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1.  Fasting serum C-peptide is useful for initial classification of diabetes mellitus in children and adolescents 
With rising obesity rates in children, it is increasingly difficult to differentiate between type 1 and type 2 diabetes mellitus (T1DM, T2DM) on clinical grounds alone. Using C-peptide as a method of classifying diabetes mellitus (DM) has been suggested. This study aimed to find a correlation between fasting C-peptide level and DM types in children and adolescents.
A total of 223 diabetic children, newly diagnosed at 5 hospitals between January 2001 and December 2012, were enrolled in this study. Initial DM classification was based on clinical and laboratory data including fasting C-peptide at diagnosis; final classification was based on additional data (pancreatic autoantibodies, human leukocyte antigen type, and clinical course).
Of 223 diabetic children, 140 were diagnosed with T1DM (62.8%) and the remaining 83 with T2DM (37.2%). The mean serum C-peptide level was significantly lower in children with T1DM (0.80 ng/mL) than in children with T2DM (3.91 ng/mL). Among 223 children, 54 had a serum C-peptide level <0.6 ng/mL; they were all diagnosed with T1DM. The proportion of children with T2DM increased in accordance with C-peptide level. Forty-nine of 223 children had a C-peptide level >3.0 ng/mL; 48 of them (97.9%) were diagnosed with T2DM.
In this study, we found that if the C-peptide level was <0.6 ng/mL at diagnosis, T2DM could be excluded; if C-peptide level was >3.0 ng/mL, a T1DM diagnosis is unlikely. This finding suggests that serum fasting C-peptide level is useful for classifying DM type at the time of diagnosis in youth.
PMCID: PMC4114050  PMID: 25077090
C-peptide; Classification; Diabetes mellitus; Child
2.  Peripheral facial palsy, the only presentation of a primitive neuroectodermal tumor of the skull base 
•A 2-month-old male infant presenting with only peripheral facial palsy was diagnosed with a primitive neuroectodermal tumor of the skull base.•Primitive neuroectodermal tumors located in the skull base are rarely detected in infants.•After subtotal resection of the tumor, asymmetrical facial expression showed mild improvement.
Peripheral facial palsy is rarely caused by primary neoplasms, which are mostly constituted of tumors of the central nervous system, head and neck, and leukemia.
Presentation of case
A 2-month-old male infant presented with asymmetric facial expression for 3 weeks. Physical examination revealed suspicious findings of right peripheral facial palsy. Computed tomography of the temporal bone revealed a suspicious bone tumor centered in the right petrous bone involving surrounding bones with extension into the middle ear cavity and inner ear. Subtotal resection of the tumor was performed due to crucial structures adjacent the mass. Histopathology and immunohistochemistry of the resected tumor was consistent with primitive neuroectodermal tumor.
We report a rare case of a primitive neuroectodermal tumor located at the skull base presenting with only peripheral facial palsy.
PMCID: PMC4756191  PMID: 26710328
Facial palsy; Primitive neuroectodermal tumor (PNET); Skull base neoplasm
3.  Development of a Multiplex and Cost-Effective Genotype Test toward More Personalized Medicine for the Antiplatelet Drug Clopidogrel 
There has been a wide range of inter-individual variations in platelet responses to clopidogrel. The variations in response to clopidogrel can be driven by genetic polymorphisms involved in the pathway of absorption, distribution, metabolism, excretion, and the target receptor P2Y12. A set of genetic variants known for causing variations in clopidogrel responses was selected, which included CYP2C19*2, *3, *17, CYP2B6*4, *6, *9, CYP3A4*18, CYP3A5*3, MDR1 2677G > T/A, 3435C > T, and P2Y12 H2 (742T > C). The simultaneous detection of these 10 variants was developed by using a multiplex PCR and single-base extension (MSSE) methodology. The newly developed genotyping test was confirmed by direct DNA sequencing in the representative positive control samples and validated in an extended set of 100 healthy Korean subjects. Genotyping results from the developed MSSE exhibited a perfect concordance with the direct DNA sequencing data and all of variants tested in 100 healthy Korean subjects were in agreement with Hardy-Weinberg equilibrium (p > 0.05). The present molecular diagnostic studies provide an accurate, convenient, and fast genotyping method for the detection of multiple variants. This would be helpful for researchers, as well as clinicians, to use genetic information toward more personalized medicine of clopidogrel and other antiplatelet drugs in the future.
