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1.  Prevalence of Trichomonas vaginalis by PCR in Men Attending a Primary Care Urology Clinic in South Korea 
Trichomonas vaginalis, a causative agent of trichomoniasis, may trigger symptomatic or asymptomatic nongonococcal urethritis and chronic prostatitis in men. Despite the availability of highly sensitive diagnostic tests, such as nucleic acid amplification tests, including PCR, few prospective studies present data on male T. vaginalis infection in South Korea. In the present study, the prevalence of T. vaginalis and associated clinical conditions were evaluated in 201 male patients from a primary care urology clinic in South Korea. The prevalence of T. vaginalis infection in our cohort was 4% (8/201) by PCR. T. vaginalis infection was common in men older than 40 years (median age, 52 years). Among the 8 Trichomonas-positive patients, 87.5% (7/8) had prostatic diseases, such as prostatitis and benign prostatic hyperplasia, and 25.0% (2/8) and 12.5% (1/8) were coinfected with Chlamydia trachomatis and Mycoplasma genitalium, respectively. Our results suggest that T. vaginalis infection is not rare in men attending primary care urology clinics in South Korea, especially in those older than 40 years, in whom it may explain the presence of prostatic disease. The possibility of T. vaginalis infection should be routinely considered in older male patients with prostatic diseases in South Korea.
doi:10.3347/kjp.2014.52.5.551
PMCID: PMC4210741  PMID: 25352707
Trichomonas vaginalis; sexually transmitted disease; diagnosis; PCR; multiplex PCR
2.  Diagnostic value of coronary CT angiography in comparison with invasive coronary angiography and intravascular ultrasound in patients with intermediate coronary artery stenosis: results from the prospective multicentre FIGURE-OUT (Functional Imaging criteria for GUiding REview of invasive coronary angiOgraphy, intravascular Ultrasound, and coronary computed Tomographic angiography) study 
Aims
The anatomical criteria for the diagnosis of ischaemia referenced by fractional flow reserve (FFR) from non-invasive coronary computed tomographic angiography (CCTA), invasive coronary angiography (ICA), and intravascular ultrasound (IVUS) have not been evaluated contemporarily in a large-scale study. The aim of this study was to assess the diagnostic value of CCTA compared with ICA and IVUS in patients with intermediate coronary stenosis.
Methods and results
CCTA, ICA, IVUS, and FFR were performed in 181 coronary lesions with intermediate severity. Minimal lumen diameter (MLD) and per cent diameter stenosis (%DS) were determined by CCTA and ICA, whereas minimal lumen area (MLA) was determined by CCTA and IVUS. Inducible ischaemia was defined by FFR ≤0.80. Diagnostic performances from non-invasive and invasive methods were compared. FFR ≤0.80 was observed in 49 (27.1%) lesions. CCTA MLD was smaller than ICA MLD (1.3 ± 0.5 vs. 1.5 ± 0.4 mm, P < 0.001), CCTA %DS was higher than ICA %DS (54.0 ± 14.0 vs. 50.3 ± 12.8%, P < 0.001), and CCTA MLA was smaller than IVUS MLA (2.2 ± 1.2 vs. 3.2 ± 1.2 mm2, P < 0.001). This trend was consistent irrespective of lesion location, lesion severity, and plaque characteristics. For the determination of ischaemia, diagnostic performance of CCTA %DS was lower than ICA %DS [area under the curve (AUC) 0.657 vs. 0.765, P = 0.04], and that of CCTA MLA was lower than IVUS MLA (AUC 0.712 vs. 0.801, P = 0.03).
Conclusion
Anatomical criteria for the diagnosis of ischaemia-producing coronary stenosis differ by non-invasive and invasive methods. Compared with invasive methods, CCTA presents overestimation in assessing lesion severity and lower diagnostic performance in assessing ischaemia.
doi:10.1093/ehjci/jeu009
PMCID: PMC4110885  PMID: 24513881
coronary computed tomographic angiography; intravascular ultrasound; fractional flow reserve; myocardial ischaemia; coronary disease
3.  Direct-to-Consumer Tobacco Marketing and Its Association with Tobacco Use Among Adolescents and Young Adults 
Objective
We assess exposure to direct-to-consumer tobacco marketing and its association with ever having tried smoking, smoking within past 30 days (‘current’), and smoking ≥100 cigarettes in lifetime (‘established’) among adolescents and young adults.
Methods
We surveyed a U.S. telephone sample of 3,342 15–23 year olds and 2,541 respondents subsequently completed a web-based survey. Among respondents completing both the telephone and web-based surveys (N=2,541 [75%]), we assessed their exposure to direct-to-consumer tobacco marketing (receiving direct mail from tobacco companies and seeing tobacco company websites) and their associations with ever having tried smoking, current smoking, and established smoking.
