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This book brings Korea's finest foreign policy minds together in contemplating the risks and rewards of finally ending the 70 year stalemate between North and South Korea through reunification. While North Korea is in conflict with the United States over denuclearization and regime security, the South Korean government is focusing on economic development preparing for the day when the two Koreas are unified. This book will help scholars, activists and policy-makers from all over the world systematically understand the current diplomatic and security issues in the Korean peninsula.

Health-related quality of life (HRQOL) in patients with fibromyalgia (FM) is lower than in patients with other chronic diseases and the general population. Although various factors affect HRQOL, no study has examined a structural equation model of HRQOL as an outcome variable in FM patients. The present study assessed relationships among physical function, social factors, psychological factors, and HRQOL, and the effects of these variables on HRQOL in a hypothesized model using structural equation modeling (SEM). HRQOL was measured using SF-36, and the Fibromyalgia Impact Questionnaire (FIQ) was used to assess physical dysfunction. Social and psychological statuses were assessed using the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), the Arthritis Self-Efficacy Scale (ASES), and the Social Support Scale. SEM analysis was used to test the structural relationships of the model using the AMOS software. Of the 336 patients, 301 (89.6%) were women with an average age of 47.9±10.9 years. The SEM results supported the hypothesized structural model (χ2 = 2.336, df = 3, p = 0.506). The final model showed that Physical Component Summary (PCS) was directly related to self-efficacy and inversely related to FIQ, and that Mental Component Summary (MCS) was inversely related to FIQ, BDI, and STAI. In our model of FM patients, HRQOL was affected by physical, social, and psychological variables. In these patients, higher levels of physical function and self-efficacy can improve the PCS of HRQOL, while physical function, depression, and anxiety negatively affect the MCS of HRQOL.

Interstitial lung diseases (ILDs) are chronic, parenchymal lung diseases with a variable clinical course and a poor prognosis. Within various clinical courses, acute exacerbation (AE) is a devastating condition with significant morbidity and high mortality. The aim of this study was to investigate the role of interleukin-6 (IL-6) to predict AE and prognosis in patients with ILD. Eighty-three patients who were diagnosed with ILD from 2016 to 2019 at the Haeundae Paik Hospital, Busan, South Korea, were included and their clinical data were retrospectively analyzed. The median follow-up period was 20 months. The mean age was 68.1 years and 65.1% of the patients were men with 60.2% of patients being ever-smokers. Among ILDs, idiopathic pulmonary fibrosis was the most common disease (68.7%), followed by connective tissue disease-associated ILD (14.5%), cryptogenic organizing pneumonia (9.6%), and nonspecific interstitial pneumonia (6.0%). The serum levels of IL-6 were measured at diagnosis with ILD and sequentially at follow-up visits. During the follow-ups, 15 (18.1%) patients experienced an acute exacerbation (AE) of ILD and among them, four (26.7%) patients died. In the multivariable analysis, high levels of IL-6 (OR 1.014, 95% CI: 1.001-1.027, p = 0.036) along with lower baseline saturations of peripheral oxygen (SpO.sub.2) were independent risk factors for AE. In the receiver operating characteristic curve analysis, the area under the curve was 0.815 (p < 0.001) and the optimal cut-off value of serum IL-6 to predict AE was 25.20 pg/mL with a sensitivity of 66.7% and specificity of 80.6%. In the multivariable Cox analysis, a high level of serum IL-6 (HR 1.007, 95% CI: 1.001-1.014, p = 0.018) was only an independent risk factor for mortality in ILD patients. In our study, a high level of serum IL-6 is a useful biomarker to predict AE and poor prognosis in patients with ILD.

Abstract Context Somapacitan is a long-acting GH derivative for treatment of GH deficiency (GHD). Objective Evaluate the efficacy and tolerability of somapacitan in children with GHD after 2 years of treatment and after the switch from daily GH. Design A randomized, multinational, open-labelled, controlled parallel group phase 3 trial, comprising a 52-week main phase and 3-year safety extension (NCT03811535). Setting Eighty-five sites across 20 countries. Patients A total of 200 treatment-naïve prepubertal patients were randomized and exposed; 194 completed the 2-year period. Interventions Patients were randomized 2:1 to somapacitan (0.16 mg/kg/wk) or daily GH (0.034 mg/kg/d) during the first year, after which all patients received somapacitan 0.16 mg/kg/wk. Main outcome measures Height velocity (HV; cm/year) at week 104. Additional assessments included HV SD score (SDS), height SDS, IGF-I SDS, and observer-reported outcomes. Results HV was sustained in both groups between 52 and 104 weeks. At week 104, mean (SD) for HV between weeks 52 and 104 was 8.4 (1.5) cm/year after continuous somapacitan treatment and 8.7 (1.8) cm/year after 1 year of somapacitan treatment following switch from daily GH. Secondary height-related endpoints also supported sustained growth. Mean IGF-I SDS during year 2 was similar between groups and within normal range (−2 to +2). Somapacitan was well tolerated, with no safety or tolerability issues identified. GH patient preference questionnaire results show that most patients and their caregivers (90%) who switched treatment at year 2 preferred once-weekly somapacitan over daily GH treatment. Conclusions Somapacitan in children with GHD showed sustained efficacy and tolerability for 2 years, and after switching from daily GH. Patients/caregivers switching from daily GH expressed a preference for somapacitan. Clinical Trial Registration NCT03811535

