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Aims: To evaluate the effects of initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase-4 (DPP-4) inhibitors as active comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI)., Materials and Methods: We used an active-comparator, new-user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP-4 inhibitor users for analysis using propensity-score matching., Results: During 13 708.59 person-years of follow-up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP-4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all-cause death and end-stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all-cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio [HR] 0.574, 95% confidence interval [CI] 0.36-0.915), all-cause death (HR 0.731, 95% CI 0.567-0.942), and ESRD (HR 0.076, 95% CI 0.018-0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI., Conclusions: The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To investigate the efficacy and safety of pioglitazone compared to placebo when added to metformin plus dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, for patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: In a multicentre study, with a randomized, double-blind, placebo-controlled design, 249 Korean patients with T2DM suboptimally managed on metformin and dapagliflozin were assigned to receive either pioglitazone (15 mg daily) or placebo for 24 weeks, followed by a 24-week pioglitazone extension. Primary outcomes included changes in glycated haemoglobin (HbA1c), with secondary outcomes assessing insulin resistance, adiponectin levels, lipid profiles, liver enzymes, body weight and waist circumference., Results: Pioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo (from 7.79% ± 0.76% to 7.69% ± 0.86%, corrected mean difference: -0.42% ± 0.08%; p < 0.01) at 24 weeks. Additional benefits from pioglitazone treatment included enhanced insulin sensitivity, increased adiponectin levels, raised high-density lipoprotein cholesterol levels and reduced liver enzyme levels, resulting in improvement in nonalcoholic fatty liver disease liver fat score. Despite no serious adverse events in either group, pioglitazone therapy was modestly but significantly associated with weight gain and increased waist circumference., Conclusions: Adjunctive pioglitazone treatment in T2DM inadequately controlled with metformin and dapagliflozin demonstrates considerable glycaemic improvement, metabolic benefits, and a low risk of hypoglycaemia. These advantages must be weighed against the potential for weight gain and increased waist circumference., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Considering the interactions between heavy metals, a comprehensive evaluation of the effects of exposure to various types of co-interacting heavy metals on health is required. This study assessed the association between dyslipidemia markers and blood mercury, lead, cadmium, iron, zinc, and nickel levels in residents of an abandoned refinery plant., Methods: A total of 972 individuals (exposed group: 567, control group: 405) living near the Janghang refinery plant in the Republic of Korea were included. Blood mercury, lead, cadmium, iron, zinc, nickel, cholesterol, and triglyceride levels were measured. The combined effect of the six heavy metals on dyslipidemia markers was evaluated using a Bayesian kernel machine regression (BKMR) model and compared with the results of a linear regression analysis. The BKMR model results were compared using a stratified analysis of the exposed and control groups., Results: In the BKMR model, the combined effect of the six heavy metals was significantly associated with total cholesterol (TC) levels both below the 45th percentile and above the 55th percentile in the total population. The combined effect range between the 25th and 75th percentiles of the six metals on TC levels was larger in the exposed group than that in the total population. In the control group, the combined effects of the changes in concentration of the six heavy metals on the TC concentration were not statistically significant., Conclusion: These results suggest that the cholesterol levels of residents around the Janghang refinery plant may be elevated owing to exposure to multiple heavy metals., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: This study aimed to evaluate exposure to various hazardous substances emitted by incineration facilities and their likely effect on the health for residents of Bugi-myeon, Cheongju, Korea, which has three incineration facilities., Methods: Heavy metals, polycyclic aromatic hydrocarbons (PAHs), and dioxin concentrations in the air and soil of exposed and control areas were measured. Moreover, the exposure levels to harmful substances and its effects on health were investigated in 1,124 exposed and 232 control adults., Results: PAHs and dioxin concentrations in the air in the exposed area were significantly higher than in the control area. Urinary cadmium and PAHs metabolite concentrations were significantly higher in the exposed group than in the control group. The exposure group also had a higher prevalence of depression and self-reported allergic symptoms than the control group., Conclusion: The possibility of residents in Bugi-myeon being exposed to hazardous substances at incineration facilities cannot be ruled out. To prevent them from further exposure to hazardous substances, it is necessary to prohibit the expansion of additional incineration facilities in this area and to implement continuous monitoring projects for residents., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Objective: Hyperuricemia might have neuroprotective or neurodegenerative effects on dementia via oxidative stress or inflammatory response regulation. Few studies have explored the association of hyperuricemia or gout with dementia. This retrospective cohort study aimed to investigate the association between gout and dementia in Korea., Methods: Altogether, 5,052 gout patients and 25,260 age- and sex-matched controls were selected from the National Health Insurance Service (NHIS)-National Sample Cohort database. The incidence and risk of dementia were evaluated by reviewing the NHIS record. We also performed a subgroup analysis according to age group (age <65 or ≥65 years) using the standard age of 65 years for elderly and nonelderly groups and sex., Results: During follow-up, 81 and 558 participants in the gout and control cohorts developed dementia, respectively. The mean follow-up duration was 4.38 years in gout patients and 4.94 years in controls. Gout patients had a hazard ratio (HR) of 0.79 for overall dementia (95% confidence interval [95% CI] 0.62-1.00) and significantly lower Alzheimer's disease risk (HR 0.73 [95% CI 0.54-0.98]) after adjusting for age, sex, household income, and comorbidities. In subgroup analysis stratified by age and sex, the inverse association between gout and the risk of overall dementia (HR 0.71 [95% CI 0.52-0.97]) and Alzheimer's disease (HR 0.67 [95% CI 0.46-0.97]) were observed in the elderly male group. On the other hand, age- and sex-adjusted analysis showed that the HR for vascular dementia of gout patients was 2.31 (95% CI 1.02-5.25) in the nonelderly male group., Conclusion: Gout decreased the risk of incident Alzheimer's disease-type dementia, especially in elderly patients. The association between gout and dementia risk may differ according to age and disease duration., (© 2022 American College of Rheumatology.)

