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Background: The rate of catastrophic health expenditure (CHE) continues to rise in South Korea. This study examined the association between changes in economic activity and CHE experiences in South Korea., Methods: This study analyzed the Korea Health Panel Survey data using a logistic regression analysis to study the association between changes in economic activity in 2014-2015 and the participants' CHE experiences in 2015. The study included a total of 12,454 individuals over the age of 19. The subgroup analyses were organized by sex, age, health-related variables, and household level variables, and the reasons for leaving economic activity., Results: Those who quit economic activities were more likely to experience CHE than those who continued to engage in economic activities (OR [odds ratio] = 2.10; 95% CI [confidence interval]: 1.31-3.36). The subgroup analysis results, according to health-related variables, showed that there is a tendency to a higher Charlson comorbidity index, a higher OR, and, in groups that quit their economic activities, people with disabilities were more likely to experience CHE than people without disabilities (OR = 5.63; 95% CI 1.71-18.59, OR = 1.82; 95% CI 1.08-3.08, respectively). Another subgroup analysis found that if the reason for not participating in economic activity was a health-related issue, the participant was more likely to experience CHE (active → inactive: OR = 2.40; 95% CI 0.61-9.43, inactive → inactive OR = 1.65; 95% CI 1.01-2.68)., Conclusions: Those individuals who became unemployed were more likely to experience CHE, especially if health problems precipitated the job loss. Therefore, efforts are needed to expand coverage for those people who suffer from high medical expenses., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: Using the Alcohol Use Disorders Identification Test-Korean revised version (AUDIT-KR), we examined the association between habitual alcohol use and risk-taking behaviors among car users., Methods: We used the data of 15,043 car users aged 20 years or older from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted between 2009 and 2013. Multivariable logistic regression analysis was used to investigate the associations between alcohol use and risk-taking behaviors (i.e., driving under the influence of alcohol, riding in a car being driven under the influence, not wearing a seat belt while driving, not wearing a seat belt in the passenger seat), while adjusting for individual-level covariates., Results: Compared to low-risk drinkers, high-risk drinkers (adjusted odds ratio [Adj.OR] 2.18, 95 % CI 1.96-2.42) and intermediate-risk drinkers (Adj.OR 1.39, 95 % CI 1.26-1.54) had higher odds of risk-taking behaviors while using a car. Stratifying by sociodemographic variables (i.e., sex, age, and region) led to differences in the relationship between alcohol-drinking level and risk-taking behaviors. Furthermore, alcohol-drinking level had significant positive associations with most of risk-taking behaviors, especially driving under the influence of alcohol and using a car with a drunken driver., Conclusion: Car users with high levels of alcohol consumption are more likely to be involved in risk-taking behaviors, especially in driving under the influence of alcohol. While causal relations cannot be established due to the nature of the cross-sectional design, it is possible that individuals' habitual alcohol consumption level can influence their risk-taking behaviors while using a car., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The genetic control of gene expression is a core component of human physiology. For the past several years, transcriptome-wide association studies have leveraged large datasets of linked genotype and RNA sequencing information to create a powerful gene-based test of association that has been used in dozens of studies. While numerous discoveries have been made, the populations in the training data are overwhelmingly of European descent, and little is known about the generalizability of these models to other populations. Here, we test for cross-population generalizability of gene expression prediction models using a dataset of African American individuals with RNA-Seq data in whole blood. We find that the default models trained in large datasets such as GTEx and DGN fare poorly in African Americans, with a notable reduction in prediction accuracy when compared to European Americans. We replicate these limitations in cross-population generalizability using the five populations in the GEUVADIS dataset. Via realistic simulations of both populations and gene expression, we show that accurate cross-population generalizability of transcriptome prediction only arises when eQTL architecture is substantially shared across populations. In contrast, models with non-identical eQTLs showed patterns similar to real-world data. Therefore, generating RNA-Seq data in diverse populations is a critical step towards multi-ethnic utility of gene expression prediction., Competing Interests: We have read the journal's policy and one author of this manuscript (Chris Gignoux) has the following competing interests: ownership of stock in 23andMe. The remaining authors have declared that no competing interests exist.

Air pollution particulate matter <2.5 μm (PM 2.5 ) exposure is associated with poor respiratory outcomes. Mechanisms underlying PM 2.5 -induced lung pathobiology are poorly understood but likely involve cellular and molecular changes to the airway epithelium. We extracted and chemically characterized the organic and water-soluble components of air pollution PM 2.5 samples, then determined the whole transcriptome response of human nasal mucociliary airway epithelial cultures to a dose series of PM 2.5 extracts. We found that PM 2.5 organic extract (OE), but not water-soluble extract, elicited a potent, dose-dependent transcriptomic response from the mucociliary epithelium. Exposure to a moderate OE dose modified the expression of 424 genes, including activation of aryl hydrocarbon receptor signaling and an IL-1 inflammatory program. We generated an OE-response gene network defined by eight functional enrichment groups, which exhibited high connectivity through CYP1A1 , IL1A , and IL1B . This OE exposure also robustly activated a mucus secretory expression program (>100 genes), which included transcriptional drivers of mucus metaplasia ( SPDEF and FOXA3 ). Exposure to a higher OE dose modified the expression of 1,240 genes and further exacerbated expression responses observed at the moderate dose, including the mucus secretory program. Moreover, the higher OE dose significantly increased the MUC5AC / MUC5B gel-forming mucin expression ratio and strongly downregulated ciliated cell expression programs, including key ciliating cell transcription factors (e.g., FOXJ1 and MCIDAS ). Chronic OE stimulation induced mucus metaplasia-like remodeling characterized by increases in MUC5AC + secretory cells and MUC5AC mucus secretions. This epithelial remodeling may underlie poor respiratory outcomes associated with high PM 2.5 exposure.

Objective: Absenteeism and presenteeism refer to loss in productivity related to sick leave and illness, respectively, which affect physical and mental health. We examined the association between presenteeism/absenteeism and level of well-being among Korean workers., Methods: We analyzed data from 44,019 participants who completed the 2017 Korean Working Conditions Survey. The World Health Organization Well-Being Index (WHO-5) was used to screen the well-being level. We examined the association between presenteeism/absenteeism and level of well-being using multiple linear regression., Results: WHO-5 scores were lower among workers who experienced presenteeism or absenteeism than those who experienced neither (presenteeism: β = -1.011, P < 0.0001, absenteeism: β = -0.403, P < 0.0001)., Conclusion: Presenteeism and absenteeism were associated with lower level of well-being. We suggest that their management is important for maintaining the health of Koreans.

Studies have been conducted on the association between physical activity (PA) and sleep, but to the best of our knowledge, a simultaneous analysis of the effects of occupational PA (OPA) and leisure time PA (LTPA) on South Korean firefighters' sleep has never been conducted. This study aims to analyze how OPA and LTPA affect these individuals' risk of suffering from insomnia with-in this specific population of subjects. The study includes data from an online self-report survey in which 9788 South Korean firefighters participated. The survey used the Insomnia Severity Index and the OPA- and LTPA-related characteristics were investigated. The independent two-sample t -test, χ 2 test, and multiple logistic regression analysis were performed. Subgroup logistic regression analyses were also completed in accordance with the OPA level. Among 9788 participants, 890 (9.1%) suffered from insomnia. A logistic regression analysis revealed that higher levels of feeling of job loading (FoJL), rising levels of physical strength utilization rate (PSUR), greater frequency levels of occupational activities, and high-intensity LTPA were significantly correlated with an increased risk of insomnia, while execution of LTPA and getting enough rest after LTPA was correlated with a decreased risk. However, the subgroup analysis showed that high-intensity LTPA was correlated with a significantly increased the risk in the group with high OPA, but this did not apply to the group with low OPA. Although the risk of suffering from insomnia was overall significantly higher in the high OPA group, the risk was significantly lower in groups getting enough rest after partaking in LTPA, regardless of the OPA level. Thus, the intensity of exercise programs pre-scribed to groups with high OPA and individuals with higher risks of suffering from insomnia, such as firefighters, police officers, and soldiers, should be considered.

