of atherosclerosis are increased in patients with inflammatory bowel disease (IBD). Ulcerative colitis (UC) is one type of IBD; however, there is controversy in the literature regarding the association between UC and stroke. The present cohort study estimated the risk of subsequent stroke among UC patients compared with that among matched comparison subjects drawn from a population-based data set in Taiwan. Methods: This investigation analyzed administrative claims data sourced from the Taiwan National Health Insurance Database. Our study consisted of a study cohort comprising 516 UC patients and a comparison cohort of 2,579 subjects without IBD. Cox proportional hazards regressions were performed to estimate the risk of subsequent stroke during the follow-up period. We also conducted additional analyses investigating the risk of subsequent stroke by age group and gender. Results: After adjusting for selected medical co-morbidities and recent prescriptions of selected pharmaceuticals, the hazard ratio (HR) for subsequent stroke among patients with UC was 2.045 (95 % confidence interval (CI) = 1.374-3.043) than that among comparison subjects. While we did not detect an association between stroke and UC among patients aged 30-40 or 40-50 years, we did detect increased risks for stroke among UC patients aged over 50 years (HR = 2.045). We also found the association to remain significant for both men (HR = 2.153) and women (HR = 2.750). Conclusions: This study detected an increased HR for subsequent stroke among Taiwanese UC patients when compared to that among matched comparison patients without IBD. [ABSTRACT FROM AUTHOR]

Abstract: Few studies investigated the association between chronic arsenic exposure and the mortality of cancers by estimating individual urinary arsenic methylation profiles. Therefore, we compared with the general population in Taiwan to calculate the standardized mortality ratio (SMR) in arseniasis-endemic area of Taiwan from 1996 to 2010 and evaluated the dose-response relationships between environmental arsenic exposure indices or urinary arsenic profiles and the mortality of cause-specific cancer. A cohort of 1563 residents was conducted and collected their urine sample and information regarding arsenic exposure from a questionnaire. All-cause death was identified using the National Death Registry of Taiwan. Urinary arsenic profiles were measured using high performance liquid chromatography–hydride generator–atomic absorption spectrometry. We used Cox proportional hazard models to evaluate the mortality risks. In results, 193 all-site cancer deaths, and 29, 71, 43 deaths respectively for liver, lung and bladder cancers were ascertained. The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. People with high urinary InAs% or low DMA% or low secondary methylation index (SMI) were the most likely to suffer bladder cancer after adjusting other risk factors. Even stopping exposure to arsenic from the artesian well water, the mortality rates of the residents were higher than general population. Finally, urinary InAs%, DMA% and SMI could be the potential biomarkers to predict the mortality risk of bladder cancer. [Copyright &y& Elsevier]

Long-term exposure to inorganic arsenic from artesian drinking well water is associated with carotid atherosclerosis in the Blackfoot Disease (BFD)-hyperendemic area in Taiwan. The current study examined the arsenic methylation capacity and its risk on carotid atherosclerosis. A total of 304 adults (158 men and 146 women) residing in the BFD-hyperendemic area were included. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Chronic arsenic exposure was estimated by an index of cumulative arsenic exposure (CAE) and the duration of artesian well water consumption. Urinary levels of inorganic arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)] were determined by high performance liquid chromatography linked on-line to a hydride generator and atomic absorption spectrometry (HPLC-HG-AAS). The percentage of arsenic species, primary methylation index [PMI=MMA(V)/(As(III)+As(V)] and secondary methylation index [SMI=DMA(V)/MMA(V)] were calculated and employed as indicators of arsenic methylation capacity. Results showed that women and younger subjects had a more efficient arsenic methylation capacity than did men and the elderly. Carotid atherosclerosis cases had a significantly greater percentage of MMA(V) [%MMA(V)] and a lower percentage of DMA [%DMA (V)] compared to controls. Subjects in the highest two tertiles of PMI with a median of CAE >0 mg/L-year had an odds ratio (OR) and a 95% confidence interval (CI) of carotid atherosclerosis of 2.61 and 0.98–6.90 compared to those in the highest two tertiles of PMI with a CAE=0 mg/L-year. We conclude that individuals with greater exposure to arsenic and lower capacity to methylate inorganic arsenic may be at a higher risk to carotid atherosclerosis. [Copyright &y& Elsevier]

