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A scarcity of research assesses the effects of exposure to a combination of chemicals on lipid profiles as well as molecular mechanisms related to dyslipidemia. A cross-sectional study of 3692 adults aims to identify the association between chemical mixtures, including blood and urine 26 chemicals, and lipid profiles among Korean adults (aged ≥ 18) using linear regression models, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR). In silico toxicogenomic data-mining, we assessed molecular mechanisms linked with dyslipidemia, including genes, miRNAs, pathways, biological processes, and diseases. In the linear regression models, heavy metals, volatile organic compound metabolites, and phthalate metabolites were found to be related to HDL-C, triglycerides, LDL-C, total lipids, and total cholesterol, and significant trends were observed for these chemical quartiles (p 0.01). The WQS index was significantly linked with HDL-C, triglycerides, LDL-C, total cholesterol, and total lipids. The qgcomp index also found a significant association between chemicals and HDL-C, triglycerides, and total lipids. In BKMR analysis, the overall effect of the chemical mixture was significantly associated with HDL-C, triglycerides, total cholesterol, and total lipids. We found that mixed chemicals interacted with the PPARA gene and were linked with dyslipidemia. Several pathways ("SREBF and miR33 in cholesterol," "estrogen receptor pathway and lipid homeostasis," and "regulation of PGC-1α"), "negative regulation of hepatocyte apoptotic process," "negative regulation of sequestering of triglycerides," "regulation of hepatocyte apoptotic process," and "negative regulation of cholesterol storage," and "abdominal obesity metabolic syndrome" were identified as key molecular mechanisms that may be affected by mixed chemicals and implicated in the development of dyslipidemia. The highest interaction and expression of miRNAs involved in the process of dyslipidemia were also described. Especially, the cutoff levels for chemical exposure levels related to lipid profiles were also provided.

Background: Converging evidence indicates prolactin (PRL) and diabetes play an important role in the pathophysiology of cognitive impairment. However, little is known about the mechanisms responsible for the effects of PRL and diabetes on cognitive impairment. Summary: We summarize and review the available literature and current knowledge of the association between PRL and diabetes on aspects of cognitive impairment. Key Messages: The phosphatidylinositol 3-kinase/protein kinase B pathway is central to the molecular mechanisms underlying how PRL and diabetes interact in cognitive impairment. Further work is needed to identify the interaction between PRL and diabetes, especially in the molecular aspects of cognitive impairment, which can suggest novel strategies for cognitive dysfunction treatment.

Little is known about the association between a mixture of heavy metals and obesity among individuals ≥50 years of age with comorbidities. Thus, we identified the associations of serum cadmium (Cd), lead (Pb), and mercury (Hg) with obesity using linear regression models; weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were conducted as secondary analyses. Of the 6434 subjects included in the analysis, 13.8% had obesity and 44.6% had abdominal obesity. In the logistic regression model, serum Hg was associated with obesity and abdominal obesity, and significant trends were observed for these heavy metal tertiles (p < 0.001). Serum Hg levels were also associated with body mass index (BMI) and waist circumference (WC). The WQS index was significantly associated with both obesity (OR = 1.43, 95% CI: 1.40-1.46) and abdominal obesity (β = 1.51, 95% CI: 1.48-1.54). The qgcomp index also found a significant association between heavy metals and both obesity (OR = 1.35, 95% CI: 1.12-1.63) and abdominal obesity (OR = 1.34, 95% CI: 1.12-1.60). Serum Hg was the most heavily weighed heavy metal in these models. In BKMR analysis, the overall effect of the mixture was significantly associated with obesity, BMI, and WC. Serum Hg showed positive trends and was observed as the most important factor associated with obesity, BMI, and WC. Our findings were largely robust to secondary analyses that used three novel mixture modeling approaches: WQS, qpcomp, and BKMR. Given increasing exposure to heavy metals, well-characterized cohorts of individuals aged ≥50 years are required to determine the mixed effects of heavy metals on obesity and related diseases.