PMCID: PMC4057700  PMID: 24857912
clopidogrel; genotypes; CYP2C19; P2Y12; SNaPshot; pharmacogenetics
4.  The effects of fucodian on senescence are controlled by the p16INK4a-pRb and p14Arf-p53 pathways in hepatocellular carcinoma and hepatic cell lines 
Fucoidan is known to have various pharmacological effects, including antitumor activity. Although it has potential as a therapeutic agent for cancer cells, the anti-senescence effects and detailed mechanism of action remain poorly understood in normal hepatic cells. We investigated the anticancer functions of fucoidan using HepG2 cells as well as the mechanisms mediating the anti-senescent actions in Chang liver cells. Fucoidan effectively inhibited HepG2 cell viability and induced apoptosis. Also, fucoidan-induced G1 phase arrest was caused by the activity of the p16INK4a-Rb and p14Arf-p53 pathways. Furthermore, upregulation of p16INK4a was critical to the antitumor activity of HepG2 cells treated with fucoidan and was correlated with inhibition of Cdk4 and pRb and upregulation of p21 expression. Our results suggest that fucoidan upregulates INK4a locus genes to induce apoptosis through p38 MAPK in HepG2 cells. Moreover, it prevents cellular senescence of Chang-L cells, by decreasing p14Arf expression as cells enter quiescence, with the reduction of p16INK4a. Fucoidan treatment also downregulated the expression of α2M. In conclusion, fucoidan can be considered a potential therapeutic agent against liver cancer that does not cause senescence in normal hepatic cells. Thus, it may be possible to use fucoidan therapeutically in both tumor suppression and aging.
PMCID: PMC4079163  PMID: 24807532
fucoidan; anti-tumor; anti-senescence; p16INK4a-Rb; p14Arf-p53; α2M
5.  Prolonged survival of islet allografts in mice treated with rosmarinic acid and anti-CD154 antibody 
Pancreatic islet transplantation can correct the abnormal glucose metabolism of Type 1 diabetes. Although immunosuppressants greatly reduce the acute rejection rate in transplant patients, the long-term side effects can be debilitating. Therefore, researchers are seeking to develop new immunosuppressive regimens that induce maximal levels of immunosuppression with minor side effects. Rosmarinic acid (Ros A) is a secondary metabolite of certain herbs and has multiple biological activities, including anti-inflammatory effects. Here, we have investigated whether treatment of mice with a combination of Ros A and anti-CD154 monoclonal antibody (MR1) improves islet allograft survival in a murine model. After transplantation, the mice were treated with either Ros A, MR1, or both (the "double" treatment). Allograft survival was prolonged in the double-treated animals compared to animals that received only Ros A or MR1. As is the case with the single-treated animals at 15 days after transplantation, the double-treated recipients did not display a significant decrease in the expression of cytokines or the population of activated T cells. Infiltrating CD3+ T cells were reduced in the MR1- or double therapy relative to control or RosA group. However, at the same time point, double-treated graft showed fewer apoptotic cells and increased expression of insulin and glucagons, compared to the single-treatment groups. Furthermore, long-term (> 150 days) allografts that were received with double therapy exhibited larger islet clusters and contained more insulin- and glucagon-positive cells, relative to the MR1-treated grafts. In conclusion, treatment with both Ros A and MR1 has a synergistic effect in murine islet allotransplantation.
PMCID: PMC2679315  PMID: 18305392
apoptosis; CD40 ligand; graft survival; immunosuppressive agents; islets of Langerhans transplantation; rosmarinic acid
6.  Challenges of Endoscopic Management of Pancreaticobiliary Complications in Surgically Altered Gastrointestinal Anatomy 
Clinical Endoscopy  2016;49(6):502-505.
Pancreaticobiliary complications following various surgical procedures, including liver transplantation, are not uncommon and are important causes of morbidity and mortality. Therapeutic endoscopy plays a substantial role in these patients and can help to avoid the need for reoperation. However, the endoscopic approach in patients with surgically altered gastrointestinal (GI) anatomy is technically challenging because of the difficulty in entering the enteral limb to reach the target orifice to manage pancreaticobiliary complications. Additional procedural complexity is due to the need of special devices and accessories to obtain successful cannulation and absence of an elevator in forward-viewing endoscopes, which is frequently used in this situation. Once bilioenteric anastomosis is reached, the technical success rates achieved in expert hands approach those of patients with intact GI anatomy. The success of endoscopic therapy in patients with surgically altered GI anatomy depends on multiple factors, including the expertise of the endoscopist, understanding of postoperative anatomic changes, and the availability of suitable scopes and accessories for endoscopic management. In this issue of Clinical Endoscopy, the focused review series deals with pancreatobiliary endoscopy in altered GI anatomy such as bilioenteric anastomosis and post-gastrectomy.
