Chronic Low-Level Cyanide Intoxication in an Electroplating Plant in Taiwan.

OBJECTIVE: This study aimed to investigate clinical symptoms among electroplating workers exposed to cyanide. METHODS: In this study, 26 silver-plating and 51 gold-plating workers completed questionnaires and were tested for urinary thiocyanates. Air cyanide, urinary thiocyanates, and clinical symptoms were compared between workers using Student t and χ 2 test and further analyzed by multivariate linear regression. RESULTS: Air cyanide and urinary thiocyanate were higher in the silver-plating plant than the gold-plating plant. In both plants, a dose-response relationship was observed between exposure status and thiocyanate levels. Silver-plating workers reported a higher frequency of almond odor detection, nasal bleeding, excessive salivation, skin scalding, and corrosion. Urinary thiocyanates were associated with the plant and exposure status, but not with smoking. CONCLUSIONS: Our study suggests that silver-plating workers had higher exposure and more symptoms. Urinary thiocyanate may be a useful biomarker for cyanide exposure.

Combined effect of polymorphisms of MTHFR and MTR and arsenic methylation capacity on developmental delay in preschool children in Taiwan.

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.

Alzheimer's Disease and Diabetes: Insulin Signaling as the Bridge Linking Two Pathologies.

Alzheimer's (or Alzheimer) disease (AD) is the most prevalent subset of dementia, affecting elderly populations worldwide. The cumulative costs of the AD care are rapidly accelerating as the average lifespan increases. Onset and risk factors for AD and AD-like dementias have been largely unknown until recently. Studies show that chronic type II diabetes mellitus (DM) is closely associated with neurodegeneration, especially AD. Type II DM is characterized by the cells' inability to take up insulin, as well as chronic hyperglycemia. In the central nervous system, insulin has crucial regulatory roles, while chronic hyperglycemia leads to formation and accumulation of advanced glycation end products (AGEs). AGEs are the major contributor to insulin resistance in diabetic cells, due to their regulatory role on sirtuin expression. Insulin activity in the central nervous system is known to interact with key proteins affected in neurodegenerative conditions, such as amyloid-ß precursor protein (AßPP or APP), huntingtin-associated protein-1 (HAP1), Abelson helper integration site-1 (AHI1 or Jouberin), kinesin, and tau. Sirtuins have been theorized to be the mechanism for insulin resistance, and have been found to be affected in neurodegenerative conditions as well. There are hints that all these neuronal proteins may be closely related, although the mechanisms remain unclear. This review will gather existing research on these proteins and highlight the link between neurodegenerative conditions and diabetes mellitus.

ICP-MS Assessment of Hair Essential Trace Elements and Minerals in Russian Preschool and Primary School Children with Attention-Deficit/Hyperactivity Disorder (ADHD).

The objective of the present study was to investigate the relationship between hair essential trace element and mineral content and ADHD in preschool (4-6 years old) and primary school children (6-10 years old) in relation to age and gender. Hair essential trace element and mineral content in 90 Russian children with ADHD and 90 age- and gender-matched neurotypical controls were assessed using inductively coupled plasma mass-spectrometry after microwave digestion. The obtained data demonstrate that hair Co, Cu, Mn, Si, and Zn contents in ADHD children was significantly reduced by 18%, 10%, 27%, 16%, and 19% as compared to the control values, respectively. The most significant decrease in children with ADHD was observed for hair Mg levels, being 29% lower than those in neurotypical children. After adjustment for age and gender, the observed difference in hair element content was more characteristic for preschool children and girls, respectively. Multiple linear regression analysis demonstrated that in a crude model (hair element levels as predictors), only hair Zn content was significantly inversely associated with ADHD (ß = - 0.169; p = 0.025). Adjustment for anthropometric parameters (model 2) did not increase the predictive ability of the model, although it improved the association between hair Zn and ADHD in children (ß = - 0.194; p = 0.014). Hypothetically, the observed alterations may at least partially contribute to neurobehavioral disturbances in children with ADHD. Moreover, the results of the present study raise the question about the potential benefits of Zn and Mg supplementation in children with ADHD. However, further detailed studies are required to investigate micronutrient deficiencies in ADHD.

Association of plasma folate, vitamin B12 levels, and arsenic methylation capacity with developmental delay in preschool children in Taiwan.

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.

Plasma selenium influences arsenic methylation capacity and developmental delays in preschool children in Taiwan.