Proton pump inhibitors (PPIs) have been the mainstay of treatment for gastric ulcer (GU) for over 30 years. However, since the discovery of a new class of acid suppressants, potassium-competitive acid blockers (P-CABs), the desire for a therapeutic agent has continued and the clinical trials on P-CABs have been conducted. In our study, a systematic review and network meta-analysis (NMA) were performed based on randomized controlled trials (RCTs) conducted since the development of P-CABs. In addition, the new methodology of the inference concept was applied to confirm the results. Our quality management system was also integrated throughout the research to guarantee the accuracy of the data. Initially, we screened 431 studies and extracted 10 homogeneous GU RCTs with 6315 participants. The odds ratios (ORs) for the 4-week cure rate in Bayesian + frequentist NMA, tegoprazan 100 mg (OR = 4.14, 95% credible interval [CI] 0.56–26.3) and pantoprazole 40 mg (OR = 4.12, 95% confidence interval [CI] 1.90–8.88) were the largest, respectively. The ORs for the 8-week cure rate in Bayesian + frequentist NMA, lansoprazole 30 mg (OR = 8.77, 95% [CI] 0.95–78.9) and lansoprazole 30 mg (OR = 7.91, 95% [CI] 2.60–24.03) was the largest, respectively. As the inference by grouping PPIs and P-CABs, the results show similar trends in terms of effectiveness between two therapeutic classes. In conclusion, our study shows that the cure rates of P-CABs in cases of GU are not inferior to those of PPIs.

Little is known about associations between depression and serum heavy metal levels, dietary vitamin intakes. Thus, we sought to determine the nature of these associations and to predict risks of depression using marginal effects. A data set of 16,371 individuals aged ≥10 years that participated in Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2009 to 2017 (excluding 2014 and 2015) was used to obtain information on sociodemographics, family histories, lifestyles, serum heavy metal levels, food intakes, and depression. Serum cadmium (Cd) and lead (Pb) levels were analyzed by graphite furnace atomic absorption spectrometry and mercury (Hg) levels using a mercury analyzer. Daily vitamin intakes were calculated by 24-h dietary recall. The results obtained showed that females are at higher risk of depression than males. A doubling of serum Cd was associated with a 21% increase in depression (AOR 1.21, 95% CI: 1.07-1.37, p = 0.002), whereas twofold increases in daily vitamin B1, B3 and vitamin A intakes reduced the risk of depression by 17% (0.83, 95% CI: 0.73-0.95, p = 0.005), 20% (0.80, 95% CI: 0.70-0.91, p = 0.001), and 8% (0.92, 95% CI: 0.85-0.99, p = 0.020), respectively. Interactions between heavy metals, vitamin intakes, and sex did not influence the risk of depression. The result shows that increased daily dietary vitamin intake might protect the public against depression. Further studies are needed to reduce the risks posed by heavy metals and to determine more comprehensively the effects of daily dietary vitamin intake on depression.

There is a scarcity of studies on the effects of mixed chemicals on total IgE. We aim to assess whether there is a link between chemical mixtures (blood and urine of 26 chemicals including lead, mercury, cadmium, t,t-muconic acid, benzylmercapturic acid , 1-hydroxypyrene, 2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-n-butyl phthalate, mono-benzyl phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-carboxyoctyl phthalate, mono-carboxy-isononly phthalate, mono (3-carboxypropyl) phthalate, bisphenol A, bisphenol F, bisphenol S, triclosan, methylparaben, ethylparaben, propylparaben, 3-phenoxybenzoic acid, and cotinine), and total IgE in 3,642 Korean adults aged ≥ 19. The effects of mixed chemical exposure on total IgE were identified using linear regression models, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR). The most relevant factors linked with IgE, according to the linear regression models, were blood or urine mercury and urine bisphenol A levels, with significant trends detected for these chemical tertiles (p 0.01). The WQS index was significantly linked with ln2-transformed levels of serum total IgE (β = 0.30, 95 %CI 0.25-0.32). The qgcomp index also found a significant link between chemicals and ln2-transformed levels of serum total IgE (β = 0.52, 95 %CI 0.21-0.82), and elevated serum total IgE levels (OR = 2.55, 95 %CI 1.14-5.71). In BKMR analysis, the overall effect of the mixture was significantly associated with ln2-transformed levels of serum total IgE. The cutoff levels for exposure levels related to serum total IgE levels/elevated serum total IgE levels were reported. We discovered that whole-body exposure to 26 chemicals was associated with serum total IgE levels after assessing the findings of these four models. More research is needed in the future to gain a better understanding of the impact of mixed chemical exposure on allergic disorders and how to minimize chemical exposure, especially for people under the age of 18.

