Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Objective: Doctors or public health doctors at the nearest institution to a disaster scene often have to treat the casualties at the scene. Therefore, disaster medical education is necessary for medical students and doctors, but such education is not properly implemented. This study investigated the status of disaster medical education in Korean medical schools and the professors' thoughts on the appropriateness and necessity of disaster medical education. Methods: A survey was conducted on working-level professors in charge of student education in emergency medicine in 40 medical schools. The survey asked the professors the current status of disaster medical education at each school and the professors' thoughts on the appropriateness and necessity of disaster medical education. Results: Thirty-seven professors (92.5%) responded to the survey. Twenty-seven schools (73.0%) had a regular curriculum of disaster medicine. Disaster drills were conducted at 34 training hospitals (91.9%), while students of 10 schools (29.4%) were officially participating in the drill. Of the responders, 31 (83.8%) responded that disaster medicine is necessary for clinicians. Thirty-seven professors (100%) thought disaster medical education was necessary for medical students, and 20 (54.1%) of them responded that their schools did not provide adequate disaster medical education. Conclusion Many schools did not have a proper course on disaster medical education. Disaster medical education is necessary for medical students, but such education is not properly implemented.

Objective: Doctors or public health doctors at the nearest institution to a disaster scene often have to treat the casualties at the scene. Therefore, disaster medical education is necessary for medical students and doctors, but such education is not properly implemented. This study investigated the status of disaster medical education in Korean medical schools and the professors' thoughts on the appropriateness and necessity of disaster medical education. Methods: A survey was conducted on working-level professors in charge of student education in emergency medicine in 40 medical schools. The survey asked the professors the current status of disaster medical education at each school and the professors' thoughts on the appropriateness and necessity of disaster medical education. Results: Thirty-seven professors (92.5%) responded to the survey. Twenty-seven schools (73.0%) had a regular curriculum of disaster medicine. Disaster drills were conducted at 34 training hospitals (91.9%), while students of 10 schools (29.4%) were officially participating in the drill. Of the responders, 31 (83.8%) responded that disaster medicine is necessary for clinicians. Thirty-seven professors (100%) thought disaster medical education was necessary for medical students, and 20 (54.1%) of them responded that their schools did not provide adequate disaster medical education. Conclusion Many schools did not have a proper course on disaster medical education. Disaster medical education is necessary for medical students, but such education is not properly implemented.

In the brain, a reduction in extracellular osmolality causes water-influx and swelling, which subsequently triggers Cl⁻- and osmolytes-efflux via volume-regulated anion channel (VRAC). Although LRRC8 family has been recently proposed as the pore-forming VRAC which is activated by low cytoplasmic ionic strength but not by swelling, the molecular identity of the pore-forming swelling-dependent VRAC (VRAC(swell)) remains unclear. Here we identify and characterize Tweety-homologs (TTYH1, TTYH2, TTYH3) as the major VRAC(swell) in astrocytes. Gene-silencing of all Ttyh1/2/3 eliminated hypo-osmotic-solution-induced Cl⁻ conductance (I(Cl,swell)) in cultured and hippocampal astrocytes. When heterologously expressed in HEK293T or CHO-K1 cells, each TTYH isoform showed a significant I(Cl,swell) with similar aquaporin-4 dependency, pharmacological properties and glutamate permeability as I(Cl,swell) observed in native astrocytes. Mutagenesis-based structure-activity analysis revealed that positively charged arginine residue at 165 in TTYH1 and 164 in TTYH2 is critical for the formation of the channel-pore. Our results demonstrate that TTYH family confers the bona fide VRAC(swell) in the brain.
Arginine ; Astrocytes ; Brain ; Cytoplasm ; Glutamic Acid ; Humans ; Osmolar Concentration ; Permeability