PMCID: PMC5152776  PMID: 27894188
Pancreaticobiliary complications; Challenge; Endotherapy; Altered anatomy
7.  Body image and depression in girls with idiopathic precocious puberty treated with gonadotropin-releasing hormone analogue 
Precocious puberty (PP) is associated with psychological and behavioral problems. This study aimed to evaluate the perception of body image and depression in girls with PP receiving gonadotropin-releasing hormone (GnRH) analogue therapy.
From March to August 2013, 82 girls with PP receiving GnRH analogue therapy were enrolled. Height, weight, body mass index, and stages of pubertal development were assessed. Participants completed a series of questionnaires on their body image perception and pubertal self-assessment. The depression score was calculated using the Korean Kovacs' Children's Depression Inventory.
The patients perceived their body to be more obese than the controls did. The mean depression score did not differ between the patients and controls. The mean depression scores according to Tanner stages (1: prepubertal, 2: early pubertal, and 3–5: mid to late pubertal stage) by self-assessment were 5.2±3.6, 6.8±4.9, and 11.4±10.1 (P<0.05), respectively. The perception of overall body build and figure (%) and the mean depression scores in patients were: dissatisfied (25.6%, 9.7±7.8) and satisfied (74.4%, 5.5±3.4) (P<0.05). In multiple linear regression analysis, self-T3 (Tanner stage 3–5 by self-awareness) and dissatisfaction about overall body build and figure were found to significantly affect the depression score(P<0.05).
The perception of pubertal status and satisfaction about height or weight are unrelated to objective physical findings. Patients with PP are prone to distorted perception about their body image and breast development. Such incorrect body image seems to contribute to depression score.
PMCID: PMC5073162  PMID: 27777908
Precocious puberty; Body image; Depression
8.  Prognostic significance of CT-emphysema score in patients with advanced squamous cell lung cancer 
Journal of Thoracic Disease  2016;8(8):1966-1973.
Although emphysema is a known independent risk factor of lung cancer, no study has addressed the prognostic impact of computed tomography (CT)-emphysema score in advanced stage lung cancer.
For 84 consecutive patients with stage IIIB and IV squamous cell lung cancer that underwent palliative chemotherapy, severity of emphysema was semi-quantitatively scored using baseline chest CT images according to the Goddard scoring system (possible scores range, 0–24). The cutoff of high CT-emphysema score was determined using the maximum chi-squared test and the prognostic significance of the high CT-emphysema score was evaluated using Kaplan-Meier analysis and Cox proportional hazards analysis.
The median CT-emphysema score was 5 (range, 0–22). Patients with a high CT-emphysema score (≥4) tended to have poorer overall survival (OS) (median: 6.3 vs. 13.7 months) than those with a score of <4 (P=0.071). Multivariable analysis revealed that a higher CT-emphysema score was a significant independent prognostic factor for poor OS [hazard ratio (HR) =2.06; 95% confidence interval (CI), 1.24–3.41; P=0.005), along with no response to first-line therapy (P=0.009) and no second-line therapy (P<0.001).
CT-emphysema score is significantly associated with poor prognosis in patients with advanced squamous cell lung cancer.
PMCID: PMC4999671  PMID: 27621848
CT-emphysema score; lung cancer; squamous cell carcinoma; chemotherapy; prognosis
9.  Effective Oocyte Vitrification and Survival Techniques for Bovine Somatic Cell Nuclear Transfer 
Cellular Reprogramming  2015;17(3):199-210.