OBJECTIVE: To examine the associations between serum cadmium, lead, and mercury and hypertension in pre- and postmenopausal women. METHODS: Serum heavy metal (cadmium, lead, and mercury) levels were analyzed in 7,226 randomly selected women who participated in Korean National Health and Nutrition Examination Surveys from 2009 to 2017. Odds ratios (ORs) for hypertension were calculated for log2-transformed serum heavy metal levels, median tertile levels of serum cadmium, mercury, and lead, and for interactions between heavy metal levels and tertiles, after covariate adjustment. RESULTS: A doubling of serum cadmium was associated with hypertension in premenopausal (OR 2.47; 95% CI, 1.01-6.10, P = 0.049) and postmenopausal women (OR 1.70; 95% CI, 1.02-2.84, P = 0.043), and significant trends were observed for cadmium tertiles (P 

Metabolic syndrome (MetS) has attracted increasing attention because its prevalence and socioeconomic burden have increased globally. We hypothesized that higher intakes of fruits, vegetables, and multiple individual nutrients are associated with a lower risk of MetS among adults with comorbidities. Therefore, we aim to explore the association between intake of multiple individual nutrients, vegetables and fruits, and MetS among Korean adults. A data set of 67,302 adults aged ≥ 18 years was collected between 2009 and 2019. Odds ratios for MetS were calculated for log

We aim to identify the association between a mixture of vitamin B1, B2, and B3 intakes and depression.Daily intake of vitamins was measured by a one-day 24 h recall. Multivariate logistic regression, weighted quantile sum (WQS), quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were used.Of 9,848 adults included in the final analysis, 4.38% had depression. In the logistic regression model, daily vitamin B1 and B3 intakes were associated with depression, and significant trends were observed for these vitamin intake tertiles (p 0.001). The WQS index was significantly associated with depression (OR = 0.24, 95% CI: 0.23-0.24). The gqcomp index also found a significant association between a mixture of vitamin B1 and B3 intake and depression (OR = 0.67, 95% CI: 0.44-0.98). Vitamin B1 intake was the most heavily weighed vitamin intake in this model. In BKMR analysis, the overall effects of vitamin B1 and B3 intake mixture were negatively associated with depression. Vitamin B1 and B3 intake showed negative trends and was observed as the most important factor associated with depression. The cutoff levels for B vitamin intake levels related to depression were reported.A 24-hour recall and cross-sectional design were used.Given the rising prevalence of depressive symptoms in Korea, an increase in daily intake of vitamin B1 and/or B3 through regular diets may help to reduce the risk of depression. Therefore, there is an ongoing need to investigate these associations between B vitamin supplementation and depression, either separately or jointly, in well-characterized cohorts of depression population.