Results
Overall, 12% of 15–17 year olds and 26% of 18–23 year olds were exposed to direct-to-consumer tobacco marketing. Racial/ethnic minority non-smoking respondents were more likely to see tobacco websites than non-smoking Whites. Respondents exposed to either form of direct-to-consumer tobacco marketing were more likely to currently smoke (adjusted odds ratio[AOR]: 2.2; 95% CI 1.3–3.8), while those exposed to both forms of marketing experienced even higher odds of currently smoking (AOR: 2.7; 95% CI 1.1–6.6). We observed similar relationships for ever having tried smoking and established smoking.
Conclusions
Direct-to-consumer tobacco marketing reaches adolescent and young adult non-smokers and is associated with smoking behavior.
doi:10.1016/j.jadohealth.2014.01.019
PMCID: PMC4241586  PMID: 24661738
4.  Higher association of coronary artery calcification with non-alcoholic fatty liver disease than with abdominal obesity in middle-aged Korean men: the Kangbuk Samsung Health Study 
Background
It is uncertain whether non-alcoholic fatty liver disease (NAFLD) or abdominal obesity is more associated with atherosclerosis. The aim of this study was to determine whether NAFLD or abdominal obesity is more strongly associated with subclinical atherosclerosis represented by coronary artery calcification (CAC).
Methods
A total of 21,335 male participa nts in a health screening program (mean age 41 years) were enrolled. Ultrasonographic measurements of fatty liver and multi-detector computed tomography were performed to determine the coronary artery calcium score (CACS). The presence of CAC was defined as CACS >0. Subjects were divided into four groups according to the presence or absence of NAFLD and/or abdominal obesity as assessed by waist-hip ratio (WHR) >0.9.
Results
The presence of CAC was detected in 2,385 subjects (11.2%). The proportion of subjects with CAC was highest in the abdominal obesity only group (23.2%). After adjustment for age, diabetes history, hypertension, cigarette smoking, and physical inactivity, the odds ratio (OR) for CAC was the highest in the group with both abnormalities [1.465 (1.324–1.623)]. The NAFLD only group showed significantly increased OR for CAC compared to that in the abdominal obesity only group [1.286 (1.151–1.436) vs. 1.076 (0.939–1.233)].
Conclusion
Non-alcoholic fatty liver disease is more closely associated with CAC than abdominal obesity as assessed by the WHR. NAFLD could be considered an independent determinant of subclinical atherosclerosis as assessed by CAC.
doi:10.1186/s12933-015-0253-9
PMCID: PMC4501081  PMID: 26169265
Coronary artery calcification; Non-alcoholic fatty liver disease; Abdominal obesity
5.  Ezetimibe improves hepatic steatosis in relation to autophagy in obese and diabetic rats 
AIM: To investigate whether ezetimibe ameliorates hepatic steatosis and induces autophagy in a rat model of obesity and type 2 diabetes.
METHODS: Male age-matched lean control LETO and obese and diabetic OLETF rats were administered either PBS or ezetimibe (10 mg/kg per day) via stomach gavage for 20 wk. Changes in weight gain and energy intake were regularly monitored. Blood and liver tissue were harvested after overnight fasting at the end of study. Histological assessment was performed in liver tissue. The concentrations of glucose, insulin, triglycerides (TG), free fatty acids (FFA), and total cholesterol (TC) in blood and TG, FFA, and TG in liver tissue were measured. mRNA and protein abundance involved in autophagy was analyzed in the liver. To investigate the effect of ezetimibe on autophagy and reduction in hepatic fat accumulation, human Huh7 hepatocytes were incubated with ezetimibe (10 μmol/L) together with or without palmitic acid (PA, 0.5 mmol/L, 24 h). Transmission electron microscopy (TEM) was employed to demonstrate effect of ezetimibe on autophagy formation. Autophagic flux was measured with bafilomycin A1, an inhibitor of autophagy and following immunoblotting for autophagy-related protein expression.