Abstract: Long-term exposure to ingested inorganic arsenic is associated with peripheral vascular disease (PVD) in the blackfoot disease (BFD)-hyperendemic area in Taiwan. This study further examined the interaction between arsenic exposure and urinary arsenic speciation on the risk of PVD. A total of 479 (220 men and 259 women) adults residing in the BFD-hyperendemic area were studied. Doppler ultrasound was used to diagnose PVD. Arsenic exposure was estimated by an index of cumulative arsenic exposure (CAE). Urinary levels of total arsenic, inorganic arsenite (AsIII) and arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) were determined. Primary methylation index [PMI = MMAV/(AsIII + AsV)] and secondary methylation index (SMI = DMAV/MMAV) were calculated. The association between PVD and urinary arsenic parameters was evaluated with consideration of the interaction with CAE and the confounding effects of age, sex, body mass index, total cholesterol, triglycerides, cigarette smoking, and alcohol consumption. Results showed that aging was associated with a diminishing capacity to methylate inorganic arsenic and women possessed a more efficient arsenic methylation capacity than men did. PVD risk increased with a higher CAE and a lower capacity to methylate arsenic to DMAV. The multivariate-adjusted odds ratios for CAE of 0, 0.1–15.4, and >15.4 mg/L × year were 1.00, 3.41 (0.74–15.78), and 4.62 (0.96–22.21), respectively (P &#60; 0.05, trend test); and for PMI ≤ 1.77 and SMI > 6.93, PMI > 1.77 and SMI > 6.93, PMI > 1.77 and SMI ≤ 6.93, and PMI ≤ 1.77 and SMI ≤ 6.93 were 1.00, 2.93 (0.90–9.52), 2.85 (1.05–7.73), and 3.60 (1.12–11.56), respectively (P &#60; 0.05, trend test). It was concluded that individuals with a higher arsenic exposure and a lower capacity to methylate inorganic arsenic to DMAV have a higher risk of developing PVD in the BFD-hyperendemic area in Taiwan. [Copyright &y& Elsevier]

Globally, anemia affects 56 million pregnant women, especially women with a low household income. Functional erythropoiesis requires a constant supply of micronutrients, and the demands significantly increase during fetal development. This study aims to identify dietary patterns for preventing gestational erythropoiesis-associated micronutrient deficiencies (e.g., iron, folic acid, and vitamin B 12 ). A Nationwide Nutrition and Health Survey in Pregnant Women, Taiwan (NAHSIT-PW), was conducted between 2017 and 2019. Data on baseline information, diet, anthropometrics, and blood biochemistry were collected during a prenatal visit. Dietary patterns were identified using a reduced rank regression (RRR). Erythropoiesis-related micronutrient deficiencies were defined as single, double, and triple micronutrient deficiencies of an iron deficiency, folate depletion, and a vitamin B 12 deficiency. In total, 1437 singleton pregnancies aged ≥20-48 years were included in the analysis. Prevalences of normal nutrition, and single, double, and triple erythropoiesis-related micronutrient deficiencies were 35.7%, 38.2%, 18.6%, and 7.5%, respectively. Anemic pregnant women with a low household income had the highest prevalence rates of double (32.5%) and triple (15.8%) erythropoiesis-related micronutrient deficiencies. Dietary pattern scores were positively correlated with nuts and seeds, fresh fruits, total vegetables, breakfast cereals/oats and related products, soybean products, and dairy products but negatively correlated with processed meat products and liver, organs, and blood products. After adjusting for covariates, the dietary pattern had 29% (odds ratio (OR): 0.71; 95% confidence interval (CI): 0.055-0.091, p = 0.006)) and 43% (OR: 0.57; 95% CI: 0.41-0.80, p = 0.001)) reduced odds of having double and triple erythropoiesis-related micronutrient deficiencies for those pregnant women with a low household income. For those women with anemia, dietary patterns had 54% (OR: 046, 95% CI: 0.27-0.78) and 67% (OR: 0.33; 95% CI: 0.170.64) reduced odds of double and triple erythropoiesis-related micronutrient deficiencies. In conclusion, increased consumption of breakfast cereals and oats, nuts, and seeds, fresh fruits and vegetables, soybean products, and dairy products may protect women against erythropoiesis-related micronutrient deficiencies during pregnancy.

