Co-exposure to lead, mercury, and cadmium induces neurobehavioral impairments in mice by interfering with dopaminergic and serotonergic neurotransmission in the striatum.

Humans are exposed to lead (Pb), mercury (Hg), and cadmium (Cd) through various routes, including drinking water, and such exposure can lead to a range of toxicological effects. However, few studies have investigated the toxic effects of exposure to mixtures of metals, particularly in relation to neurotoxicity. In this study, 7-week-old male mice were exposed to Pb, Hg, and Cd individually or in combination through their drinking water for 28 days. The mice exposed to the metal mixture exhibited significantly reduced motor coordination and impaired learning and memory abilities compared to the control group and each of the single metal exposure groups, indicating a higher level of neurotoxicity of the metal mixture. The dopamine content in the striatum was significantly lower in the metal mixture exposure group than in the single metal exposure groups and the control group. Furthermore, compared to the control group, the metal mixture exposure group showed a significantly lower expression level of tyrosine hydroxylase (TH) and significantly higher expression levels of dopamine transporter (DAT), tryptophan hydroxylase 1 (TPH1), and serotonin reuptake transporter (SERT). Notably, there were no significant differences in SERT expression between the single metal exposure groups and the control group, but SERT expression was significantly higher in the metal mixture exposure group than in the single metal and control groups. These findings suggest that the key proteins involved in the synthesis and reuptake of dopamine (TH and DAT, respectively), as well as in the synthesis and reuptake of serotonin (TPH1 and SERT, respectively), play crucial roles in the neurotoxic effects associated with exposure to metal mixtures. In conclusion, this study demonstrates that simultaneous exposure to different metals can impact key enzymes involved in dopaminergic and serotonergic neurotransmission processes, leading to disruptions in dopamine and serotonin homeostasis and consequently a range of detrimental neurobehavioral effects.

Association of mercury exposure with the serum high-sensitivity C-reactive protein level in Korean adults.

Although there is evidence that mercury (Hg) exposure may be a potential risk factor for cardiovascular disease (CVD), few nationwide epidemiological researches have analyzed the association between blood Hg concentration and serum high-sensitivity C-reactive protein (hs-CRP) level as a biomarker of CVD. The present population-based national study was performed with data from the 2016-2017 National Health and Nutrition Examination Survey. In the total sample of 3,773 adults aged ≥20 years, the serum hs-CRP concentrations were 1.03 mg/L among participants in the lowest quartile of blood Hg level and 1.18 mg/L among those in highest quartile. The trend for the prevalence of a risky (>1.0 mg/L) hs-CRP level (moderate risk and high risk) was significantly related to an increased quartile blood Hg concentration. After adjustment for confounders, participants with the highest quartiles of blood Hg had increased odds of a risky (>1.0 mg/L) hs-CRP level (adjusted odds ratio = 1.34; 95% confidence interval, 1.02-1.77) compared with those with the lowest quartile of blood Hg. These findings demonstrate that a high blood Hg level increases the concentration of serum hs-CRP, a sensitive marker of chronic low-grade inflammation, and imply that the increased body burden associated with high blood Hg is a potential risk factor in the development of many inflammatory diseases, including CVD.

Association between Heavy Metal Exposure and Parkinson's Disease: A Review of the Mechanisms Related to Oxidative Stress.

Parkinson's disease (PD) is a gradually progressing neurodegenerative condition that is marked by a loss of motor coordination along with non-motor features. Although the precise cause of PD has not been determined, the disease condition is mostly associated with the exposure to environmental toxins, such as metals, and their abnormal accumulation in the brain. Heavy metals, such as iron (Fe), mercury (Hg), manganese (Mn), copper (Cu), and lead (Pb), have been linked to PD and contribute to its progression. In addition, the interactions among the components of a metal mixture may result in synergistic toxicity. Numerous epidemiological studies have demonstrated a connection between PD and either single or mixed exposure to these heavy metals, which increase the prevalence of PD. Chronic exposure to heavy metals is related to the activation of proinflammatory cytokines resulting in neuronal loss through neuroinflammation. Similarly, metals disrupt redox homeostasis while inducing free radical production and decreasing antioxidant levels in the substantia nigra. Furthermore, these metals alter molecular processes and result in oxidative stress, DNA damage, mitochondrial dysfunction, and apoptosis, which can potentially trigger dopaminergic neurodegenerative disorders. This review focuses on the roles of Hg, Pb, Mn, Cu, and Fe in the development and progression of PD. Moreover, it explores the plausible roles of heavy metals in neurodegenerative mechanisms that facilitate the development of PD. A better understanding of the mechanisms underlying metal toxicities will enable the establishment of novel therapeutic approaches to prevent or cure PD.