Nonalcoholic fatty liver disease (NAFLD), a spectrum of liver diseases characterized by excessive fat accumulation, is the leading cause of chronic liver disease. The global prevalence of NAFLD is increasing in both adults and children. In Korea, the prevalence of pediatric NAFLD increased from 8.2% in 2009 to 12.1% in 2018 according to a national surveillance study. For early screening of pediatric NAFLD, laboratory tests including aspartate aminotransferase and alanine aminotransferase; biomarkers including hepatic steatosis index, triglyceride glucose index, and fibrosis-4 index; and imaging studies including ultrasonography and magnetic resonance imaging are required. Insulin resistance plays a major role in the pathogenesis of NAFLD, which promotes insulin resistance. Thus, the association between NAFLD and insulin resistance, diabetes mellitus, and metabolic syndrome has been reported in many studies. This review addresses issues related to the epidemiology and investigation of NAFLD as well as the association between NAFLD and insulin resistance and metabolic syndrome with focus on pediatric NAFLD.

The aim of this registry study was to analyze the long-term safety and effectiveness of recombinant human growth hormone (rhGH) in South Korean pediatric patients (≥2 years of age) with growth hormone deficiency GHD) of idiopathic or organic etiology, idiopathic short stature, Turner syndrome, small for gestational age and chronic renal failure. The study patients were followed-up till two years after the epiphyseal closure, with visits scheduled every six months. The outcome measures included the incidence of adverse events (AEs, in particular, neoplasia, glucose intolerance and hypothyroidism), as well as height standard deviation score (Ht SDS) and annual height velocity. The results of the interim analysis of a 5-year accumulated data for 2,024 patients (7,342 patient-years, PY) are presented. A total of 14 neoplasms were diagnosed (191/100,000 PY); 7 out of 9 malignancies were recurrent craniopharyngioma found in patients with organic GHD. Seven cases of glucose intolerance (95/100,000 PY) and 22 cases of hypothyroidism (300/100,000 PY) were detected; about half of the cases (4 and 10 cases each) were considered to be related with rhGH treatment. Most of the growth-retarded patients showed continuous improvement in Ht SDS, with the most prominent effect observed within a year of treatment initiation. The beneficial effect of rhGH on Ht SDS gain was maintained for 2-4 years. The incidence of AEs of interest in rhGH-treated patients was low, and most of the neoplasms were benign and/or non-related to rhGH. Most patients benefited from the therapy in terms of height increment.

Growing evidence suggests that early life stress (ELS) has long-lasting effects on glucocorticoid receptor (GR) expression and behavior via epigenetic changes of the GR exon 17 promoter. However, it remains unclear whether ELS regulates histone modifications of the GR exon 17 promoter across the life span. We investigated the effects of maternal separation (MS) on histone acetylation and methylation of GR exon 17 promoter in the hippocampus, according to the age of adults. Depression-like behavior and epigenetic regulation of GR expression were examined at young and middle adulthood in mice subjected to MS from postnatal day 1 to 21. In the forced swimming test, young adult MS mice showed no effect on immobility time, but middle-aged MS mice significantly increased immobility time. Young adult and middle-aged MS mice showed decreased GR expression. Their two ages showed decreased histone acetylation with increased histone deacetylases (HDAC5) levels, decreased permissive methylation, and increased repressive methylation at the GR exon 17 promoter. The extent of changes in gene expression and histone modification in middle adulthood was greater than in young adulthood. These results indicate that MS in early life causes long-term negative effects on behavior via histone modification of the GR gene across the life span.