Vitamin D is involved in the pathophysiology of anemia. This cross-sectional study was conducted using the Nationwide Nutrition and Health Survey in Pregnant Women in Taiwan database. We investigated associations among dietary patterns (DPs), vitamin D, and iron-related biomarkers in pregnant women. The principal component analysis revealed four DPs. Linear and logistic regression analyses were performed to investigate the association of DPs with anemia-related biomarkers. Plant-based, carnivore, and dairy and nondairy alternatives DPs were positively associated with serum vitamin D levels. After adjusting covariates, the pregnant women consuming plant-based DPs at the mid-tertile (T2) were associated with reduced risks of low serum folate and vitamin D levels, and those consuming carnivore DPs at higher tertiles (T2 and/or T3) were correlated with an increased risk of low serum iron levels but decreased risks of low serum transferrin saturation, vitamin B 12 , and vitamin D levels. The pregnant women consuming dairy and nondairy alternatives DPs at the highest tertile (T3) were associated with reduced risks of low serum folate and vitamin B 12 levels. However, the processed food DP was not correlated with anemia-related biomarkers. Thus, plant-based, carnivore, and dairy and nondairy alternatives DPs were associated with the risk of low-serum-anemia-related variables.

Sugar intake may increase the risk of obesity, cardiovascular disease, diabetes, and dental caries. In Taiwan, people frequently consume sugar-sweetened beverages (SSBs). This study explored the energy and sugar content of Taiwanese SSBs and evaluated them using the Chilean warning label system (>70 kcal/100 mL and >5 g sugar/100 mL) and the World Health Organization (WHO) sugar guideline (≤25 g sugar). A total of 341 SSBs with volumes ≤600 mL were analyzed. No significant differences were observed in sugar per serving among different types of SSBs, but a great variation in portion size (i.e., package size for individual consumption) was noted. The energy and sugar ratios per serving were lower in soft drinks and coffee and tea containing >1 serving than in those containing only one serving. The calorie and sugar ratios per portion were higher in all types of SSBs containing >1 serving per portion than in those containing exactly one serving. Approximately 70.0% of Taiwanese SSBs were classified as high sugar according to the Chilean criteria, and 41.6% of SSBs exceeded the WHO guideline. Moreover, 40.8% of SSBs that were not considered as high sugar according to the Chilean criteria contained >25 g sugar per portion. For individual consumption, it is more clear that nutrition labeling is based on portion rather than serving. Evaluating SSBs on sugar/portion rather than sugar/100 mL will help consumers make better choices.

Metal exposure and lifestyle are important risk factors for osteoporosis. Our study aimed to investigate the association between red blood cell lead and cadmium, total urinary arsenic, and plasma selenium levels and bone mineral density (BMD). In addition, we explored whether alcohol and coffee consumption modified the association between BMD and metals and metalloids. In total, 437 participants who underwent adult or senile physical examinations were recruited. Bone loss was defined as a calcaneus BMD T-score of <-1. Blood cadmium and lead and plasma selenium levels were measured using inductively coupled plasma mass spectrometry. Levels of urinary arsenic species were determined using high-performance liquid chromatography-hydride generator-atomic absorption spectrometry. The total urinary arsenic level was defined as the sum of the levels of urinary arsenic species. The BMD T-scores decreased significantly with increasing blood lead levels. The BMD T-scores also showed a downward trend with increasing total urinary arsenic levels. The odds ratio (OR) and 95% confidence interval (CI) for bone loss in patients with blood lead levels >57.58 versus 35.74 μg/dL were 1.98 and 1.17-3.34. In addition, the greater the lead or arsenic exposure and alcohol intake was the higher the OR for bone loss with multivariate ORs of 2.57 (95% CI 1.45-4.56) and 2.96 (95% CI 1.67-5.22), respectively. To the best of our knowledge, this study is the first to demonstrate that high total urinary arsenic or blood lead levels and frequent or occasional alcohol consumption had a significant multiplicative interaction for increasing the OR for bone loss., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hsueh, Huang, Chen, Shiue, Lin and Hsieh.)

Heavy metals causing chronic nephrotoxicity may play a key role in the pathogenesis of chronic kidney disease (CKD). This study hypothesized that plasma folate and vitamin B 12 would modify the association of CKD with total urinary arsenic and blood lead and cadmium levels. We recruited 220 patients with CKD who had an estimated glomerular filtration rate of <60 mL/min/1.73 m 2 for ≥3 consecutive months and 438 sex- and age-matched controls. We performed inductively coupled plasma mass spectrometry to measure blood cadmium and lead levels. The urinary arsenic level was determined using a high-performance liquid chromatography-hydride generator-atomic absorption spectrometry. Plasma vitamin B 12 and folate levels were measured through the SimulTRAC-SNB radioassay. Compared with patients with plasma vitamin B 12 ≤ 6.27 pg/mL, the odds ratio (OR) and 95% confidence interval of CKD for patients with plasma vitamin B 12 > 9.54 pg/mL was 2.02 (1.15-3.55). However, no association was observed between plasma folate concentration and CKD. A high level of plasma vitamin B 12 combined with high levels of blood lead and cadmium level and total urinary arsenic tended to increase the OR of CKD in a dose-response manner, but the interactions were nonsignificant. This is the first study to demonstrate that patients with high plasma vitamin B 12 level exhibit increased OR of CKD related to high levels of blood cadmium and lead and total urinary arsenic.