RESULTS: In the OLETF rats that received ezetimibe (10 mg/kg per day), liver weight were significantly decreased by 20% compared to OLETF control rats without changes in food intake and body weight (P < 0.05). Lipid parameters including TG, FFA, and TC in liver tissue of ezetimibe-administrated OLETF rats were dramatically decreased at least by 30% compared to OLETF controls (P < 0.01). The serum glucose, insulin, HOMA-IR, and lipid profiles were also improved by ezetimibe (P < 0.05). In addition, autophagy-related mRNA expression including ATG5, ATG6, and ATG7 and the protein level of microtubule-associated protein light chain 3 (LC3) were significantly increased in the liver in rats that received ezetimibe (P < 0.05). Likewise, for hepatocytes cultured in vitro, ezetimibe treatment significantly decreased PA-induced fat accumulation and increased PA-reduced mRNA and protein expression involved in autophagy (P < 0.05). Ezetimibe-increased autophagosomes was observed in TEM analysis. Immunoblotting analysis of autophagy formation with an inhibitor of autophagy demonstrated that ezetimibe-increased autophagy resulted from increased autophagic flux.
CONCLUSION: The present study demonstrates that ezetimibe-mediated improvement in hepatic steatosis might involve the induction of autophagy.
doi:10.3748/wjg.v21.i25.7754
PMCID: PMC4491962  PMID: 26167075
Autophagy; Ezetimibe; Hepatic steatosis; Nonalcoholic fatty liver disease
6.  Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury 
Journal of Korean Medical Science  2015;30(7):943-952.
Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-κB (NF-κB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-κB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.
Graphical Abstract
doi:10.3346/jkms.2015.30.7.943
PMCID: PMC4479950  PMID: 26130959
Agmatine; Traumatic Brain Injury; Brain Edema; Blood-Brain Barrier; Aquaporins; Mitogen-Activated Protein Kinases
8.  The Korean guideline for cervical cancer screening 
Journal of Gynecologic Oncology  2015;26(3):232-239.
The incidence rate of cervical cancer in Korea is still higher than in other developed countries, notwithstanding the national mass-screening program. Furthermore, a new method has been introduced in cervical cancer screening. Therefore, the committee for cervical cancer screening in Korea updated the recommendation statement established in 2002. The new version of the guideline was developed by the committee using evidence-based methods. The committee reviewed the evidence for the benefits and harms of the Papanicolaou test, liquid-based cytology, and human papillomavirus (HPV) testing, and reached conclusions after deliberation. The committee recommends screening for cervical cancer with cytology (Papanicolaou test or liquid-based cytology) every three years in women older than 20 years of age (recommendation A). The cervical cytology combined with HPV test is optionally recommended after taking into consideration individual risk or preference (recommendation C). The current evidence for primary HPV screening is insufficient to assess the benefits and harms of cervical cancer screening (recommendation I). Cervical cancer screening can be terminated at the age of 74 years if more than three consecutive negative cytology reports have been confirmed within 10 years (recommendation D).
doi:10.3802/jgo.2015.26.3.232
PMCID: PMC4510341  PMID: 26197860
Mass Screening; Papanicolaou Test; Uterine Cervical Neoplasms
9.  Lateral Oropharyngeal Wall Coverage with Buccinator Myomucosal and Buccal Fat Pad Flaps 
Archives of Plastic Surgery  2015;42(4):453-460.
Background
Reconstruction of oropharyngeal defects after resection of oropharyngeal cancer is a significant challenge. The purpose of this study is to introduce reconstruction using a combination of a buccinator myomucosal flap and a buccal fat pad flap after cancer excision and to discuss the associated anatomy, surgical procedure, and clinical applications.
Methods
In our study, a combination of a buccinator myomucosal flap with a buccal fat pad flap was utilized for reconstruction after resection of oropharyngeal cancer, performed between 2013 and 2015. After oropharyngectomy, the defect with exposed vital structures was noted. A buccinator myomucosal flap was designed and elevated after an assessment of the flap pedicle. Without requiring an additional procedure, a buccal fat pad flap was easily harvested in the same field and gently pulled to obtain sufficient volume. The flaps were rotated and covered the defect. In addition, using cadaver dissections, we investigated the feasibility of transposing the flaps into the lateral oropharyngeal defect.
Results
The reconstruction was performed in patients with squamous cell carcinoma. The largest tumor size was 5 cm×2 cm (length×width). All donor sites were closed primarily. The flaps were completely epithelialized after four weeks, and the patients were followed up for at least six months. There were no flap failures or postoperative wound complications. All patients were without dietary restrictions, and no patient had problems related to mouth opening, swallowing, or speech.
Conclusions
A buccinator myomucosal flap with a buccal fat pad flap is a reliable and valuable option in the reconstruction of oropharyngeal defects after cancer resection for maintaining functionality.
doi:10.5999/aps.2015.42.4.453
PMCID: PMC4513054  PMID: 26217566
Surgical flap; Oropharyngeal neoplasms; Reconstructive surgical procedures
10.  Functional Outcomes of Multiple Sural Nerve Grafts for Facial Nerve Defects after Tumor-Ablative Surgery 
Archives of Plastic Surgery  2015;42(4):461-468.