This study examines Korean college students' rates and the severity of various negative consequences resulting from the frequency and quantity of alcohol consumption and the unique factors that are affecting this problem in the Korean context in comparison to other countries. It assesses how much gender, age and other associated respondent characteristics mediate alcohol use and the resulting negative consequences among the population. A stratified representative sample of 4803 valid student respondents attending 82 colleges participated in the alcohol consumption survey, of which 95% reported drinking in past 12 months. Drinking is measured by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screening tool. Based on this test, composite scores for each participant were computed and students were grouped into four risk groups: (a) nondrinkers, (b) light drinkers, (c) moderate drinkers and (d) heavy drinkers. Outcome measures include 21 validated items evaluating self-reported alcohol-related negative consequences. Rates of negative consequences are reported for each drinking risk group stratified by gender. Descriptive statistics, stepwise regression, multivariate linear regression and MANOVA tests were used to analyze the data. The study found that female respondents in the sample who consumed alcohol in the past 12 months drank 11.5 percent less than males (AUDIT-C score μ = 6.0 and 6.7, respectively), and there was a greater proportion of females (5.1 percent) who were nondrinkers than males (4.6 percent). Yet, when females drank, they experienced 11.8 percent more negative consequences on average than males (μ = 1.9 and 1.7, respectively). The study attempts to explain this apparent contradiction. The self-reported rates for many individual negative consequences also varied discernibly by gender. The study concludes with suggestions for how alcohol prevention on Korean college campuses would benefit from targeting females and males differently.

The type 2 cytokine-high asthma endotype (T2H) is characterized by IL-13-driven mucus obstruction of the airways. To further investigate this incompletely understood pathobiology, we characterize IL-13 effects on human airway epithelial cell cultures using single-cell RNA sequencing, finding that IL-13 generates a distinctive transcriptional state for each cell type. Specifically, we discover a mucus secretory program induced by IL-13 in all cell types which converts both mucus and defense secretory cells into a metaplastic state with emergent mucin production and secretion, while leading to ER stress and cell death in ciliated cells. The IL-13-remodeled epithelium secretes a pathologic, mucin-imbalanced, and innate immunity-depleted proteome that arrests mucociliary motion. Signatures of IL-13-induced cellular remodeling are mirrored by transcriptional signatures characteristic of the nasal airway epithelium within T2H versus T2-low asthmatic children. Our results reveal the epithelium-wide scope of T2H asthma and present candidate therapeutic targets for restoring normal epithelial function., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Air pollution is a risk factor for depression or depressive symptoms. However, few studies have examined an effect modifier as a protective factor against depressive symptoms associated with air pollution, including social support. Notably, less is known about a married relationship in the association between exposure to air pollution and depressive symptoms among the elderly., Methods: This study included 2122 marrieds and 607 non-marrieds, recruited in 2014-2017 from different regions of South Korea. Depressive symptoms were measured by the Korean version of the Geriatric Depression Scale Short Form (SGDS-K). After adjustment for potential confounders using propensity score of being assigned to the marrieds, we examined the extent of whether the effects of exposure to air pollutants (PM 10 , PM 2.5 , and NO 2 ) on depressive symptoms were different between marrieds and non-marrieds. Subgroup analyses by gender and residence area were also performed., Results: Marrieds than non-marrieds were less likely to have depressive symptoms and had smaller SGDS-K associated with increased exposure to PM 10 and PM 2.5 concentrations, respectively. After stratification of subjects by gender and residence area, the interaction term appeared to be significant among men and the non-metropolitan group, indicating the protective effect of married relationships on depressive symptoms attributable to air pollution exposure in them., Limitations: Although we adjusted the propensity score, our findings might be confounded by the contextual effect associated with married relationships., Conclusions: A married relationship, as a social tie, may attenuate the effect of exposure to air pollution on depressive symptoms among the elderly. Nonetheless, additional research is worthwhile to explore the extent of other social relationships in the association between air pollution exposure and depressive symptoms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Baseline lung function, quantified as forced expiratory volume in the first second of exhalation (FEV 1 ), is a standard diagnostic criterion used by clinicians to identify and classify lung diseases. Using whole-genome sequencing data from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine project, we identified a novel genetic association with FEV 1 on chromosome 12 in 867 African American children with asthma ( P = 1.26 × 10 -8 , β = 0.302). Conditional analysis within 1 Mb of the tag signal (rs73429450) yielded one major and two other weaker independent signals within this peak. We explored statistical and functional evidence for all variants in linkage disequilibrium with the three independent signals and yielded nine variants as the most likely candidates responsible for the association with FEV 1 Hi-C data and expression QTL analysis demonstrated that these variants physically interacted with KITLG (KIT ligand, also known as SCF ), and their minor alleles were associated with increased expression of the KITLG gene in nasal epithelial cells. Gene-by-air-pollution interaction analysis found that the candidate variant rs58475486 interacted with past-year ambient sulfur dioxide exposure ( P = 0.003, β = 0.32). This study identified a novel protective genetic association with FEV 1 , possibly mediated through KITLG , in African American children with asthma. This is the first study that has identified a genetic association between lung function and KITLG , which has established a role in orchestrating allergic inflammation in asthma., (Copyright © 2020 by the Genetics Society of America.)

Few studies have researched the gender-specific effects of electronic nicotine delivery systems on the metabolic syndrome (MetS) and/or its risk factors (central obesity, raised triglycerides, decreased HDL cholesterol, raised blood pressure, raised fasting plasma glucose). Thus, this study investigated the association between smoking behavior (cigarette type, smoking history) and MetS in a nationally representative sample of Korean men and women. Our study employed data for 5,462 cases of MetS and 12,194 controls from the Korea National Health and Nutritional Examination Survey (KNHANES) for the years 2014 to 2017. Logistic regression analysis was employed to determine the association between type of cigarette (non-smoker, ex-smoker, and current smoker-conventional only, current smoker-conventional and electronic) and the prevalence of metabolic syndrome and its risk factors. Smoking history was clinically quantified by pack-year. No association between cigarette type and MetS was found for men. For women, relative to non-smokers, smokers of conventional cigarettes (OR 1.80, 95% CI 1.02-3.18) and both conventional and electronic cigarettes (OR 4.02, 95% CI 1.48-10.93) had increased odds of MetS. While there was no association between smoking history and MetS for women, for men, conventional smoking history was associated with MetS for individuals with a smoking history of > 25 pack-years (> 25 to ≤ 37.5 OR 1.45, 95% CI 1.04-2.02; > 37.5 to ≤ 50 OR 1.53, 95% CI 1.08-2.18; > 50 OR 1.56, 95% CI 1.07-2.27). Sex differences were found in the association between smoking behavior and MetS. Such findings reveal sociodemographic differences that should be considered for interventions regarding conventional and/or e-cigarette users at risk of metabolic complications.

Background: There have been no health-related studies of pre-employed firefighters without firefighter-specific job-related factors (FSJRF). This study aimed to evaluate the sleep quality of pre-employed firefighters and to examine the relationship between sleep quality and psychosocial factors., Methods: We conducted a self-report questionnaire survey for 602 pre-employed firefighters at 3 Fire Service Academies after brief lecture about sleep. Sleep quality and psychosocial variables such as depression, anxiety, stress and social support were evaluated. The independent 2 sample t-test, χ 2 test and multiple logistic regression analysis were used to evaluate the effect of the variables on the sleep quality of pre-employed firefighters., Results: Among a total of 602 people, 347 (57.6%) had good sleep quality and 255 (42.4%) had poor sleep quality. Pittsburgh Sleep Quality Index score of them was 3.29 ± 1.41) and 7.87 ± 2.20), respectively. 24 (4.0%) were evaluated to have insomnia by Insomnia Severity Index. Logistic regression analyses showed that the depression (adjusted odds ratio [aOR]: 5.940, 95% confidence interval [CI]: 3.124-11.292), anxiety (aOR: 4.233, 95% CI: 2.138-8.381), stress (aOR: 2.880, 95% CI: 1.915-4.330) and social support (aOR: 0.959, 95% CI: 0.939-0.980) have a significant effect on sleep quality after adjusted by sex, age, smoking status, drinking status, caffeine intake, past shift working and circadian rhythm type., Conclusions: Depression, anxiety, stress and social support were associated with sleep quality among pre-employed firefighters. Repeated follow-up studies of pre-employed firefighters are needed to further assess their change of sleep quality and identify the FSJRF that may affect the sleep quality of firefighters., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2020 Korean Society of Occupational & Environmental Medicine.)

