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The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components.

Aim: Previous ovarian surgery for endometriosis results in decreased ovarian reserve and poor response to treatment in women with infertility. However, the impact of previous overall ovarian surgery on the incidence of infertility is unclear. Therefore the authors investigated impact of previous ovarian surgery on infertility incidence. Materials and Methods: This is a case-control study using retrospectively collected data in women who received infertility treatment (cases) or delivered babies (controls) at a tertiary center between 2003 and 2012. Results: The frequency of previous ovarian surgery was similar in both groups (p > 0.05) but it was higher in women with tubal infertility than their matched controls (p < 0.05). Also, the frequency of previous reproductive organ surgery was higher in the case group and in women with tubal or unexplained infertility (p < 0.05). Conclusion: Previous ovarian surgery is not associated with entire infertility, but may increase tubal factor infertility through adhesion formation and damage to adjacent tubes.

Kiyoung Lee,1,2 Ie Byung Park,1,2 Seung Hee Yu,2 Soo-Kyung Kim,3 So Hun Kim,4 Da Hea Seo,4 Seongbin Hong,4 Ja Young Jeon,5 Dae Jung Kim,5 Soo Wan Kim,6 Cheol Soo Choi,1,2 Dae Ho Lee1,21Department of Internal Medicine, Gachon University College of Medicine, Incheon, Republic of Korea; 2Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea; 3Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea; 4Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea; 5Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea; 6Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of KoreaAim: We aimed to evaluate the clinical utility of blood ketone measurement and to test the performance of the diagnostic criteria for diabetic ketoacidosis (DKA) issued by the American Diabetes Association, the Joint British Diabetes Societies, and the American Association of Clinical Endocrinologists and the American College of Endocrinology.Methods: This retrospective analysis included 278 patients with suspected DKA who were hospitalized at 4 university hospitals and aged ≥16 years with a blood glucose level of >200 mg/dL and a blood ketone level of ≥1.0 mmol/L as well as other biochemical data. The patients were categorized into four subgroups (ketosis, typical DKA, atypical DKA, and DKA + lactic acidosis). Atypical DKA in each analysis was defined by our supplementary criteria if the biochemical data did not meet each set of diagnostic criteria from the aforementioned societies.Results: Blood ketone levels in patients with diabetic ketosis and those with DKA varied widely, 1.05–5.13 mmol/L and 1.02–15.9 mmol/L, respectively. Additionally, there were significant discrepancies between the guidelines in the diagnosis of DKA. Thus, the proportion of patients with atypical DKA ranged from 16.5% to 42.4%. Notably, the in-hospital mortality was comparable between patients with typical and atypical DKA, with a very high mortality in patients with DKA + lactic acidosis (blood lactate >5 mmol/L).Conclusions: Our results showed that considering variable presentations of DKA, blood ketone data need to be interpreted cautiously along with other biochemical data and suggested that a new system is required to better characterize DKA.Keywords: Diabetic ketoacidosis, ketone bodies, diagnosis, lactic acidosis, acid base imbalance

Yong Suk Jo,1 Sung Kyoung Kim,2 Seoung Ju Park,3 Soo-Jung Um,4 Yong-Bum Park,5 Ki Suck Jung,6 Deog Kyeom Kim,7 Kwang Ha Yoo8 1Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; 2Department of Internal Medicine, Division of Pulmonology, St Vincent’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea; 3Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea; 4Department of Internal Medicine, Division of Pulmonology, Dong-A University Hospital, Busan, Republic of Korea; 5Department of Internal Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; 6Department of Internal Medicine, Division of Pulmonary Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Republic of Korea; 7Department of Internal Medicine, Seoul Metropolitan Government, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 8Department of Internal Medicine, Division of Pulmonary and Allergy Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea Background and objective: FEV1 is the gold standard for assessment of COPD. We compared efficacy of FEV1, inspiratory capacity (IC), and IC to total lung capacity (TLC) ratio in the evaluation of COPD and their association with exacerbation.Methods: We analyzed the association of dyspnea severity, quality of life status, and lung function with lung function measurements and exacerbation risk in 982 patients enrolled in the Korea COPD Subgroup Registry and Subtype Research study. Exacerbation and longitudinal lung function change were evaluated in 3 years’ follow-up.Results: The FEV1, IC, and IC to TLC ratio showed comparable negative correlations with dyspnea severity and quality of life status, and positive correlation with exercise capacity. In patients with >2 events/year, annual rate of change in FEV1 and IC tended to decline more rapidly in those with FEV1 50% (-14.46±19.40 mL/year vs 12.29±9.24 mL/year, P=0.213; -4.75±17.28 mL/year vs -78.05±34.16 mL/year, P=0.056 for FEV1 and IC, respectively), without significance.Conclusion: Longitudinal changes in IC and FEV1 were not significantly associated with exacerbation risk. Keywords: COPD, exacerbation, FEV1, inspiratory capacity