Background
Functional restoration of the facial expression is necessary after facial nerve resection to treat head and neck tumors. This study was conducted to evaluate the functional outcomes of patients who underwent facial nerve cable grafting immediately after tumor resection.
Methods
Patients who underwent cable grafting from April 2007 to August 2011 were reviewed, in which a harvested branch of the sural nerve was grafted onto each facial nerve division. Twelve patients underwent facial nerve cable grafting after radical parotidectomy, total parotidectomy, or schwannoma resection, and the functional facial expression of each patient was evaluated using the Facial Nerve Grading Scale 2.0. The results were analyzed according to patient age, follow-up duration, and the use of postoperative radiation therapy.
Results
Among the 12 patients who were evaluated, the mean follow-up duration was 21.8 months, the mean age at the time of surgery was 42.8 years, and the mean facial expression score was 14.6 points, indicating moderate dysfunction. Facial expression scores were not influenced by age at the time of surgery, follow-up duration, or the use of postoperative radiation therapy.
Conclusions
The results of this study indicate that facial nerve cable grafting using the sural nerve can restore facial expression. Although patients were provided with appropriate treatment, the survival rate for salivary gland cancer was poor. We conclude that immediate facial nerve reconstruction is a worthwhile procedure that improves quality of life by allowing the recovery of facial expression, even in patients who are older or may require radiation therapy.
doi:10.5999/aps.2015.42.4.461
PMCID: PMC4513055  PMID: 26217567
Facial nerve; Sural nerve; Surgery; Radiotherapy; Age groups
11.  Assessment of radiation exposure from cesium-137 contaminated roads for epidemiological studies in Seoul, Korea 
Objectives
We aimed to assess the radiation exposure for epidemiologic investigation in residents exposed to radiation from roads that were accidentally found to be contaminated with radioactive cesium-137 (137Cs) in Seoul.
Methods
Using information regarding the frequency and duration of passing via the 137Cs contaminated roads or residing/working near the roads from the questionnaires that were obtained from 8875 residents and the measured radiation doses reported by the Nuclear Safety and Security Commission, we calculated the total cumulative dose of radiation exposure for each person.
Results
Sixty-three percent of the residents who responded to the questionnaire were considered as ever-exposed and 1% of them had a total cumulative dose of more than 10 mSv. The mean (minimum, maximum) duration of radiation exposure was 4.75 years (0.08, 11.98) and the geometric mean (minimum, maximum) of the total cumulative dose was 0.049 mSv (<0.001, 35.35) in the exposed.
Conclusions
An individual exposure assessment was performed for an epidemiological study to estimate the health risk among residents living in the vicinity of 137Cs contaminated roads. The average exposure dose in the exposed people was less than 5% of the current guideline.
doi:10.5620/eht.e2015005
PMCID: PMC4509455  PMID: 26184047
Accidental contamination; Cesium-137; Epidemiological studies; Radiation exposure assessment
12.  Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model 
Scientific Reports  2015;5:11555.
Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, but its role in neuropathic pain remains unclear. In this study, we examined the ER stress and the unfolded protein response (UPR) activation in a L5 spinal nerve ligation (SNL)-induced rat neuropathic pain model. SNL-induced neuropathic pain was assessed behaviorally using the CatWalk system, and histologically with microglial activation in the dorsal spinal horn. L5 SNL induced BIP upregulation in the neuron of superficial laminae of dorsal spinal horn. It also increased the level of ATF6 and intracellular localization into the nuclei in the neurons. Moreover, spliced XBP1 was also markedly elevated in the ipsilateral spinal dorsal horn. The PERK-elF2 pathway was activated in astrocytes of the spinal dorsal horn in the SNL model. In addition, electron microscopy revealed the presence of swollen cisternae in the dorsal spinal cord after SNL. Additionally, inhibition of the ATF6 pathway by intrathecal treatment with ATF6 siRNA reduced pain behaviors and BIP expression in the dorsal horn. The results suggest that ER stress might be involved in the induction and maintenance of neuropathic pain. Furthermore, a disturbance in UPR signaling may render the spinal neurons vulnerable to peripheral nerve injury or neuropathic pain stimuli.
doi:10.1038/srep11555
PMCID: PMC4479804  PMID: 26109318
13.  Relationship between Metabolic Syndrome and Lower Urinary Tract Symptoms: Hallym Aging Study 
BioMed Research International  2015;2015:130917.