Bovine somatic cell nuclear transfer (SCNT) using vitrified–thawed (VT) oocytes has been studied; however, the cloning efficiency of these oocytes is not comparable with that of nonvitrified (non-V) fresh oocytes. This study sought to optimize the survival and cryopreservation of VT oocytes for SCNT. Co-culture with feeder cells that had been preincubated for 15 h significantly improved the survival of VT oocytes and their in vitro developmental potential following SCNT in comparison to co-culture with feeder cells that had been preincubated for 2, 5, or 24 h (p<0.05). Spindle assessment via the Oosight Microscopy Imaging System and microtubule staining revealed that vitrified metaphase II oocytes (VT group) were not suitable for SCNT. However, enucleating and/or activating oocytes prior to freezing enhanced their developmental potential and suitability for SCNT. The cloning efficiency of the enucleated–activated–vitrified–thawed (EAVT) group (21.6%) was better than that of the other vitrification groups [enucleated–vitrified–thawed (EVT) group, 13.7%; VT group, 15.0%; p<0.05] and was comparable with that of the non-V group (25.9%). The reactive oxygen species level was significantly lower in the EAVT group than in the other vitrification groups (p<0.05). mRNA levels of maternal genes (ZAR1, BMP15, and NLRP5) and a stress gene (HSF1) were lower in the vitrification groups than in the non-V group (p<0.05), whereas the level of phospho-p44/42 mitogen-activated protein kinase did not differ among the groups. Among the vitrification groups, blastocysts in the EAVT group had the best developmental potential, as judged by their high mRNA expression of developmental potential–related genes (POU5f1, Interferon-tau, and SLC2A5) and their low expression of proapoptotic (CASP3) and stress (Hsp70) genes. This study demonstrates that SCNT using bovine frozen–thawed oocytes can be successfully achieved using optimized vitrification and co-culture techniques.
PMCID: PMC4487599  PMID: 25984830
11.  Risk factors for tuberculosis after gastrectomy in gastric cancer 
World Journal of Gastroenterology  2016;22(8):2585-2591.
AIM: To examine incidence of tuberculosis (TB) in gastrectomy patients and investigate the risk factors for developing TB after gastrectomy in patients with gastric cancer.
METHODS: A retrospective cohort study of gastrectomy patients with gastric cancer was performed at a university-affiliated hospital in Seoul, South Korea between January 2007 and December 2009. We reviewed patient medical records and collected data associated with the risk of TB, surgery, and gastric cancer. Standardized incidence ratios (SIRs) of TB were calculated to compare the incidence of TB in gastrectomy patients with that in the general Korean population, and risk factors for TB after gastrectomies were analyzed.
RESULTS: Among the 1776 gastrectomy patients, 0.9% (16/1776) developed post-gastrectomy TB, with an incidence of 223.7 cases per 100000 patients per year. The overall incidence of TB in gastrectomy patients, adjusted by sex and age, was significantly higher than that in the general population (SIR = 2.22, 95%CI: 1.27-3.60). Previous TB infection [odds ratio (OR) = 7.1, P < 0.001], lower body mass index (BMI) (kg/m2; OR = 1.21, P = 0.043) and gastrectomy extent (total gastrectomy vs subtotal gastrectomy) (OR = 3.48, P = 0.017) were significant risk factors for TB after gastrectomy in a multivariate analysis.
CONCLUSION: TB incidence after gastrectomy is higher than that in the general population. Previous TB infection, lower BMI, and total gastrectomy are risk factors for TB after gastrectomy in patients with gastric cancer.
PMCID: PMC4768204  PMID: 26937146
Tuberculosis; Gastrectomy; Body mass index; Risk factor; Gastric cancer
12.  Effect of dual-type oligosaccharides on constipation in loperamide-treated rats 
Nutrition Research and Practice  2016;10(6):583-589.
Constipation is a condition that can result from intestinal deformation. Because humans have an upright posture, the effects of gravity can cause this shape deformation. Oligosaccharides are common prebiotics and their effects on bowel health are well known. However, studies of the physiological functionality of a product that contains both lactulose and galactooligosaccharides are insufficient. We investigated the constipation reduction effect of a dual-type oligosaccharide, Dual-Oligo, in loperamide-treated rats.
Dual-Oligo consists of galactooligosaccharides (15.80%) and lactulose (51.67%). Animals were randomly divided into four groups, the normal group (normal), control group (control), low concentration of Dual-Oligo (LDO) group, and high concentration of Dual-Oligo (HDO) group. After 7 days of oral administration, fecal pellet amount, fecal weight, water content of fecal were measured. Blood chemistry, short-chain fatty acid (SCFA), gastrointestinal transit ratio and length and intestinal mucosa were analyzed.