Cadmium (Cd) is a ubiquitous environmental pollutant with an exceptionally long biological half-life. The liver is a major organ for Cd metabolism, but the toxicity of Cd is unclear. This study sought to determine whether blood Cd (BCd) level (representing recent exposure [months] to Cd) was associated with liver function in Korean adults, both cross-sectionally and longitudinally. The baseline cross-sectional study involved 2,086 adults (male: 908, female: 1,178) in 2010 - 2011, and 503 of them (male: 207, female: 296) were followed up in 2014 - 2015. BCd was measured by graphite-furnace atomic absorption spectrometry, and liver function indices (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and γ-glutamyltransferase [GGT]) were determined. Liver damage was defined as an abnormal elevation of more than one liver function index. The geometric mean of BCd (1.07 μg/L) was higher in females than in males (1.16 vs. 0.96 μg/L). Liver function indices increased significantly in a dose-dependent manner according to the BCd levels, except for ALT in males, and were higher in males than in females. BCd level was also associated with the risk of liver damage in both sexes. No significant changes in BCd were observed between baseline and follow-up. The liver function indices in 2014 - 2015 were comparable to those in 2010 - 2011 in males, while ALT and GGT were significantly increased in 2014 - 2015 compared to 2010 - 2011 in females with relatively high BCd. These findings suggest that even a low level of environmental Cd exposure, short- and long-term, may affect liver function, and females appear more susceptible than males., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Three industrial waste incinerators (IWIs) were built in 1999, 2001, and 2010, within a 3 km radius of a town with a population of around 5000 in Korea. This study evaluated whether residents near these three IWIs had increased cancer incidence than those from other areas in Korea using regional health data., Methods: Standardized incidence ratios (SIR) were calculated using the frequency of cancer cases in the National Cancer Registry of the exposed area (Buki-myeon), Chungcheongbuk-do (Chungbuk, state including Buki-myeon), and whole Korea from 1999 to 2017. A retrospective cohort was created using National Health Insurance System data from 2002 to 2018. The exposed group was defined as those having a residential history in the exposed area. The control group was defined as those having a residential history in nearby towns or counties in Chungbuk, excluding counties having living and cultural areas in other provinces and cities. Hazard ratio (HR) and 95% confidence intervals (CI) were estimated using the Cox proportional hazard model adjusted for age, level of health insurance fee, and smoking history., Results: In the ecological study using National Cancer Registry data, the risk of all cancers, all cancers excluding thyroid, esophageal, stomach, and lung cancers in the exposed area were 1.13 (95% CI 1.03-1.24), 1.15 (95% CI 1.04-1.26), 1.91 (95% CI 1.13-2.89), 1.39 (95% CI 1.14-1.66), and 1.29 (95% CI 1.03-1.57) times higher than in whole Korea among exposed males, respectively. In the retrospective cohort, 4300 males (26,821 person-years) and 3796 females (24,746 person-years) in exposed group, 150,964 males (1,212,010 person-years) and 134,535 females (1,104,025 person-years) in control group were analyzed. After adjusting for several confounding factors, the risks for gallbladder cancer among males and kidney cancer among females were 2.65 (95% CI 1.38-5.06) and 2.82 (95% CI 1.13-7.03) times higher in the exposed group versus the control group, respectively., Conclusions: Cancer risk was higher in Koreans having residential history living near IWIs compared to the other areas. Further study warrants nationwide effects and longer follow-up of WIs for cancers in Korea., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Arsenic is a human carcinogen. Data on urinary arsenic species analyses of Koreans are limited. This study evaluated the arsenic exposure level, contributing factors, and health effects in Korean adults. Dietary intake information and urine samples were obtained from 2044 participants. Arsenic exposure was assessed based on urinary concentrations of arsenic species, such as inorganic arsenic, As(III) and As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB), using high-performance liquid chromatography with inductively coupled plasma mass spectrometry, followed by determination of biomarkers, malondialdehyde and c-peptide. The geometric mean concentrations were 30.9 μg/L for the sum of inorganic arsenic and their metabolites, and 84.7 μg/L for the total sum of arsenic measured. Urinary concentrations of arsenic species were influenced by age, inhabitant area (inland or coastal), and seafood intake, which was positively correlated with inorganic arsenic, DMA, and AsB. Rice intake was positively correlated with inorganic arsenic and its metabolites but not with AsB. Additionally, malondialdehyde and c-peptide levels were significantly associated with urinary concentrations of various arsenic species. Seafood and rice are major sources of organic/inorganic arsenic exposure in Korean adults; however, it is necessary to evaluate whether their overconsumption could have a potentially detrimental effect on human health., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Few current preoperative risk assessment tools provide essential, optimized treatment for gastric cancer. The purpose of this study was to develop and validate a nomogram that uses preoperative data to predict survival and risk assessments., Methods: A survival prediction model was constructed using data from a developmental cohort of 1251 patients with stage I to III gastric cancer who underwent curative resection between January 2005 and December 2008 at Ajou University Hospital, Korea. The model was internally validated for discrimination and calibrated using bootstrap resampling. To externally validate the model, data from a validation cohort of 2012 patients with stage I to III gastric cancer who underwent surgery at multiple centers in Korea between January 2001 and June 2006 were analyzed. Analyses included the model's discrimination index (C-index), calibration plots, and decision curve that predict overall survival., Results: Eight independent predictors, including age, sex, clinical tumor size, macroscopic features, body mass index, histology, clinical stages, and tumor location, were considered for developing the nomogram. The discrimination index was 0.816 (adjusted C-index) in the developmental cohort and 0.781 (adjusted C-index) in the external validation cohort. Additionally, in both the developmental and validation datasets, age and tumor size were significantly correlated with each other and were independent indicators for survival (P < 0.05)., Conclusions: We developed a new nomogram by using the most common and significant preoperative parameters that can help to identify high-risk patients before treatment and help clinicians to make appropriate decisions for patients with stage I to III gastric cancer., (© 2021. Society of Surgical Oncology.)

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

The enhanced assessment of groundwater contamination vulnerability is necessary for the management and conservation of groundwater resources because groundwater contamination has been much increased continuously in the world by anthropogenic origin. The purpose of this study is to determine the best model among three ANFIS-MOA models (the adaptive neuro-fuzzy inference system (ANFIS) combined with metaheuristic optimization algorithms (MOAs) such as genetic algorithm (GA), differential evolution algorithm (DE) and particle swarm optimization (PSO)) in assessing groundwater contamination vulnerability at a nitrate contaminated area. The Miryang City of South Korea was selected as the study area because the nitrate contamination was widespread in the city with two functions of urban and rural activities. Eight parameters (depth to water, net recharge, topographic slope, aquifer type, impact to vadose zone, hydraulic conductivity and landuse) were classified into the numerical ratings on basis of modified DRASTIC method (MDM) for the input variables of ANFIS-MOA models. The Original ANFIS, and 3 combined models of ANFIS-PSO, ANFIS-DE and, ANFIS-GA used 95 adjusted vulnerability indices (AVI) as the target data of training (70% data) and testing (30% data) processing. The performance of 4 models was evaluated by mean absolute errors (MAE), root mean square errors (RMSE), correlation coefficients (R), ROC/AUC curves and predicted AVI (PAVI) maps. The statistical results, spatial vulnerability maps and correlation coefficients between PAVIs and nitrate concentrations revealed that the order of model excellence was ANFIS-PSO, ANFIS-DE, ANFIS-GA, and Original ANFIS, and that ANFIS-PSO showed the highest performance in training and testing processing. The performance rates of ANFIS-MOA models were also compared with 10 recent popular worldwide models using the correlation coefficients between PVI and nitrate concentrations, and they were superior to other recent popular models. ANFIS-MOA models were also useful for resolving the subjectivity of physical and hydrogeological parameters in original DRASTIC method (ODM) and MDM. It is expected that ANFIS-PSO models will produce the excellent results in assessing groundwater contamination vulnerability and that they can greatly contribute to the groundwater security in other areas of the world as well as Miryang City of South Korea., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To investigate the quality of life (QOL) of patients after laparoscopic sentinel node navigation surgery (SNNS) compared to conventional laparoscopy-assisted distal gastrectomy (LADG) in early gastric cancer patients., Methods: Patients recruited for laparoscopic SNNS surgery between July 2010 and April 2013 were assessed for their QOL. A historical control group was established, consisting of patients who underwent conventional LADG with radical lymphadenectomy from the same institution. QOL questionnaire was taken serially from preoperative week 1 until 12 months postoperatively (1, 3, 6, and 12 months) using the Korean version of the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire-core (QLQ-C30) and gastric cancer-specific questionnaire (STO22)., Results: A total of 80 prospectively gathered patients who received SNNS were categorized into the comparison group (SNNS group). The QOL was compared with 78 patients identified to have received LADG from the gastric cancer database of our institution and were sorted into the control group (LADG group). In QLQ-C30, SNNS group showed better functioning scales in all except role functioning and better scores from the symptom scales in fatigue, insomnia, and diarrhea compared to the LADG group. In QLQ-STO22, scores on dysphagia, eating restriction, anxiety, and body image disturbance were better in SNNS group., Conclusions: Postoperative QOL in laparoscopic gastrectomy combined with SNNS is superior compared to conventional laparoscopic distal gastrectomy in patients with stage I gastric cancer.

The explosive outbreak of COVID-19 led to a shortage of medical resources, including isolation rooms in hospitals, healthcare workers (HCWs) and personal protective equipment. Here, we constructed a new model, non-contact community treatment centres to monitor and quarantine asymptomatic and mildly symptomatic COVID-19 patients who recorded their own vital signs using a smartphone application. This new model in Korea is useful to overcome shortages of medical resources and to minimise the risk of infection transmission to HCWs.

In addition to somatic mutations, germline genetic predisposition to hematologic malignancies is currently emerging as an area attracting high research interest. In this study, we investigated genetic alterations in Korean acute lymphoblastic leukemia/lymphoma (ALL) patients using targeted gene panel sequencing. To this end, a gene panel consisting of 81 genes that are known to be associated with 23 predisposition syndromes was investigated. In addition to sequence variants, gene-level copy number variations (CNVs) were investigated as well. We identified 197 somatic sequence variants and 223 somatic CNVs. The IKZF1 alteration was found to have an adverse effect on overall survival (OS) and relapse-free survival (RFS) in childhood ALL. We found recurrent somatic alterations in Korean ALL patients similar to previous studies on both prevalence and prognostic impact. Six patients were found to be carriers of variants in six genes associated with primary immunodeficiency disorder (PID). Of the 81 genes associated with 23 predisposition syndromes, this study found only one predisposition germline mutation (TP53) (1.1%). Altogether, our study demonstrated a low probability of germline mutation predisposition to ALL in Korean ALL patients.