The aim of the study was to test the hypothesis that the metabolic syndrome (MS) is linked to lower urinary tract symptoms (LUTS) in Korean men. This was a longitudinal study that used data collected from 328 men aged 50–89 years who were randomly selected among 1,520 participants in 2004. We collected information from 224 (68.3%) men among the original responders on the biological, medical, psychological, social, lifestyle, and economic factors in 2007. The prevalence of the MS was 187/328 (57.0%) in 2004 and 125/224 (55.8%) in 2007 among men, respectively. There was no significantly greater increase in the IPSS in men with the MS than in men without the MS over a 3-year period of time (2.0 ± 9.37 versus 3.0 ± 8.44, p = 0.402, resp.). In the multivariate logistic regression analysis with control for age and life style factors, the risk factors for moderate/severe LUTS were age and erectile dysfunction (p < 0.05). However, the presence of the MS did not increase the risk of moderate/severe LUTS (OR = 1.09, 95% CI 0.63–1.89, p = 0.748). Our cross-sectional and longitudinal risk factor analyses do not support the hypothesis that the MS is linked to LUTS in Korean men.
doi:10.1155/2015/130917
PMCID: PMC4493267  PMID: 26199934
14.  Electrophilic activity-based RNA probes reveal a self-alkylating RNA for RNA labeling 
Nature chemical biology  2014;10(12):1049-1054.
Probes that form covalent bonds with RNA molecules based on their chemical reactivity would advance our ability to study the transcriptome. We developed a set of electrophilic activity-based RNA probes designed to react with unusually nucleophilic RNAs. We used these probes to identify reactive genome-encoded RNAs, resulting in the discovery of a 42-nt catalytic RNA from an archaebacterium that reacts with a 2,3-disubstituted epoxide at N7 of a specific guanosine. Detailed characterization of the catalytic RNA revealed the structural requirements for reactivity. We developed this catalytic RNA into a general tool to selectively conjugate a small molecule to an RNA of interest. This strategy enabled up to 500-fold enrichment of target RNA from total mammalian RNA or from cell lysate. We demonstrated the utility of this approach by selectively capturing proteins in yeast cell lysate that bind to the ASH1 mRNA.
doi:10.1038/nchembio.1655
PMCID: PMC4232462  PMID: 25306441
16.  Multivariate Analysis of Risk Factors Associated With the Nonreversal Ileostomy Following Sphincter-Preserving Surgery for Rectal Cancer 
Annals of Coloproctology  2015;31(3):98-102.
Purpose
A loop ileostomy is used to protect an anastomosis after anal sphincter-preserving surgery, especially in patients with low rectal cancer, but little information is available concerning risk factors associated with a nonreversal ileostomy. The purpose of this study was to identify risk factors of ileostomy nonreversibility after a sphincter-saving resection for rectal cancer.
Methods
Six hundred seventy-nine (679) patients with rectal cancer who underwent sphincter-preserving surgery between January 2004 and December 2011 were evaluated retrospectively. Of the 679, 135 (19.9%) underwent a defunctioning loop ileostomy of temporary intent, and these patients were divided into two groups, that is, a reversal group (RG, 112 patients) and a nonreversal group (NRG, 23 patients) according to the reversibility of the ileostomy.
Results
In 23 of the 135 rectal cancer patients (17.0%) that underwent a diverting ileostomy, stoma reversal was not possible for the following reasons; stage IV rectal cancer (11, 47.8%), poor tone of the anal sphincter (4, 17.4%), local recurrence (2, 8.7%), anastomotic leakage (1, 4.3%), radiation proctitis (1, 4.3%), and patient refusal (4, 17.4%). The independent risk factors of the nonreversal group were anastomotic leakage or fistula, stage IV cancer, local recurrence, and comorbidity.
Conclusion
Postoperative complications such as anastomotic leakage or fistula, advanced primary disease (stage IV), local recurrence and comorbidity were identified as risk factors of a nonreversal ileostomy. These factors should be considered when drafting prudential guidelines for ileostomy closure.
doi:10.3393/ac.2015.31.3.98
PMCID: PMC4496460  PMID: 26161377
Sphincter-preserving surgery; Ileostomy; Rectal cancer
17.  Differences in two-point discrimination and sensory threshold in the blind between braille and text reading: a pilot study 
Journal of Physical Therapy Science  2015;27(6):1919-1922.