Hepcidin is a regulator of iron metabolism. Diet affects the body's iron status, but how it influences hepcidin concentrations and the risk of gestational iron-deficiency anemia (IDA) remains unclear. We investigated relationships of food and nutrient intake with serum hepcidin levels in relation to the iron status at a population scale. A retrospective cross-sectional study was conducted based on data obtained from the Nationwide Nutrition and Health Survey in pregnant women, Taiwan (2017~2020). In total, 1430 pregnant women aged 20~45 years with a singleton pregnancy were included. Data from blood biochemistry, 24-h dietary recall, and a food frequency questionnaire were collected during a prenatal checkup. Adjusted multivariate linear and logistic regression analyses were employed to measure the beta coefficient (ß) and 95% confidence interval (CI) of serum hepcidin and the odds ratio (OR) of IDA. In IDA women, serum hepcidin levels were positively correlated with the intake frequency of Chinese dim sum and related foods (β = 0.037 (95% CI = 0.015~0.058), p = 0.001) and dark leafy vegetables (β = 0.013 (0.001~0.025), p = 0.040), but they were negatively correlated with noodles and related products (β = -0.022 (-0.043~-0.001), p = 0.038). An adjusted multivariate logistic regression analysis showed that dietary protein [OR: 0.990 (0.981~1.000), p = 0.041], total fiber [OR: 0.975 (0.953~0.998), p = 0.031], and rice/rice porridge [OR: 1.007 (1.00~1.014), p = 0.041] predicted gestational IDA. Total carbohydrates [OR: 1.003 (1.000~1.006), p = 0.036], proteins [OR: 0.992 (0.985~0.999), p = 0.028], gourds/shoots/root vegetables [OR: 1.007 (0.092~1.010), p = 0.005], and to a lesser extent, savory and sweet glutinous rice products [OR: 0.069 (0.937~1.002), p = 0.067] and dark leafy vegetables [OR: 1.005 (0.999~1.011), p = 0.088] predicted IDA. The risk of IDA due to vegetable consumption decreased with an increasing vitamin C intake ( p for trend = 0.024). Carbohydrates and vegetables may affect the gestational iron status through influencing hepcidin levels. Vitamin C may lower the risk of gestational IDA due to high vegetable consumption.

Vitamin D's function in the development of gestational diabetes mellitus (GDM) is not consistent in the literature. We examined the association between maternal plasma 25(OH)D concentration and GDM risk. A national cross-sectional study (1497 pregnant women) was conducted between 2017 and 2019 across Taiwan. Blood samples were drawn at recruitment to assess 25(OH)D concentrations, including vitamin D deficiency (VDD) (<20 ng/mL), insufficiency (<32 ng/mL), and sufficiency (≥32 ng/mL). GDM was detected from 24 to 28 weeks of gestation with the results extracted from the antenatal visit records. The prevalence of GDM was 2.9%. Logistic model analysis showed that 25(OH)D concentrations were not significantly associated with the risk of GDM (adjusted odds ratio (AOR) = 0.97, p = 0.144). However, subjects with VDD had a significantly greater risk of GDM (AOR = 2.26, p = 0.041), but not in those with vitamin D insufficiency (AOR = 1.20, p = 0.655). Furthermore, cubic piecewise spline regression was used to explore the relationship between five-unit intervals of 25(OH)D and the predicted probability of GDM. As the proportion of GDM increased for low 25(OH)D concentrations, it decreased at moderate concentrations and increased again at higher concentrations. These findings revealed a nonlinear relationship between 25(OH)D and GDM risk. VDD would be risky for GDM occurrence.