Objectives: Systemic rheumatic disease is characterized by autoimmunity and systemic inflammation and affects multiple organs. Few studies have investigated whether autoimmune diseases increase the risk of dementia. Herein, we evaluate the relationship between systemic rheumatic disease and dementia through a population-based study using the Korean National Health Insurance Service (NHIS) claims database., Methods: We conducted a nationwide population-based study using the Korean NHIS database, consisting of individuals who submitted medical claims from 2002-2013. Dementia was defined as having an acetylcholinesterase inhibitors (AChEIs) prescription along with symptoms satisfying the Alzhemier's disease (AD) International Classification of Diseases (ICD)-10 codes (F00 or G30), or vascular dementia (VaD; ICD-10 or F01) criteria. Control subjects were matched to the dementia patients by age and sex. The study group was limited to those diagnosed with rheumatic disease at least 6 months prior to diagnosis of dementia. Rheumatic disease was defined by the following ICD-10 codes: Rheumatoid arthritis (RA: M05), Sjögren's syndrome (SS: M35), systemic lupus erythematosus (SLE: M32), and Behcet's disease (BD: M35.2)., Results: Of the 6,028 dementia patients, 261 (4.3%) had RA, 108 (1.6%) had SS, 12 (0.2%) had SLE, and 6 (0.1%) had BD. SLE history was significantly higher in dementia patients (0.2%) than in controls (0.1%) and was associated with dementia (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.19-5.15). In subgroup analysis, SLE significantly increased dementia risk, regardless of dementia type (AD: OR, 2.29; 95% CI, 1.06-4.91; VaD: OR, 4.54; 95% CI, 1.36-15.14). However, these associations were not sustained in the mild CCI or elderly group., Conclusion: SLE was independently associated with a higher risk of dementia, including AD and VaD when compared to the control group, even after adjustment. SLE patients (<65 years old) are a high-risk group for early vascular dementia and require screening for early detection and active prevention., Competing Interests: The authors have declared that no competing interests exist.

People living near abandoned mines are at increased risk of exposure to toxic metals. We surveyed 4500 inhabitants with the mean age of 68.5 years old (male: 1768, female: 2732) living near 104 abandoned metal mines from 2013 to 2017 (the 2nd phase health survey in Korea). We conducted personal interviews, blood and urine sampling, and analyzed the concentrations of lead (Pb) and cadmium (Cd) in whole blood and Cd in urine using a graphite furnace atomic absorption spectrometer. The geometric means of blood Pb, blood Cd, and urine Cd were 2.27 μg/dL, 1.42 μg/L, and 1.66 μg/g creatinine, respectively. The level of metal exposure was lower than that reported from the first phase health survey in Korea (2008‒2011) but was higher than in the general population of Korea. Blood Pb was higher in males while blood Cd and urine Cd were significantly higher in females. Blood Pb was highest in the 40‒59 age group, while blood and urine Cd levels continuously increased until age 80 or older. The Cd levels in blood and urine were affected by consumption of locally produced rice and duration of residence near abandoned mines. Furthermore, negative correlations were observed between blood Pb and blood and urine Cd levels. Additionally, 252 of the 4500 subjects exceeded the thresholds of blood Cd or urine Cd levels. Together, these findings suggest that Cd has more sustainable and adverse health effects on the abandoned mine inhabitants, who are mostly aged. Therefore, continuous biomonitoring and risk assessment to environmental health risks are necessary for environmental pollution control and health promotion.

Objectives: This study sought to obtain large-scale evidence supporting the clinical usefulness of ergonovine echocardiography., Background: The role of noninvasive ergonovine provocation testing with echocardiographic monitoring of ventricular wall motion (ergonovine echocardiography) needs to be defined., Methods: Clinical data of patients who underwent ergonovine echocardiography in 3 tertiary referral hospitals in South Korea were analyzed., Results: Ergonovine echocardiography was performed in 14,012 patients (mean age 52.8 ± 11.1 years; 6,213 [44.3%] women) after exclusion of significant coronary arterial stenosis by functional (treadmill or perfusion scan, n = 9,824) or anatomic test (invasive or computerized tomographic coronary angiography, n = 4,188). Premature termination developed in 0.4% (n = 51), and a positive result was observed in 2,144 patients (15.3%), with variable frequencies according to the diagnosis (acute coronary syndrome [38.2%], variant angina [31.8%], effort angina [14.9%], aborted sudden cardiac death [17.6%], syncope [9.9%]). There was no mortality or development of myocardial infarction during the test. During median follow-up of 11.4 (interquartile range: 7.2 to 15.8) years, death of any cause and cardiovascular death occurred in 494 and 143 patients, respectively. The 10-year overall (96.7 ± 0.2% vs. 91.5 ± 0.6%; p < 0.0001) and cardiovascular mortality-free (99.2 ± 0.1% vs. 96.7 ± 0.4%; p < 0.0001) survival rates were lower in patients with positive ergonovine echocardiography. Regarding patients with positive test results, the functional test group and the anatomic test group did not show a significant difference in the survival rates. After adjustment of age and male sex, a positive test was an independent risk factor associated with all-cause mortality (hazard ratio: 1.879, 95% confidence interval: 1.548 to 2.280; p < 0.001) and cardiovascular death (hazard ratio: 2.903, 95% confidence interval: 2.061 to 4.089; p < 0.001)., Conclusions: Ergonovine echocardiography for coronary vasospasm diagnosis could be safely performed even without angiographic documentation of fixed coronary stenosis depending on the clinical presentation, and provided important prognostic implication. Ergonovine echocardiography can replace the invasive spasm provocation testing, which has been overlooked unfairly., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Social jetlag, the circadian misalignment reflecting the discrepancy between the circadian clock and social clock, has been implicated in weight-related issues. The objective of the present study was to determine whether there was an association between social jetlag and body weight change among adults in a large, nationally representative general population. This study was based on data from the Korean National Health and Nutrition Examination Survey, conducted during 2016-2017 by the Korean Ministry of Health and Welfare. Of the 16,277 participants, data from 8295 adults were included in the analysis. Men with social jetlag > 2 h had a significantly higher risk of weight gain (odd ratios (OR): 1.787; 95% confident interval (CI): 1.192-2.679) than those with social jetlag < 1 h, after adjustment for age, sociodemographic factors, lifestyle behaviors, chronic disease, obesity and average sleep duration. Women with weight gain had a higher social jetlag (>2 h), and women with social jetlag > 2 h had a higher proportion of weight gain. However, we did not find a significant association of social jetlag with weight gain after adjusting for confounding factors in women. There was no significant association between social jetlag and weight loss in men and women. Higher social jetlag was independently associated with an increased risk of weight gain in men. We propose that social jetlag may contribute to the obesogenic tendency in men, and that there is a potential for body weight to be managed with a circadian approach.

A Gram stain negative, motile, non-spore-forming, rod-shaped, strictly aerobic, beige-pigmented bacterium, designated strain BO-7 T , was isolated from soil of cattle farm, in Seosan, Republic of Korea. On the basis of 16S rRNA gene sequencing, strain BO-7 T clustered with species of the genus Ochrobactrum and appeared closely related to O. haematophilum CCUG 38531 T (98.9%), O. daejeonense KCTC 22458 T (98.1%), O. rhizosphaerae DSM 19824 T (98.1%), O. pituitosum DSM 22207 T (98.0%), and O. pecoris DSM 23868 T (98.0%). The digital DNA-DNA hybridization and average nucleotide identity between strain BO-7 T and the closely related strains were 21.9-39.1%, 78.5-89.5%, respectively, indicating that BO-7 T is a novel species of the genus Ochrobactrum. The DNA G + C content of the genomic DNA was 57.1 mol%, and ubiquinone Q-10 was the predominant respiratory quinone. The polar lipids consisted of phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylmonomethyl-ethanolamine, di-phosphatidylglycerol, the major polyamines were spermidine, putrescine, and sym-homospermidine. The major cellular fatty acids (> 5%) were C 16:0 , C 19:0 cycle ω7c, and C 18:1 ω7c and/or C 18:1 ω6c (summed feature 8). ANI calculation, digital DNA-DNA hybridization, physiological and biochemical characteristics indicated that strain BO-7 T represents a novel species of the genus Ochrobactrum, for which the name Ochrobactrum soli sp. nov. is proposed. The type strain is BO-7 T (= KACC 19676 T  = LMG 30809 T ).

Purpose: This cross-sectional study aimed to assess the effect of environmental cadmium (Cd) exposure and essential metal imbalance on renal tubular damage and oxidative stress in 979 adults living in a Cd-polluted area near an abandoned copper (Cu) refinery., Methods: We analyzed urinary Cd concentrations, renal tubular damage and oxidative stress markers, such as beta-2 microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) activity and urine malondialdehyde (MDA) levels. The serum copper-to-zinc ratio (CZR) was used as an essential metal imbalance indicator. We divided the subjects into two Cd exposure groups based on the reference level of urinary Cd for renal dysfunction (2 μg/g creatinine)., Results: The geometric mean concentration of urinary Cd in all subjects was 2.25 μg/g creatinine. In both low and high Cd exposure groups, urinary Cd levels were positively correlated with urinary NAG activity, but not with serum CZR. After multivariate adjustment, serum CZR was strongly associated with urinary β2-MG levels in the low Cd exposure group (β = 1.360, P = 0.019) and was significantly associated with urinary MDA levels, regardless of Cd exposure level. In addition, the risk of renal tubular damage was significantly associated with urinary Cd level, particularly in the lowest or highest CZR tertile groups., Conclusions: Essential metal imbalance may be a determinant of oxidative stress and renal tubular damage in a chronically Cd-exposed population, and proper zinc supplementation will be effective in preventing adverse health effects due to Cd exposure.