Thorough resistivity measurements on single crystals of CeZn11 under pressure p and magnetic field H are presented. At ambient pressure, CeZn11 orders antiferromagnetically at TN=2 K. The pressure dependence of the resistivity reveals an increase of the Kondo effect. We determine the pressure evolution of the magnetic exchange interaction between conduction and localized 4f electrons. It qualitatively reproduces the pressure evolution of the magnetic ordering temperature TO1 (with T O1=TN at ambient pressure). In addition to TO1, a new anomaly TO2 appears under pressure. Both anomalies are found to increase with applied pressure up to 4.9 GPa, indicating that CeZn 11 is far from a pressure induced quantum critical point. Complex T-H phase diagrams are obtained under pressure which reveal the instability of the ground state in this compound. © 2013 American Physical Society.

We sequenced reduced representation libraries by means of Illumina technology to generate over 1.5 Mb of orthologous sequence from a representative of each of the four extant gibbon genera (Nomascus, Hylobates, Symphalangus, and Hoolock). We used these dat

The population genetic structure of Native Hawaiians has yet to be comprehensively studied, and the ancestral origins of Polynesians remain in question. In this study, we utilized high-resolution genome-wide SNP data and mitochondrial genomes of 148 and 16

Madhusmita Dhupal,1,2 Jae-Min Oh,3 Dipti Ranjan Tripathy,4 Soo-Ki Kim,2 Sang Baek Koh,5 Kyu-Sang Park6 1Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea; 2Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea; 3Department of Chemistry and Medical Chemistry, College of Science and Technology, Yonsei University, Wonju, Republic of Korea; 4Department of Neurology, Gauhati Medical College and Hospital, Gauhati, India; 5Department of Preventive Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea; 6Department of Physiology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea Background: Titanium dioxide nanoparticles (TiO2 NPs) represent a scientific breakthrough in the areas of biological and medicinal applications. Interaction of TiO2 NPs with components of innate immune system remains elusive. Aim: This study explored in vitro immunotoxicity of murine macrophage RAW 264.7 to TiO2 NPs (20 nm, negative charge) and its underlying molecular mechanism by way of immunoredox profiling. Materials and methods: In this study, chemically synthesized BSA-functionalized TiO2 NPs (20 nm, negative charge) were characterized and immunotoxicity was investigated on RAW 264.7 cells. Results: We found that reactive oxygen species levels significantly increased with increasing nitric oxide production, whereas depleting endogenous antioxidant super oxide dismutase as well as nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels. Furthermore, NPs exposure increased the expression of apoptotic factors such as BAX, BIM, and PUMA with disruption of mitochondrial membrane potential (ΔΨm) that lead to decrease in immunocytes. Molecular immune profiling revealed the activation of multiple toll-like receptors (TLRs) 4/9/12/13 simultaneously with the phosphorylation of p-p38MAPK and p-SAPK/c-Jun N-terminal kinase (JNK) compared to untreated control. Conclusion: Collectively, this study shows that the molecular nature of TiO2SA20(-) NP-induced immunotoxicity in RAW 264.7 macrophage is simultaneous induction of immunocyte apoptosis and multiple TLRs signaling through oxidative stress-dependent SAPK/JNK and p38 mitogen-associated protein kinase activation. This is the first study to address newer molecular mechanism of TiO2SA20(-) NP-induced immunotoxicity. Keywords: titanium dioxide, toll-like receptors, MAPK pathways, apoptosis, nanoparticles, oxidative stress

Radiative decays of the radially excited charmonium resonance, (Formula presented) into (Formula presented) (Formula presented) and (Formula presented) final states have been measured in a sample of (Formula presented) (Formula presented) events collected by the BES Collaboration. The branching ratios (Formula presented) and (Formula presented) are obtained. When compared to the corresponding radiative (Formula presented) decays, the observed (Formula presented) radiative decay rates into (Formula presented) and (Formula presented) are consistent with the prediction of the “12%” rule. © 2003 The American Physical Society.

Radiative decays of the radially excited charmonium resonance, (Formula presented) into (Formula presented) (Formula presented) and (Formula presented) final states have been measured in a sample of (Formula presented) (Formula presented) events collected by the BES Collaboration. The branching ratios (Formula presented) and (Formula presented) are obtained. When compared to the corresponding radiative (Formula presented) decays, the observed (Formula presented) radiative decay rates into (Formula presented) and (Formula presented) are consistent with the prediction of the “12%” rule. © 2003 The American Physical Society.

The branching fraction of the ψ(2S) decay into τ+τ - has been measured for the first time using the BES detector at the Beijing Electron-Positron Collider. The result is Bττ=(2.710. 43±0.55)× 10-3, where the first error is statistical and the second is systematic. This value, along with those for the branching fractions into e+e- and μ+ μ- of this resonance, satisfy well the relation predicted by the sequential lepton hypothesis. Combining all these values with the leptonic width of the resonance, the total width of the ψ(25) is determined to be (252±37) keV. ©2002 The American Physical Society.