High total urinary arsenic concentrations and low estimated glomerular filtration rate (eGFR) increase the risk of renal cell carcinoma (RCC). This study aimed to determine whether other metals or metalloids can affect RCC. A total of 401 patients with RCC and 774 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Surgical resection or image-guided biopsy of renal tumors was performed to pathologically verify RCC. High-performance liquid chromatography linked to a hydride generator and atomic absorption spectrometer were used to measure the urinary arsenic species concentrations. Inductively coupled plasma mass spectrometry was used to determine plasma selenium and red blood cell cadmium and lead concentration. Plasma selenium levels were inversely related to RCC, whereas red blood cell cadmium levels were directly related to RCC. The odds ratio (OR) and 95% confidence interval (CI) were 0.14 (95% CI, 0.10-0.20) and 1.33 (95% CI, 1.03-1.72), respectively. A low plasma selenium level tended to interact with high total urinary arsenic levels or with high red blood cell cadmium concentration to increase the OR of RCC. In particular, low eGFR multiplicatively interacted with high red blood cell cadmium concentration to increase the OR of RCC (P interaction =0.003). This study was the first to find a significant multiplicative interaction between eGFR and the red blood cell cadmium levels on the increased OR of RCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

This study aimed to determine the interaction of red blood cell cadmium and lead, total urinary arsenic, and plasma selenium in chronic kidney disease (CKD). We recruited 220 CKD patients as well as 438 gender- and age-matched controls, and we defined CKD as <60 mL/min/1.73 m 2 estimated glomerular filtration rate (eGFR) for three or more consecutive months. Plasma selenium and red blood cell cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined via HPLC-HG-AAS and were summed to determine the total urinary arsenic concentration. Plasma selenium was positively correlated to eGFR, and subjects with high plasma selenium levels (>243.90 μg/L) had a significantly lower odds ratio (OR) and 95% confidence interval (CI) (0.23, 0.13-0.42) for CKD compared to those with low plasma selenium levels (≤ 196.70 μg/L). High plasma selenium and low red blood cell cadmium or lead concentrations interacted to decrease the OR and 95% CI for CKD (0.12, 0.06-0.26; 0.09, 0.04-0.19). High plasma selenium and low red blood cell lead levels also interacted to increase the eGFR (20.70, 15.56-26.01 mL/min/1.73 m 2 ). This study is the first to suggest that selenium modifies the eGFR and OR in CKD induced by environmental toxicants., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: While screening of thyroid peroxidase antibody (TPOAb) has been recommended in women with primary ovarian insufficiency, the relationship between thyroid autoimmunity (TAI) and ovarian reserve remains undetermined. Because the TAI prevalence was reported to be different between different ethnic/racial groups, this study aimed to investigate the TAI prevalence in Chinese women with variable ovarian reserve., Methods: This is a cross-sectional study conducted in a university infertility clinic between October 2013 and March 2016. Among patients at their first entry to the infertility clinic, a total of 1044 patients with available results of anti-Müllerian hormone (AMH), thyrotropin (TSH), TPOAb, and thyroglobulin antibody (TgAb) were enrolled. The TSH levels and the prevalence of positive TPOAb and positive TgAb were compared between patients with low, normal, and high ovarian reserve categorized with age-specific AMH levels., Results: For the whole study population, the TSH levels, TPOAb positivity, and TgAb positivity were comparable between patients with variable ovarian reserve. However, after patients with known causes compromising ovarian reserve (iatrogenic or genetic) were excluded, only TPOAb positivity became significantly different between patients with low (22.7%), normal (14.0%), and high ovarian reserve (10.3%; p = 0.012). The TPOAb levels were not significantly correlated to AMH levels (Spearman's ρ = -0.027; p = 0.413). For the infertile subgroup, TPOAb positivity was significantly associated with idiopathic low ovarian reserve in unexplained infertility (low ovarian reserve: 28.6%; normal: 15.7%; high: 9.5%; p = 0.020)., Conclusions: Idiopathic low ovarian reserve was associated with more frequent positive TPOAb rather than thyroid function or TgAb positivity in Chinese women.

