Background: Neurogenic differentiation 1 (NeuroD1) is a representative small cell lung cancer (SCLC) transcription regulator involved in the carcinogenesis and behavior of SCLC.Histone modifications play an important role in transcription, and H3 lysine 4 trimethylation (H3K4me3) is primarily associated with promoter regions. Methods: We investigated the association between single nucleotide polymorphisms (SNPs) in NeuroD1 and H3K4me3 coincident regions, selected using ChIP sequencing (ChIP-seq), and the clinical outcomes of 261 patients with SCLC. Results: Among 230 SNPs, two were significantly associated with both the chemotherapy response and overall survival (OS) of patients with SCLC. RNF145 rs2043268A>G was associated with worse chemotherapy response and OS (under a recessive model, adjusted odds ratio [aOR], 0.50, 95% confidence interval [CI], 0.26–0.94, P = 0.031, and adjusted hazard ratio [aHR], 1.88, 95% CI, 1.38–2.57, P < 0.001). CINP rs762105A>G was also associated with worse chemotherapy response and OS (under a dominant model, aOR, 0.47, 95% CI, 0.23–0.99, P = 0.046, and aHR, 2.03, 95% CI, 1.47–2.82, P < 0.001). ChIP–quantitative polymerase chain reaction and luciferase assay confirmed that the two SNPs were located in the active promoter regions and influenced the promoter activity of each gene. Conclusion To summarize, among SNPs selected using ChIP-seq in promoter regions with high peaks in both NeuroD1 and H3K4me3, RNF145 rs2043268A>G and CINP rs762105A>G were associated with clinical outcomes in patients with SCLC and also affected the promoter activity of each gene.

BACKGROUND: Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. METHODS: Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of b2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. RESULTS: Tyr-NO-b2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-b2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. CONCLUSION This is the first discovery of a new target molecule of NO, b2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-b2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.

Background: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

Objectives: The prevalence of obstructive sleep apnea (OSA) and its association with perioperative comorbidities in patients who undergo bariatric surgery remain unclear in South Korea. We investigated the prevalence of OSA and its association with metabolic parameters in patients who underwent bariatric surgery. Methods: This retrospective study included 144 patients who underwent bariatric surgery; 98 patients underwent a sleep study and were included in this study. Patients were categorized into two groups based on the apnea-hypopnea index (AHI) cut-off value of 15/hour. Results: Overall, 52 (53.1%) of the patients showed an AHI ≥15/hour. The neck circumference was larger (43.0±4.7 cm vs. 40.5±3.6 cm, p=0.005) and prevalence of diabetes was higher (65.4% vs. 45.7%, p=0.049) in patients with AHI ≥15/hour than in those with AHI <15/hour. Furthermore, fasting blood glucose levels were higher (134.7±50.5 mg/dL vs. 114.8±34.3 mg/dL , p= 0.028) and serum high-density lipoprotein levels were lower (46.8±9.9 mg/dL vs. 52.8±13.3 mg/dL, p=0.013) in the AHI ≥15/hour than in the AHI <15/hour group. Conclusions More than 50% of patients who underwent bariatric surgery had moderate-to-severe OSA. The prevalence of metabolic comorbidities was higher in those with moderate-to-severe OSA than in those without. OSA screening may be useful for evaluation of the metabolic complications of morbid obesity.

Background: and Purpose The aim of this study was to survey the expert opinions on treatments for convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE) in adults. Methods: Forty-two South Korean epileptologists participated in this survey. They completed an online questionnaire regarding various patient scenarios and evaluated the appropriateness of medications used to treat CSE and NCSE. Results: Initial treatment with a benzodiazepine (BZD) followed by either a second BZD or an antiepileptic drug (AED) monotherapy was the preferred treatment strategy. More than two-thirds of the experts used a second BZD when the first one failed, and consensus was reached for 84.8% of the survey items. The preferred BZD was intravenous (IV) lorazepam for the initial treatment of status epilepticus. IV fosphenytoin and IV levetiracetam were chosen for AED monotherapy after the failure of BZD. The treatments for NCSE were similar to those for CSE. Continuous IV midazolam infusion was the treatment of choice for iatrogenic coma in refractory CSE, but other AEDs were preferred over iatrogenic coma in refractory NCSE. Conclusions The results of this survey are consistent with previous guidelines, and can be cautiously applied in clinical practice when treating patients with CSE or NCSE.