Dual-Oligo increased the fecal weight, and water content of feces in rats with loperamide-induced constipation. Gastrointestinal transit ratio and length and area of intestinal mucosa significantly increased after treatment with Dual-Oligo in loperamide-induced rats. A high concentration of Dual-Oligo tended to produce more acetic acid than that observed for the control group, and Dual-Oligo affected the production of total SCFA. Bifidobacteria concentration of cecal contents in the high-concentration oligosaccharide (HDO) and low-concentration oligosaccharide (LDO) groups was similar to the result of the normal group.
These results showed that Dual-Oligo is a functional material that is derived from a natural food product and is effective in ameliorating constipation.
PMCID: PMC5126407  PMID: 27909555
Oligosaccharides; constipation; loperamide; gastrointestinal transit; Alcian Blue
13.  The miR-125 family is an important regulator of the expression and maintenance of maternal effect genes during preimplantational embryo development 
Open Biology  2016;6(11):160181.
Previously, we reported that Sebox is a new maternal effect gene (MEG) that is required for early embryo development beyond the two-cell (2C) stage because this gene orchestrates the expression of important genes for zygotic genome activation (ZGA). However, regulators of Sebox expression remain unknown. Therefore, the objectives of the present study were to use bioinformatics tools to identify such regulatory microRNAs (miRNAs) and to determine the effects of the identified miRNAs on Sebox expression. Using computational algorithms, we identified a motif within the 3′UTR of Sebox mRNA that is specific to the seed region of the miR-125 family, which includes miR-125a-5p, miR-125b-5p and miR-351-5p. During our search for miRNAs, we found that the Lin28a 3′UTR also contains the same binding motif for the seed region of the miR-125 family. In addition, we confirmed that Lin28a also plays a role as a MEG and affects ZGA at the 2C stage, without affecting oocyte maturation or fertilization. Thus, we provide the first report indicating that the miR-125 family plays a crucial role in regulating MEGs related to the 2C block and in regulating ZGA through methods such as affecting Sebox and Lin28a in oocytes and embryos.
PMCID: PMC5133438  PMID: 27906131
Sebox; Lin28a; miR-125 family; translational regulation; bioinformatics
14.  Effects of nurse staffing, work environments, and education on patient mortality: An observational study 
While considerable evidence has been produced showing a link between nursing characteristics and patient outcomes in the U.S. and Europe, little is known about whether similar associations are present in South Korea.
To examine the effects of nurse staffing, work environment, and education on patient mortality.
This study linked hospital facility data with staff nurse survey data (N=1,024) and surgical patient discharge data (N = 76,036) from 14 high-technology teaching hospitals with 700 or more beds in South Korea, collected between January 1, 2008 and December 31, 2008. Logistic regression models that corrected for the clustering of patients in hospitals were used to estimate the effects of the three nursing characteristics on risk-adjusted patient mortality within 30 days of admission.
Risk-adjusted models reveal that nurse staffing, nurse work environments, and nurse education were significantly associated with patient mortality (OR 1.05, 95% CI 1.00–1.10; OR 0.52, 95% CI 0.31–0.88; and OR 0.91, CI 0.83–0.99; respectively). These odds ratios imply that each additional patient per nurse is associated with an 5% increase in the odds of patient death within 30 days of admission, that the odds of patient mortality are nearly 50% lower in the hospitals with better nurse work environments than in hospitals with mixed or poor nurse work environments, and that each 10% increase in BSN nurse is associated with a 9% decrease in patient deaths.
Nurse staffing, nurse work environments, and percentages of BSN nurses in South Korea are associated with patient mortality. Improving hospital nurse staffing and work environments and increasing the percentages of BSN nurses would help reduce the number of preventable in-hospital deaths.
PMCID: PMC4286441  PMID: 25213091
Mortality; Nursing education; Nurse staffing; Nurse work environment; Patient outcomes
15.  Cycles of circadian illuminance are sufficient to entrain and maintain circadian locomotor rhythms in Drosophila 
Scientific Reports  2016;6:37784.