Kyung Hoon Kim,1 Hye Seon Kang,2 Ju Sang Kim,3 Hyoung Kyu Yoon,4 Sung Kyoung Kim,5 Chin Kook Rhee1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, 3Division of Pulmonary Medicine, Department of Internal Medicine, Incheon St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 5Division of Pulmonary Medicine, Department of Internal Medicine, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea Introduction: Roflumilast is a phosphodiesterase-4 inhibitor, which can decrease exacerbation in patients with chronic obstructive pulmonary disease (COPD). However, adverse effects are a major barrier to medication use, and little is known regarding the risk factors for discontinuation of roflumilast in COPD patients.Method: A search of the clinical databases identified all patients who were prescribed roflumilast between December 2012 and April 2015 in the four hospitals of The Catholic University of Korea, Korea. The study subjects were limited to patients who had taken 500 µg of roflumilast. We studied the factors associated with drug discontinuation and drug adverse events by univariate and multivariate analyses.Results: Among 154 eligible patients, 54 (35.1%) discontinued their roflumilast prescription. Most patients were elderly, male, current or former smokers, and had moderate-to-severe airflow limitation. Low–body mass index (BMI) patients were more likely to undergo drug discontinuation (1-unit decrease in BMI: odds ratio [OR] =1.165, p=0.006; BMI

Myoung Jin Oh,1 Young Hoon Cho,1 So Yoon Cha,1 Eun Ok Lee,2 Jin Wook Kim,2 Sun Ki Kim,2 Chang Seo Park1 1Department of Chemical and Biochemical Engineering, Dongguk University, Chung-gu, Seoul, 2LCS Biotech, Gwonseon-gu, Suwon-si, Gyeonggi-do, Republic of Korea Abstract: Ceramides in the human stratum corneum (SC) are a mixture of diverse N-acylated fatty acids (FAs) with different chain lengths. C24 is the major class of FAs of ceramides. However, there are also other classes of ceramides with diverse chain lengths of FAs, and these lengths generally range from C16 to C26. This study aimed to prepare several types of phytoceramide containing diverse chain lengths of N-acylated FAs and compare them with C18-ceramide N-stearoyl phytosphingosine (NP) in terms of their effects on the physiological properties of the SC. We chose natural oils, such as horse fat oil, shea butter, sunflower oil, and a mixture of macadamia nut, shea butter, moringa, and meadowfoam seed oil, as sources of FAs and phytosphingosine as a sphingoid backbone to synthesize diverse phytoceramides. Each phytoceramide exhibited a distinctive formation of the lamellar structure, and their FA profiles were similar to those of their respective natural oil. The skin barrier properties, as analyzed in human skin, clearly demonstrated that all the phytoceramides improved the recovery rate of the damaged SC and enhanced hydration better than C18-ceramide NP did. In conclusion, natural oil-derived phytoceramides could represent a novel class of ceramides for cosmetic applications in the development of an ideal skin barrier moisturizer. Keywords: fatty acid, chain length, phytoceramide, skin barrier, natural oil

Sun Kyung Kim, Myonghwa Park Education and Research Center for Evidence Based Nursing Knowledge, College of Nursing, Chungnam National University, Daejeon, Republic of Korea Background: Person-centered care is a holistic and integrative approach designed to maintain well-being and quality of life for people with dementia, and it includes the elements of care, the individual, the carers, and the family.Aim: A systematic literature review and meta-analysis were undertaken to investigate the effectiveness of person-centered care for people with dementia.Methods: Literature searches were undertaken using six databases including Medline, EMBASE, CINAHL, PsycINFO, Cochrane Database, and KoreaMed using the following keywords: cognition disorder, dementia, person-centered care, patient-centered care, client-centered care, relationship-centered care, and dementia care. The searches were limited to interventional studies written in English and Korean and included randomized controlled studies and noncontrolled studies for people with dementia living in any setting.Results: Nineteen interventional studies, including 3,985 participants, were identified. Of these, 17 studies were from long-term care facilities and two studies were from homecare settings. The pooled data from randomized controlled studies favored person-centered care in reducing agitation, neuropsychiatric symptoms, and depression and improving the quality of life. Subgroup analysis identified greater effectiveness of person-centered care when implemented for people with less severe dementia. For agitation, short-term interventions had a greater effect (standardized mean difference [SMD]: -0.434; 95% conference interval [CI]: -0.701 to -0.166) than long-term interventions (SMD: -0.098; 95% CI: -0.190 to 0.007). Individualized activities resulted in a significantly greater beneficial effect than standard care (SMD: 0.513; 95% CI: -0.994 to -0.032). However, long-term, staff education, and cultural change interventions had a greater effect on improving the quality of life for people with dementia (SMD: 0.191; 95% CI: 0.079 to 0.302).Conclusion: This systematic review and meta-analysis provided evidence for person-centered care in clinical practice for people with dementia. Person-centered care interventions were shown to reduce agitation, neuropsychiatric symptoms, and depression and to improve the quality of life. Person-centered care interventions can effectively reduce agitation for a short term using intensive and activity-based intervention. However, an educational strategy that promotes learning and skill development of internal care staff is needed to enhance patient’s quality of life and to ensure the sustainability of the effects of behavioral problems. The feasibility and effectiveness of the intervention, the severity of patient disease, and intervention type and duration should be considered as part of an intervention design. Keywords: dementia, meta-analysis, patient-centered care, person-centered care, neuropsychiatric symptoms, systematic review