Lipopolysaccharides (LPS) are a major component of the outer membrane of Gram-negative bacteria and are pathogen-associated molecular patterns recognized by the TLR4/MD2 complex that induces an inflammatory response. Recently, the cytosolic receptors caspase-4/-5/-11 that bind LPS inside the cell and trigger inflammasome activation or pyroptosis, have been identified. Despite the important roles of caspase-4 in human immune responses, few studies have investigated its biochemical characteristics and interactions with LPS. Since caspase-4 (C258A) purified from an Escherichia coli host forms aggregates, monomeric proteins including full-length caspase-4, caspase-4 (C258A), and the CARD domain of caspase-4 have been purified from the insect cell system. Here, we report the overexpression and purification of monomeric caspase-4 (C258A) and CARD domain from E . coli and demonstrate that purified caspase-4 (C258A) and CARD domain bind large LPS micelles and disaggregate them to small complexes. As the molar ratio of caspase-4 to LPS increases, the size of the caspase-4/LPS complex decreases. Our results present a new function of caspase-4 and set the stage for structural and biochemical studies, and drug discovery targeting LPS/caspase-4 interactions by establishing a facile purification method to obtain large quantities of purified caspase-4 (C258A) and the CARD domain.

Growth hormone deficiency (GHD) and idiopathic short stature (ISS) are the major etiologies of short stature in children. For the diagnosis of GHD and ISS, meticulous evaluations are required, including growth hormone provocation tests, which are invasive and burdensome for children. Additionally, sella magnetic resonance imaging (MRI) is necessary for assessing etiologies of GHD, which cannot evaluate hormonal secretion. Recently, radiomics has emerged as a revolutionary technique that uses mathematical algorithms to extract various features for the quantitative analysis of medical images. This study aimed to develop a machine learning-based model using sella MRI-based radiomics and clinical parameters to diagnose GHD and ISS. A total of 293 children with short stature who underwent sella MRI and growth hormone provocation tests were included in the training set, and 47 children who met the same inclusion criteria were enrolled in the test set from different hospitals for this study. A total of 186 radiomic features were extracted from the pituitary glands using a semiautomatic segmentation process for both the T2-weighted and contrast-enhanced T1-weighted image. The clinical parameters included auxological data, insulin-like growth factor-I, and bone age. The extreme gradient boosting algorithm was used to train the prediction models. Internal validation was conducted using 5-fold cross-validation on the training set, and external validation was conducted on the test set. Model performance was assessed by plotting the area under the receiver operating characteristic curve. The mean absolute Shapley values were computed to quantify the impact of each parameter. The area under the receiver operating characteristic curves (95% CIs) of the clinical, radiomics, and combined models were 0.684 (0.590-0.778), 0.691 (0.620-0.762), and 0.830 (0.741-0.919), respectively, in the external validation. Among the clinical parameters, the major contributing factors to prediction were BMI SD score (SDS), chronological age-bone age, weight SDS, growth velocity, and insulin-like growth factor-I SDS in the clinical model. In the combined model, radiomic features including maximum probability from a T2-weighted image and run length nonuniformity normalized from a T2-weighted image added incremental value to the prediction (combined model vs clinical model, P=.03; combined model vs radiomics model, P=.02). The code for our model is available in a public repository on GitHub. Our model combining both radiomics and clinical parameters can accurately predict GHD from ISS, which was also proven in the external validation. These findings highlight the potential of machine learning-based models using radiomics and clinical parameters for diagnosing GHD and ISS.

We investigated the modified triglycerides-glucose (TyG) indices and other markers for non-alcoholic fatty liver disease (NAFLD) in 225 participants aged 10–19 years, and the participants were divided into subgroups according to their NAFLD grade. We performed logistic regression analysis and calculated the odds ratios (ORs) with 95% confidence intervals (CIs) of tertiles 2 and 3 for each parameter, with those of tertile 1 as a reference. The area under the receiver operating characteristic (ROC) curve was calculated to compare the parameters for identifying NAFLD. TyG and modified indices, aspartate transaminase-to-platelet ratio index (APRI)-body mass index (BMI), APRI-BMI standard deviation score (SDS), APRI waist-to-hip ratio, fibrosis-4 index (FIB)-4, and hepatic steatosis index (HSI) were higher in participants with NAFLD than in those without NAFLD. The ORs and 95% CIs for NAFLD progressively increased across tertiles of each parameter. TyG and modified TyG indices, FIB-4, HSI, and modified APRIs, except APRI waist-to-height ratio, predicted NAFLD significantly through ROC curves. Modified TyG indices, APRI-BMI SDS, and HSI were superior to the other markers for NAFLD prediction. Modified TyG indices, APRI-BMI SDS, and HSI appear to be useful for assessing NAFLD in youths.