Inefficient arsenic methylation capacity has been associated with developmental delay in preschool children. Selenium has antioxidant and anti-inflammatory properties that protect experimental animals from chemically induced neurotoxicity. The present study was designed to explore whether plasma selenium levels affects arsenic methylation capacity related to developmental delay in preschool children. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 178 children with a developmental delay and 88 children without a delay were recruited. High-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry were used to determine urinary arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV). Plasma selenium levels were measured by inductively coupled plasma mass spectrometry. As results, plasma selenium concentration was significantly inversely associated with the odds ratio (OR) of developmental delay. Plasma selenium concentration was positively associated with arsenic methylation capacity [percentage of inorganic arsenic and percentage of MMAV (MMAV%) decreased, and percentage of DMAV (DMAV%) increased]. High plasma selenium concentration and high DMA% significantly and additively interacted to decrease the OR of developmental delay; the OR and 95% confidence interval were 0.40 (0.18-0.90). This is the first study to show a combined dose-response effect of plasma selenium concentration and that efficient arsenic methylation capacity decreased the OR of developmental delay in preschool children.

Hair Trace Element Levels in Han and Indigenous Hualien Inhabitants in Taiwan.

The objective of the present study was to assess the impact of ethnicity on hair trace element content in Han and aboriginal inhabitants of Hualien in Taiwan. Fifty Han (female/male = 35/15) and 50 aboriginal (female/male = 40/10) Hualien inhabitants aged 40-60 years were involved in the present study. Anthropometric data and dietary patterns were recorded. Hair mineral, essential, and toxic trace element levels were assessed using inductively coupled plasma mass spectrometry at NexION 300D (PerkinElmer Inc., USA) equipped with ESI SC-2 DX4 autosampler (Elemental Scientific Inc., USA). No group difference in gender, age, body weight, height, or physical activity was observed. Fish intake was more frequent in Han inhabitants, whereas aborigines consumed significantly more nuts. Indigenous people were characterized by higher hair Al (45%), Ca (threefold), Co (71%), Fe (twofold), I (74%), K (60%), Mg (2.5-fold), Na (62%), P (6%), Sn (78%), and V (46%) content. In turn, Han Hualien inhabitants had higher hair Be (twofold), Li, Se, Si levels as compared to indigenous counterparts. Multiple regression analysis demonstrated that ethnicity was significantly associated with hair Ca (ß = 0.302), Mn (ß = 0.284), P (ß = 0.387), and Se (ß = - 0.310) levels after adjustment for other confounders. At the same time, the overall models were significant for Ca, Mn, Se, and As. The obtained data may provide a background for monitoring and correction of trace element status in patients of different ethnic groups. However, further detailed studies are required to highlight the mechanisms underlying the observed associations.

Cadmium and atherosclerosis: A review of toxicological mechanisms and a meta-analysis of epidemiologic studies.

Cadmium has been proposed to be the one of the factors of atherosclerosis development, although the existing data are still controversial. The primary objective of the present study is the review and the meta-analysis of studies demonstrating the association between Cd exposure and atherosclerosis as well as review of the potential mechanisms of such association. We performed a systematic search in the PubMed-Medline database using the MeSH terms cadmium, cardiovascular disease, atherosclerosis, coronary artery disease, myocardial infarction, stroke, mortality and humans up through December 20, 2017. Elevated urinary Cd levels were associated with increased mortality for cardiovascular disease (HR = 1.34, 95% CI: 1.07-1.67) as well as elevated blood Cd levels (HR = 1.78, 95% CI: 1.24-2.56). Analysis restricted to never smokers showed similar, though more imprecise, results. Consistently, we also observed an association between Cd exposure markers (blood and urine) and coronary heart disease, stroke, and peripheral artery disease. Moreover, Cd exposure was associated with atherogenic changes in lipid profile. High Cd exposure was associated with higher TC levels (OR = 1.48, 95% CI: 1.10-2.01), higher LDL-C levels (OR = 1.31, 95% CI 0.99-1.73) and lower HDL-C levels (OR = 1.96, 95% CI: 1.09-3.55). The mechanisms of atherogenic effect of cadmium may involve oxidative stress, inflammation, endothelial dysfunction, enhanced lipid synthesis, up-regulation of adhesion molecules, prostanoid dysbalance, as well as altered glycosaminoglycan synthesis.

Comparative Hair Trace Element Profile in the Population of Sakhalin and Taiwan Pacific Islands.