Background: To determine whether the presence of a capsule regulator gene [i.e., regulator of mucoid phenotype A (rmpA) gene] contributes to virulence on extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) with serotype non-K1/K2 strains., Methods: Twenty-eight ESBL-KP and non-ESBL-KP isolates were collected from the Tri-Service General Hospital (Taipei, Taiwan). The impact of the virulent rmpA gene in different capsular polysaccharide serotypes on ESBL-KP and non-ESBL-KP isolates was studied by a neutrophil phagocytosis reaction, a serum bactericidal assay, and an animal survival model., Results: Resistance to broad spectrum antibiotics was more prevalent in ESBL-KP strains than in non-ESBL-KP strains (p < 0.01). The ESBL-KP strains had different molecular patterns from non-ESBL-KP strains, based on pulsed-field gel electrophoresis. The frequency of serum-resistant isolates was the highest among ESBL-KP strains with rmpA (i.e., rmpA(+)) [71.4% (5/7)] than among of non-ESBL-KP rmpA(+) strains [42.8% (6/14)], ESBL-KP strains without rmpA (rmpA(-)) [33.3% (7/21)], and non-ESBL-KP rmpA(-) strains [14.2% (2/14)]. The most significant increase in neutrophil resistance occurred in the ESBL-KP rmpA(+) strains in comparison to the non-ESBL-KP rmpA(+), ESBL-KP rmpA(-), and non-ESBL-KP rmpA(-) strains (p < 0.01). The results of the animal survival model were compatible with the neutrophil phagocytosis reaction and serum bactericidal assay., Conclusion: We conclude that the pathogenic potential is greater in rmpA(+) ESBL-KP strains than in rmpA(-) ESBL-KP and non-ESBL-KP strains., (Copyright © 2014. Published by Elsevier B.V.)

Objective: This study examined the extent to which maternal mortality in Taiwan is underreported in officially published mortality statistics., Materials and Methods: We used National Health Insurance claims data collected from two million samples, which were linked with the officially published mortality data, to identify women aged 15-49 years, who were admitted to a hospital with pregnancy-related diagnoses during 2000-2009 and died during the pregnancy or within 42 days after the termination of pregnancy., Results: Based on these linked data, we identified 26 maternal deaths, only nine of which were reported in the original officially published mortality data; thus, the rate of underreporting was 65% [(26 - 9)/26]. The revised maternal mortality ratio was 14.1 deaths per 100,000 live births (95% confidence interval: 8.7-19.5), which was approximately three times higher than the official reported ratio of 4.9 (95% confidence interval: 1.7-8.1). The most common cause of maternal deaths was amniotic fluid embolism (n = 10), followed by eclampsia and preeclampsia (n = 4)., Conclusion: Approximately two-thirds of the maternal deaths in Taiwan were unreported in the officially published mortality data. Hence, routine nationwide data linkage is essential to monitor maternal mortality in Taiwan accurately., (Copyright © 2015. Published by Elsevier B.V.)

A recent study demonstrated that an increased risk of chronic kidney disease (CKD) was associated with high urinary total arsenic levels. However, whether genomic instability is related to CKD remains unclear. An association between CKD and genetic polymorphisms of regulation enzymes of the renin-angiotensin-aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AT1R), and aldosterone synthase (CYP11B2) has not been shown. The aim of the present study was to investigate the relationship between arsenic, genetic polymorphisms of RAAS enzymes and CKD. A total of 233 patients and 449 age- and gender-matched controls were recruited from the Taipei Medical University Hospital, Taipei Municipal Wan Fang Hospital and the Shin Kong Wu Ho-Su Memorial Hospital. Concentrations of urinary arsenic were determined by a high-performance liquid chromatography-linked hydride generator, and atomic absorption spectrometry. Polymorphisms of ACE(I/D), AGT(A[-20]C), (T174M), (M235T), AT1R(A1166C) and CYP11B2(C[-344]T) were examined by polymerase chain reaction and restriction fragment length polymorphism. Subjects carrying the CYP11B2 TT genotype had a higher odds ratio (OR), 1.39 (0.96-2.01), of CKD; while those with the AGT(A[-20]C) CC genotype had an inverse OR of CKD (0.20 (0.05-0.81)), and a high-risk genotype was defined as A/A+A/C for AGT(A[-20C]) and T/T for CYP11B2(C[-344]T). The trend test showed a higher OR for CKD in patients who had either high urinary total arsenic levels or carried the high-risk genotype, or both, compared to patients with low urinary total arsenic levels, who carried the low-risk genotype, and could also be affected by the hypertension or diabetes status., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Inorganic arsenic (iAs) is carcinogenic to humans. Methylated metabolites of arsenic (As) found in the urine could serve as potential tools for screening and early detection of cancer in populations exposed to As. Relatively little information is available regarding changes in As methylation profiles after cessation of As exposure., Objective: We examined the changes in urinary arsenic (uAs) species profiles over 15 years in a cancer-free population that has ceased heavy and prolonged ingestion of As., Methods: In 1989, a cohort study was carried out with 1,081 adults who resided in three villages in southwestern Taiwan where arseniasis was hyperendemic. After 15 years of follow-up, a subgroup of 205 cancer-free participants had completed all interviews and had uAs methylation data available. We used this group in our statistical analysis. Arsenic species were measured by high-performance liquid chromatography-hydride generation-atomic absorption spectrometry., Results: We compared the initial analyses from 1989 with those performed 15 years later and found that the average differences for the proportion of urinary iAs, monomethylarsonic acid (MMA(V)), and dimethylarsinic acid (DMA(V)) were -4.90%, -6.80%, and 11.69%, respectively. The elderly and those residents with longer periods of consuming high-As artesian well water exhibited greater changes (decreases) in %MMA(V)., Conclusion: The As methylation profiles indicate increased efficiency in As metabolism in residents after cessation of long-term exposure to high-level As. Moreover, the decreased %MMA(V) was more pronounced in the elderly cancer-free subcohort subjects.