Persons with underlying noncommunicable diseases (NCDs) are more likely to acquire severe coronavirus disease 2019 disease and to die from coronavirus disease 2019. An urgent need for potential therapy to prevent and control NCDs is critical. We hypothesized that higher intakes of multiple individual nutrients, fruits, or vegetables would be linked with a low risk of NCDs in the Korean population. Thus, we aim to explore the association between NCDs, including cardiovascular diseases, type 2 diabetes mellitus (T2DM), arthritis, depression, and dietary factors. A total of 56,462 adults aged 18 years (2009-2019) were included. Dietary factors, including intakes of multiple individual nutrients, fruits, and vegetables, were assessed. Multivariable-adjusted logistic regression models were used to explore the associations between dietary factors and NCDs. Interactions were found between intakes of multiple individual nutrients and sex for T2DM, hypertension, stroke, myocardial infarction, arthritis, and osteoarthritis. Only in women was a 2-fold increase in daily multiple individual nutrient intake (vitamins A, B1, B2, B3, C; potassium, protein; phosphorus; calcium; iron; monounsaturated fatty acid and polyunsaturated fatty acid; n-3 fatty acid and n-6 fatty acid; and water) associated with a lower prevalence of T2DM, hypertension, stroke, myocardial infarction, arthritis, and osteoarthritis. In both women and men, high fruit or vegetable consumption was linked with a lower risk of T2DM, hypertension, dyslipidemia, osteoarthritis, and depression than low consumption. Our findings found higher intakes of fruits, vegetables, and multiple individual nutrients are linked with a lower risk of NCDs in the Korean adult population. Further work is needed to identify whether interactions between intake of multiple individual nutrients, vegetables, and fruits affect the presence of NCDs., Graphical Abstract Image, graphical abstract

We aim to examine the association between chemical mixtures and obesity. Blood and urinary levels of tween-six chemicals were measured in adults who participated in the KoNEHS. We identified the associations of chemicals with obesity using linear regression models. Weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were conducted as secondary analyses. Of the 3,692 participants included in the analysis, 18.0% had obesity. In the logistic regression model, mercury (Hg), lead (Pb), and 3PBA levels were associated with obesity, and significant trends were observed for these chemical tertiles (p

We aim to evaluate the association between curry-rice consumption, cardiovascular diseases (CVDs), type 2 diabetes (T2DB), arthritis, and depression.17,625 participants aged ≥18 years were recruited to obtain data on sociodemographic characteristics, lifestyle, medical history, current medications, family history, and food consumption. The association between curry-rice consumption, CVDs, T2DB, arthritis, and depression was examined using multivariable-adjusted analyses.In the logistic model, risks of elevated triglyceride (OR 0.89; 95% CI, 0.82-0.97, p = 0.006), elevated HbA1c (OR 0.81; 95% CI, 0.73-0.91, p 0.001), and elevated glucose (OR 0.86; 95% CI, 0.79-0.94, p 0.001) were significantly lower in the high curry-rice consumption group than in the low curry-rice consumption group. Risk of hypertension (OR 0.88; 95% CI, 0.78-0.98, p = 0.044), T2DB (OR, 0.82; 95% CI, 0.68-0.98, p 0.001), and depression (OR 0.82; 95% CI, 0.70-0.97, p = 0.026) was significantly lower among the high curry-rice consumption group than in the low curry-rice consumption group. These findings were consistent with the results of the analysis when curry-rice consumption was treated as a continuous variable.The potential health benefits resulting from the intake of curry-rice via an ordinary diet could protect the public from the burden of non-communicable diseases (NCDs) and mental health. These results highlight an ongoing need to understand the role of curry-rice in NCDs and mental health.