Chan Ho Lee, Eun Kyung Goag, Su Hwan Lee, Kyung Soo Chung, Ji Ye Jung, Moo Suk Park, Young Sam Kim, Se Kyu Kim, Joon Chang, Joo Han Song Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea Background: Iron-catalyzed oxidative stress contributes to lung injury after exposure to various toxins, including cigarette smoke. An oxidant/antioxidant imbalance is considered to play a critical role in the pathogenesis of COPD. Ferritin is a key protein in iron homeostasis, and its capacity to oxidize and sequester the metal preventing iron prooxidant activity implicates its possible role in the alteration of antioxidant imbalance. We investigated the relationship among cigarette smoking, lung function, and serum ferritin concentration in a large cohort representative of the Korean adult population. Materials and methods: Among 50,405 participants of the Korean National Health and Nutrition Examination Survey from 2010 to 2014, 15,239 adult subjects older than 40 years with serum ferritin levels and spirometric data were selected for this study. Results: The mean age was 56.5 years for men (43%) and 56.9 years for women (57%). The prevalence of airway obstruction was 13.4%, which was significantly higher in men than in women, and increased in former or current smokers. The median levels of serum ferritin were highest in the airway obstruction group, followed by the restrictive pattern group, and lowest in the normal lung function group. The median ferritin levels were increased by smoking status and amounts in each spirometric subgroup. In multivariable regression analysis, serum ferritin was positively associated with forced expiratory volume in 1 second and forced expiratory volume in 1 second/forced vital capacity, whereas the smoking amount was negatively associated with the adjustment with age, sex, height, and weight. Conclusion: Serum ferritin levels were increased in former or current smokers and were increased with smoking amount in all subgroups of participants categorized according to spirometric results. The result was also evident in the subgroups divided by obstructive severity. While smoking amount was inversely related to lung function, higher levels of serum ferritin were associated with enhanced spirometric results in a representative sample of the general Korean adult population. Future prospective studies will be needed to clarify the causality between serum ferritin and lung functions and their role in COPD morbidity. Keywords: airway obstruction, ferritin, smoking

Hye Seon Kang, Chin Kook Rhee, Sung Kyoung Kim, Jin Woo Kim, Sang Haak Lee, Hyung Kyu Yoon, Joong Hyun Ahn, Yong Hyun Kim Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Purpose: We compared the clinical characteristics and treatment outcomes of patients with eosinophilic and neutrophilic COPD exacerbations requiring hospital admission. Patients and methods: This was a retrospective multicenter study performed between January 2010 and December 2014. In all, 1,688 COPD patients admitted via the outpatient clinics or emergency departments of six university hospitals were enrolled. The patients were grouped by complete blood counts: eosinophilic group, >2% peripheral blood eosinophils, and neutrophilic group, >65% peripheral blood neutrophils or >11,000 leukocytes/mL. The patients with radiographic evidence of pneumonia at the time of admission, those with lung cancer, those admitted for treatment of other medical problems, and those who chronically used steroids were excluded. Results: A total of 605 patients hospitalized with COPD exacerbations (177 eosinophilic and 380 neutrophilic) were included. Pulmonary functions, including the forced expiratory volume in 1 second and forced vital capacity, were better in patients with eosinophilic exacerbations. Treatment outcomes, including the rate of admission to the intensive care unit and mortality, were poorer in patients with neutrophilic exacerbations (4.5% vs 12.4%, P=0.004; 1.1% vs 4.5%, P=0.043, respectively). Congestive heart failure (odds ratio [OR] =3.40, 95% confidence interval [CI]: 1.28–9.01) and neutrophilic exacerbation (OR =2.81, 95% CI: 1.21–6.52) were independent risk factors for intensive care unit admission. Conclusion: COPD patients with neutrophilic exacerbations experienced worse clinical outcomes than did those with eosinophilic exacerbations. The peripheral blood eosinophil count may be a useful predictor of clinical progress during hospitalization of COPD patients with acute exacerbations. Keywords: eosinophilia, neutrophilia, pulmonary disease, chronic obstructive, exacerbations, intensive care unit