The objective of the current study is to perform a comparative analysis of hair trace element content in 393 apparently healthy adults living in Taipei, Taiwan, Republic of China (94 women and 46 men) and Yuzhno-Sakhalinsk, Sakhalin, Russia (186 women and 67 men). The obtained data indicate that Yuzhno-Sakhalinsk inhabitants were characterized by significantly higher hair Co, Cr, Mn, and V levels, exceeding the respective Taipei values by a factor of 3, 2, 7, and 5, respectively (all p < 0.001). Hair Cu, Fe, and Si levels were also higher in examinees from Yuzhno-Sakhalinsk than those from Taipei by 10% (p = 0.001), 61% (p < 0.001), and 68% (p < 0.001), respectively. It is notable that the only essential element, being significantly higher (+ 30%; p < 0.001) in Taipei inhabitants, is selenium. Yuzhno-Sakhalinsk inhabitants were characterized by 60% higher levels of hair Sn, and nearly two- and threefold higher scalp hair content of Be and Cd in comparison to Taipei values, respectively (all p < 0.001). Oppositely, the examinees from Taipei had 14% (p = 0.040) and 47% (p = 0.001) higher levels of hair As and Hg as compared to Yuzhno-Sakhalinsk inhabitants. Further analysis demonstrated that men from both Yuzhno-Sakhalinsk and Taipei were characterized by significantly higher hair Mn, As, and Pb levels in comparison to women. The intensive development of heavy industry in Yuzhno-Sakhalinsk may result in increased metal emissions, whereas fish consumption may result in elevation of hair Hg, As, and Se levels in Taiwan inhabitants.

Association between sleep duration and sleep quality, and metabolic syndrome in Taiwanese police officers.

OBJECTIVES: This study's objective was to examine association between sleep duration and sleep quality, and metabolic syndrome (MetS) and its components in Taiwanese male police officers. MATERIAL AND METHODS: Male police officers who underwent annual health examinations were invited to join the study and eventually a total of 796 subjects was included in it. The study subjects were divided into 5 groups according to the length (duration) of sleep: < 5, 5-5.9, 6-6.9, 7-7.9 and ≥ 8 h per day, and the global Pittsburgh Sleep Quality Index was used to categorize their sleep quality as good or poor. To analyze the association between sleep problems and MetS, adjusted odds ratio and respective 95% confidence intervals (CI) were computed. RESULTS: The prevalence of MetS in Taiwanese male police officers was 24.5%. Abdominal obesity had the highest proportion (36.2%) among 5 components of MetS. More than 1/2 of the police officers (52.3%) had poor sleep quality. Police officers with higher scores of sleep disturbances had a higher prevalence of MetS (p = 0.029) and abdominal obesity (p = 0.009). After adjusting for age, low-density lipoprotein cholesterol, smoking status, alcohol drinking habit, physical habitual exercise, snoring and type of shift work, the police officers who slept less than 5 h were 88% more likely to suffer from abdominal obesity than those who slept 7-7.9 h (95% CI: 1.01-3.5). Sleep quality was not associated with MetS and its components. CONCLUSIONS: The police officers who slept less than 5 h were more likely to experience abdominal obesity in Taiwan, and those with higher scores of sleep disturbances had a higher prevalence of MetS and abdominal obesity. It is recommended that police officers with short sleep duration or sleep disturbances be screened for MetS and waist circumference in order to prevent cardiovascular diseases.

Association Between Organization Culture, Health Status, and Presenteeism.

OBJECTIVE: The aim of this study was to examine relationships of organizational culture and health behaviors with presenteeism. METHOD: Data of a self-reported questionnaire were collected from 816 employees, who joined the study on a voluntary basis, in seven enterprises in northern Taiwan. RESULTS: Organizational culture and health behaviors were found to be significantly associated with presenteeism. After adjusting for confounding factors, the number of health complaints seemed to be more suitable than chronic diseases in predicting presenteeism. CONCLUSIONS: This study result implied that advantage could be taken of organizational culture and employees' health behaviors to reduce presenteeism in the workplace.

Huntingtin-associated protein 1 interacts with breakpoint cluster region protein to regulate neuronal differentiation.

Alterations in microtubule-dependent trafficking and certain signaling pathways in neuronal cells represent critical pathogenesis in neurodegenerative diseases. Huntingtin (Htt)-associated protein-1 (Hap1) is a brain-enriched protein and plays a key role in the trafficking of neuronal surviving and differentiating cargos. Lack of Hap1 reduces signaling through tropomyosin-related kinases including extracellular signal regulated kinase (ERK), resulting in inhibition of neurite outgrowth, hypothalamic dysfunction and postnatal lethality in mice. To examine how Hap1 is involved in microtubule-dependent trafficking and neuronal differentiation, we performed a proteomic analysis using taxol-precipitated microtubules from Hap1-null and wild-type mouse brains. Breakpoint cluster region protein (Bcr), a Rho GTPase regulator, was identified as a Hap1-interacting partner. Bcr was co-immunoprecipitated with Hap1 from transfected neuro-2a cells and co-localized with Hap1A isoform more in the differentiated than in the nondifferentiated cells. The Bcr downstream effectors, namely ERK and p38, were significantly less activated in Hap1-null than in wild-type mouse hypothalamus. In conclusion, Hap1 interacts with Bcr on microtubules to regulate neuronal differentiation.