Rationale: Severe early-life respiratory illnesses, particularly those caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV), are strongly associated with the development of asthma in children. Puerto Rican children in particular have a strikingly high asthma burden. However, prior studies of the potential associations between early-life respiratory illnesses and asthma in Puerto Rican and other minority populations have been limited., Objectives: We sought to determine whether early-life respiratory illness was associated with asthma in Puerto Rican, Mexican American, and African American children., Methods: Using a logistic regression analysis, we examined the association between early-life respiratory illnesses (report of upper respiratory infection (URI), pneumonia, bronchitis, and bronchiolitis/RSV) within the first two years of life and physician-diagnosed asthma after the age of two in a large cohort of Puerto Rican, Mexican American, and African American children., Measurements and Main Results: While early-life respiratory illnesses were associated with greater asthma odds in Puerto Ricans, Mexican Americans, and African Americans, these associations were stronger among Puerto Rican children. Specifically, in Puerto Ricans, the odds was 6.15 (95% CI: 4.21-9.05) if the child reported at least one of the following respiratory illness: URI, pneumonia, bronchitis or bronchiolitis. The odds were also higher in Puerto Ricans when considering these conditions separately., Conclusions: We observed population-specific associations between early-life respiratory illnesses and asthma, which were especially significant and stronger in Puerto Ricans. Taken together with the known high burden of RSV in Puerto Rico, our results may help explain the high burden of asthma in Puerto Ricans., Competing Interests: The authors have declared that no competing interests exist.

Atherosclerosis is a progressive inflammation in systemic vessels, and pesticide exposure has been emerging as its risk factor. This cross-sectional study investigated the association between pesticide exposure and the risk of atherosclerosis in a rural population in Korea using carotid intima-media thickness (CIMT). This study used dataset from the baseline survey of the Korea Farmers Cohort Study between November 2005 and January 2008, and the final analysis included 477 participants. Well-structured questionnaires were used to estimate pesticide exposure. CIMT ≥ 0.9 mm was established for carotid atherosclerosis. Multiple logistic regression analyses were undertaken to evaluate the association between pesticide exposure and atherosclerosis, adjusting demographic and health-related confounders. Even after adjustments, the increased risk of atherosclerosis was significantly associated with pesticide exposure, such as a lifetime history of farming (odds ratio [OR] 3.25 95% confidence interval [CI] 1.51-6.98), a history of using pesticide (OR 3.42 95% CI 1.63-7.16), using pesticide 10 times or more annually (OR 2.55 95% CI 1.21-5.39), and higher cumulative exposure index level (OR 3.63 95% CI 1.65-7.97). Further prospective studies are required to elucidate effects of pesticide exposure on the risk of atherosclerosis., Competing Interests: The authors declare no conflict of interest.

Microbial production of many lipophilic compounds is often limited by product toxicity to host cells. Engineering cell walls can help mitigate the damage caused by lipophilic compounds by increasing tolerance to those compounds. To determine if the cell wall engineering would be effective in enhancing lipophilic compound production, we used a previously constructed squalene-overproducing yeast strain (SQ) that produces over 600 mg/L of squalene, a model membrane-damaging lipophilic compound. This SQ strain had significantly decreased membrane rigidity, leading to increased cell lysis during fermentation. The SQ strain was engineered to restore membrane rigidity by activating the cell wall integrity (CWI) pathway, thereby further enhancing its squalene production efficiency. Maintenance of CWI was associated with improved squalene production, as shown by cell wall remodeling through regulation of Ecm33, a key regulator of the CWI pathway. Deletion of ECM33 in the SQ strain helped restore membrane rigidity and improve stress tolerance. Moreover, ECM33 deletion suppressed cell lysis and increased squalene production by approximately 12% compared to that by the parent SQ strain. Thus, this study shows that engineering of the yeast cell wall is a promising strategy for enhancing the physiological functions of industrial strains for production of lipophilic compounds.

Extended-spectrum β-lactam antimicrobials have been broadly used in food animals and humans to control infectious diseases. However, the emergence and rapid spread of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, mainly Escherichia coli , have seriously threatened global health in recent decades. In this study, we determined the prevalence, antimicrobial susceptibility, and genetic properties of ESBL-producing E. coli (ESBL-EC) strains isolated from food animals in South Korea. A total of 150 fecal samples from healthy chickens ( n = 34), pigs ( n = 59), and cattle ( n = 57) were screened from January to July 2018. Among these, 77 non-duplicate cefotaxime-resistant ESBL-EC strains were isolated from 32 chicken, 41 pig, and 4 cattle samples, with the corresponding occurrence rates of 94.1, 69.5, and 7.0%, respectively. All the isolates showed multidrug resistance (MDR) and produced at least one type of β-lactamase, including CTX-M (98.7%) and TEM (40.3%). CTX-M-14 (53.1%), CTX-M-55 (53.7%), and CTX-M-65 (50.0%) were the predominant genotypes in the chicken, pig, and cattle samples, respectively. Multilocus sequence typing revealed 46 different sequence types (STs), including the human-associated extraintestinal pathogenic E. coli ST131 ( n = 2), ST10 ( n = 5), ST38 ( n = 1), ST410 ( n = 4), ST354 ( n = 2), ST58 ( n = 3), ST117 ( n = 1), and ST457 ( n = 1). To the best of our knowledge, this is the first report of pandemic E. coli ST131 in non-human isolates in South Korea. Our results demonstrate the high prevalence and diversity of MDR-ESBL-EC in food animals and highlight them as potential pathogenic ESBL-EC reservoirs that may pose a high risk to human health., (Copyright © 2020 Song, Oh, Kim, Park and Shin.)

The hypothesized central role of RNA in the origin of life suggests that RNA propagation predated the advent of complex protein enzymes. A critical step of RNA replication is the template-directed synthesis of a complementary strand. Two experimental approaches have been extensively explored in the pursuit of demonstrating protein-free RNA synthesis: template-directed nonenzymatic RNA polymerization using intrinsically reactive monomers and ribozyme-catalyzed polymerization using more stable substrates such as biological 5'-triphosphates. Despite significant progress in both approaches in recent years, the assembly and copying of functional RNA sequences under prebiotic conditions remains a challenge. Here, we explore an alternative approach to RNA-templated RNA copying that combines ribozyme catalysis with RNA substrates activated with a prebiotically plausible leaving group, 2-aminoimidazole (2AI). We applied in vitro selection to identify ligase ribozymes that catalyze phosphodiester bond formation between a template-bound primer and a phosphor-imidazolide-activated oligomer. Sequencing revealed the progressive enrichment of 10 abundant sequences from a random sequence pool. Ligase activity was detected in all 10 RNA sequences; all required activation of the ligator with 2AI and generated a 3'-5' phosphodiester bond. We propose that ribozyme catalysis of phosphodiester bond formation using intrinsically reactive RNA substrates, such as imidazolides, could have been an evolutionary step connecting purely nonenzymatic to ribozyme-catalyzed RNA template copying during the origin of life., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Tumor cell resistance to anti-cancer drugs is a major obstacle in tumor therapy. In this study, we investigated the mechanism of cordycepin-mediated resensitization to cisplatin in T24R2 cells, a T24-derived cell line. Treatment with cordycepin or cisplatin (2 μg/mL) alone failed to induce cell death in T24R2 cells, but combination treatment with these drugs significantly induced apoptosis through mitochondrial pathways, including depolarization of mitochondrial membranes, decrease in anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1, and increase in pro-apoptotic proteins Bak and Bax. High expression levels of MDR1 were the cause of cisplatin resistance in T24R2 cells, and cordycepin significantly reduced MDR1 expression through inhibition of MDR1 promoter activity. MDR1 promoter activity was dependent on transcription factor Ets-1 in T24R2 cells. Although correlation exists between MDR1 and Ets-1 expression in bladder cancer patients, active Ets-1, Thr38 phosphorylated form (pThr38), was critical to induce MDR1 expression. Cordycepin decreased pThr-38 Ets-1 levels and reduced MDR1 transcription, probably through its effects on PI3K signaling, inducing the resensitization of T24R2 cells to cisplatin. The results suggest that cordycepin effectively resensitizes cisplatin-resistant bladder cancer cells to cisplatin, thus serving as a potential strategy for treatment of cancer in patients with resistance to anti-cancer drugs.