Kyung Soo Chung,1,2 Ji Ye Jung,1,2 Moo Suk Park,1,2 Young Sam Kim,1,2 Se Kyu Kim,1,2 Joon Chang,1,2 Joo Han Song1,2 1Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea Background: Forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6 seconds (FEV6) has been proposed as an alternative to FEV1/forced vital capacity (FVC) for detecting airway obstruction. A fixed cut-off value for FEV1/FEV6 in a Korean population is lacking. We investigated a fixed cut-off for FEV1/FEV6 as a surrogate for FEV1/FVC for detecting airway obstruction.Materials and methods: We used data obtained in the 5 years of the Fifth and Sixth Korean National Health and Nutrition Examination Survey. A total of 14,978 participants aged ≥40 years who underwent spirometry adequately were the study cohort. “Airway obstruction” was a fixed cut-off FEV1/FVC

Joo Kyung Kim,1 Soo Haeng Lee,1 Bho Hyeon Lee,1 Chang Youl Lee,2 Do Jin Kim,3 Kyung Hoon Min,4 Sung Kyoung Kim,5 Kwang Ha Yoo,6 Ki-Suck Jung,1 Yong Il Hwang1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University, 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, St Vincent’s Hospital, The Catholic University of Korea, Suwon, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Republic of Korea Introduction: COPD exacerbation negatively impacts the patient’s quality of life and lung function, increases mortality, and increases socioeconomic costs. In a real-world setting, the majority of patients with COPD have mild-to-moderate airflow limitation. Therefore, it is important to evaluate COPD exacerbation in patients with mild-to-moderate airflow limitation, although most studies have focused on the patients with moderate or severe COPD. The objective of this study was to evaluate factors associated with COPD exacerbation in patients with mild-to-moderate airflow limitation. Methods: Patients registered in the Korean COPD Subtype Study cohort were recruited from 37 tertiary referral hospitals in Korea. We obtained their clinical data including demographic characteristics, past medical history, and comorbidities from medical records. Patients were required to visit the hospital to document their COPD status using self-administered questionnaires every 6 months. Results: A total of 570 patients with mild-to-moderate airflow limitation were enrolled. During the first year of follow-up, 30.5% patients experienced acute exacerbation, with exacerbations being more common in patients with poor lung function. Assessed factors associated with COPD exacerbation included COPD assessment test scores, modified Medical Research Council dyspnea assessment test scores, St George’s Respiratory Questionnaire for COPD scores, a previous history of exacerbation, and histories of pneumonia and allergic rhinitis. Logistic regression tests revealed St George’s Respiratory Questionnaire for COPD scores (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.00–1.04; P=0.034), a previous history of exacerbation (OR, 3.12; 95% CI, 1.35–7.23; P=0.008), and a history of pneumonia (OR, 1.85; 95% CI, 1.06–3.25; P=0.032) as risk factors for COPD exacerbation. Conclusion: Our results suggest that COPD exacerbation in patients with mild-to-moderate airflow limitation is associated with the patient’s quality of life, previous history of exacerbation, and history of pneumonia. Keywords: COPD, exacerbation, risk factors

Ah Young Leem, Se Kyu Kim, Joon Chang, Young Ae Kang, Young Sam Kim, Moo Suk Park, Song Yee Kim, Eun Young Kim, Kyung Soo Chung, Ji Ye Jung Division of Pulmonology, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea Background: Heavy metal exposure may contribute to inflammation in the lungs via increased oxidative stress, resulting in tissue destruction and obstructive lung function (OLF). In this study, we evaluated the relationship between lead and cadmium levels in blood, and lung function in the Korean population.Methods: Pooled cross-sectional data from 5,972 subjects who participated in the Korean National Health and Nutrition Examination Survey 2008–2012 were used for this study. OLF was defined as forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC)

Hee Jin Park, Ah Young Leem, Sang Hoon Lee, Ju Han Song, Moo Suk Park, Young Sam Kim, Se Kyu Kim, Joon Chang, Kyung Soo Chung Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Institute of Chest Disease, Yonsei University College of Medicine, Seoul, South Korea Background: Comorbidities can occur frequently in patients with chronic obstructive pulmonary disease (COPD) and can influence mortality and morbidity independently. It is increasingly recognized that many patients with COPD have comorbidities that have a major impact on their quality of life and survival. Therefore, we investigated the prevalence of comorbidities in Korean COPD populations. Methods: We used data obtained in the 6 years of the fourth and fifth Korean National Health and Nutrition Examination Survey (KNHANES) IV and V. Among 50,405 subjects, 16,151 subjects aged ≥40 years who performed spirometry adequately were included in this study. Airway obstruction was defined as forced expiratory volume in 1 second/forced vital capacity