Hyaluronan regulates PPARγ and inflammatory responses in IL-1ß-stimulated human chondrosarcoma cells, a model for osteoarthritis.

The carbohydrate polymer, hyaluronan, is a major component of the extracellular matrix in animal tissues. Exogenous hyaluronan has been used to treat osteoarthritis (OA), a degenerative joint disease involving inflammatory changes. The underlying mechanisms of hyaluronan in OA are not fully understood. Pro-inflammatory interleukin (IL)-1ß downregulates peroxisome proliferator-activated receptor gamma (PPARγ), and increases expression of matrix metalloproteinases (MMPs) which are responsible for the degeneration of articular cartilage. The effects of low- and high-molecular-weight hyaluronan (oligo-HA and HMW-HA) on the inflammatory genes were determined in human SW-1353 chondrosarcoma cells. HMW-HA antagonized the effects of IL-1ß by increasing PPARγ and decreasing cyclooxygenase (COX)-2, MMP-1, and MMP-13 levels. It promoted Akt, but suppressed mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NFκB) signaling, indicating anti-inflammatory effects. In contrast, the cells had overall opposite responses to oligo-HA. In conclusion, HMW-HA and oligo-HA exerted differential inflammatory responses via PPARγ in IL-1ß-treated chondrosarcoma cells.

Visible light-responsive core-shell structured In2O3@CaIn2O4 photocatalyst with superior bactericidal properties and biocompatibility.

Antibacterial activity of photocatalytic substrates is primarily induced by ultraviolet light irradiation. Visible light-responsive photocatalysts were recently discovered, offering greater opportunity to use photocatalysts as disinfectants in our living environment. The development of antibacterial photocatalysts, however, has mainly focused on titanium oxide (TiO(2))-related materials with antibacterial properties not comparable with conventional chemical disinfectants. This study demonstrated that a core-shell structured In(2)O(3)@CaIn(2)O(4) substrate has superior visible light-induced bactericidal properties, as compared with several commercially available and laboratory-prepared visible light-responsive photocatalysts. The high performance is enhanced by more easily photoexcited electron transfer between the interfaces of In(2)O(3) and CaIn(2)O(4) to minimize the electron-hole recombination during photocatalysis. Additionally, when compared with TiO(2)-based photocatalysts, In(2)O(3)@CaIn(2)O(4) treatments did not induce significant cell death and tissue damage, implying a superior biocompatibility. These findings suggest that In(2)O(3)@CaIn(2)O(4) may have potential application in the development of a safer and highly bactericidal photocatalyst. FROM THE CLINICAL EDITOR: A photocatalytic susbstrate is described that functions in visible light, possesses bactericidal properties and better biocompatibility than the standard TiO(2) based methods.

Risk factors and predictors of non-alcoholic fatty liver disease in Taiwan.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: Ultrasound assessment of the severity of non-alcoholic fatty liver disease (NAFLD) shows substantial observer variability. The purpose of this retrospective study is to develop a more objective, quantitative, and applicable assessment method for all physicians. MAIN RESULTS: Male gender, and increases in age, body mass index, alanine aminotransferase (ALT), triglycerides (TG), and total cholesterol (TC) were found to be significantly correlated to higher scores. The following algorithm, derived from a 3,275 member training group, for predicting the extent of fatty liver infiltration was then constructed using these parameters. In (π(1)/π(0)) = -8.360-0.065*Gender+0.010*age+0.256*BMI+0.024*ALT+0.03*TG+0.002*TC. In (π(2)/π(0))= -19.0.92+0.482*Gender+0.043*age+0.529*BMI+0.046*ALT+0.005*TG+0.005*TC. π(0): the probability of non fatty liver. π(1): the probability of degree 1 fatty liver. π(2): the probability of degree 2-3 fatty liver. π(0) + π(1) + π(2) = 1. The resulting algorithm was tested for its predictive power a 1,065 member validation group. The algorithm predicted the actual ultrasound fatty liver score in the validation group with 87.9, 14.2, and 72.6% accuracy for those with no, grade 1, and grade 2-3 fatty liver, respectively. For prediction of grade 2-3 fatty liver, its sensitivity was 70.8%, its specificity 85.2%, its positive predictive power 63.2% and its negative predictive power 88.8%. CONCLUSIONS: The algorithm developed here is fast and has substantial predictive power for grade 2-3 fatty liver. No specialized equipment or expertise is needed, and it can be easily used by the general practitioner to predict the extent of fatty infiltration in cases of NAFLD.