Colistin is a last-resort antimicrobial against multidrug-resistant gram-negative bacteria. The occurrence and spread of colistin resistance in humans and animals have been reported globally. This study was performed to investigate the prevalence and antimicrobial susceptibility of mcr-harboring colistin-resistant Enterobacteriaceae from retail vegetables and food animals in South Korea in 2018. The mcr-1 gene was detected in Escherichia coli isolates from 0.076% (1/1324) of vegetables, 5.9% (2/34) of chickens, 6.8% (4/59) of pigs, and 0% (0/57) of cattle. Other mcr genes were not detected. All seven of the mcr-1-positive isolates showed multidrug resistance and co-produced β-lactamases. Multilocus sequence typing analysis revealed five known E. coli sequence types (STs), including ST10 in the vegetable sample. The study findings demonstrated that the mcr-1 gene has emerged in vegetables and is increasingly detected in food animals in South Korea, highlighting the importance of continuous monitoring and control of colistin-resistant Enterobacteriaceae to prevent them from being transmitted to humans., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Campus alcohol policy has been associated with student alcohol consumption in numerous studies. However, more information is required to assess the extent to which school policy affects student drinking behavior; especially when both individual-level sociodemographic characteristics of students and area-level characteristics of college campuses are controlled for. Thus, this paper explores the association between campus alcohol policy and student alcohol consumption among a nationally representative sample of college students in South Korea, while controlling for both individual and area-level characteristics., Methods: We surveyed and analyzed the data of 4592 students from 82 colleges. Multilevel (hierarchical) linear modeling was used to identify the association between campus alcohol policy and alcohol consumption levels, measured via the AUDIT-C (Alcohol Use Disorders Identification Test - Consumption). Controlled individual-level characteristics included sex, year level, major, GPA (grade point average), pocket money, smoking status, stress level, depressive thoughts, suicidal thoughts, and number of clubs/organizations. Controlled area-level characteristics included college type, number of students, number of faculty members, number of workers/administrators, and region., Results: Compared to students unaware of their school's campus alcohol policy, students who self-reported that their campuses allow drinking in outdoor spaces (β = 0.755 p = 0.010) or in all areas (β = 0.820, p = 0.044) had higher AUDIT-C scores. Students attending schools with a large number of students, males, freshmen, students with low GPA, students with high amounts of pocket money, and smokers also had higher alcohol consumption scores relative to their peers. Alcohol education experience in the form of lectures, mail, and/or campaigns were not associated with student alcohol consumption levels., Conclusion: Our results suggest an association between self-reported campus alcohol policy and student alcohol consumption. College educators and administrators must be aware that relative to students unaware of their school's campus alcohol policy, students at colleges that allow drinking in outdoor spaces or all areas consume higher amounts of alcohol than their peers; even when area-level factors are controlled for., Trial Registration: Yonsei IRB (IRB number: Y-2017-0084). https://irb.yonsei.ac.kr Date of registration: 01/2017. Date of enrolment of first participant to trial: 03/01/2017. Y-2017-0084.

Background: In cystic fibrosis (CF), the spectrum and frequency of CFTR variants differ by geography and race/ethnicity. CFTR variants in White patients are well-described compared with Latino patients. No studies of CFTR variants have been done in patients with CF in the Dominican Republic or Puerto Rico., Methods: CFTR was sequenced in 61 Dominican Republican patients and 21 Puerto Rican patients with CF and greater than ​​​​60 mmol/L sweat chloride. The spectrum of CFTR variants was identified and the proportion of patients with 0, 1, or 2 CFTR variants identified was determined. The functional effects of identified CFTR variants were investigated using clinical annotation databases and computational prediction tools., Results: Our study found 10% of Dominican patients had two CFTR variants identified compared with 81% of Puerto Rican patients. No CFTR variants were identified in 69% of Dominican patients and 10% of Puerto Rican patients. In Dominican patients, there were 19 identified CFTR variants, accounting for 25 out of 122 disease alleles (20%). In Puerto Rican patients, there were 16 identified CFTR variants, accounting for 36 out of 42 disease alleles (86%) in Puerto Rican patients. Thirty CFTR variants were identified overall. The most frequent variants for Dominican patients were p.Phe508del and p.Ala559Thr and for Puerto Rican patients were p.Phe508del, p.Arg1066Cys, p.Arg334Trp, and p.I507del., Conclusions: In this first description of the CFTR variants in patients with CF from the Dominican Republic and Puerto Rico, there was a low detection rate of two CFTR variants after full sequencing with the majority of patients from the Dominican Republic without identified variants., (© 2019 Wiley Periodicals, Inc.)

Background: Global gene expression levels are known to be highly dependent upon gross demographic features including age, yet identification of age-related genomic indicators has yet to be comprehensively undertaken in a disease and treatment-specific context., Methods: We used gene expression data from CD4+ lymphocytes in the Asthma BioRepository for Integrative Genomic Exploration (Asthma BRIDGE), an open-access collection of subjects participating in genetic studies of asthma with available gene expression data. Replication population participants were Puerto Rico islanders recruited as part of the ongoing Genes environments & Admixture in Latino Americans (GALA II), who provided nasal brushings for transcript sequencing. The main outcome measure was chronic asthma control as derived by questionnaires. Genomic associations were performed using regression of chronic asthma control score on gene expression with age in years as a covariate, including a multiplicative interaction term for gene expression times age., Results: The SMARCD1 gene (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1) interacted with age to influence chronic asthma control on inhaled corticosteroids, with a doubling of expression leading to an increase of 1.3 units of chronic asthma control per year (95% CI [0.86, 1.74], p = 6 × 10 - 9 ), suggesting worsening asthma control with increasing age. This result replicated in GALA II (p = 3.8 × 10 - 8 ). Cellular assays confirmed the role of SMARCD1 in glucocorticoid response in airway epithelial cells., Conclusion: Focusing on age-dependent factors may help identify novel indicators of asthma medication response. Age appears to modulate the effect of SMARCD1 on asthma control with inhaled corticosteroids.