Light at night disrupts the circadian clock and causes serious health problems in the modern world. Here, we show that newly developed four-package light-emitting diodes (LEDs) can provide harmless lighting at night. To quantify the effects of light on the circadian clock, we employed the concept of circadian illuminance (CIL). CIL represents the amount of light weighted toward the wavelengths to which the circadian clock is most sensitive, whereas visual illuminance (VIL) represents the total amount of visible light. Exposure to 12 h:12 h cycles of white LED light with high and low CIL values but a constant VIL value (conditions hereafter referred to as CH/CL) can entrain behavioral and molecular circadian rhythms in flies. Moreover, flies re-entrain to phase shift in the CH/CL cycle. Core-clock proteins are required for the rhythmic behaviors seen with this LED lighting scheme. Taken together, this study provides a guide for designing healthful white LED lights for use at night, and proposes the use of the CIL value for estimating the harmful effects of any light source on organismal health.
PMCID: PMC5121609  PMID: 27883065
16.  Chicken soup for teaching and learning ESD 
Endoscopic submucosal dissection (ESD) is becoming a popular procedure for the diagnosis and treatment of superficial mucosal lesions, and has the advantage of en bloc resection which yields a higher complete resection and remission rate compared to endoscopic mucosal resection (EMR). However, the learning process of this advanced endoscopic procedure requires a lengthy training period and considerable experience to be proficient. A well framed training protocol which is safe, effective, easily reproducible and cost-effective is desirable to teach ESD. In addition, the training course may need to be tailored around settings such as ethnicity, culture, workload, and disease incidence. In Asian countries with a large volume of early gastric lesions which need endoscopic treatment, endoscopists would be able to learn ESD expanding their skills from EMR to ESD under the supervision of experts. Whereas, in Western countries due to the low incidence of superficial gastric tumors, trials have utilized simulator models to improve learning. In Korea, the Korean Society of Gastrointestinal Endoscopy (KSGE) is playing an important role in training many gastroenterologists who have shown an interest in performing ESD by providing an annual live demonstration and a nationwide tutoring program. The purpose of this article is to introduce our ESD tutoring experience, review the published papers related to this topic, and propose several suggestions for future directions in teaching and learning ESD.
PMCID: PMC3110923  PMID: 21677829
Endoscopic submucosal dissection; Learning; Teaching
17.  Health-Related Quality of Life in Korean Adults with Hearing Impairment: The Korea National Health and Nutrition Examination Survey 2010 to 2012 
PLoS ONE  2016;11(10):e0163999.
As the global population ages, disabling hearing impairment (HI) have been increased rapidly. The impact of HI on health-related quality of life (HRQoL) is of great importance to aid the development of strategic plans and to guide therapeutic interventions.
To evaluate HRQoL in Korean adults with different degrees of HI using EuroQol five-dimensional (EQ-5D) and EQ-visual analogue scale (VAS), the preference-based generic measures of HRQoL.
Using a representative dataset from the Korea National Health and Nutrition Examination Survey (KNHANES) from January 2010 to December 2012, EQ-5D questionnaire and EQ- VAS scores of subjects with HI were compared with those of subjects without HI. Logistic regression analysis, with adjustment for covariates, was used to evaluate the impact of HI on HRQoL scales. HI was defined according to the hearing thresholds of pure-tone averages at 0.5, 1, 2, and 3 kHz of the better hearing ear as follows; mild HI (26 to < 40 dB) and moderate to severe HI (≥ 40 dB).
Of the 16,449 Korean adults in KNHANES (age, 45.0 ± 0.2 years; male, 49.7%), 1757 (weighted prevalence, 7.6%) had mild HI and 890 (3.6%) had moderate to severe HI. Subjects with HI had impaired HRQoL as compared with subjects without HI (EQ-5D, 0.96 ± 0.00 vs. 0.88±0.00 vs. 0.86 ± 0.01 for control vs. mild HI vs. moderate to severe HI, p < 0.001; EQ-VAS, 75.10 ± 0.18 vs. 67.48 ± 0.63 vs. 66.24 ± 0.92 for control vs. mild HI vs. moderate to severe HI, p < 0.001). After adjusting for socio-demographic factors (age, gender, household income, education level, presence of spouse) and health-related behaviors (smoking status, alcohol intake, regular exercise), psychological stress, and the presence of comorbidities (diabetes, hypercholesterolemia, hypertension, decreased eGFR, and tinnitus), EQ-VAS remained impaired in the moderate to severe HI group (61.72±1.69) as compared with the control group (65.68 ± 1.26, p = 0.004), but EQ-5D impairment disappeared (0.86 ± 0.02 vs.0.88±0.01 for moderate to severe HI vs. control, p = 0.058).
After adjusting for socio-demographic and psychosocial factors and comorbidities, Korean adults with moderate to severe HI rated their health statuses lower than subjects without HI.