[Purpose] This study investigated two-point discrimination (TPD) and the electrical sensory threshold of the blind to define the effect of using Braille on the tactile and electrical senses. [Subjects and Methods] Twenty-eight blind participants were divided equally into a text-reading and a Braille-reading group. We measured tactile sensory and electrical thresholds using the TPD method and a transcutaneous electrical nerve stimulator. [Results] The left palm TPD values were significantly different between the groups. The values of the electrical sensory threshold in the left hand, the electrical pain threshold in the left hand, and the electrical pain threshold in the right hand were significantly lower in the Braille group than in the text group. [Conclusion] These findings make it difficult to explain the difference in tactility between groups, excluding both palms. However, our data show that using Braille can enhance development of the sensory median nerve in the blind, particularly in terms of the electrical sensory and pain thresholds.
doi:10.1589/jpts.27.1919
PMCID: PMC4500011  PMID: 26180348
Electrical sensory threshold; Pain threshold; The blind
18.  Exendin-4 Inhibits the Expression of SEPP1 and Fetuin-A via Improvement of Palmitic Acid-Induced Endoplasmic Reticulum Stress by AMPK 
Endocrinology and Metabolism  2015;30(2):177-184.
Background
Selenoprotein P (SEPP1) and fetuin-A, both circulating liver-derived glycoproteins, are novel biomarkers for insulin resistance and nonalcoholic fatty liver disease. However, the effect of exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, on the expression of hepatokines, SEPP1, and fetuin-A, is unknown.
Methods
The human hepatoma cell line HepG2 was treated with palmitic acid (PA; 0.4 mM) and tunicamycin (tuni; 2ug/ml) with or without exendin-4 (100 nM) for 24 hours. The change in expression of PA-induced SEPP1, fetuin-A, and endoplasmic reticulum (ER) stress markers by exendin-4 treatment were evaluated using quantitative real-time reverse transcription polymerase chain reaction and Western blotting. Transfection of cells with AMP-activated protein kinase (AMPK) small interfering RNA (siRNA) was performed to establish the effect of exendin-4-mediated AMPK in the regulation of SEPP1 and fetuin-A expression.
Results
Exendin-4 reduced the expression of SEPP1, fetuin-A, and ER stress markers including PKR-like ER kinase, inositol-requiring kinase 1α, activating transcription factor 6, and C/EBP homologous protein in HepG2 cells. Exendin-4 also reduced the expression of SEPP1 and fetuin-A in cells treated with tunicamycin, an ER stress inducer. In cells treated with the AMPK activator 5-aminoidazole-4-carboxamide ribonucleotide (AICAR), the expression of hepatic SEPP1 and fetuin-A were negatively related by AMPK, which is the target of exendin-4. In addition, exendin-4 treatment did not decrease SEPP1 and fetuin-A expression in cells transfected with AMPK siRNA.
Conclusion
These data suggest that exendin-4 can attenuate the expression of hepatic SEPP1 and fetuin-A via improvement of PA-induced ER stress by AMPK.
doi:10.3803/EnM.2015.30.2.177
PMCID: PMC4508262  PMID: 26194078
Exendin-4; Palmitic acid; Endoplasmic reticulum stress; AMP-activated protein kinases; Selenoprotein P; Fetuin-A; Hepatokine
19.  Comparison of Serum Adipocytokine Levels according to Metabolic Health and Obesity Status 
Endocrinology and Metabolism  2015;30(2):185-194.
Background
Metabolic health is an emerging concept that is highly correlated with various metabolic complications, and adipocytokines have been causally linked to a wide range of metabolic diseases. Thus, this study compared serum adipocytokine levels according to metabolic health and obesity status.
Methods
Four hundred and fifty-six nondiabetic subjects (mean age, 40.5 years) were categorized into four groups according to metabolic health and obesity status: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUHNO), and metabolically unhealthy obese (MUHO). Being metabolically healthy was defined as the presence of fewer than two of the following five metabolic abnormalities: high blood pressure, high fasting blood glucose, high triglyceride, low high density lipoprotein cholesterol, and being in the highest decile of the homeostatic model assessment of insulin resistance index. Obesity status was assessed using body mass index (BMI), with obesity defined as a BMI higher than 25 kg/m2. Levels of serum interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor α (TNF-α), and adipocyte fatty acid binding protein (A-FABP) were also evaluated.
Results
Of the 456 subjects, 247 (54.2%) were in the MHNO group, 66 (14.5%) were in the MHO group, 66 (14.5%) were in the MUHNO group, and 77 (16.9%) were in the MUHO group. There were no significant differences in IL-6 or MCP-1 levels among the groups, but levels of TNF-α and A-FABP were significantly higher in the MUHNO group compared to the MHNO group.