Trends and Factors Associated with Oral Contraceptive Use among Korean Women.

Although oral contraceptives (OC) are widely used, few national-level epidemiologic studies have evaluated the prevalence of OC use and factors related to their use in Korea. We performed a population-based cross-sectional study on OC use by premenopausal women aged 20-59 years residing in Korea. We used secondary data from the 2010-2019 National Health and Nutrition Examination Survey to examine trends in the annual prevalence of OC use between 2010 and 2019, and factors influencing OC use. Based on data from 14,386 premenopausal women, the average annual prevalence of OC use was 8.2-10.7% between 2010 and 2014; it increased to 12.6-14.4% during 2015-2019. The prevalence of OC use was significantly higher in women with higher (≥5) than lower gravidity (<5). In addition, among sociodemographic factors, education level, household income, cigarette smoking, and alcohol drinking were significantly associated with OC use in Korean women. As OC use is affected by sociodemographic factors, a contraceptive plan that considers sociodemographic factors is needed to establish an effective family planning policy.

Combined Exposure to Metals in Drinking Water Alters the Dopamine System in Mouse Striatum.

Environmental exposure to arsenic (As), lead (Pb), and cadmium (Cd) frequently occurs; however, data on the specific effects of combined exposure on neurotransmission, specifically dopaminergic neurotransmission, are lacking. In this study, motor coordination and dopamine content, along with the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors (DRs), were examined in the striatum of adult male mice following exposure to drinking water containing As, Pb, and/or Cd. We found that exposure to a metal mixture impaired motor coordination. After 4 weeks of treatment, a significant decrease in dopamine content and expression of TH, DAT, and VMAT2 was observed in the striatum of metal-mixture-treated mice, compared to the controls or single-metal-exposed groups. However, DRD1 and DRD2 expression did not significantly change with metal treatment. These results suggest that altered dopaminergic neurotransmission by the collective action of metals may contribute to metal-mixture-induced neurobehavioral disorders.

Machine-learning models predicting osteoarthritis associated with the lead blood level.

Lead is one of the most hazardous environmental pollutants in industrialized countries; lead exposure is a risk factor for osteoarthritis (OA) in older women. Here, the performance of several machine-learning (ML) algorithms in terms of predicting the prevalence of OA associated with lead exposure was compared. A total of 2224 women aged 50 years and older who participated in the Korea National Health and Nutrition Examination Surveys from 2005 to 2017 were divided into a training dataset (70%) for generation of ML models, and a test dataset (30%). We built and tested five ML algorithms, including logistic regression (LR), a k-nearest neighbor model, a decision tree, a random forest, and a support vector machine. All afforded acceptable predictive accuracy; the LR model was the most accurate and yielded the greatest area under the receiver operating characteristic curve. We found that various ML models can be used to predict the risk of OA associated with lead exposure effectively, using data from population-based survey.

Generality of likelihood ratio decisions.