PMCID: PMC5053436  PMID: 27711203
18.  Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index (ALI) in Patients with Small Cell Lung Cancer_ Comparison with Original ALI 
PLoS ONE  2016;11(10):e0164056.
Advanced lung cancer inflammation index (ALI, body mass index [BMI] x serum albumin/neutrophil-lymphocyte ratio [NLR]) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). CT enables skeletal muscle to be quantified, whereas BMI cannot accurately reflect body composition. The purpose was to evaluate prognostic value of modified ALI (mALI) using CT-determined L3 muscle index (L3MI, muscle area at L3/height2) beyond original ALI.
L3MIs were calculated using the CT images of 186 consecutive patients with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR. Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the prognostic values of low ALI and low mALI were tested using Kaplan-Meier method and Cox proportional hazards analysis. Finally, deviance statistics was used to test whether the goodness of fit of the prognostic model is improved by adding mALI as an extra variable.
Patients with low ALI (cut-off, 31.1, n = 94) had shorter OS than patients with high ALI (median, 6.8 months vs. 15.8 months; p < 0.001), and patients with low mALI (cut-off 67.7, n = 94) had shorter OS than patients with high mALI (median, 6.8 months vs. 16.5 months; p < 0.001). There was no significant difference in estimates of median survival time between low ALI and low mALI (z = 0.000, p = 1.000) and between high ALI and high mALI (z = 0.330, p = 0.740). Multivariable analysis showed that low ALI was an independent prognostic factor for shorter OS (HR, 1.67, p = 0.004), along with advanced age (HR, 1.49, p = 0.045), extensive disease (HR, 2.27, p < 0.001), supportive care only (HR, 7.86, p < 0.001), and elevated LDH (HR, 1.45, p = 0.037). Furthermore, goodness of fit of this prognostic model was not significantly increased by adding mALI as an extra variable (LR difference = 2.220, p = 0.136).
The present study confirms mALI using CT-determined L3MI has no additional prognostic value beyond original ALI using BMI. ALI is a simple and useful prognostic indicator in SCLC.
PMCID: PMC5051688  PMID: 27706243
19.  Is There a Role for Adjuvant Therapy in R0 Resected Gallbladder Cancer?: A Propensity Score-Matched Analysis 
The purpose of this study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer (GBC) patients who have undergone R0 resection.
Materials and Methods
Clinical data were collected on 441 consecutive patients who underwent R0 resection for stage I-III GBC. Eligible patients were classified into adjuvant therapy and surveillance only groups. Propensity score matching (PSM) between the two groups was performed, adjusting clinical factors.
In total, 84 and 279 patients treated with adjuvant therapy and followed up with surveillance only, respectively, were included in the analysis. Before PSM, the 5-year relapse-free survival (RFS) rate was lower in the adjuvant therapy group than in the surveillance only group (50.8% vs. 74.8%, p < 0.001), although there was no statistically significant difference in the 5-year overall survival (OS) rate (66.2% vs. 79.5%, p=0.089). After the PSM, baseline characteristics became comparable and there were no differences in the 5-year RFS (50.8% vs. 64.8%, p=0.319) and OS (66.2% vs. 70.4%, p=0.703) rates between the two groups.
The results suggest that fluoropyrimidine-based adjuvant therapy is not indicated in stage I-III GBC patients who have undergone R0 resection.
PMCID: PMC5080804  PMID: 26875193
Gallbladder neoplasms; Adjuvant chemotherapy; Adjuvant chemoradiotherapy; Survival; Propensity score
20.  A wide variation of the quality of colonoscopy reporting system in the real clinical practice in southeastern area of Korea 
Intestinal Research  2016;14(4):351-357.
Establishment of a colonoscopy reporting system is a prerequisite to determining and improving quality. This study aimed to investigate colonoscopists' opinions and the actual situation of a colonoscopy reporting system in a clinical practice in southeastern area of Korea and to assess the factors predictive of an inadequate reporting system.
Physicians who performed colonoscopies in the Daegu-Gyeongbuk province of Korea and were registered with the Korean Society of Gastrointestinal Endoscopy (KSGE) were interviewed via mail about colonoscopy reporting systems using a standardized questionnaire.