Aim/background: This research aims to prevent progression from mild cognitive impairment (MCI) to Alzheimer's disease. A Japanese study of leprosy patients revealed that the incidence of dementia in leprosy patients was lower than that in patients taking dapsone who had never been treated. But a similar study the following year refuted the finding of less dementia in leprosy patients taking dapsone. According to conflicting reports, Mycobacterium leprae was a factor in reducing the incidence of Alzheimer's disease. Thus, we formed a hypothesis that if dapsone is administered to patients without leprosy but with MCI and the prophylactic effect of dementia syndrome is observed over a long period of time, we can determine whether dapsone can prevent the progression of MCI to dementia syndrome. If dementia does not occur after treating inflammation in brain cells while dementia develops after a certain long-term period (usually within 2-3 years), brain cell inflammation can be demonstrated as the cause of dementia., Methods: This is a prospective cohort research. We report on an elderly patient diagnosed with MCI from February 2008 to January 2019. The patient took dapsone 100 mg once a day from 2010 to 2015 for the treatment of MCI. Since 2016, the production of dapsone has ceased in Korea. In June 2018, the patient was diagnosed with Alzheimer's disease. The patient took Aricept for the treatment of Alzheimer's disease but complained of serious side effects. And dapsone was re-administered to the patient from November 2018., Results: The patient recovered to MCI and improved her daily life owing to the treatment with dapsone. The drug controls the inflammatory response in the brain, irrespective of whether proteins are deposited in neurons., Conclusions: This finding means that dementia syndrome is an inflammatory disease. This research suggests that diagnostic criteria for Alzheimer's disease should be based on the presence or absence of inflammation in neurons. Because inflammation in neurons can occur in middle age due to various causes, we can treat inflammation in neurons and prevent and treat dementia syndrome, including Alzheimer's disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that develops in the pleural and outer layer of tissues surrounding the lungs. MPM is primarily caused by occupational exposure to asbestos and results in a poor prognosis. Effective therapeutics as well as early diagnostics for the MPM are still lacking. To identify potential diagnostic biomarkers for MPM, we performed bioinformatics analysis of public database., Methods: Utilizing databases from Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO), we identified several potential candidates that could act as MPM biomarkers. We carried out additional molecular analyses of these potential markers using MPM patient tissue samples via quantitative polymerase chain reaction., Results: We identified Lysyl oxidase (LOX), Lysyl oxidase homologs 1&2 (LOXL1& LOXL2) Zinc Finger Protein, FOG Family Member 2 (ZFPM2) as potential diagnostic biomarkers for MPM. In this study, we found that the LOX family and ZFPM2 showed comparable diagnostic ability to Fibulin-3 or mesothelin (MSLN) and would be better potential biomarkers than Sulfatase 1 (SULF1), Thrombospondin 2 (THBS2) and Cadherin 11 (CDH11)., Conclusions: LOX family and ZPFM2 were identified as novel MPM diagnostic biomarkers which could strengthen MPM clinical diagnostic capabilities., Competing Interests: Competing interestThe authors have no conflict of interest., (© The Author(s). 2020.)

Background: Bronchoscopy for the diagnosis of peripheral pulmonary lesions continues to present clinical challenges, despite increasing experience using newer guided techniques. Robotic bronchoscopic platforms have been developed to potentially improve diagnostic yields. Previous studies in cadaver models have demonstrated increased reach into the lung periphery using robotic systems compared to similarly sized conventional bronchoscopes, although the clinical impact of additional reach is unclear., Objectives: This study was performed to evaluate the performance of a robotic bronchoscopic system's ability to reach and access artificial tumor targets simulating peripheral nodules in human cadaveric lungs., Methods: Artificial tumor targets sized 10-30 mm in axial diameter were implanted into 8 human cadavers. CT scans were performed prior to procedures and all cadavers were intubated and mechanically ventilated. Electromagnetic navigation, radial probe endobronchial ultrasound, and fluoroscopy were used for all procedures. Robotic-assisted bronchoscopy was performed on each cadaver by an individual bronchoscopist to localize and biopsy peripheral lesions., Results: Sixty-seven nodules were evaluated in 8 cadavers. The mean nodule size was 20.4 mm. The overall diagnostic yield was 65/67 (97%) and there was no statistical difference in diagnostic yield for lesions <20 mm compared with lesions measuring 21-30 mm, the presence of a concentric or eccentric radial ultrasound image, or relative distance from the pleura., Conclusions: The robotic bronchoscopic system was successful at biopsying 97% of peripheral pulmonary lesions 10-30 mm in size in human cadavers. These findings support further exploration of this technology in prospective clinical trials in live human subjects., (© 2019 S. Karger AG, Basel.)

Firefighters have a high risk of developing cardiovascular and mental disorders due to their physical and chemical environments. However, in Korea, few studies have been conducted on environmental risk of firefighters. The Firefighter Research on the Enhancement of Safety and Health (FRESH) study aimed to discover the risk factors for cardiovascular disease and mental disorders among firefighters. Former and current firefighters were recruited from three university hospitals. A total of 1022 participants completed baseline health examinations from 2016 to 2017. All participants were scheduled for follow-ups every 2 years. Baseline health survey, laboratory testing of blood and urine samples, blood heavy metal concentration, urine polycyclic aromatic hydrocarbons (PAHs) metabolites, stress-related hormone test, natural killer cell activity, as well as physical and mental health examinations that focused on cardiovascular and mental disorders, were conducted. In addition, 3 Tesla (3T) brain magnetic resonance imaging (MRI) and neuropsychological tests were also performed to investigate structural and functional changes in the brains of 352 firefighters aged >40 years or new hires with less than 1 year of service., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

Background/Aim: Given a fast-growing aging population in South Korea, the prevalence of cognitive impairment in elderly is increasing. Despite growing evidence of air pollution exposure as one of the risk factors for declining cognition, few studies have been conducted on gender difference in the relation of cognitive function associated with outdoor air pollution. The aim of this study is to investigate the effect modification of gender difference in the association between cognitive function and air pollutant exposure (PM 10 , PM 2.5-10 , and NO 2 ). Methods: The study focused on elderly, and the resulting sample included 1,484 participants aged 55 and older with no neurologic diseases, recruited from the four regions in Korea (Seoul, Incheon, Pyeongchang, and Wonju). We used the Mini-Mental State Examination (MMSE) score (with the conventional cut-off point "23-24") to assess cognitive decline as the primary outcome of the study. Air pollution data used in this study were based on the 5-year average of predicted PM 10 and NO 2 concentrations, as well as the 2015 average PM 2.5 concentration. Additionally, a survey questionnaire was utilized to obtain information about general health assessment. To explore gender differences in the effects of air pollution exposure on cognitive function, we used penalized logistic regression, negative binomial regression, and generalized linear mixed model analyses. Subgroup analyses were also performed by the geographic location of residence (metropolitan vs. non-metropolitan). Results: We found that women than men had a higher risk for decreased cognitive function associated with increased exposure to PM 10 and PM 2.5-10 , respectively, even after adjustments for confounding factors (OR 1.01 [95%CI 1.00-1.03] in PM 10 ; OR 1.03 [95%CI 1.01-1.07] in PM 2.5-10 ). After stratification by metropolitan status, we also found that the adverse effect of NO 2 exposure on cognitive function was higher in women than men [OR 1.02 [95%CI 1.00-1.05] in metropolitan; OR 1.12 [95%CI 1.04-1.20] in non-metropolitan]. Notably, the magnitude of the effect sizes was greater among those in non-metropolitan regions than metropolitan ones. Conclusions: Although our findings suggest that the adverse effects of outdoor air pollution on cognitive function appeared to be higher in women than men, this should be tentatively reflected due to some limitations in our results. While additional research is warranted to confirm or dispute our results, our findings suggest an indication of the need for developing and implementing prevention or interventions with a focus on elderly women with increased risk for air pollution exposure., (Copyright © 2019 Kim, Noh, Noh, Oh, Koh and Kim.)

Several studies have shown that the airways of asthma patients contain higher diversity of bacteria and are enriched in pathogenic species. However, sampling the airways in children is challenging. Here we aimed to identify differences in the salivary bacterial composition between African Americans children with and without asthma. Saliva samples from 57 asthma cases and 57 healthy controls were analyzed by means of 16S ribosomal RNA amplicon profiling. Measurements of bacterial diversity and genus relative abundance were compared between cases and controls using the nonparametric Wilcoxon test and multivariate regression models. A total of five phyla and a mean of 56 genera were identified. Among them, 15 genera had a relative abundance greater than 1%, being Prevotella, Haemophilus, Streptococcus, and Veillonella the most abundant genera. Differences between cases and controls were found in terms of diversity, as well as in relative abundance for Streptococcus genus (13.0% in cases vs 18.3% in controls; P = .003) and Veillonella genus (11.1% in cases vs 8.0% in controls; P = .002). These differences remained significant after correction for multiple comparisons and when potential confounders were taken into account in logistic regression models. In conclusion, we identified changes in the salivary microbiota associated with asthma among African Americans., (© 2019 Wiley Periodicals, Inc.)