The burden of metabolic syndrome (MetS) has increased worldwide, especially during the COVID-19 pandemic, and this phenomenon is related to environmental, dietary, and lifestyle risk factors. We aimed to determine the association between the levels of serum heavy metals, hs-CRP, vitamins, and curry intake and to predict risks of MetS based on marginal effects. A data set of 60,256 Koreans aged ≥ 15 years between 2009 and 2017 was used to obtain information on sociodemographic, lifestyle, family history characteristics, MetS, food intake survey, and serum heavy metals. Daily intake of vitamins was measured by a one-day 24 h recall, and curry consumption was calculated using a food frequency questionnaire. Serum heavy metal levels were quantified by graphite furnace atomic absorption spectrometry and using a mercury analyzer. We found that vitamin B1, B2, B3, C, and A intakes were significantly lower in subjects with than without MetS. In contrast, serum levels of Pb, Hg, Cd, vitamin A, E, and hs-CRP were significantly higher in subjects with MetS. The risk of MetS was significantly lower for high curry consumers than low curry consumers (adjusted odds ratio 0.85, 95%CI 0.74–0.98). The risks of MetS were reduced by 12% and 1%, when vitamin B1 and C intakes increased by one mg, respectively, but were increased by 14%, 3%, and 9%, when serum levels of Pb, Hg, and hs-CRP increased by one unit. These results show that the potential health benefits resulting from vitamin and curry intakes could protect the public against the dual burden of communicable and non-communicable diseases. Further studies are required to reduce risk factors associated with serum heavy metal levels and to determine whether interactions between vitamin and curry consumption influence the presence of MetS.

PURPOSE Evogliptin is one of the latest dipeptidyl peptidase-4 (DPP-4) inhibitor, and a number of clinical trials have been performed following its development, including several randomized controlled trials (RCTs) performed to evaluate its efficacy and tolerability. In our study, we performed a systematic review and meta-analysis of its efficacy and tolerability by collecting RCTs and confirmed the results with Bayesian inference. Moreover, an updated quality-management system was integrated into the study process of systematic review. METHODS PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched for literature published between May 1990 and November 2020. We selected 6 homogeneous RCTs in 1017 subjects for efficacy and 1070 subjects for tolerability analysis. Regarding the efficacy profile, the mean differences from baseline (95% CIs) in hemoglobin (Hb) A1c and fasting plasma glucose (FPG) were generated as end points and derived from each study. Regarding the tolerability profile, risk ratios of adverse events (AEs), serious AEs, adverse drug reactions, and hypoglycemia were generated from baseline to outcome measurements as derived from each study. A subsequent meta-analysis was performed with Bayesian inference. FINDINGS For HbA1c and FPG, the results suggested a statistically significant improvement with evogliptin versus placebo (HbA1c, -0.44 [95% CI, -0.54 to -0.34; P < 0.00001] and posterior median, -0.38 [95% CI, -0.51 to -0.24]; FPG, -0.61 [95% CI, -0.90 to -0.31; P < 0.0001] and posterior median, -0.48 [95% CI, -0.90 to -0.16]), but no statistically significant difference with evogliptin versus other DPP-4 inhibitors (HbA1c, -0.01 [95% CI, -0.14 to 0.12] and posterior median, -0.06 [95% CI, -0.25 to 0.12]; FPG, 0.17 [95% CI, -0.10 to 0.44] and posterior median, 0.27 [95% CI, -0.12 to 0.65]). In terms of tolerability, the overall prevalence of adverse events, including hypoglycemia, was similar between evogliptin and other DPP-4 inhibitors and placebo. IMPLICATIONS Evogliptin appears more efficacious in terms of changes in HbA1c and FPG compared with placebo, with an efficacy comparable to those of other DPP-4 inhibitors, although with the limited data studied and the minuscule sample sizes, the predictions of posterior medians, mean differences, and risk ratios of HbA1c, FPG, and AEs by Bayesian inference were consistent with our findings through our quality-management system.