Of 181 endoscopists invited to participate, 125 responded to the questionnaires (response rate, 69%). Most responders were internists (105/125, 84%) and worked in primary clinics (88/125, 70.4%). Seventy-one specialists (56.8%) held board certifications for endoscopy from the KSGE. A median of 20 colonoscopies (interquartile range, 10–47) was performed per month. Although 88.8% of responders agreed that a colonoscopy reporting system is necessary, only 18.4% (23/125) had achieved the optimal reporting system level recommended by the Quality Assurance Task Group of the National Colorectal Cancer Roundtable. One-third of endoscopists replied that they did not use a reporting document for the main reasons of "too busy" and "inconvenience." Non-endoscopy specialists and primary care centers were independent predictive factors for failure to use a colonoscopy reporting system.
The quality of colonoscopy reporting systems varies widely and is considerably suboptimal in actual clinical practice settings in southeastern Korea, indicating considerable room for quality improvements in this field.
PMCID: PMC5083264  PMID: 27799886
Colonoscopy; Report; Survey; Quality
21.  A Case of Solitary Brain Metastasis from Uterine Mullerian Adenosarcoma with Sarcomatous Overgrowth 
Uterine adenosarcoma (AS) are rare tumors and have more favorable outcomes than the aggressive uterine carcinosarcomas. Uterine adenosarcoma with sarcomatous overgrowth (ASSO) is a variant form of AS and exhibits aggressive growth of tumor and the prognosis is relatively poor compared with typical AS. Usually patterns of metastasis have been known to behave like endometrial carcinoma and spread through the lymphatics. Brain metastasis from uterine AS is extremely rare. Herein, we report a case of successfully surgically removed solitary brain metastasis without any extracranial recurrence from uterine ASSO after 4 years of primary treatment.
PMCID: PMC5114186  PMID: 27867926
Adenosarcoma of the uterus; Brain; Metastasis
22.  The role of Rad51 in safeguarding mitochondrial activity during the meiotic cell cycle in mammalian oocytes 
Scientific Reports  2016;6:34110.
Rad51 is a conserved eukaryotic protein that mediates the homologous recombination repair of DNA double-strand breaks that occur during mitosis and meiosis. In addition, Rad51 promotes mitochondrial DNA synthesis when replication stress is increased. Rad51 also regulates cell cycle progression by preserving the G2/M transition in embryonic stem cells. In this study, we report a novel function of Rad51 in regulating mitochondrial activity during in vitro maturation of mouse oocytes. Suppression of Rad51 by injection of Rad51 dsRNA into germinal vesicle-stage oocytes resulted in arrest of meiosis in metaphase I. Rad51-depleted oocytes showed chromosome misalignment and failures in spindle aggregation, affecting the completion of cytokinesis. We found that Rad51 depletion was accompanied by decreased ATP production and mitochondrial membrane potential and increased DNA degradation. We further demonstrated that the mitochondrial defect activated autophagy in Rad51-depleted oocytes. Taken together, we concluded that Rad51 functions to safeguard mitochondrial integrity during the meiotic maturation of oocytes.
PMCID: PMC5039699  PMID: 27677401
23.  A Rare Case of Bleeding Ectopic Lingual Thyroid Presenting as Hematemesis 
Yonsei Medical Journal  2015;56(4):1163-1164.
PMCID: PMC4479850  PMID: 26069145
24.  Clinical Endoscopy as One of Leading Journals in Gastrointestinal Endoscopy 
Clinical Endoscopy  2015;48(4):312-316.
Clinical Endoscopy (CE) is an official open access journal published bimonthly by the Korean Society of Gastrointestinal Endoscopy (KSGE, and is listed on PMC, PubMed and SCOPUS. The KSGE was established on August 14, 1976, and the journal of the KSGE was published in Korean for the first time in November 1981. The journal was then titled the "Korean Journal of Gastrointestinal Endoscopy" and was published in Korean untill the July 2011 issue. The journal was published in English from the September 2011 issue under the official title of CE. In this review, the past and present of CE are discussed and future perspectives are introduced. In addition, the efforts to progress to a "first come, first served journal" in the field of gastrointestinal endoscopy and to be indexed in Science Citation Index will be described.
PMCID: PMC4522423  PMID: 26240805
Clinical Endoscopy; Korean Society of Gastrointestinal Endoscopy; English; Journal; Open access
25.  Practical Suggestions to Train Better-Performing Endosonographers 
Gut and Liver  2015;9(3):261-262.
PMCID: PMC4413961  PMID: 25918257

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