BACKGROUND: Periodic revision of assessment tools is essential to ensure risk assessment reliability and validity. Despite the recent revision of the Korea Occupational Safety and Health Agency (KOSHA) 2018, there is no evidence showing that the revision is superior to other cardio-cerebrovascular diseases (CVDs) risk-assessment tools for workplace health management. We conducted a comparative analysis using the Framingham risk score (FRS) as a gold standard to identify the most relevant CVDs risk-assessment tool for workplace health management. METHODS: We included 4,460 shipyard workers who had undergone a workers' health examination during January–December 2016. Risk levels for CVDs were calculated based on the FRS, KOSHA 2013, KOSHA 2017, KOSHA 2018 (2 methods), National Health Screening Program health risk appraisal (NHS HRA) 2017, and NHS HRA 2018. Study participants were categorized into low-risk, moderate-risk, or high-risk groups. Sensitivity, specificity, correlation, and agreement of each risk-assessment tool were calculated compared with the FRS as a gold standard. For statistical analyses, Spearman's rank correlation coefficient and the linearly weighted kappa coefficient were calculated. RESULTS: Sensitivity of the risk assessments was highest in the KOSHA 2018 (health risk appraisal [HRA]). The FRS showed correlation coefficients of 0.354 with the KOSHA 2013, 0.396 with the KOSHA 2017, 0.386 with the KOSHA 2018, 0.505 with the KOSHA 2018 (HRA), 0.288 with the NHS HRA 2017, and 0.622 with the NHS HRA 2018. Kappa values, calculated to examine the agreement in relation to the KOSHA 2013, KOSHA 2017, KOSHA 2018, KOSHA 2018 (HRA), NHS HRA 2017, and NHS HRA 2018 with the FRS, were 0.268, 0.322, 0.352, 0.136, 0.221, and 0.559, respectively. CONCLUSIONS: The NHS HRA 2018 risk calculation method is a useful risk-assessment tool for CVDs, but only when appropriate classification criteria are applied. In order to enhance the risk-group identification capability of the KOSHA guideline, we propose to apply the classification criteria set in this study based on the risk group definition of the 2018 Korean Society of Hypertension guidelines for the management of hypertension instead of the current classification criteria of the KOSHA 2018.
Classification ; Cross-Sectional Studies ; Health Status Indicators ; Humans ; Hypertension ; Korea ; Male ; Mass Screening ; Methods ; Occupational Health ; Reproducibility of Results ; Risk Assessment ; Sensitivity and Specificity

Aldose reductase (AR) protein, a member of the NADPH-dependent aldo-keto reductase family, reduces a wide range of aldehydes and enhances cell survival by inhibition of oxidative stress. Oxidative stress is known as one of the major pathological factor in ischemia. Since the precise function of AR protein in ischemic injury is fully unclear, we examined the function of AR protein in hippocampal neuronal (HT-22) cells and in an animal model of ischemia in this study. Cell permeable Tat-AR protein was produced by fusion of protein transduction domain in Tat for delivery into the cells. Tat-AR protein transduced into HT-22 cells and significantly inhibited cell death and regulated the mitogen-activate protein kinases (MAPKs), Bcl-2, Bax, and Caspase-3 under oxidative stress condition. In an ischemic animal model, Tat-AR protein transduced into the brain tissues through the blood-brain barrier (BBB) and drastically decreased neuronal cell death in hippocampal CA1 region. These results indicate that transduced Tat-AR protein has protective effects against oxidative stress-induced neuronal cell death in vitro and in vivo, suggesting that Tat-AR protein could be used as potential therapeutic agent in ischemic injury.
Aldehyde Reductase ; Aldehydes ; Blood-Brain Barrier ; Brain ; CA1 Region, Hippocampal ; Caspase 3 ; Cell Death ; Cell Survival ; Humans ; In Vitro Techniques ; Ischemia ; Models, Animal ; Neurons ; Oxidative Stress ; Oxidoreductases ; Protein Kinases