Moo-Yong Rhee,1 Sang Hong Baek,2 Weon Kim,3 Chang Gyu Park,4 Seung Woo Park,5 Byung-Hee Oh,6 Sang-Hyun Kim,7 Jae-Joong Kim,8 Joon-Han Shin,9 Byung-Su Yoo,10 Se-Joong Rim,11 Jong-Won Ha,12 Joon Hyung Doh,13 Youngkeun Ahn,14 Jei Keon Chae,15 Jeong Bae Park,16 Soon-Kil Kim,17 Cheol Ho Kim18 1Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, 2Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, 3Cardiovascular Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, 4Division of Cardiology, Guro Hospital, Korea University College of Medicine, Seoul, 5Division of Cardiology, Samsung Medical Center, Seoul, 6Department of Internal Medicine, Seoul National University Hospital, Seoul, 7Division of Cardiology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, 8Division of Cardiology, Asan Medical Center, Seoul, 9Division of Cardiology, Ajou University Hospital, Suwon, 10Division of Cardiology, Wonju Severance Christian Hospital, Wonju, 11Division of Cardiology, GangNam Severance Hospital, Seoul, 12Division of Cardiology, Severance Hospital, Seoul, 13Division of Cardiology, Inje University Ilsan Hospital, Goyang, 14Department of Cardiology, Chonnam National University Hospital, Gwangju, 15Chonbuk National University Hospital, Jeonju, 16Department of Cardiology, Cheil General Hospital, Dankook University College of Medicine, Seoul, 17Department of Cardiology, Hanyang University Guri Hospital, Guri, 18Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Background: The study reported here compared the blood pressure (BP)-lowering efficacy of fimasartan alone with that of fimasartan/hydrochlorothiazide (HCTZ) combination in patients whose BP goal was not achieved after 4 weeks of treatment with once-daily fimasartan 60 mg.Methods: Patients with sitting diastolic blood pressure (siDBP) ≥90 mmHg with 4 weeks of once-daily fimasartan 60 mg were randomly assigned to receive either once-daily fimasartan 60 mg/HCTZ 12.5 mg or fimasartan 60 mg for 4 weeks. After 4 weeks, the dose was increased from fimasartan 60 mg/HCTZ 12.5 mg to fimasartan 120 mg/HCTZ 12.5 mg or from fimasartan 60 mg to fimasartan 120 mg if siDBP was ≥90 mmHg.Results: Of the 263 randomized patients, 256 patients who had available efficacy data were analyzed. The fimasartan/HCTZ treatment group showed a greater reduction of siDBP compared to the fimasartan treatment group at Week 4 (6.88±8.10 mmHg vs 3.38±7.33, P=0.0008), and the effect persisted at Week 8 (8.67±9.39 mmHg vs 5.02±8.27 mmHg, P=0.0023). Reduction of sitting systolic BP in the fimasartan/HCTZ treatment group was also greater than that in the fimasartan treatment group (at Week 4, 10.50±13.76 mmHg vs 5.75±12.18 mmHg, P=0.0069 and, at Week 8, 13.45±15.15 mmHg vs 6.84±13.57 mmHg, P=0.0007). The proportion of patients who achieved a reduction of siDBP ≥10 mmHg from baseline and/or a mean siDBP

Cheol-Su Kim,1,* Hai-Duong Nguyen,1,* Rosa Mistica Ignacio,2 Jae-Hyun Kim,1 Hyeon-Cheol Cho,1 Eun Ho Maeng,3 Yu-Ri Kim,4 Meyoung-Kon Kim,4 Bae-Keun Park,5 Soo-Ki Kim1,5 1Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea; 2Department of Environmental Medical Biology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea; 3Healthcare Laboratory, Medical Device Evaluation Team, Korea Testing and Research Institute, Gimpo-si, Gyeonggi-do, Republic of Korea; 4Department of Biochemistry and Molecular Biology, Medical School and College, Korea University, Seoul, Republic of Korea; 5Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea *These authors contributed equally to this work Abstract: While zinc oxide (ZnO) nanoparticles (NPs) have been recognized to have promising applications in biomedicine, their immunotoxicity has been inconsistent and even contradictory. To address this issue, we investigated whether ZnO NPs with different size (20 or 100 nm) and electrostatic charge (positive or negative) would cause immunotoxicity in vitro and in vivo, and explored their underlying molecular mechanism. Using Raw 264.7 cell line, we examined the immunotoxicity mechanism of ZnO NPs as cell viability. We found that in a cell viability assay, ZnO NPs with different size and charge could induce differential cytotoxicity to Raw 264.7 cells. Specifically, the positively charged ZnO NPs exerted higher cytotoxicity than the negatively charged ones. Next, to gauge systemic immunotoxicity, we assessed immune responses of C57BL/6 mice after oral administration of 750 mg/kg/day dose of ZnO NPs for 2 weeks. In parallel, ZnO NPs did not alter the cell-mediated immune response in mice but suppressed innate immunity such as natural killer cell activity. The CD4+/CD8+ ratio, a marker for matured T-cells was slightly reduced, which implies the alteration of immune status induced by ZnO NPs. Accordingly, nitric oxide production from splenocyte culture supernatant in ZnO NP-fed mice was lower than control. Consistently, serum levels of pro/anti-inflammatory (interleukin [IL]-1Β, tumor necrosis factor-α, and IL-10) and T helper-1 cytokines (interferon-γ and IL-12p70) in ZnO NP-fed mice were significantly suppressed. Collectively, our results indicate that different sized and charged ZnO NPs would cause in vitro and in vivo immunotoxicity, of which nature is an immunosuppression. Keywords: immunosuppression, cytokine, ZnO, immune response, cytotoxicity, innate immunity