Conclusion
High TNF-α and A-FABP levels are significantly associated with metabolically unhealthiness in nonobese Korean individuals.
doi:10.3803/EnM.2015.30.2.185
PMCID: PMC4508263  PMID: 25325281
Obesity; Metabolic health; Adipocytokine
20.  The Impact of Improving Suicide Death Classification in South Korea: A Comparison with Japan and Hong Kong 
PLoS ONE  2015;10(5):e0125730.
Introduction
The suicide rate of South Korea has increased dramatically during the past decades, as opposed to steadily decreasing trends in Japan and Hong Kong. Although the recent increase of suicide in South Korea may be related to changing socioeconomic conditions and other contextual factors, it may also reflect, in part, a reduction of misidentified suicide cases due to improving classification of manner of death.
Method
We compared the annual proportional change of suicide, undetermined death, and accidental death from South Korea with those of Japan and Hong Kong from 1992 to 2011; a greater proportional change of the manner-of-death categories during the period is indicative of a relatively less stable registration and hence a greater potential for misclassification bias on reported suicide trends. Subgroup analyses stratifying the deaths by methods were also conducted. To estimate the impact, the age-standardized rates of these three death categories in each site were calculated.
Results
We found that, during the 20-year observation period, the proportional change of suicide, undetermined death, and accidental death in South Korea was significantly greater than Japan and Hong Kong. Similar observations were made in subgroup analyses. While death rates of the three manners in Japan and Hong Kong generally moved in a parallel fashion, the increase of suicide in South Korea occurred concomitantly with a significant reduction of its accidental death rate. 43% of the increase in suicides could be attributed to the decrease in accidental deaths, while 57% of the increase could be due to fundamental causes.
Conclusion
Our data suggest that, during the mid-1990s and after, the increasing burden of suicide in South Korea initially was masked, in part, by misclassification. Thus, the later apparently rapid increase of suicides reflected steadily improving classification of manner of death, as well as a more fundamental increase in the suicide rate.
doi:10.1371/journal.pone.0125730
PMCID: PMC4439106  PMID: 25992879
21.  A Novel Immunochromatographic Test Applied to a Serological Survey of Japanese Encephalitis Virus on Pig Farms in Korea 
PLoS ONE  2015;10(5):e0127313.
Among vertebrate species, pigs are a major amplifying host of Japanese encephalitis virus (JEV) and measuring their seroconversion is a reliable indicator of virus activity. Traditionally, the hemagglutination inhibition test has been used for serological testing in pigs; however, it has several limitations and, thus, a more efficient and reliable replacement test is required. In this study, we developed a new immunochromatographic test for detecting antibodies to JEV in pig serum within 15 min. Specifically, the domain III region of the JEV envelope protein was successfully expressed in soluble form and used for developing the immunochromatographic test. The test was then applied to the surveillance of Japanese encephalitis (JE) in Korea. We found that our immunochromatographic test had good sensitivity (84.8%) and specificity (97.7%) when compared with an immunofluorescence assay used as a reference test. During the surveillance of JE in Korea in 2012, the new immunochromatographic test was used to test the sera of 1,926 slaughtered pigs from eight provinces, and 228 pigs (11.8%) were found to be JEV-positive. Based on these results, we also produced an activity map of JEV, which marked the locations of pig farms in Korea that tested positive for the virus. Thus, the immunochromatographic test reported here provides a convenient and effective tool for real-time monitoring of JEV activity in pigs.
doi:10.1371/journal.pone.0127313
PMCID: PMC4439121  PMID: 25992769
22.  The Gender-Dependent Association between Obesity and Age-Related Cataracts in Middle-Aged Korean Adults 
PLoS ONE  2015;10(5):e0124262.
The aim of this study was to investigate the association of central and abdominal obesity with the prevalence of cataracts in a middle-aged Korean population. This retrospective cross-sectional study was based on the data collected from the Korea National Health and Nutrition Examination Survey 2008–2009, in which 4,914 subjects were examined. Ophthalmological examinations were performed to determine the presence of a nuclear, cortical, or posterior subcapsular cataract. Both general obesity (a body mass index ≥25 kg/m2) and abdominal obesity (a waist circumference ≥90 cm for men and ≥80 cm for women) were significantly associated with the occurrence of cataracts among middle-aged women [adjusted odds ratio (aOR), 1.32; 95% confidence interval (CI), 1.03–1.69; and aOR, 1.40; 95% CI, 1.06–1.85, respectively], while abdominal obesity was significantly inversely associated with the occurrence of cataracts among middle-aged men (aOR, 0.76; 95% CI, 0.58–1.01; and aOR, 0.66; 95% CI, 0.49–0.89, respectively). We report a difference in the association between obesity and the prevalence of cataracts based on gender.
doi:10.1371/journal.pone.0124262
PMCID: PMC4431863  PMID: 25974257
23.  Osmophobia and allodynia are critical factors for suicidality in patients with migraine 
Background
Sensory hypersensitivities are common phenomena in migraine. We examined the role of sensory hypersensitivities on suicidality in patients with migraine.