Background: There is limited data comparing the Xience everolimus-eluting stent (EES) and the Resolute zotarolimus-eluting stent (ZES) with the BioMatrix biolimus-eluting stent (BES)., Methods: This open-label, randomized, noninferiority trial enrolled all-comer patients to be randomly treated with either BES, EES, or ZES in a 1:1:1 ratio in 15 centers across South Korea. The primary end point was a device-oriented composite outcome consisting of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization at 24 months. The BES was compared with the EES and the ZES by intention-to-treat analyses with a noninferiority margin of 3.8%, respectively., Results: Because of slow recruitment and low event rates, this trial was prematurely terminated after enrollment of 1935 (75%) of the intended 2580 patients. Of the 1911 patients randomized to either EES (n=638), BES (n=634), or ZES (n =639), the rate of device-oriented composite outcome was 3.6%, 2.2%, and 3.9%, respectively, at 24 months (BES versus EES: absolute risk difference -1.4% [upper limit of 1-sided 95% CI: -3.2%]; P for noninferiority <0.001; BES versus ZES: absolute risk difference -1.7% [upper limit of 1-sided 95% CI: -3.6%]; P for noninferiority <0.001)., Conclusions: The BES was noninferior to either the EES or the ZES in all-comer patients for device-oriented composite outcome at the 24-month follow-up. However, caution is advised regarding interpretation of these results due to the premature termination of this study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01397175.

This study is to assess the hydrogeochemical characteristics of groundwater at the deltaic region of the Nakdong River Basin in the Busan Metropolitan City of Korea. The study area is covered by the Quaternary sedimentary deposits and the Cretaceous granites associated with unconformity. The thick sedimentary deposits consists of two aquifers, i.e., unconfined and confined aquifers on the basis of clay deposit. Groundwater samples were collected from seven boreholes: two from unconfined aquifer and five from confined aquifer systems during the wet season of 2017 year. ORP and DO indicates that the groundwater of the unconfined aquifer exists in the oxidization condition and that of the confined aquifer pertains in the reduction condition. Piper's trilinear diagram shows CaSO 4 type for groundwater of the unconfined aquifer, and NaCl type for that of the confined aquifer. Ionic concentrations of groundwater increase in the confined aquifer because of direct and reverse ion exchange processes. Carbonate weathering and evaporation are other mechanisms in the water-rock interaction. Saturation indices of dolomite and calcite are observed as oversaturated, while halite reveals undersaturation. Hierarchical cluster analysis (HCA) exhibits that cluster 1 and cluster 2 represents the properties of groundwater in unconfined and confined aquifers, respectively. Factor analysis shows that groundwater of the confined aquifer is much influenced by seawater, and includes heavy metals of iron and aluminum. Groundwater samples in unconfined and confined aquifers are located at the rock weathering and evaporation zones in the Gibbs diagram. Inverse geochemical modeling of PHREEQC code suggests that carbonate dissolution and ion exchange of major ions are the prevailing geochemical processes. This comprehensive research provides the distinguished hydrogeochemical characteristics of groundwater in confined and unconfined aquifer systems of the Nakdong River Basin in Busan City, Korea.

Aims: The aim of this study was to compare the effect of gemigliptin, a dipeptidyl peptidase-4 inhibitor, and dapagliflozin, a sodium glucose co-transporter-2 inhibitor, on glycaemic variability in type 2 diabetes patients., Materials and Methods: In this randomized, blinded end point, multicentre clinical trial, we enrolled 71 patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve. The participants were randomized to receive gemigliptin 50 mg (n = 35) or dapagliflozin 10 mg (n = 36) daily for 12 weeks. Glycaemic variability was estimated by mean amplitude of glycaemic excursions (MAGE), standard deviation (SD) and coefficient of variation (CV) using a 6-day continuous glucose monitoring system. The primary efficacy endpoint was change in MAGE after 12 weeks compared to baseline., Results: Intergroup differences in baseline characteristics were not significant. The adjusted mean change (± standard error) in MAGE after 12 weeks in the gemigliptin and dapagliflozin groups was -27.2 ± 4.4 mg/dL and -7.9 ± 4.9 mg/dL, respectively. Between-group comparisons showed a significantly larger reduction in MAGE in the gemigliptin group (-19.2 mg/dL; 95% CI, -31.3 to -7.2; P = .002). Measures of SD and CV also showed a significantly larger reduction in the gemigliptin group. Average glycaemic control, estimated by HbA1c, fasting glucose and safety profiles, was comparable between the two groups., Conclusions: Compared to dapagliflozin, gemigliptin significantly improved glycaemic variability, with similar glucose-lowering efficacy and safety profiles in patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve., (© 2019 John Wiley & Sons Ltd.)

Objectives: There are insufficient evidences supporting the use of spirometric indices along with tests for airway inflammation to improve diagnostic accuracy for asthma. We aimed to study the utility of combination of spirometric indices and fractional exhaled nitric oxide (FeNO) measured at the initial visit in diagnosing asthma., Methods: Consecutive children aged 8-16 years who were referred for evaluation of possible asthma were included. At referral, all participants completed FeNO measurements and spirometry. The diagnosis of asthma was established with conventional criteria. Diagnostic performance of the spirometric indices and FeNO was determined using receiver-operator characteristic (ROC) curve analyses., Results: Of 275 participants, 191 children were diagnosed with asthma and showed lower spirometric indices and higher FeNO than non-asthmatics. In the ROC curve analyses, forced expiratory flow between 25% and 75% of vital capacity (FEF 25-75 ) percent predicted demonstrated diagnostic performance with the area under the ROC curve (AUC) value of 0.81 (95% CI: 0.76-0.87) which was significantly higher than those for forced expiratory volume in the first second (FEV 1 ) percent predicted and FEV 1 /forced vital capacity. The combined use of FEF 25-75 percent predicted and FeNO improved the AUC to 0.90 (95% CI: 0.86-0.93). In addition, compared to FEF 25-75 percent predicted or FeNO alone, this combination improved sensitivity with comparable specificity., Conclusions: FEF 25-75 percent predicted had a better diagnostic value in detection of childhood asthma than other standard spirometric indices and its combination with FeNO improves the diagnostic accuracy for childhood asthma., (© 2019 John Wiley & Sons Ltd.)

Background: The factors that trigger spontaneous pneumothorax have not been sufficiently evaluated. The purpose of this study is to analyze the relationship between the development of spontaneous pneumothorax and meteorological parameters, including air pollutants., Methods: This is a retrospective study using the medical records of 379 patients who were admitted for spontaneous pneumothorax (SP) over a period of 4 years. Meteorological and air pollution data were obtained from the National Meteorological Office and the Ministry of Environment. We employed a case-crossover design to evaluate the short-term association between SP and meteorological factors including air pollutants. Conditional logistic regression was used to analyze bi-directional matched data., Results: Increase of relative humidity (RH) and of carbon monoxide (CO) were associated with the risk of pneumothorax, with odds ratio (OR) for RH = 1.18 (1.02-1.36), CO = 1.23 (1.02-1.48). Moreover, as air pressure (AP) decreased, risk of pneumothorax increased, with OR = 1.30 (1.05-1.59) but others did not. In the stratified analysis, the effect of RH was positive in ex-smokers (OR = 3.31) and non-smokers (OR = 1.32), but negative in current smokers (OR = 0.72). The effect of AP was significant in younger patients (OR = 1.33), males (OR = 1.40), and non-smokers (OR = 1.36). CO was related only with non-smokers (OR = 1.35)., Conclusion: The triggering factors for spontaneous pneumothorax were relative humidity, carbon monoxide, and air pressure. The effect of the trigger was prominent in patients who were younger (<45 years), non- or ex-smokers, and male. The reviews of this paper are available via the supplemental material section.