A basic assumption of Signal Detection Theory - a special case of Bayesian Decision Theory - is that decisions are based on likelihood ratios (the likelihood ratio hypothesis). In a preceding paper, Glanzer et al. (2009) tested this assumption in recognition memory tasks. The tests consisted of formal proofs and computational demonstrations that decisions based on likelihood ratios produce three regularities (1. the Mirror Effect, 2. the Variance Effect, and 3. the z-ROC Length Effect). Glanzer et al. found that the three implied regularities do indeed hold for a wide range of item recognition memory studies taken from the literature. We now claim that the likelihood ratio regularities hold for decisions generally: decisions about sensory events, reasoning, weather forecasting, etc. An examination of past decision studies supports the generalization. We also report new experimental studies of decisions in two additional areas, semantic memory and mental rotation, further supporting the generalization. The results highlight the optimal characteristics of decision making in contrast to the current emphasis on its inefficiencies.

Comparisons among Machine Learning Models for the Prediction of Hypercholestrolemia Associated with Exposure to Lead, Mercury, and Cadmium.

Lead, mercury, and cadmium are common environmental pollutants in industrialized countries, but their combined impact on hypercholesterolemia (HC) is poorly understood. The aim of this study was to compare the performance of various machine learning (ML) models to predict the prevalence of HC associated with exposure to lead, mercury, and cadmium. A total of 10,089 participants of the Korea National Health and Nutrition Examination Surveys 2008-2013 were selected and their demographic characteristics, blood concentration of metals, and total cholesterol levels were collected for analysis. For prediction, five ML models, including logistic regression (LR), k-nearest neighbors, decision trees, random forests, and support vector machines (SVM) were constructed and their predictive performances were compared. Of the five ML models, the SVM model was the most accurate and the LR model had the highest area under receiver operating characteristic (ROC) curve of 0.718 (95% CI: 0.688-0.748). This study shows the potential of various ML methods to predict HC associated with exposure to metals using population-based survey data.

Perinatal Exposure to Arsenic in Drinking Water Alters Glutamatergic Neurotransmission in the Striatum of C57BL/6 Mice.

Although exposure to arsenic (As) induces developmental neurotoxicity, there is a lack of data regarding its specific effects on glutamatergic neurotransmission in offspring from dams exposed to As during gestation and lactation. In this study, the body weight, glutamate content, and expression of vesicular glutamate transporter 2 (VGLUT2) and metabotropic glutamate receptors mGluR2 and mGluR3 was examined in the striatum of offspring following treatment of the dams with As (10 or 100 mg/L NaAsO2 in drinking water). At postnatal day 21, body weight was decreased significantly, whereas the glutamate content in the striatum of offspring in the 100-mg/L As group were not significantly different from those in the control group. Although mGluR3 expression was not significantly different, VGLUT2 and mGluR2 expression was significantly lower in the striatum of offspring of As-exposed dams. These data indicate that altered glutamatergic neurotransmission may contribute to As-induced developmental neurotoxic effects.

One mirror effect: The regularities of recognition memory.

The mirror effect is a pattern of results generally found in two-condition recognition memory experiments that is consistent with normative signal detection theory as a model of recognition. However, the claim has been made that there is a distinct mirror effect, the "strength mirror effect," that differs from the normative one. This claim is based on experiments on recognition memory in which repetition or study time is varied to produce differences in accuracy, where typically the ordinary mirror effect pattern is absent. If this claim is correct, it has major implications for theories of recognition memory. Therefore, a full examination of the data that support the claim was called for. To do that, we replicated the basic demonstration of the no-mirror-effect data and analyzed it further in a series of experiments. The analysis showed the following: (1) Whether or not the mirror effect occurs is determined by whether the experimenter furnishes effective discriminanda that distinguish the weak and strong conditions for the participant. (2) Once Finding 1 is taken into account, no adjustments of or additions to the normative signal detection theory explanations are necessary. (3) There is only one mirror effect, and no separate "strength mirror effect."

Depression and Its Association with Health-Related Quality of Life in Postmenopausal Women in Korea.