Ribozymes are functional RNA molecules that can catalyze biochemical reactions. Since the discovery of the first catalytic RNA, various functional ribozymes (e.g., self-cleaving ribozymes, splicing ribozymes, RNase P, etc.) have been uncovered, and their structures and mechanisms have been identified. Ribozymes have the advantage of possessing features of "RNA" molecules; hence, they are highly applicable for manipulating various biological systems. To fully employ ribozymes in a broad range of biological applications in synthetic biology, a variety of ribozymes have been developed and engineered. Here, we summarize the main features of ribozymes and the methods used for engineering their functions. We also describe the past and recent efforts towards exploiting ribozymes for effective and novel applications in synthetic biology. Based on studies on their significance in biological applications till date, ribozymes are expected to advance technologies in artificial biological systems., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In this study, we looked into the association between the diagnosis of metabolic syndrome (MetS) and nutritional label awareness. This study used data from the Korea National Health and Nutritional Examination Survey (KNHANES) for the years 2007 to 2015. The study population consisted of a total of 41,667 Koreans of which 11,401 (27.4%) were diagnosed with metabolic syndrome and 30,266 (72.6%) were not. Groups not using nutritional labeling had a 24% increase in odds risk (OR: 1.24, 95% CI 1.14-1.35) of MetS compared to groups using nutritional labeling. Use of nutritional labeling was associated with all components of MetS. Central obesity showed the highest increase in odds risk (OR: 1.23, 95% CI 1.13-1.35) and high blood pressure showed the lowest increase in odds risk (OR: 1.11, 95% CI 1.02-1.20). Subgroup analysis revealed that statistically significant factors were smoking status, drinking status and stress status. Groups that smoke, groups that do not drink and groups with high stress were more vulnerable to MetS when not using nutritional labeling. People not using food labels tends to develop metabolic syndromes more than people using foods labels. In the subgroup analysis, drinking status, smoking status and stress status were significant factors.

The purpose of this study was to examine the association between the different types of treatment for diabetes and depressive symptoms. In particular, this study assessed the presence of depressive symptoms in patients with diabetes who are undergoing pharmacological treatments in terms of sex. This study used data from the 2011-2016 Korea Community Health Survey, which included responses from 50,774 male and 48,978 female participants with diabetes who were receiving pharmacological treatments. Patients aged ≥30 years were included. Logistic regression analysis was conducted to examine the significance of the association. Male participants treated with insulin injection were more likely to experience depressive symptoms than those taking oral hypoglycemic (oral agents) only (odds ratio (OR) = 1.27; 95% confidence interval (CI): 1.04-1.56). Male patients treated with both oral agents and insulin injection had the highest OR value of depressive symptoms among different types of treatments (OR = 1.41, 95% CI: 1.25-1.60). The same tendency was observed in female participants. In female patients, however, the association between depressive symptoms and insulin injection was statistically insignificant (both oral agents and insulin injection OR = 1.35, 95% CI: 1.22-1.50, insulin injection OR = 1.17, 95% CI: 0.98-1.41). The association between depressive symptoms and the type of diabetes treatment was more significant in male than in female patients. Those who were treated with oral agents and insulin injection were more likely to have depressive symptoms than those receiving oral agents of treatment., Competing Interests: The authors declare that there is no conflict of interest.

American Thoracic Society guidelines recommend inhaled corticosteroid (ICS) therapy, plus a short-acting bronchodilator, in patients with persistent asthma. However, few prior studies have examined the efficacy of this combination in children of all racial/ethnic groups. We evaluated the association between ICS use and bronchodilator response (BDR) in three pediatric populations with persistent asthma (656 African American, 916 Puerto Rican, and 398 Mexican American children). The association was assessed using multivariable quantile regression. After adjusting for baseline forced expiratory volume in one second and use of controller medications, ICS use was significantly associated with increased BDR only among Mexican Americans (1.56%, P = 0.028) but not African Americans (0.49%, P = 0.426) or Puerto Ricans (0.16%, P = 0.813). Our results demonstrate that ICS augmentation is disproportionate across racial/ethnic groups, where improved BDR is observed in Mexican Americans only. This study highlights the complexities of treating asthma in children, and reinforces the importance of investigating the influence of race/ethnicity on pharmacological response., (© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)

Despite considerable interest in the development of biosensors that can measure analyte concentrations with a dynamic range spanning many orders of magnitude, this goal has proven difficult to achieve. We describe here a modular biosensor architecture that integrates two different readout mechanisms into a single-molecule construct that can achieve target detection across an extraordinarily broad dynamic range. Our dual-mode readout DNA biosensor combines an aptamer and a DNAzyme to quantify adenosine triphosphate (ATP) with two different mechanisms, which respond to low (micromolar) and high (millimolar) concentrations by generating distinct readouts based on changes in fluorescence and absorbance, respectively. Importantly, we have also devised regulatory strategies to fine-tune the target detection range of each sensor module by controlling the target-sensitivity of each readout mechanism. Using this strategy, we report the detection of ATP at a dynamic range spanning 1-500 000 μM, more than 5 orders of magnitude, representing the largest dynamic range reported to date with a single biosensor construct.

Background: Despite the fact that solitary drinking is becoming more common in Korea, few studies have investigated the association between drinking alone and mental health. This study aimed to investigate the relationship between solitary drinking, depressive symptoms, and suicidal ideation in Korean college students., Method: Primary data on a nationally representative sample of college students were used. Data were collected by Yonsei University and the Korean Center for Disease Control in 2017 to investigate alcohol-related behaviors and health consequences in students. The association between solitary drinking, depressive symptoms, and suicidal ideation were measured using multivariate logistic regression analysis., Results: A total of 3,935 students were analyzed, in which 11.5% had depressive symptoms and 2.8% suicidal ideation. Compared to non-solitary drinkers, solitary drinkers were more likely to have depressive symptoms [Odds Ratio (OR) 2.28, 95% Confidence Interval (95% CI) 1.72-3.02] and suicidal ideation (OR 2.24, 95% CI 1.32-3.81). Moreover, larger differences were found in individuals with higher alcohol use disorders identification test (AUDIT) scores and with more frequent underage drinking experience., Limitations: As this study was cross-sectional in design, causal inferences cannot be made on the association between solitary drinking, depressive symptoms, and suicidal ideation., Conclusion: Solitary drinking is associated with higher likelihoods of depressive symptoms and suicidal ideation in college students. The results suggest the importance of monitoring solitary drinkers as they may be more vulnerable to the negative mental health effects of alcohol., (Copyright © 2019. Published by Elsevier B.V.)

Background: Telomere length (TL) can serve as a potential biomarker for conditions associated with chronic oxidative stress and inflammation, such as asthma. Air pollution can induce oxidative stress. Understanding the relationship between TL, asthma, and air pollution is important for identifying risk factors contributing to unhealthy aging in children., Objectives: We sought to investigate associations between exposures to ambient air pollutants and TL in African American children and adolescents and to examine whether African ancestry, asthma status, and steroid medication use alter the association., Methods: Linear regression was used to examine associations between absolute telomere length (aTL) and estimated annual average residential ozone (O 3 ) and fine particulate matter with a diameter of 2.5 μm or less (PM 2.5 ) exposures in a cross-sectional analysis of 1072 children in an existing asthma case-control study. African ancestry, asthma status, and use of steroid medications were examined as effect modifiers., Results: Participants' aTLs were measured by using quantitative PCR. A 1-ppb and 1 μg/m 3 increase in annual average exposure to O 3 and PM 2.5 were associated with a decrease in aTL of 37.1 kilo-base pair (kb; 95% CI, -66.7 to -7.4 kb) and 57.1 kb (95% CI, -118.1 to 3.9 kb), respectively. African ancestry and asthma were not effect modifiers; however, exposure to steroid medications modified the relationships between TL and pollutants. Past-year exposure to O 3 and PM 2.5 was associated with shorter TLs in patients without steroid use., Conclusion: Exposure to air pollution was associated with shorter TLs in nonasthmatic children and adolescents. This was not the case for asthmatic children as a group, but those receiving steroid medication had less shortening than those not using steroids. Reduced exposure to air pollution in childhood might help to preserve TL., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Severe fever with thrombocytopenia syndrome virus (SFTSV) is tick-borne and causes this disease (SFTS) in humans. We determined the complete genome sequences of two SFTSV strains isolated from serum from a human with SFTS and a dog with asymptomatic infection using reverse transcription and rapid amplification of cDNA ends PCR., (Copyright © 2019 Lee et al.)