A novel Gram-stain-negative, yellowish-pigmented bacterial strain, designated LA-38 T , was isolated from activated sludge of wastewater treatment plants in Hanam city, South Korea. Cell of LA-38 T were rod-shaped, aerobic, motile and non-spore-forming. In phylogenetic analyses based on 16S rRNA genes, LA-38 T clustered with species of the genus Hydrogenophaga and appeared closely related to Hydrogenophaga intermedia DSM 5680 T (99.2 % similarity), Hydrogenophaga palleronii DSM 63 T (98.2 %), Hydrogrenophaga laconesensis KCTC 42478 T (98.1 %), Hydrogenophaga. atypica DSM 15342 T (98.1 %), Hydrogenophaga defluvii DSM 15341 T (98.0 %) and Hydrogenophaga taeniospiralis DSM 2082 T (97.2 %). The average nucleotide identities between LA-38 T and the closely related strains were 79.3-88.5 %, indicating that LA-38 T represents a novel species of the genus Hydrogenophaga . The DNA G+C content of the genomic DNA was 69.9 mol% and ubiquinone Q-8 was the predominant respiratory quinone. The major cellular fatty acids (>5 %) were C 16 : 0 , cyclo-C 19 : 0 , C 16 : 1 ω7 c and/or C 16 : 1 ω6 c (summed feature 3), and C 18 : 1 ω7 c and/or C 18 : 1 ω6 c (summed feature 8). The major polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine, the major polyamines were 2-hydroxyputrescine and putrescine. ANI calculation, physiological and biochemical characteristics indicated that LA-38 T represents a novel species of the genus Hydrogenophaga , for which the name Hydrogenophaga borbori sp. nov. is proposed. The type strain is LA-38 T (=KACC 19730 T =LMG 30805 T ).

A Gram-stain positive, facultatively aerobic, motile and rod-shaped bacterial strain, designated THG-SMD2.3 T , was isolated from a soil sample collected in a tangerine field, Republic of Korea. According to the 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus Cellulomonas and to be closely related to Cellulomonas fimi ATCC 484 T (98.5%), Cellulomonas biazotea DSM 20112 T (98.3%), Cellulomonas chitinilytica X.bu-b T (98.0%), Cellulomonas xylanilytica XIL11 T (97.2%), Cellulomonas humilata ATCC 25174 T (97.1%) and Cellulomonas composti TR7-06 T (97.0%). The 16S rRNA gene sequence similarities with other current species of the genus Cellulomonas were in the range 95.4-96.6%. Catalase and oxidase tests were found to be positive. The DNA G+C content was determined to be 73.0 mol%. DNA-DNA hybridization values between strain THG-SMD2.3 T and C. fimi ATCC 484 T , C. biazotea DSM 20112 T , C. chitinilytica X.bu-b T , C. xylanilytica XIL11 T , C. humilata ATCC 25174 T and C. composti TR7-06 T were 58.1 ± 1.6%, 56.7 ± 0.8%, 30.3 ± 1.6%, 22.8 ± 1.6%, 19.9 ± 1.6%, and 13.5 ± 3.0%, respectively. Strain THG-SMD2.3 T was also found to be able to grow at 20-42 °C, at 0-3% NaCl and at pH 5.5-10. The major fatty acids were identified as anteiso-C 15:0 , iso-C 15:0 , anteiso-C 17:0 and iso-C 14:0 . The predominant menaquinone was identified as tetrahydrogenated menaquinones with nine isoprene units [MK-9(H 4 )]. The polar lipids were found to be diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminolipids and two unidentified phospholipids. Based on these phenotypic, genotypic and phylogenetic characterisations strain THG-SMD2.3 T (= KACC 19341 T  = CGMCC 1.16303 T ) is concluded to represent a novel species of the genus Cellulomonas, for which the name Cellulomonas aurantiaca sp. nov. is proposed.

Although corporate social responsibility (CSR) activities are common in the pharmaceutical industry, there is little empirical evidence on consumer responses to CSR practices. We investigated public awareness, preferences, and expectations regarding social contribution of the pharmaceutical industry's CSR activities, and identified the factors associated with such activities. We conducted an online survey with 1,298 respondents comprising two groups: healthy individuals (546) and patients (752). Most respondents (78%) expressed interest in CSR activities undertaken by pharmaceutical companies. However, they reported a lack of awareness and experience thereof; only 26.9% were aware of and 7.9% had experience with such activities. Among our six CSR activity categories, both survey groups showed the highest preference for the "promoting public health" (healthy group: 6.34/10; patient group: 6.37/10) and "emergency disaster relief support" (6.31 and 6.35) categories. Among sub-categories, activities related to "development of innovative drugs in untreated areas" (6.63 and 6.82) and "support for research on new drug development" (6.59 and 6.84) received the highest scores. The mean expectation score of social contribution of all CSR activities was slightly higher than the mean preference score (6.37 and 6.06, respectively). The patient group exhibited a larger difference between the highest and lowest expectation scores than the healthy group (1.11 and 0.64, respectively). The results of the regression analysis revealed that being a patient, being male, and having positive attitudes toward CSR and its expected effects significantly and positively affected public preferences regarding CSR activities. We can conclude that CSR activities with high public preference might be an effective strategy to improve public awareness of the pharmaceutical industry's CSR activities. Furthermore, the highest preference for CSR activities relates to new drug development, indicating that our society believes the pharmaceutical industry's key CSR activity should be to pursue its intrinsic mission: to fulfill unmet medical needs by developing new drugs., Competing Interests: The authors have declared that no competing interests exist.

A Gram-stain-negative, facultatively anaerobic, non-motile and rod-shaped bacterial strain, designated THG-SD5.5 T , was isolated from a soil sample collected in a tangerine field, Republic of Korea. According to the 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus Chitinophaga and to be closely related to Chitinophaga ginsengihumi KACC 17604 T (97.9%) and Chitinophaga rupis KACC 14521 T (97.5%). The 16S rRNA gene sequence similarities with other species of the genus Chitinophaga were in the range 92.8-95.5%. Catalase test was positive. Oxidase test was negative. The DNA G + C content was determined to be 46.1 mol%. DNA-DNA hybridization values between strain THG-SD5.5 T and C. ginsengihumi KACC 17604 T and C. rupis KACC 14521 T were 45.1% and 15.6%, respectively. Strain THG-SD5.5 T was also found to be able to grow at 24-33 °C, at 0-5% NaCl and at pH 5.5-9.0. The major fatty acids were identified as anteiso-C 15:0 , C 16:0 , anteiso-C 17:0 and C 18:0 . The dominant respiratory quinone was identified as menaquinone-7 (MK-7). The polar lipids were found to be diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an unidentified aminolipid, two unidentified phospholipids and three unidentified lipids. Based on these phenotypic, genotypic and phylogenetic characterisations, strain THG-SD5.5 T (= KACC 19338 T  = CGMCC 1.16304 T ) is concluded to represent a novel species of the genus Chitinophaga, for which the name Chitinophaga aurantiaca sp. nov. is proposed.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Diabetes Association.)

Background: Early-onset diabetes results in longer lifetime hyperglycemic exposure that consequently leads to earlier chronic diabetes complications and premature death. The aim of this study was to quantify the prevalence and risk factors of undiagnosed diabetes and undiagnosed prediabetes in apparently healthy young adults aged <40 years. Methods: This study used data from the Korean National Health and Nutrition Examination Survey, a cross-sectional, nationally representative survey conducted by the Korean Ministry of Health and Welfare from 2014 to 2017. A total of 4442 apparently healthy young adults enrolled in this study. Multivariate logistic regression analyses were conducted separately to evaluate associated risk factors with undiagnosed diabetes and undiagnosed prediabetes in groups stratified by sex. Results: The prevalence of undiagnosed diabetes and undiagnosed prediabetes was 1.2% and 25.0%, respectively. Obesity (body mass index ≥ 30.0 kg/m 2 ) was a significant risk factor of undiagnosed diabetes regardless of sex (men, odds ratio (OR): 9.808, 95% confidence interval (CI): 1.619-59.412; women, OR: 7.719, 95% CI: 1.332-44.747). Family history of diabetes was significantly associated with undiagnosed diabetes (OR: 3.407, 95% CI: 1.224-9.481) in women only. Increased age, obesity status, and family history of diabetes were significant risk factors for undiagnosed prediabetes. Alcohol consumption was found to be negatively associated with undiagnosed prediabetes in women. Conclusions: Increased attention and implementation of precise strategies for identifying young adults at high risk for undiagnosed diabetes would allow for increased wellbeing as well as reduced healthcare burdens associated with diabetes.