Arsenic-metabolism-related genes can regulate the arsenic methylation process and may influence susceptibility to cancer. We evaluated the roles of arsenic metabolism genes on urinary arsenic profiles of repeated measurement with 15-year follow-up (1988-2004) through general linear model (GLM) and assessed the effect of the changed extent of urinary arsenic profiles on cancer risk. Questionnaire information and blood samples and two urines (1988 and 2004) were collected from 208 subjects in an arseniasis hyperendemic area in Taiwan. Profiles for concentrations of urinary arsenic were determined using HPLC-HG-AAS. The relative proportion of each arsenic species was calculated by dividing the concentration of each arsenic species by the total arsenic concentration. Genotyping was done using the 5' nuclease allelic discrimination (Taqman) assay. The incidence of cancer was identified through linking to the National Cancer Registry Systems. The Cox proportional hazards model and survival curves were used in the analyses. After a 15-year follow-up, baseline monomethylarsonic acid percentage (MMA%) and change in MMA% exhibited a significant dose-response relationship with cancer risk. Individuals with a higher baseline MMA% and a lower change in MMA% had the earliest cancer incidence (statistically significant). Through GLM, significant gene effects of arsenic (+3 oxidation state)-methyltransferase (AS3MT) on MMA%, dimethylarsinic acid percentage (DMA%) and DMA/MMA, purine nucleoside phosphorylase (PNP) on DMA% and glutathione S-transferase omega 2 (GSTO2) on inorganic arsenics (InAs%) were found. Our results show that MMA% might be a potential predictor of cancer risk. The change in MMA% was linked to individual cancer susceptibility related to AS3MT rs3740393.

The risk of urothelial carcinoma (UC) and urinary arsenic speciation have been evaluated in a few case-control studies; however, the association has not been verified in a prospective cohort study. The aim of this study was to examine the association between urinary arsenic speciation and the incidence of UC in a cohort study. A total of 1,078 residents of southwestern Taiwan were followed for an average of 12 years. A high-performance liquid chromatography/hydride generator and an atomic absorption spectrometry were used to measure urinary arsenite, arsenate, monomethylarsonic acid (MMA(V)), and dimethylarsinic acid (DMA(V)). The incidence of UC was estimated by examining the National Cancer Registry of Taiwan between January 1985 and December 2001. There were 37 newly diagnosed cases of UC during a follow-up period of 11,655 person-years. Significantly higher percentages of MMA(V) and lower percentages of DMA(V) existed among the patients with UC than among the healthy residents. After adjustment for age, gender, educational level, and smoking status, the percentage of urinary DMA(V) was shown to have an inverse association with the risk of UC, having a relative risk (RR) of the tertile strata of 1.0, 0.3, and 0.3, respectively (p < 0.05 for the trend test). The RR (95% confidence interval) of residents with a cumulative arsenic exposure (CAE) of >/=20 mg/l-year and a higher percentage of MMA(V) or a CAE of > or =20 mg/l-year and a lower percentage of DMA(V) was 3.7 (1.2-11.6) or 4.2 (1.3-13.4) compared to residents with a CAE of <20 mg/l-year and a lower percentage of MMA(V) or a CAE of <20 mg/l-year and a higher percentage of DMA(V )respectively. There was a significant association between inefficient arsenic methylation and the development of UC in the residents in the high CAE exposure strata in an area of southwestern Taiwan endemic for arseniasis.