Menopause is associated with depressive symptoms that can significantly affect a woman's quality of life. The objective of this study was to evaluate the association between depression and health-related quality of life (HRQoL) in postmenopausal women. In this cross-sectional descriptive study, participants (n = 3860) were selected from the 2013⁻2015 Korea National Health and Nutrition Examination Survey (KNHANES). The sociodemographic characteristics, medical history of depression, and EQ-5D scores of the participants were obtained from the KNHANES dataset. Age, educational level, and income were associated with HRQoL in these participants. Moreover, depression exerted a considerable influence on HRQoL in postmenopausal women. The adjusted odds ratios in participants with depression for the EQ-5D dimensions were as follows: 5.52 (95% CI = 4.04⁻7.55, p < 0.001) for anxiety/depression, 3.86 (95% CI = 2.78⁻5.36, p < 0.001) for usual activities, and 2.52 (95% CI = 1.68⁻3.78, p < 0.001) for self-care. Our findings suggest a strong association between depression and HRQoL. Hence, preventing the onset or exacerbation of depression may significantly improve quality of life in postmenopausal women.

Concentrations of 2,4-Dichlorophenol and 2,5-Dichlorophenol in Urine of Korean Adults.

Humans are exposed to the environmental pollutants 2,4-dichlorophenol (2,4-DCP) and 2,5-dichlorophenol (2,5-DCP) through air, the use of water and the consumption of products. In this study, we evaluated the urinary concentrations of these compounds in Korean people between the ages of 18 to 69 years, by making use of data from the Korean National Human Biomonitoring Survey that was completed in 2009. Of 1865 representative Koreans, 63.4% and 97.9% were found to have concentrations of 2,4-DCP and 2,5-DCP > 0.05 µg/L (limit of detection) in their urine, respectively. The geometric mean of urinary concentrations was 0.14 µg/L (confidence interval of 95% = 0.13-0.16) and 0.44 µg/L (confidence interval = 0.41-0.48), respectively. It was found that the adjusted proportional changes in 2,4-DCP concentrations were significantly associated with body mass index, whereas those of 2,5-DCP concentrations were influenced by place of residence. From these findings, it is evident that most adults in Korea have levels of 2,4-DCP and 2,5-DCP that are detectable in their urine and the burden of these compounds on their bodies varies depending on numerous demographic factors.

Urinary Levels of 4-Nonylphenol and 4-t-Octylphenol in a Representative Sample of the Korean Adult Population.

4-Nonylphenol (4-NP) and 4-t-octylphenol (4-t-OP) are xenoestrogen compounds to which humans are exposed via contaminated food, water, and air. This study assessed the body burden of 4-NP and 4-t-OP in Koreans aged 18-69 years using data from the Korean National Human Biomonitoring Survey conducted in 2009. Based on data from 1865 representative Koreans, 83.2% and 91.8% had urinary 4-NP and 4-t-OP concentrations >0.05 ng/mL (limit of detection). Of the Korean adult population, the geometric mean urinary concentrations of 4-NP and 4-t-OP were 3.70 ng/mL (95% confidence interval (CI) = 3.20-4.27) and 0.60 ng/mL (95% CI = 0.55-0.66), respectively. Urine 4-NP concentrations were significantly associated with place of residence and smoking status, whereas urine 4-t-OP concentrations were not correlated with any of the demographic factors. These findings suggest that most Koreans have detectable levels of 4-NP and 4-t-OP in their urine and that the body burden of 4-NP, but not 4-t-OP, varies according to some demographic factors.

Association of Perceived Stress with Atopic Dermatitis in Adults: A Population-Based Study in Korea.

Atopic dermatitis (AD) is a widely prevalent skin disease that affects both children and adults. The aim of the study was to assess the association of perceived stress (single-item, self-reported) with AD (self-reported) in a sample of Korean adults using a cross-sectional research design. A cross-sectional study was conducted using data from 33,018 adults aged 20 years and older collected in the 2007-2012 Korea National Health and Nutrition Examination Surveys (KNHANES). An increased level of self-reported stress was positively associated with an increased prevalence of AD in Korean adults (p for trend <0.001). After adjusting for covariates, the odds ratios (ORs) of AD among participants reporting high and very high levels of stress were 1.81 (95% confidence interval (CI): 1.22, 2.67) and 2.17 (95% CI: 1.38, 3.42), respectively, compared with those who reported low levels of stress. This study found a statistically significant association between perceived stress and AD among Korean adults.