Gram-positive, aerobic, non-motile, pale-yellow, and rodshaped bacterium, designated as Gsoil 188 T , was isolated from the soil of a ginseng field in Pocheon, South Korea. A phylogenetic analysis based on 16S rRNA gene sequence comparison revealed that the strain formed a distinct lineage within the genus Brevibacterium and was most closely related to B. epidermidis NBRC 14811 T (98.4%), B. sediminis FXJ8.269 T (98.2%), B. avium NCFB 3055 T (98.1%), and B. oceani BBH7 T (98.1%), while it shared less than 98.1% identity with the other species of this genus. The DNA G + C content was 68.1 mol%. The predominant quinone was MK-8(H 2 ). The major fatty acids were anteiso-C 15:0 and anteiso-C 17:0 . The cell wall peptidoglycan of strain Gsoil 188 T contained meso-diaminopimelic acid. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, and an unidentified aminolipid. The physiological and biochemical characteristics, low DNA-DNA relatedness values, and taxonomic analysis allowed the differentiation of strain Gsoil 188 T from the other recognized species of the genus Brevibacterium. Therefore, strain Gsoil 188 T represents a novel species of the genus Brevibacterium, for which the name Brevibacterium anseongense sp. nov. is proposed, with the type strain Gsoil 188 T (= KACC 19439 T = LMG 30331 T ).

A Gram-reaction-negative, strictly aerobic, non-motile and rod-shaped bacterium, designated strain BXN5-31 T , was isolated from soil of a ginseng field, and its taxonomic position was investigated using a polyphasic approach. Strain BXN5-31 T grew at 18-37 °C and at pH 6.0-8.0 on R2A medium. Based on 16S rRNA gene sequence similarity, strain BXN5-31 T was shown to belong to the genus Mucilaginibacter and was closely related to Mucilaginibactersoyangensis HME6664 T , Mucilaginibacterximonensis XM-003 T and Mucilaginibacterpuniceus WS71 T . The DNA G+C content was 43.6 %. The predominant respiratory quinone was menaquinone 7 (MK-7) and the major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (comprising C16 : 1ω6c and/or C16 : 1ω7c). The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine. The DNA-DNA hybridization values between strain BXN5-31 T and three reference strains (M. soyangensis HME6664 T , M. ximonensis XM-003 T and M. puniceus WS71 T ) were 9.4±1.9, 8.2±1.3 and 5.7±0.7 %, respectively. The DNA G+C content and chemotaxonomic data supported the affiliation of strain BXN5-31 T to the genus Mucilaginibacter. Moreover, the physiological and biochemical results and low level of DNA-DNA relatedness allowed the phenotypic and genotypic differentiation of strain BXN5-31 T from recognized species of the genus Mucilaginibacter. The isolate therefore represents a novel species, for which the name Mucilaginibacter panaciglaebae sp. nov. is proposed. The type strain is BXN5-31 T (=KACC 14957 T =JCM 17085 T ).

Background: Lead (Pb) is a ubiquitous toxic metal present in the environment that poses adverse health effects to humans. Inter-individual variation in blood Pb levels is affected by various factors, including genetic makeup. However, limited data are available on the association between genetic variation and blood Pb levels. The purpose of this study was to identify the genetic markers associated with blood Pb levels in the Korean population., Methods: The study subjects consisted of 1,483 healthy adults with no history of occupational exposure to Pb. We measured blood Pb levels and calculated probable daily intake of Pb according to dietary data collected using 24-hour recall. We conducted exome-wide association screening using Illumina Human Exome-12v1.2 platform (n = 500) and a replication analysis using VeraCode Goldengate assay (n = 1,483)., Results: Among the 244,770 single nucleotide polymorphisms (SNPs) tested, 12 SNPs associated with blood Pb level were identified, with suggestive significance level (P < 1 × 10 -4 ). In the Goldengate assay for replication, three SNPs (C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671) were associated with statistically suggestively significant differences in blood Pb levels. When stratified by drinking status, a potential association of C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671 with blood Pb level was observed only in drinkers. A marginally significant gene-environment interaction between ALDH2 rs671 and alcohol consumption was observed in relation to blood Pb levels. The effects of the three suggestively significant SNPs on blood Pb levels was dependent on daily calcium intake amounts., Conclusions: This exome-wide association study indicated that C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671 polymorphisms are linked to blood Pb levels in the Korean population. Our results suggest that these three SNPs are involved in the determination of Pb levels in Koreans via the regulation of alcohol drinking behavior, and that their negative effects may be compensated by appropriate calcium intake.

Although several studies reported genetic polymorphisms in protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) and their associations with gastric cancer risk, few have evaluated associations between Helicobacter pylori infection and PRKAA1 gene-environment interactions. Here, we evaluated the effects of interactions between H. pylori infection and PRKAA1 polymorphisms on gastric cancer risk in Koreans. In this hospital-based case-control study, PRKAA1 genotypes were analyzed and H. pylori infection and CagA status were examined using a serologic method in 846 pairs of gastric cancer patients and controls matched for age and sex. H. pylori seropositivity was associated with a 1.43-fold [95% confidence interval: 1.12-1.81] increase in the risk of gastric cancer, and CagA low-positive titers during H. pylori infection increased the risk by 1.85-fold (95% confidence interval, 1.38-2.48). Significant positive interaction between the PRKAA1 rs13361707 genotype and H. pylori infection was verified on an additive scale [relative excess risk due to interaction, 0.55; 95% confidence interval, 0.05-1.04; P = 0.030], and the gene-environment interaction between PRKAA1 rs13361707 and CagA status was also statistically significant (relative excess risk due to interaction, 0.50; 95% confidence interval, 0.30-0.70; P < 0.001). Our results indicated that H. pylori infection, CagA status, and PRKAA1 polymorphisms were risk factors for gastric cancer in Koreans, and that the combination of two of these factors rather than their independent effects synergistically increased the risk., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Rotavirus (RV) is one of the most important viral etiologic agents of acute gastroenteritis (AGE) in children. Although effective RV vaccines (RVVs) are now used worldwide, novel genotypes and outbreaks resulting from rare genotype combinations have emerged. This study documented RV genotypes in a Korean population of children with AGE 5 yr after the introduction of RVV and assessed potential genotype differences based on vaccination status or vaccine type. Children less than 5-yr-old diagnosed with AGE between October 2012 and September 2013 admitted to 9 medical institutions from 8 provinces in Korea were prospectively enrolled. Stool samples were tested for RV by enzyme immunoassay and genotyped by multiplex reverse-transcription polymerase chain reaction. In 346 patients, 114 (32.9%) were RV-positive. Among them, 87 (76.3%) patients were infected with RV alone. Eighty-six of 114 RV-positive stool samples were successfully genotyped, and their combinations of genotypes were G1P[8] (36, 41.9%), G2P[4] (12, 14.0%), and G3P[8] (6, 7.0%). RV was detected in 27.8% of patients in the vaccinated group and 39.8% in the unvaccinated group (P=0.035). Vaccination history was available for 67 of 86 cases with successfully genotyped RV-positive stool samples; RotaTeq (20, 29.9%), Rotarix (7, 10.4%), unvaccinated (40, 59.7%). The incidence of RV AGE is lower in the RV-vaccinated group compared to the unvaccinated group with no evidence of substitution with unusual genotype combinations.