Background: Shift work has well-known adverse effects on health. However, few studies have investigated the relationship between shift work and hepatic disorders. This study aimed to evaluate the association between shift work and abnormal level of liver enzymes., Methods: The aggregated data from the 2007-2009, 2010-2012, and 2013-2015 cycles of the Korea National Health and Nutrition Examination Survey was used for this study. The χ 2 test and multiple logistic regression analysis were used to assess relationship between shift work and abnormal level of liver enzymes stratified by gender., Results: The odds ratio (OR) of abnormal serum level of alanine aminotransferase (abnormal ALT) in female shift workers was higher with 1.31 (95% confidence interval: 1.00-1.71) compared with day workers after adjusting for covariates. After dividing into subgroups of the shift work pattern, the ORs of abnormal liver enzymes for each pattern compared with day work were not significantly higher., Conclusions: This study provides limited support for the hypothesis that shift work is related to liver enzyme abnormalities, but offers some evidence in favor of the idea that shift work affects female workers more than males on abnormal ALT. Further studies are needed to define the relationship between shift work and abnormal liver enzymes to be carried out as well as the gender difference in the association., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2019 Korean Society of Occupational & Environmental Medicine.)

Introduction : This study aims to investigate the association between gender discrimination in the workplace and pregnancy planning/childbirth experiences among working women in South Korea. Methods : We analyzed data from the Korean Longitudinal Survey of Women and Families (KLoWF) for the years 2007 to 2016. The study population consisted of 7996 working women, between the ages of 19 and 45. Gender discrimination was measured through the 6-item Workplace Gender Discrimination Scale, evaluating discrimination in terms of recruitment, promotions, pay, deployment, training and lay-offs. Multiple logistic regression analysis was employed to measure the association between gender discrimination and the pregnancy planning/childbirth experience. Results : Compared to individuals experiencing no discrimination in the workplace, those experiencing low [odds ratio (OR): 0.78, 95% confidence interval (95% CI) 0.61-0.99] or medium (OR: 0.69, 95% CI: 0.54-0.89) levels of discrimination had decreased odds of pregnancy planning. Likewise, individuals scoring low (OR: 0.70, 95% CI 0.54-0.92), medium (OR: 0.68, 95% CI: 0.51-0.92), or high (OR: 0.47, 95% CI: 0.27-0.80) levels of discrimination also had decreased odds of childbirth experience when compared to the no-experience group. When stratified by income, compared to individuals experiencing no discrimination in the workplace, those experiencing gender discrimination had decreased odds of pregnancy planning for low income (low OR: 0.64, 95% CI: 0.45-0.92; medium OR: 0.55, 95% CI: 0.52-0.97; high OR: 0.45, 95% CI: 0.24-0.87), medium income (medium OR: 0.53, 95% CI: 0.37-0.77; high OR: 0.29, 95% CI: 0.14-0.63), and high income groups (low OR: 0.64, 95% CI: 0.49-0.84; medium OR: 0.69, 95% CI: 0.52-0.92). Conclusions : The present study finds that gender discrimination in the workplace is associated with decreased odds of pregnancy planning/childbirth experience among working South Korean women. Furthermore, low and medium income groups were especially more likely to be affected by the level of gender discrimination in the workplace when planning pregnancy.

Objective: To investigate changes in the incomes of workers, particularly those in the construction sector, who experienced industrial accidents according to their status of return to work. Methods: We used data from the fifth Panel Study of Workers' Compensation Insurance. A repeated measures ANOVA was used to compare annual differential incomes before and after the industrial accident, and a linear mixed model was used to investigate the changes in income from before to after the industrial accident according to the industry and return-to-work status. Results: A comparison of the industrial categories revealed that construction industry workers exhibited the greatest incomes before the accident and the greatest decrease in income after the industrial accident. Regression analysis for assessing changes in income after the industrial accident showed that a comparison by industry revealed a significantly greater reduction in income in the construction than service industry. A comparison by work status revealed significantly greater decreases in income in the reemployment and non-return to work groups than among those who returned to their original work. Conclusions: The economic statuses of the victims of industrial accidents decreased relative to the pre-accident statuses in all industries. The ability to return to original work is important for preserving the accident victim's economic status.

Fluorescence of DNA-templated copper nanoparticles (DNA-CuNPs) is not stable over time which limits applications in cellular imaging. This is due to the presence of oxygen during synthesis which oxidizes Cu(0) to Cu(II) and also produces the free hydroxyl radical. The authors have prepared DNA-CuNPs with enhanced temporal stability of fluorescence by optimizing the reaction conditions so as to minimize the deleterious effects of oxygen. The operational lifetime of DNA-CuNPs was increased from 25 min to 200 min. Fluorescence spectra of DNA-CuNPs in optimized condition show an emission peak at 650 nm when excited at 340 nm. DNA-CuNPs synthesized in this manner were used for cell imaging. As a proof of concept, the nucleus of a human colon cell line (HCT116) was stained. The method does not involve any chemicals other that copper sulfate and ascorbate. This new approach for generating DNA-CuNPs improves imaging of biological processes and provides a basis for developing other types of DNA-templated nanomaterials. Graphical abstract Schematic presentation of the formation of fluorescent DNA-templated copper nanoparticles (DNA-CuNPs). A large amount of ascorbate provides long operational lifetime for cellular imaging under the condition exposed to oxygen. *Asc - and **DHA stand for ascorbate and dehydroascorbic acid.

Background: Maternal smoking during pregnancy is a risk factor for chronic disease later in life and has been associated with variability of DNA methylation at specific cytosine-phosphate-guanine (CpG) loci. We assessed the role of DNA methylation as a potential mediator of adverse effects of in utero tobacco smoke exposures on asthma outcomes in Latino children from the US mainland and Puerto Rico., Methods: Relationships between self-reported exposure and DNA methylation at CpG loci previously reported to be associated with maternal smoking were assessed in a subsample consisting of 572 children aged 8-21 years (310 cases with asthma, 262 healthy controls), sampled from a larger asthma case-control study. Subsequently, we assessed associations between top loci and asthma-related outcomes, followed by mediation analysis for loci for which associations with outcomes were observed., Results: Self-reported maternal smoking was associated with a -1.5% (95% confidence interval (CI) = -2.4%, -0.6%) lower methylation at CpG locus cg05575921 on the AHRR gene; a 1% increase in DNA methylation at the same locus resulted in an odds ratio (OR) of 0.90 (95% CI = 0.83, 0.96) for the odds of asthma. The OR for the indirect effect of maternal smoking on asthma mediated through methylation at the cg05575921 locus was 1.18 (95% CI = 1.07, 1.68), compared to the OR for the total effect of exposure in the parent study of 1.48 (95% CI = 1.03, 2.11)., Conclusions: Our findings suggest potential mediation by DNA methylation in the association between maternal smoking during pregnancy and asthma status., Competing Interests: Sponsorships or competing interests that may be relevant to content are disclosed at the end of the article.