BACKGROUND: Since the 1980s, restructuring, which includes downsizing, closures, mergers, and privatization, has expanded worldwide, and various studies have investigated its effect on health. However, previous studies have mainly focused on restructuring accompanied by massive lay-offs, and the effect of a merger on workers’ health is still controversial. This study aims to investigate changes in worker depression and job stress after a merger without downsizing, which is unusual in Korea. METHODS: Repeated surveys were done in April 2014, April 2015, and April 2016 involving the participation of 209 subjects. Participants were divided into two groups, which were comprised of blue-collar workers (104) and white-collar workers (105). Sociodemographic characteristics, including age, education level, job tenure, gender, marital status, smoking status, and alcohol consumption, were measured via a survey. To determine the level of depression, the Korean version of the Center for Epidemiologic Studies Depression Scale (CES-D) was employed, and to investigate job stress, the Korean Occupational Stress Scale-Short Form (KOSS-SF) was used. For statistical analyses, Pearson’s chi-square test, the Student’s t-test, and repeated measure analysis of variance (ANOVA) were performed. RESULTS: The results showed that depression (CES-D, F[2, 400] = 0.466, p = 0.628) was changed but without significance and job stress (KOSS-SF, F[1.899, 379.831] = 3.192, p = 0.045) were significantly different. The between-group difference in the CES-D score between the blue- and white-collar workers by survey administration time was not statistically significant (F = 0.316, p = 0.574). The interaction between the survey time and occupational group was also not statistically significant (F = 0.967, p = 0.381). The between-group difference in the KOSS-SF total score was not statistically significant (F = 1.132, p = 0.289), and the interaction between the survey administration time and occupational group was also not significant (F = 0.817, p = 0.437). In the job stress subgroup analyses Job insecurity and Lack of reward showed a significant difference by survey administration time. CONCLUSION: This study showed that a merger without massive downsizing can cause negative health effects such as an changes in depression and increase in job stress. To improve the health of workers, both the immediate negative effects on health, and the long-term effects or their resolution over time should be considered prior to the merger.
Alcohol Drinking ; Depression ; Education ; Epidemiologic Studies ; Humans ; Korea ; Marital Status ; Occupational Groups ; Privatization ; Reward ; Smoke ; Smoking

BACKGROUND AND OBJECTIVES: This trial evaluated the safety and efficacy of the Genoss drug-eluting coronary stent. METHODS: This study was a prospective, multicenter, randomized trial with a 1:1 ratio of Genoss drug-eluting stent (DES)™ and Promus Element™. Inclusion criteria were the presence of stable angina, unstable angina, or silent ischemia. Angiographic inclusion criteria were de novo coronary stenotic lesion with diameter stenosis >50%, reference vessel diameter of 2.5–4.0 mm, and lesion length ≤40 mm. The primary endpoint was in-stent late lumen loss at 9-month quantitative coronary angiography follow-up. Secondary endpoints were in-segment late lumen loss, binary restenosis rate, death, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis during 9 months of follow-up. RESULTS: We enrolled 38 patients for the Genoss DES™ group and 39 patients for the Promus Element™ group. In-stent late lumen loss at 9 months was not significantly different between the 2 groups (0.11±0.25 vs. 0.16±0.43 mm, p=0.567). There was no MI or stent thrombosis in either group. The rates of death (2.6% vs. 0%, p=0.494), TLR (2.6% vs. 2.6%, p=1.000), and TVR (7.9% vs. 2.6%, p=0.358) at 9 months were not significantly different. CONCLUSION: This first-in-patient study of the Genoss DES™ stent showed excellent angiographic outcomes for in-stent late lumen loss and major adverse cardiac events over a 9-month follow-up.
Angina, Stable ; Angina, Unstable ; Constriction, Pathologic ; Coronary Angiography ; Coronary Artery Disease ; Drug-Eluting Stents ; Follow-Up Studies ; Humans ; Ischemia ; Mortality ; Myocardial Infarction ; Polymers* ; Prospective Studies ; Sirolimus ; Stents* ; Thrombosis