Background: The oil tanker Hebei Spirit spilled 12,547kL of oil near the western coastline of Korea on December 7, 2007. We aimed to investigate the relationship between oil spill exposure and oxidative stress in residents living near the affected area., Methods: Study subjects were 671 residents who participated in a health examination between February and September 2009. As surrogates for oil spill exposure, we used the total duration of clean-up work and levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs), 1-hydroxypyrene (1-OHP) and 2-naphthol (2-NAPH). Oxidative stress was measured using urinary levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), indicators of lipid peroxidation and oxidative DNA damage, respectively., Results: Levels of oxidative stress biomarkers were significantly increased with longer involvement in clean-up work over one year after the Hebei Spirit oil spill (MDA, p-trend<0.0001; 8-OHdG, p-trend<0.0001). As more time elapsed since the last involvement in clean-up, the total duration of clean-up work participation and levels of PAH metabolites (1-OHP and 2-NAPH), as well as levels of the oxidative stress biomarkers (MDA and 8-OHdG) decreased further. The level of 1-OHP had a significant positive correlation with the total duration of clean-up work involvement, with a higher level found in those who participated in clean-up for >100 days. Increasing levels of 1-OHP were significantly associated with increased MDA and 8-OHdG after adjusting for covariates, while the strength of association weakened as time passed since the last participation in clean-up work. The significance of the association was maintained for up to 12 months after the last clean-up work., Conclusions: The results suggested that oil exposure from prolonged clean-up activity likely induced oxidative stress in clean-up participants up to at least one year after the last exposure., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Few studies in epidemiology have evaluated the effects of gene-environment interaction on oxidative stress, even though this interaction is an important etiologic factor in lung carcinogenesis. We investigated the effects of the genetic polymorphisms of paraoxonase 1 (PON1), smoking, and the interaction between the two on lung cancer risk and oxidative stress., Methods: This study's subjects consisted of 416 newly diagnosed lung cancer patients and an equal number of matched controls. The GoldenGate assay was used for genotypic analyses of the PON1 gene. Urinary 8-hydroxydeoxyguanosine (8-OHdG) and thiobarbituric acid reactive substances levels were measured as indicators of oxidative stress., Results: The PON1 rs662 AA genotype showed a significantly lower risk of lung cancer than the GG genotype (OR = 0.60, 95% CI: 0.36-0.99). The protective effect of the PON1 rs662 AA genotype on lung cancer risk was limited to non-smokers. Lung cancer patients who had the rs662 A allele showed a dose-dependent association between smoking status and oxidative stress markers. Among non-smoking lung cancer patients, urinary 8-OHdG levels were significantly lower in individuals with the rs662 GA and AA genotypes than in those with the GG genotype. Furthermore, we found a significant interaction effect between PON1 rs662 and smoking status on urinary 8-OHdG levels in lung cancer patients., Conclusions: Our results suggest that the protective effect of PON1 rs662 SNP against lung carcinogenesis and the induction of oxidative stress might be modulated by the interaction between PON1 genetic polymorphisms and tobacco smoking.

Surgical resection is the treatment of choice for bile duct cancers. The aim of this study was to investigate disease recurrence patterns and prognostic factors for recurrence of distal bile duct cancers after surgical resection. A retrospective study was performed on 122 patients with distal bile duct cancers who underwent R0 or R1 surgical resection at Korea University Guro Hospital from 1991 to 2010. Sites of initial disease recurrence were classified as locoregional or distant. Univariate and multivariate analyses were performed to investigate the factors affecting recurrence. Of the 122 patients, 80 patients developed recurrence. The disease-free survival rate was 63.1 per cent at one year and 36.4 per cent at three years. The patterns of recurrence at diagnosis were locoregional in 25 patients, locoregional and distant metastasis in 14 patients, and distant metastasis in 41 patients. Multivariate analyses revealed that recurrence pattern, lymph node metastasis, and differentiation are independent prognostic factors affecting disease-free survival. R status (marginal significance) and tumor differentiation were independent prognostic factors associated with locoregional recurrence. Differentiation and lymph node metastasis were independent prognostic factors associated with distant metastasis. The prognosis after recurrence was poor with a 1-year survival rate after recurrence of 26.1 per cent. Adjuvant chemo- or radiation therapy, delivered in patients mainly with R1 resection or with presence of lymph node metastasis, did not demonstrate the survival benefit. Significant factors for recurrence were tumor differentiation and lymph node metastasis. Therefore, close follow-up and adjuvant therapy will be necessary in patients with lymph node metastasis or poorly differentiated tumor.

Background/aims: This study was conducted to evaluate whether medical costs can be reduced using endoscopic submucosal dissection (ESD) instead of conventional surger-ies in patients with early gastric cancer (EGC)., Methods: Pa-tients who underwent open gastrectomy (OG), laparoscopy-assisted gastrectomy (LAG), and ESD for EGC were recruited from three medical institutions in 2009. For macro-costing, the medical costs for each patient were derived from the ex-penses incurred during the patient's hospital stay and 1-year follow-up. The overall costs in micro-costing were determined by multiplying the unit cost with the resources used during the patients' hospitalization., Results: A total of 194 patients were included in this study. The hospital stay for ESD was 5 to 8 days and was significantly shorter than the 12-day hospital stay for OG or the 11- to 17-day stay for LAG. Using macro-costing, the average medical costs for ESD during the hospital stay ranged from 2.1 to 3.4 million Korean Won (KRW) per patient, and the medical costs for conventional surgeries were estimated to be between 5.1 million and 8.2 million KRW. There were no significant differences in the 1-year follow-up costs between ESD and conventional surger-ies., Conclusions: ESD patients had lower medical costs than those patients who had conventional surgeries for EGC with conservative indications. (Gut Liver, 2015;9174-180).

There have been numerous reports on the relationship between eosinophilia and toxocariasis. The present study investigated seropositive rates of toxocariasis among healthy people with or without eosinophilia in urban and rural areas, and assessed risk factors for positive antibody test. A total of 610 healthy people, who visited health check-up (Medicheck®, Korea Association of Health Promotion), 310 from Seoul and 300 from Gyeongsangnam-do, were subjected for this study. Their serum samples were tested by ELISA with the crude antigen of Toxocara canis larvae. Cross-reactions with other tissue invading helminth antigens were also investigated. Total antibody positive rate of toxocariasis was 8.7% of the 610 subjects. When the subjects were grouped into 3 by their eosinophil counts, the antibody positive rates significantly differed by the groups; 5.9% (18/306) in the group<350/µL, 10.0% (11/110) in the group 350-500/µL, and 12.4% (24/194) in the group>500/µL (P=0.028). A total of 22 serum samples cross-reacted with other tissue-invading helminth antigens. A questionnaire analysis recognized drinking alcohol and smoking as significant risk factors of toxocariasis. In conclusion, toxocariasis antibody positive rate is correlated with eosinophil counts. It is recommended that healthy subjects with eosinophilia by routine health examination and risk factors undergo Toxocara serology by multiantigen ELISA to investigate etiology.

Aim: To investigate the influence of the resection margin on local recurrence and survival in gastric cancer patients., Methods: We reviewed the medical records of 1788 patients who had undergone gastrectomy for gastric cancer at the Seoul National University Bundang Hospital, South Korea, between May 2003 and July 2009. The patients were divided into early and advanced gastric cancer groups. In each group, we analyzed the relationship between clinicopathologic factors and survival outcomes, and compared the hazard rates of event occurrence between patients with resection margins above and below the cut-off value, using a Cox proportional hazard model., Results: The early and advanced gastric cancer groups included 1001 and 787 patients, respectively. The hazard rates of event occurrence did not significantly differ between the patients with resection margins above the cut-off value and those with resection margins below the cut-off value (P > 0.05, in all comparisons). Based on the multivariable analyses, the proximal and distal resection margins were not significantly associated with survival outcomes and local recurrence (P > 0.05, in all analyses)., Conclusion: The proximal or distal resection margins did not affect the prognosis of patients with gastric cancer if the margins were pathologically negative.

Aim: To evaluate the association between genetic polymorphisms of the gene encoding AMP-activated protein kinase (PRKAA1) and the risk of gastric cancer., Methods: The study subjects consisted of 477 age- and sex-matched case-control pairs. Genotyping was performed for 5 tag single nucleotide polymorphisms (SNPs): rs13361707, rs154268, rs3805486, rs6882903, and rs10074991. Associations between gastric cancer and putative risk factors (including the SNPs) were analyzed with multivariate conditional logistic regression models, after adjusting for potential confounding factors. Multiple testing corrections were implemented following methodology for controlling the false discovery rate. Gene-based association tests were performed by using the versatile gene-based association study (VEGAS) method., Results: In the dominant model, SNPs rs13361707 [odds ratio (OR) = 1.51, 95%CI: 1.07-2.11)], rs154268 (OR = 1.65, 95%CI: 1.22-2.22), rs6882903 (OR = 1.48, 95%CI: 1.09-2.00), and rs10074991 (OR = 1.53, 95%CI: 1.09-2.16) were significantly associated with an increased risk of gastric cancer. In the recessive model, SNPs rs154268 (OR = 1.66, 95%CI: 1.22-2.26), rs3805486 (OR = 0.63, 95%CI: 0.46-0.85), and rs10074991 (OR = 1.47, 95%CI: 1.15-1.88) were significant risk or protective factors for gastric cancer. In the codominant model, the ORs of each of the 5 SNPs were statistically significant. All SNPs in the model showed a dose-response relationship between the minor allele frequency and the risk of gastric cancer. Most notably, subjects with a homozygous minor allele in SNP rs10074991 showed 2.15 times the risk of gastric cancer as subjects without a minor allele. The PRKAA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test., Conclusion: All 5 tested tag SNPs of the PRKAA1 gene (rs13361707, rs154268, rs3805486, rs6882903, and rs10074991) were significantly associated with gastric cancer.