Short-acting β 2 -adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African-American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used linear regression models adjusting for age, sex, body mass index (BMI) and genetic ancestry to test for an association between BDR and genotype at single-nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1830 Latinos (total = 2779). Finally, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. We identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p = 7.69 × 10 -9 ). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p ≤ 5 × 10 -8 ). Our results failed to replicate in three additional populations of 416 Latinos and 1615 African Americans. Our findings indicate that both population-specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.

: This cross-sectional study investigated the association between long working hours and prevalence of poor self-rated health (SRH) in Korean young workers using data from the 6th Korea Youth Panel Survey 2007. A total of 3317 young wage workers were included. Weekly working hours were divided into four groups (36 to 40 hours, 41 to 52 hours, 53 to 60 hours, and more than 60 hours per week). Multiple logistic regression was performed to investigate the association between long working hours and SRH, adjusting for demographic and work-related factors. Long working hours were associated with increased risk of poor SRH, in both the men and women. Legal restriction on working hours should be suitably applied to help improve the health status of Korean young workers.

Background: Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome-wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response., Objective: We aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings., Methods: A meta-analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10 -6 were followed up for replication in 1697 asthmatic patients from six European studies. Associations of ICS response described in published GWAS were followed up for replication in the admixed populations., Results: A total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10 -6 ). One of them, located in the intergenic region of APOBEC3B and APOBEC3C, showed evidence of replication in Europeans (rs5995653, P = 7.52 × 10 -3 ) and was also associated with change in lung function after treatment with ICS (P = 4.91 × 10 -3 ). Additionally, the reported association of the L3MBTL4-ARHGAP28 genomic region was confirmed in admixed populations, although a different variant was identified., Conclusions and Clinical Relevance: This study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment., (© 2019 John Wiley & Sons Ltd.)

Background: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis., Objective: We sought to identify differential DNA methylation in newborns and children related to childhood asthma., Methods: Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions., Results: In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2., Conclusion: Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium., (Published by Elsevier Inc.)

N-Myc downstream-regulated gene 2 (NDRG2) was characterized as a tumor suppressor, inducing anti-metastatic and anti-proliferative effects in several tumor cells. However, NDRG2 functions on anticancer drug sensitivity, and its molecular mechanisms are yet to be fully investigated. In this study, we investigated the mechanism of NDRG2-induced sensitization to As 2 O 3 in the U937 cell line, which is one of the most frequently used cells in the field of resistance to As 2 O 3 . NDRG2-overexpressing U937 cells (U937-NDRG2) showed a higher sensitivity to As 2 O 3 than mock control U937 cell (U937-Mock). The higher sensitivity to As 2 O 3 in U937-NDRG2 was associated with Mcl-1 degradation through glycogen synthase kinase 3β (GSK3β) activation. Inhibitory phosphorylation of GSK3β was significantly reduced in U937-NDRG2, and the reduction was diminished by okadaic acid, a protein phosphatase inhibitor. NDRG2 mediated the interaction between GSK3β and protein phosphatase 2A (PP2A), inducing dephosphorylation of GSK3β at S9 by PP2A. Although the C-terminal deletion mutant of NDRG2 (ΔC NDRG2), which could not interact with PP2A, interacted with GSK3β, the mutant failed to dephosphorylate GSK3β at S9 and increased sensitivity to As 2 O 3 . Our findings suggest that NDRG2 is a kind of adaptor protein mediating the interaction between GSK3β and PP2A, inducing GSK3β activation through dephosphorylation at S9 by PP2A, which increases sensitivity to As 2 O 3 in U937 cells.

Background: Acculturation is an important predictor of asthma in Latino youth, specifically Mexican Americans. Less is known about acculturation and pulmonary function measures., Objective: We sought to estimate the association of acculturation measures with asthma and pulmonary function in Latino youth and determine whether this association varies across Latino subgroups., Methods: We included 1849 Latinos (302 Caribbean Spanish, 193 Central or South Americans, 1136 Mexican Americans, and 218 other Latino children) aged 8 to 21 years from 4 urban regions in the United States. Acculturation measures include nativity status, age of immigration, language of preference, and generation in the United States. We used multivariable logistic and linear regression models to quantify the association of acculturation factors with the presence of asthma (case-control study) and pulmonary function (case-only study), adjusting for demographic, socioenvironmental, and clinical variables., Results: For all acculturation measures (nativity status, age of immigration, language of preference, and generation in the United States), greater levels of acculturation were associated with greater odds of asthma. Among cases, high (English preference) and medium (equal preference for Spanish and English) levels of language acculturation were associated with decreased bronchodilator response compared with low (Spanish preference) levels (P = .009 and .02, respectively). Similarly, high language acculturation was associated with increased FEV 1 compared with low language acculturation (P = .02). There was insufficient evidence of heterogeneity for associations across Latino subgroups., Conclusions: Acculturation was associated with diagnosed asthma and pulmonary function in Latino children and is an important factor to consider in the management of Latino youth with asthma., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Intimate partner violence (IPV) is a serious social problem that is often hidden, unnoticed or ignored. However, few studies have explored the effects of partner violence onset and/or persistence on the mental health of individuals. Thus, we aimed to investigate the association between IPV onset and depressive symptoms in both married men and women., Methods: In this study, nationally representative data from the Korea Welfare Panel Study were employed to track 1040 men and 3732 women for a period of six years (2010-2015). Depressive symptoms were scored according to the 11-item Center for Epidemiologic Studies Depression Scale (CES-D-11)., Results: Of our study population, 415 men (39.9%) and 866 women (23.2%) suffered from continuous intimate partner violence, meaning that they reported experience of IPV in both the previous and current year of investigation. Such subjects had significantly higher CES-D-11 scores (men β: 1.745, p ≤  0001; women β: 1.970, p  ≤  0001) as did subjects whose partners turned violent from non-violent (men β: 1.623, p  ≤  0001; women β: 1.594, p  ≤  0001) than those with continuously non-violent partners (reference group). Subjects whose partners turned non-violent from violent continued to be more depressed (men β: 0.312, p  ≤  009; women β: 0.880, p  ≤  000) than those with continuously non-violent partners. Through subgroup analysis, we also found that lower SES, as a covariate relative to educational attainment, household income, and economic status, was associated with worsened depression following IPV onset. Unemployed women with consistently violent partners (β: 2.957, p  ≤ .0001) and unemployed men with newly violent partners (β: 3.010, p  ≤ .0001) were more depressed than the employed or self-employed., Conclusion: Our findings reveal that continuous IPV, as well as its onset, can have serious consequences for the mental health of its victims., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Overt and subclinical thyroid dysfunction has been reported to be related to depression. Thyroid diseases have been known to occur more frequently in women. However, scarce data are available on effects and sex differences of changes in thyroid-stimulating hormone (TSH) levels, with a normal range of thyroid hormones, on depression. This study aimed to investigate the association between TSH levels and depressive symptoms, according to sex, in individuals from the general population with free thyroxine (fT4) values within the normal range., Methods: Data from the 2014 Korea National Health and Nutritional Examination Survey were used for this study. The study population of 1651 Korean adults was categorized by tertiles of TSH levels. The presence of depressive symptoms was determined using a cut-off score of 5 in the Patient Health Questionnaire-9., Results: The highest TSH tertile group was 1.92 times more likely to have depressive symptoms in men after adjustment for covariates than the lowest TSH tertile (adjusted odds ratio: 1.92, 95% confidence interval: 1.11-3.31, P = 0.019). Contrastingly, the highest TSH tertile was associated with an approximately 35% lower prevalence of depressive symptoms in women (adjusted odds ratio: 0.65, 95% confidence interval: 0.43-0.97, P = 0.034)., Limitations: Cross-sectional design and unrecognized confounding factors, are the main limitations of our study., Conclusions: Sex may play a substantial role in the relationship between TSH and depressive symptoms. Sex differences might be associated with differences in thyroid response, TSH blunting, thyroid autoimmunity, and sex hormone levels., (Copyright © 2019 Elsevier B.V. All rights reserved.)