Methods
Patients with migraine (with or without aura) were consecutively recruited from our headache clinic. We asked them if they experienced photophobia, phonophobia, osmophobia, and allodynia during migraine attack. The Mini International Neuropsychiatric Interview was used to diagnose current major depressive disorder (MDD), current generalized anxiety disorder (GAD) and suicidality.
Results
Among 220 subjects, 25.5 % had current MDD, 17.3 % had current GAD, and 31.8 % had suicidality. Patients with suicidality were more like to have a low household income, chronic migraine (CM), medication overuse headache, high headache intensity, osmophobia, allodynia, high disability, MDD, and GAD than those without suicidality. The strongest risk factor for suicidality by multivariate analyses was osmophobia (adjusted Odds Ratio [AOR] 3.12, 95 % confidence interval [CI] 1.57-6.21, p = 0.001), followed by current MDD (AOR 2.99, 95 % CI 1.33-6.76, p = 0.008), CM (AOR 2.48, 95 % CI 1.21-5.09, p = 0.013), current GAD (AOR 3.11, 95 % CI 1.22-7.91, p = 0.017), and allodynia (AOR 2.72, 95 % CI 1.19-6.21, p = 0.018).
Conclusions
Osmophobia and allodynia are critical factors for suicidality in patients with migraine, after controlling for depression, anxiety, and CM.
doi:10.1186/s10194-015-0529-1
PMCID: PMC4434243  PMID: 25968102
Suicide; Osmophobia; Allodynia; Migraine; Risk factor; Depression; Anxiety
24.  Cytokine Expression of Microscopic Colitis Including Interleukin-17 
Gut and Liver  2014;9(3):381-387.
Background/Aims
Microscopic colitis is characterized by chronic watery diarrhea with specific pathological changes that can be diagnosed by microscopic examination. We performed immunohistochemical analysis of proinflammatory cytokines to investigate the pathogenic mechanism of microscopic colitis.
Methods
This study consisted of six patients with lymphocytic colitis, six patients with collagenous colitis, and six patients with functional diarrhea but normal pathology. We performed an immunohistochemical analysis of the colonic mucosal biopsies to assess the expression of cyclo-oxygenase-2, interleukin-17, nuclear factor-κB, interferon-γ, inducible nitric oxide synthase, and tumor necrosis factor-α. We compared the quantity score of immunohistochemical staining among the groups.
Results
The microscopic colitis group showed significantly higher expression of cyclo-oxygenase-2, interleukin-17, nuclear factor-κB, and interferon-γ compared with the control group. Cytokine expression was similar between collagenous colitis and lymphocytic colitis. However, the expression of cyclo-oxygenase-2 was higher in collagenous colitis.
Conclusions
Proinflammatory cytokines, including interleukin-17 and interferon-γ, are highly expressed in microscopic colitis. The expression of cyclo-oxygenase-2 was higher in collagenous colitis than in lymphocytic colitis. This study is the first on interleukin-17 expression in microscopic colitis patients.
doi:10.5009/gnl13439
PMCID: PMC4413972  PMID: 25071069
Colitis; collagenous; Immunohistochemistry; Colitis; lymphocytic; Colitis; microscopic
25.  Risks of Lung Cancer due to Radon Exposure among the Regions of Korea 
Journal of Korean Medical Science  2015;30(5):542-548.
Radon is likely the second most common cause of lung cancer after smoking. We estimated the lung cancer risk due to radon using common risk models. Based on national radon survey data, we estimated the population-attributable fraction (PAF) and the number of lung cancer deaths attributable to radon. The exposure-age duration (EAD) and exposure-age concentration (EAC) models were used. The regional average indoor radon concentration was 37.5 95 Bq/m3. The PAF for lung cancer was 8.3% (European Pooling Study model), 13.5% in males and 20.4% in females by EAD model, and 19.5% in males and 28.2% in females by EAC model. Due to differences in smoking by gender, the PAF of radon-induced lung cancer deaths was higher in females. In the Republic of Korea, the risk of radon is not widely recognized. Thus, information about radon health risks is important and efforts are needed to decrease the associated health problems.
Graphical Abstract
doi:10.3346/jkms.2015.30.5.542
PMCID: PMC4414636  PMID: 25931783
Epidemiology; Lung Neoplasms; Risk Assessment; Radon; Republic of Korea

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