This study aimed to estimate the risks for renal tubular damage and osteoporosis in individuals with long-term environmental Cd exposure. This cross-sectional study comprised 1086 residents living in the vicinity of a copper refinery plant. As the urinary Cd levels increased, the proportion of female subjects with β₂-MG ≥300 μg/g creatinine also increased significantly, but this was not observed in the male subjects. The prevalence of osteoporosis was significantly higher in men with urinary Cd >5 μg/g creatinine than in those with urinary Cd ≤5 μg/g creatinine. This difference was not observed in the corresponding female groups. The association between increased urinary excretion of β₂-MG and decreased BMD was statistically significant only in the female subjects. We suggest that an increased Cd body burden directly decreases the BMD in male subjects; however, in female subjects, it first induces renal microtubular damage, which can lead to osteoporosis., (Copyright © 2014. Published by Elsevier B.V.)

Purpose: Mercury (Hg) is a nonessential and toxic metal that is widely distributed in the environment. This study was performed to estimate the representative blood Hg level, to determine the contributing factors to Hg exposure, and to analyze the association of blood Hg with metabolic syndrome in Korean adults., Methods: Mercury exposure is assessed by total Hg concentration in blood. A total of 2,114 healthy adults who have not been exposed to Hg occupationally were sampled by the multistaged, sex-, and age-stratified probability method. Information was collected regarding the subjects' demographic characteristics, lifestyles, and past medical history. The participants then underwent physical examination and blood sampling., Results: The geometric mean concentration of Hg in whole blood was 3.90 μg/L, which was significantly influenced by sex, age, smoking, alcoholic consumption, residence area, and seafood intake after adjustment for confounders. Significant increases in body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyceride were observed according to the blood Hg levels after adjustment for covariates. Also, Hg exposure was significantly associated with metabolic syndrome and their components such as obesity and increased fasting glucose., Conclusion: The blood Hg level in Korean adults is higher than that in USA and other Western countries, while it is similar to or lower than that in other Asian countries. The blood Hg level is influenced by sociodemographic factors and individual lifestyles including dietary habits. Furthermore, blood Hg is associated with metabolic syndrome, in which Hg exposure may play a role as a possible risk factor for cardiovascular diseases.

Background: The new estimated glomerular filtration (eGFR) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, was recently introduced. We compared the prevalence of CKD examined by the CKD-EPI equation with that by the Modification of Diet in Renal Disease (MDRD) equation., Methods: We analyzed the data from a total of 14,605 Korean adults (age ≥20 years), who were enrolled in the Korean National Health and Nutrition Examination Survey in 2007, 2009, and 2010. CKD stages 1 and 2 were defined as eGFR ≥60 mL/min/1.73 m(2) with proteinuria measured by dipstick. CKD stages 3-5 were defined as eGFR <60 mL/min/1.73 m(2) ., Results: The eGFRs calculated by the CKD-EPI equation were higher than those calculated by the MDRD equation (P < 0.001), especially in women and young people. The prevalence of CKD stages 3-5 calculated by the MDRD equation was 6.8%, 3.0%, and 3.0% in 2007, 2009, and 2010, respectively. The prevalence of CKD stages 3-5 calculated by CKD-EPI equation was 7.7%, 2.7%, and 2.6% in 2007, 2009, and 2010, respectively. When defining the CKD using the CKD-EPI equation, 55 (32.7%) of 350 cases were reclassified into more advanced stages and 295 cases (67.3%) were reclassified into less-advanced stages., Conclusion: The CKD-EPI equation caused an overall low prevalence of CKD compared to the MDRD. Therefore, CKD-EPI equation might be helpful to prevent an overestimation of CKD., (© 2014 Wiley Periodicals, Inc.)

Background: Data are lacking regarding the oncologic safety of laparoscopic gastrectomy (LG) for the treatment of gastric cancer. The aim of this study was to compare the long-term outcomes of LG with open gastrectomy (OG) for the treatment of gastric cancer., Methods: A total of 1,874 patients underwent curative distal or total gastrectomy for gastric adenocarcinoma between May 2003 and December 2009 and were included in this retrospective study. Recurrence-free survival and recurrence pattern were compared according to each tumor stage, and a subgroup analysis was performed in advanced gastric cancer patients who underwent D2 lymphadenectomy., Results: Of 1,874 patients, 816 were treated with OG and 1,058 with LG. No differences were observed in recurrence-free survival rates between the LG and the OG groups for any tumor stage. The number of harvested lymph nodes was similar between the two groups when analyzed according to tumor progression, operative procedure, and extent of lymphadenectomy. There were no differences between the 2 groups when we compared recurrence patterns after stratifying for tumor stage. The subgroup analysis in advanced gastric cancer patients who underwent D2 lymphadenectomy showed that there was no difference in the recurrence-free survival rates for any tumor stage between the 2 groups. Multivariate analysis indicated that the type of operative approach did not influence recurrence in either early or advanced gastric cancer patients., Conclusion: LG for gastric cancer is an oncologically safe procedure with comparable long-term outcomes with OG., (Copyright © 2014 Mosby, Inc. All rights reserved.)

A Gram-staining negative, strictly aerobic, motile by gliding, non-spore-forming, pale yellow pigmented and rod-shaped bacterium designated strain THG-107(T) was isolated from soil of a ginseng field on Ganghwa Island in the Republic of Korea and its taxonomic position was investigated by using a polyphasic study. Growth of strain THG-107(T) was found to occur at 4-37 °C (optimum, 20-30 °C), at pH 5.5-10 (optimum, pH 7.0) and in the presence of 0-1 % (w/v) NaCl (optimum, absence) on R2A agar. On the basis of 16S rRNA gene sequence similarity, strain THG-107(T) was shown to belong to the family Flavobacteriaceae and was related to Flavobacterium denitrificans ED5(T) (99.1 % similarity). The G+C content of the genomic DNA was determined to be 34.2 mol%. These results are consistent with characteristics of members of the genus Flavobacterium. The only isoprenoid quinone detected in strain THG-107(T) was menaquinone-6 (MK-6) and the major polyamine was identified as homospermidine (82.9 %). The major polar lipid detected was phosphatidylethanolamine and the major cellular fatty acids were identified as iso-C15:0 (26.3 %), iso-C17:0 3OH (12.6 %) and summed feature 3 (comprising C16:1 ω7c and/or C16:1 ω6c; 11.6 %). Flexirubin-type pigments were found to be present. Strain THG-107(T) has β-glucosidase activity to convert ginsenosides Rb1 and Rd into Gyp17 and F2. DNA-DNA hybridization with F. denitrificans ED5(T) was 52 %. Strain THG-107(T) could be distinguished from F. denitrificans ED5(T) and the other species of the genus Flavobacterium by its phylogenetic and genetic distinctiveness and by several phenotypic properties. Therefore, strain THG-107(T) is considered to represent a novel species in the genus Flavobacterium, for which the name Flavobacterium kyungheensis sp. nov. is proposed (type strain THG-107(T) = KACC 16219(T) = LMG 26575(T)).

A Gram-reaction-negative, strictly aerobic, non-motile, non-spore-forming and rod-shaped bacterial strain, designated THG-45(T), was isolated from soil of a ginseng field of Pocheon province in the Republic of Korea and its taxonomic position was investigated by a polyphasic approach. Growth occurred at 4-30 °C, at pH 5.5-9.0 and with 0-2 % (w/v) NaCl on nutrient agar. On the basis of 16S rRNA gene sequence similarity, strain THG-45(T) was shown to belong to the genus Pedobacter and was related to Pedobacter borealis G-1(T) (98.8 %), P. alluvionis NWER-II11(T) (97.9 %), P. agri PB92(T) (97.9 %), P. terrae DS-57(T) (97.5 %), P. suwonensis 15-52(T) (97.4 %), P. sandarakinus DS-27(T) (97.0 %) and P. soli 15-51(T) (97.0 %), but DNA relatedness between strain THG-45(T) and these strains was below 36 %. The G+C content of the genomic DNA was 39 mol%. The only isoprenoid quinone detected in strain THG-45(T) was menaquinone-7 (MK-7). The predominant fatty acids were iso-C15 : 0, summed feature 3 (comprising C16 : 1ω6c and/or C16 : 1ω7c) and iso-C17 : 0 3-OH, and the major polar lipids were phosphatidylethanolamine and an unidentified aminophosphoglycolipid. Phenotypic data and phylogenetic inference supported the affiliation of strain THG-45(T) to the genus Pedobacter, and a number of biochemical tests differentiated strain THG-45(T) from the recognized species of the genus Pedobacter. Therefore, the novel isolate represents a novel species, for which the name Pedobacter ginsenosidimutans sp. nov. is proposed, with THG-45(T) as the type strain ( = KACC 14530(T) = JCM 16721(T)).