Yu-Ri Kim,1,* Seung-Young Lee,3,* Eun Jeong Lee,1 Sung Ha Park,4 Nak-won Seong,3 Heung-Sik Seo,3 Sung-Sup Shin,3 Seon-Ju Kim,3 Eun-Ho Meang,3 Myeong-Kyu Park,3 Min-Seok Kim,3 Cheol-Su Kim,5 Soo-Ki Kim,5 Sang Wook Son,2 Young Rok Seo,6 Boo Hyon Kang,7 Beom Seok Han,8 Seong Soo A An,9 Beom-Jun Lee,10 Meyoung-Kon Kim1 1Department of Biochemistry and Molecular Biology, 2Department of Dermatology, Korea University Medical School and College, 3General Toxicology Team, Korea Testing and Research Institute, Seoul, Republic of Korea; 4Department of Biochemistry, University of Bath, Bath, UK; 5Department of Microbiology, Wonju College of Medicine, Yonsei University, Gangwon, 6Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, 7Nonclinical Research Institute, Chemon Inc, Gyeonggi, 8Toxicological Research Center, Hoseo University, Chungnam, 9Department of Bionanotechnology, Gachon University, Gyeonggi, 10College of Veterinary Medicine, Chungbuk National University, Chungbuk, Republic of Korea *These authors contributed equally to this work Abstract: This study was undertaken to investigate the potential toxicity and establish the no observed adverse effect level (NOAEL) and target organ(s) of negatively charged colloidal silica particles of different sizes, ie, SiO2EN,20(-) (20 nm) or SiO2EN,100(-) (100 nm), administered by gavage in Sprague-Dawley rats. After verification of the physicochemical properties of the SiO2 particles to be tested, a preliminary dose range-finding study and 90-day repeated dose study were conducted according to the Organisation for Economic Cooperation and Development test guideline. Based on the results of the 14-day dose range-finding study, a high dose was determined to be 2,000 mg/kg, and middle and low doses were set at 1,000 and 500 mg/kg, respectively. In the 90-day toxicity study, there were no animal deaths in relation to administration of SiO2 particles of either size. In addition, no treatment-related clinical changes or histopathological findings were observed in any of the experimental groups. Moreover, no difference in toxic effects from chronic exposure to SiO2EN,20(-) (20 nm) or SiO2EN,100(-) (100 nm) was observed. The results of this study indicate that the NOAEL for SiO2EN,20(-) and SiO2EN,100(-) would most likely be 2,000 mg/kg, and no target organ was identified in rats of either sex. Keywords: silica nanoparticles, particle size, 90-day oral dose toxicity, no observed adverse effect level

Yu-Ri Kim,1,* Jong-Il Park,2,* Eun Jeong Lee,1 Sung Ha Park,3 Nak-won Seong,2 Jun-Ho Kim,2 Geon-Yong Kim,2 Eun-Ho Meang,2 Jeong-Sup Hong,2 Su-Hyon Kim,2 Sang-Bum Koh,2 Min-Seok Kim,2 Cheol-Su Kim,4 Soo-Ki Kim,4 Sang Wook Son,5 Young Rok Seo,6 Boo Hyon Kang,7 Beom Seok Han,8 Seong Soo A An,9 Hyo-In Yun,9 Meyoung-Kon Kim1 1Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea; 2General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea; 3Department of Biochemistry, University of Bath, Bath, UK; 4Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon, Korea; 5Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, Korea; 6Nonclinical Research Institute, Chemon Inc., Yongin, Gyeonggi, Korea; 7Toxicological Research Center, Hoseo University, Ansan, Chungnam, Korea; 8Department of Bionanotechnology, Gachon University, Seongnam, Gyeonggi, Korea; 9College of Veterinary Medicine, Chungnam National University, Daejon, Korea *These authors contributed equally to this work Abstract: Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnOAE100[-]) or positively (ZnOAE100[+]) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnOAE100(-) and ZnOAE100(+) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg. Keywords: zinc oxide nanoparticles, surface charge, 90-day oral dose toxicity, no observed adverse effect level