This study sets out to investigate the preferences of the elderly in northern Taiwan with regard to various types of long-term care services. Taking into consideration sociodemographics, health condition, and access to such medical care services, our study examined both economic and family factors in an attempt to gain an understanding of the knowledge of and attitudes toward, the various types of long-term care among the elderly. An interview survey was carried out by local public health nurses among a sample of 562 elderly Taiwanese residents (people aged 65 years or older) from 7 counties/cities in northern Taiwan, all of whom had been selected by means of multistage sampling. The survey was conducted using a questionnaire based on the Andersen and Newman model of health care utilization, with the intention being to gain a better understanding of the related factors. The results indicate that both ethnic background and the requirement for additional medical care services had significant effects on the long-term care preferences of the elderly in Taiwan, a finding that should help to provide a better understanding of the preferences for and availability of such long-term care services among the elderly. Such improved understanding could result in improving the quality of life for the elderly, particularly if they feel that their preferences have been taken into consideration and their needs have ultimately been met.

Background: Cumulative arsenic exposure (CAE) from drinking water has been shown to be associated with hypertension in a dose-response pattern. This study further explored the association between arsenic methylation capability and hypertension risk among residents of arseniasis-hyperendemic areas in Taiwan considering the effect of CAE and other potential confounders., Method: There were 871 subjects (488 women and 383 men) and among them 372 were diagnosed as having hypertension based on a positive history or measured systolic blood pressure >or=140 mm Hg and/or diastolic blood pressure >or=90 mm Hg. Urinary arsenic species were determined by high-performance liquid chromatography-hydride generator and atomic absorption spectrometry. Primary arsenic methylation index [PMI, defined as monomethylarsonic acid (MMA(V)) divided by (As(III)+As(V))] and secondary arsenic methylation index (SMI, defined as dimethylarsinic acid divided by MMA(V)) were used as indicators for arsenic methylation capability., Results: The level of urinary arsenic was still significantly correlated with cumulative arsenic exposure (CAE) calculated from a questionnaire interview (p=0.02) even after the residents stopped drinking the artesian well water for 2-3 decades. Hypertensive subjects had higher percentages of MMA(V) and lower SMI than subjects without hypertension. However, subjects having CAE >0 mg/L-year had higher hypertension risk than those who had CAE=0 mg/L-year disregard a high or low methylation index., Conclusion: Inefficient arsenic methylation ability may be related with hypertension risk.

This study examined nursing research performance in Taiwan from 1991 to 2004 by conducting bibliometric analysis of papers published by researchers affiliated with nursing institutes in Taiwan. Bibliometric information of papers that were published between 1991 and 2004 and had contact address including the words "Taiwan", and "nursing" were downloaded from the ISI Web of Knowledge website. The information used for this research included number of papers, number of authors, number of references listed, impact factors of publishing journals, times cited, and whether the paper was written through international or domestic collaboration. The information was coded and tabulated. Bibliometric characteristics were compared between 1995- 1999 and 2000-2004. Furthermore, an exponential model was fitted to show the past growth trend in research outputs. The results showed that there was a significant growth in quantity of papers from 1991 to 2004. In general, recent papers had averaged more authors, more domestic collaboration, more international collaboration, higher impact factors, and more references listed than earlier papers. Papers written with collaboration tended to have a higher average number of authors and more references listed, and tended to be published in journals with higher impact factors. The exponential model proved to be in good fit with the past growth pattern. The authors speculate that the recent increase in research collaboration, both internationally and domestically, may have contributed to the significant increase in output. It is not clear whether the growth in quantity of papers will continue or for how long. Based on past data, however, no sign of leveling off has been observed. More research is needed to understand what societal and individual level factors were involved in fueling such a dramatic increase in quantity in the last decade. Furthermore, as the quantity of papers has increased steadily, more focus can be placed on improving the quality of research papers.

The objective of this study was to assess individual variation in inorganic arsenic methylation capability and the association between selenium levels in urine and blood, and inorganic arsenic methylation capability among residents of the Lanyang Basin who drank groundwater and were exposed to high concentrations of inorganic arsenic. According to the arsenic concentration of their drinking water, they were equally and randomly classified into four groups of 252 persons. It turned out that the higher the concentration of arsenic in well water was and thus the cumulative arsenic exposure, the higher the total inorganic arsenic metabolites in urine (total As(i)) and the overall inorganic and organic arsenic in urine (overall As(i+o)) were. The percentage of inorganic arsenic significantly decreased and the DMA percentage significantly increased as the concentration of urinary selenium and serum alpha-tocopherol increased. It appeared that urinary selenium levels increased the metabolism by methylation of arsenic, a finding that requires further investigation.