Status epilepticus (SE) is one of the most serious neurologic emergencies. SE is a condition that encompasses a broad range of semiologic subtypes and heterogeneous etiologies. The treatment of SE primarily involves the management of the underlying etiology and the use of antiepileptic drug therapy to rapidly terminate seizure activities. The Drug Committee of the Korean Epilepsy Society performed a review of existing guidelines and literature with the aim of providing practical recommendations for antiepileptic drug therapy. This article is one of a series of review articles by the Drug Committee and it summarizes staged antiepileptic drug therapy for SE. While evidence of good quality supports the use of benzodiazepines as the first-line treatment of SE, such evidence informing the administration of second- or third-line treatments is lacking; hence, the recommendations presented herein concerning the treatment of established and refractory SE are based on case series and expert opinions. The choice of antiepileptic drugs in each stage should consider the characteristics and circumstances of each patient, as well as their estimated benefit and risk to them. In tandem with the antiepileptic drug therapy, careful searching for and treatment of the underlying etiology are required.

Background: Obesity, obstructive sleep apnea (OSA), and excessive daytime sleepiness (EDS) are common conditions and are interrelated. Obesity is a risk factor for OSA and independently associated with EDS. We aimed to evaluate frequency of EDS in morbid obese patients with OSA and to identify contribution factor for EDS. Methods: This was a retrospective cross-sectional study in single sleep center. Consecutive patients with OSA (with apnea-hypopnea index 5/h or more) with morbid obesity (body mass index over 35 kg/m2) was enrolled. EDS were defined as Epworth Sleepiness Scale of 10 points or more. Clinical and polysomnographic variables were compared between those with and without EDS. Results: Total 110 morbid obese patients with OSA were enrolled, and 34 (31%) of them had EDS. Those with EDS had higher subjective symptom of insomnia and depression. Rapid eye movement sleep latency was shorter and minimum saturation was lower for those with EDS. Multivariate logistic regression analysis identified insomnia severity (odds ratio, 1.117) and minimum saturation (odds ratio, 0.952) as independent contribution factor for EDS. Conclusions Result of this study suggest that 31.4% of morbid obese patients with OSA have EDS, and it can be affected by insomnia severity and desaturation during sleep.

Background/Aims: Genome wide and candidate gene association studies have identified polymorphisms associated with the risk of lung cancer in never-smokers. This study was conducted to evaluate the association between 11 polymorphisms identified in female never smokers and the lung cancer risk in male smokers. Methods: This study included 714 lung cancer patients and 626 healthy controls. The polymorphisms were genotyped using SEQUENOM MassARRAY iPLEX assay or Taq-Man assay. Results: Two polymorphisms were associated with the risk of lung cancer in male smokers, as in female never smokers. Male smokers carrying the rs4975616 variant allele had a significantly decreased risk of lung cancer (in a codominant model: odds ratio, 0.77; 95% confidence interval, 0.61 to 0.96; p = 0.02). The rs9387478 polymorphism also reduced lung cancer risk in male smokers (in a codominant model: odds ratio, 0.85; 95% confidence interval, 0.73 to 0.997; p = 0.046). In a stratified analysis, the association between these polymorphisms and the risk of lung cancer was predominant in lighter smokers and for cases of adenocarcinoma. Conclusions These results suggest that a subset of polymorphisms known to be associated with the risk of lung cancer in female never smokers is also associated with the risk of lung cancer in male smokers.

Antiepileptic drugs (AEDs) are the primary treatment strategy for epilepsy. As the use of AEDs has become more widespread and diverse over the past century, it has become necessary to refine the associated prescription strategies. This prompted the Drug Committee of the Korean Epilepsy Society to perform a systemic review of both international and domestic guidelines as well as literature related to medical treatment of epilepsy, and prepared a series of reviews to provide practical guidelines for clinicians to follow. This article is the first in a series on AED treatments for epilepsy in South Korea.

The incidence and prevalence of epilepsy are highest in elderly people, and the etiologies of epilepsy in the elderly differ from those in other age groups. Moreover, diagnosing and treating epilepsy in elderly people may be challenging due to differences in clinical characteristics and physiological changes associated with aging. This review focuses on the pharmacological treatment of epilepsy in elderly patients.