Gender differences in the association between self-reported stress and cigarette smoking in Korean adolescents.

BACKGROUND: The aim of this study was to examine the relationship between stress and smoking among Korean adolescents, as well as the influence of gender on this relationship. METHODS: A cross-sectional study was conducted using data from 3930 adolescents aged 12-18 years, collected in the 2007-2012 Korea National Health and Nutrition Examination Surveys. RESULTS: An increased level of self-reported stress was positively associated with increasing levels of smoking in both girls and boys (p for trend < 0.001). After adjusting for age, the odds ratios of smoking among girls and boys reporting very high levels of stress were 15.99 (95 % confidence interval (CI), 4.17-61.30) and 2.34 (95 % CI, 1.07-5.11), respectively, compared with those who reported low levels of stress. CONCLUSIONS: This study found a statistically significant association between stress and smoking among Korean adolescents and this association was stronger in girls than boys. Further research is needed to understand more fully the link between stress and smoking in adolescents, with particular attention to sex differences.

Urinary benzophenone concentrations and their association with demographic factors in a South Korean population.

Benzophenone (BP) and its derivatives are widely used in various cosmetics, personal care products, and food packaging ink. The use of BP has raised concerns about the potential health risks associated with its endocrine-disrupting effects. This study evaluated urinary concentrations of BP derivatives in a national sample of the South Koreans population aged 6-89 years. From July to September in each 2010 and 2011, 1576 urine samples were collected. Urinary concentrations of benzophenone-1 (BP-1), benzophenone-2 (BP-2), benzophenone-3 (BP-3), benzophenone-4 (BP-4), benzophenone-8 (BP-8), and 4-hydroxybenzophenone (4-OH-BP) were analyzed using liquid chromatography-mass spectrometry. The detection rate for BP-1 and 4-OH-BP were 56% [limit of detection (LOD) 0.59ng/mL] and 88% (LOD 0.04ng/mL), respectively, whereas those for BP-2, BP-3, BP-4, and BP-8 were all below 25%. The geometric means of urinary BP-1 and 4-OH-BP concentrations were 1.24ng/mL and 0.45ng/mL, respectively. Multiple linear regression analysis indicated that concentrations of BP-1 in and of 4-OH-BP in adults were associated with sex and age. The BP-1 and 4-OH-BP concentration of children and adolescents was associated with sex, age, income, and current area of residence. The correlation was observed between urinary concentrations of BP derivatives, which is an important indication of exposure biomarkers and the metabolic pathways from BP-3. This is the first national study to evaluate the presence of BP derivatives in urine samples from the South Korean population, stratified by demographic factors.

Prevalence of potent skin sensitizers in oxidative hair dye products in Korea.

OBJECTIVES: The objective of the present study was to elucidate the prevalence of potent skin sensitizers in oxidative hair dye products manufactured by Korean domestic companies. METHODS: A database on hair dye products made by domestic companies and selling in the Korean market in 2013 was used to obtain information on company name, brand name, quantity of production, and ingredients. The prevalence of substances categorized as potent skin sensitizers was calculated using the hair dye ingredient database, and the pattern of concomitant presence of hair dye ingredients was analyzed using network analysis software. RESULTS: A total of 19 potent skin sensitizers were identified from a database that included 99 hair dye products manufactured by Korean domestic companies. Among 19 potent skin sensitizers, the four most frequent were resorcinol, m-aminophenol, p-phenylenediamine (PPD), and p-aminophenol; these four skin-sensitizing ingredients were found in more than 50% of the products studied. Network analysis showed that resorcinol, m-aminophenol, and PPD existed together in many hair dye products. In 99 products examined, the average product contained 4.4 potent sensitizers, and 82% of the products contained four or more skin sensitizers. CONCLUSION: The present results demonstrate that oxidative hair dye products made by Korean domestic manufacturers contain various numbers and types of potent skin sensitizers. Furthermore, these results suggest that some hair dye products should be used with caution to prevent adverse effects on the skin, including allergic contact dermatitis.