The present study aimed to determine thiamine intake levels and the association between thiamine intake, diabetes, cardiovascular diseases and mental health. Participants were interviewed to obtain data on socio-demographic characteristics, lifestyle, current medications, medical and family history. The daily intake of thiamine was assessed by a 24-h recall. The mean age of the 34 700 study subjects was 42⋅9 years (sd 22⋅8, min–max: 1–80) and 19 342 (55⋅7 %) were women. The levels of thiamine intake were 1⋅126 mg (2016), 1⋅115 mg (2017) and 1⋅087 mg (2018) for women, which were equal to or only slightly above the recommended intake of 1⋅10 mg/d for women. The levels of thiamine intake from 2014–15 and 2016–18 significantly decreased. The estimated percentage of insufficient thiamine intake was 37⋅8 % (95 % CI 37⋅3, 38⋅4). Multivariable regression analysis adjusted for potential confounders showed that thiamine intake was critically associated with lower risks of hypertension, MI or angina, type 2 diabetes, depression and dyslipidemia. The daily thiamine intake from food can reversal the risks of hypertension (OR 0⋅95; 95 % CI 0⋅90, 0⋅99), MI or angina (OR 0⋅84; 95 % CI 0⋅74, 0⋅95), type 2 diabetes (OR 0⋅86; 95 % CI 0⋅81, 0⋅93), depression (OR 0⋅90; 95 % CI 0⋅83, 0⋅97) and dyslipidemia (OR 0⋅90; 95 % CI 0⋅86, 0⋅95), respectively. Further works are needed to identify the effects of thiamine and non-communicable diseases (NCDs) and mental health. A preventive thiamine supplementation strategy should be adopted to target NCDs and mental health and risk factors associated with thiamine deficiency. The optimisation of NCD control and mental health protection is also a vital integral part of Korea's public health system.

The burden of metabolic syndrome (MetS) is increasing worldwide especially in the coronavirus disease 2019 (COVID-19). This phenomenon can be related to environmental, dietary, and lifestyle risk factors. We aimed to determine the association between the levels of serum heavy metals, vitamins, and curry intake, subsequently predict the risks for MetS by margin effects. Daily intake of vitamins was measured by 24-h recall was calculated using a food frequency questionnaire. Heavy metals were quantified by graphite furnace atomic absorption spectrometry, and mercury analyzer. The risk of MetS was significantly lower in the high curry consumption than in the low curry consumption, risks of Mets were reduced by 7%, 13%, 1%, and 1%, when the levels of vitamin B1, B2, B3, and C intake increased by one mg, respectively. However, risks of Mets were increased by 9%, 3%, 5%, when the levels of serum Pb, Hg, and CRP increased by one unit. The potential health benefits resulting from vitamin and curry supplementation could guard the public against the dual burden of communicable and non-communicable diseases. Further works are required to thwart risk factors related to heavy metals and determine the mechanistic dual effects of vitamins and curry in MetS.

There is growing evidence that thiamine supplementation could reverse non-communicable diseases such as diabetes and cardiovascular diseases. However, the role of thiamine in metabolic syndrome (MetS) remains unclear. We hypothesized whether an increased intake of thiamine diminishes the risk of MetS in the Korean population with various comorbidities. This study aimed to assess the association between thiamine intake and MetS among adults with comorbidities.57,523 eligible participants aged over 18 years between 2009 and 2019 were recruited to obtain data on sociodemographic characteristics, medical history, current medications, lifestyle, and family history. A 24-h recall was used to determine thiamine intake. Odds ratio (OR) for MetS was calculated for log2-transformed thiamine intake values, subsequently predicting the risk of MetS based on the marginal effect.The risk of MetS was significantly higher in subjects with comorbidities than in those without comorbidities. A doubling of daily thiamine intake was significantly associated with a decrease in MetS among adults with comorbidities by 7% (OR 0.93; 95%CI 0.89-0.97).The potential health benefits result from the intake of thiamine through an ordinary diet in the clinical management of MetS. Therefore, there is an ongoing need to look into these links between thiamine supplementation and MetS in well-characterized cohorts of participants with comorbidities.

In response to the globalization of drug development, regulatory inspection of Good Clinical Practice (GCP) has recently been conducted not only by International Conference on Harmonisation (ICH) regions but also non-ICH regions. To promote the international implementation of GCP, consistent understanding and interpretation of its concept among regions are important. This article summarizes the background and past activities of the E6 Discussion Group, established under the Regulators Forum.