Jae-Hyun Kim,1,* Cheol-Su Kim,1,* Rosa Mistica Coles Ignacio,2,* Dong-Heui Kim,2 Ma Easter Joy Sajo,2 Eun Ho Maeng,3 Xu-Feng Qi,4 Seong-Eun Park,5 Yu-Ri Kim,7 Meyoung-Kon Kim,7 Kyu-Jae Lee,2 Soo-Ki Kim1,5,6 1Department of Microbiology, 2Department of Environmental Medical Biology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea; 3Healthcare Laboratory, Medical Device Evaluation, Korea Testing and Research Institute, Wonju-si, Gangwon-do, Republic of Korea; 4Key Laboratory for Regenerative Medicine of Ministry of Education and Department of Developmental and Regenerative Biology, School of Life Science and Technology, Ji Nan University, Guangzhou, People’s Republic of China; 5Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea; 6Institute of Biomaterials, Yonsei University, Wonju Campus, Wonju-si, Gangwon-do, Republic of Korea; 7Department of Biochemistry and Molecular Biology, Medical School and College, Korea University, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: Silicon dioxide (SiO2) nanoparticles (NPs) have been widely used in the biomedical field, such as in drug delivery and gene therapy. However, little is known about the biological effects and potential hazards of SiO2. Herein, the colloidal SiO2 NPs with two different sizes (20 nm and 100 nm) and different charges (L-arginine modified: SiO2EN20[R], SiO2EN100[R]; and negative: SiO2EN20[-], SiO2EN100[-]) were orally administered (750 mg/kg/day) in female C57BL/6 mice for 14 days. Assessments of immunotoxicity include hematology profiling, reactive oxygen species generation and their antioxidant effect, stimulation assays for B- and T-lymphocytes, the activity of natural killer (NK) cells, and cytokine profiling. In vitro toxicity was also investigated in the RAW 264.7 cell line. When the cellularity of mouse spleen was evaluated, there was an overall decrease in the proliferation of B- and T-cells for all the groups fed with SiO2 NPs. Specifically, the SiO2EN20(-) NPs showed the most pronounced reduction. In addition, the nitric oxide production and NK cell activity in SiO2 NP-fed mice were significantly suppressed. Moreover, there was a decrease in the serum concentration of inflammatory cytokines such as interleukin (IL)-1Β, IL-12 (p70), IL-6, tumor necrosis factor-α, and interferon-γ. To elucidate the cytotoxicity mechanism of SiO2 in vivo, an in vitro study using the RAW 264.7 cell line was performed. Both the size and charge of SiO2 using murine macrophage RAW 264.7 cells decreased cell viability dose-dependently. Collectively, our data indicate that different sized and charged SiO2 NPs would cause differential immunotoxicity. Interestingly, the small-sized and negatively charged SiO2 NPs showed the most potent in vivo immunotoxicity by way of suppressing the proliferation of lymphocytes, depressing the killing activity of NK cells, and decreasing proinflammatory cytokine production, thus leading to immunosuppression. Keywords: silicon dioxide, nanoparticle, immunotoxicity, oxidative stress, cytokines, immunosuppression

Jung-Hoon Kim, Sa Kang Kim, Sang Beom Han, Seung-Jun Lee, Moosang KimDepartment of Ophthalmology, School of Medicine, Kangwon National University, Chuncheon, KoreaAbstract: A 31-year-old man presented to our clinic for an ocular trauma to his left eye. His best-corrected visual acuity was 20/200 OS (left eye). Anterior segment examination showed an epithelial defect, which implies a direct injury to the cornea. A marked focal stromal edema accompanied by Descemet’s membrane folds were located at 10 o’clock in the paraxial area, about 4 mm apart from the corneal center. Anterior segment optical coherence tomography (AS-OCT) revealed marked corneal swelling of the lesion. Five days later, the patient’s best-corrected visual acuity improved to 20/50 OS. The stromal edema resolved showing no signs of epithelial defect, although small opacity remained. AS-OCT revealed complete resolution of corneal swelling. Despite the resolution of corneal edema, however, specular microscopy showed substantially decreased endothelial cell density in the lesion compared to the fellow eye. Here we report a case of traumatic corneal stromal edema discovered by AS-OCT.Keywords: AS-OCT, stromal edema, trauma

Kang HS, Rhee CK, Kim SK, Kim JW, Lee SH, Yoon HK, Ahn JH, Kim YH. Int J Chron Obstruct Pulmon Dis. 2016;11:2467–2473.Page 2467, Abstract, Results section, line 1, the text “COPD exacerbations (177 eosinophilic and 380 neutrophilic) were included” should read “COPD exacerbations (177 eosinophilic, 380 neutrophilic and 48 paucigranulocytic) were included. Of these, we compared patients with eosinophilic and neutrophilic COPD exacerbations”.Read the original article