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26.  Is Endoscopic Retrograde Cholangiopancreatography Safe in Patients 90 Years of Age and Older? 
Gut and Liver  2014;8(5):552-556.
This case-control study evaluated the safety and efficacy of endoscopic retrograde cholangiopancreatography (ERCP) in patients 90 years of age and older.
From January 2005 to August 2011, 5,070 cases of ERCP were performed at our institution. Of these, 43 cases involved patients 90 years of age and older (mean age, 91.7±1.9 years). A control group of 129 cases (mean age, 65.7±14.8 years) was matched by the patient sex, sphincterotomy, and presence of choledocholithiasis using a propensity score. The patients’ medical records were retrospectively reviewed for comorbidity, periampullary diverticulum, urgent procedure, conscious sedation, technical success, procedure duration, ERCP-related complication, and death.
Between the case and control groups, there was no significant difference with regard to comorbidity, periampullary diverticulum, and urgent procedure. Conscious sedation was performed significantly less in the patient group versus the control group (28 [65%] vs 119 [92%], respectively; p=0.000). There was no significant difference in the technical success, procedure duration, or ERCP-related complications. In both groups, there was no major bleeding or perforation related to ERCP. Post-ERCP pancreatitis occurred significantly less in the patient group compared to the control group (0 vs 13 [10%], respectively; p=0.004). One death occurred from respiratory arrest in the case group.
ERCP can be performed safely and successfully in patients aged 90 years and older without any significant increase in complications.
PMCID: PMC4164253  PMID: 25228977
Cholangiopancreatography; endoscopic retrograde; Safety; Aged; 90 and over
27.  Tropical influenza and weather variability among children in an urban low-income population in Bangladesh 
Global Health Action  2014;7:10.3402/gha.v7.24413.
Influenza seasonality in the tropics is poorly understood and not as well documented as in temperate regions. In addition, low-income populations are considered highly vulnerable to such acute respiratory disease, owing to limited resources and overcrowding. Nonetheless, little is known about their actual disease burden for lack of data. We therefore investigated associations between tropical influenza incidence and weather variability among children under five in a poor urban area of Dhaka, Bangladesh.
Acute respiratory illness data were obtained from a population-based respiratory and febrile illness surveillance dataset of Kamalapur, a low-income urban area in southeast Dhaka. Analyzed data were from January 2005 through December 2008. Nasopharyngeal wash specimens were collected from every fifth eligible surveillance participant during clinic visits to identify influenza virus infection with viral culture and reverse transcriptase–polymerase chain reaction. Time series analysis was conducted to determine associations between the number of influenza cases per week and weather factors. Zero-inflated Poisson and generalized linear Poisson models were used in the analysis for influenza A and B, respectively.
Influenza A had associations with minimum temperature, relative humidity (RH), sunlight duration, and rainfall, whereas only RH was associated with influenza B. Although associations of the other weather factors varied between the two subtypes, RH shared a similar positive association when humidity was approximately 50–70%.
Our findings of a positive RH association is consistent with prior studies, and may suggest the viral response in the tropics. The characteristics of settlement areas, population demographics, and typical overcrowding of urban poverty may also contribute to different impacts of rainfall from higher economic population. Further investigations of associations between tropical influenza and weather variability for urban low-income populations are required for better understanding.
PMCID: PMC4134673  PMID: 25128806
influenza; tropics; weather; low-income; poor; urban; children; time series
28.  KISS1 Gene Polymorphisms in Korean Girls with Central Precocious Puberty 
Journal of Korean Medical Science  2014;29(8):1120-1125.
Kisspeptin/G-protein couple receptor-54 (GPR54) system plays a key role in the activation of the gonadotropic axis at puberty. Central precocious puberty (CPP) is caused by the premature activation of hypothalamic gonadotropin-releasing hormone secretion. This study was aimed to identify KISS1 gene variations and to investigate the associations between KISS1 gene variations and CPP in Korean girls. All coding exons of KISS1 gene were sequenced in Korean girls with CPP (n = 143) and their healthy controls (n = 101). Nine polymorphisms were identified in KISS1 gene. A novel single-nucleotide polymorphism (SNP), 55648176 T/G, was identified for the first time. SNP 55648184 C/G and 55648186 -/T were detected more frequently in CPP group than in control group. SNP 55648176 T/G was detected less frequently in CPP group than in control group. Haplotype GGGC-ACCC was detected less frequently in CPP group. The genetic variations of KISS1 gene can be contributing factors of development of CPP. The association between the gene variations and CPP should be validated by further evidence obtained from large-scaled and functional studies.
Graphical Abstract
PMCID: PMC4129205  PMID: 25120323
KISS1 Gene; Kisspeptins; G-Protein Coupled Receptor-54; Precocious Puberty, Central
29.  Comparative Study of Clinical and Radiological Outcomes of a Zero-Profile Device Concerning Reduced Postoperative Dysphagia after Single Level Anterior Cervical Discectomy and Fusion 
This study analyzed clinical and radiological outcomes of a zero-profile anchored spacer (Zero-P) and conventional cage-plate (CCP) for single level anterior cervical discectomy and fusion (ACDF) to compare the incidence and difference of postoperative dysphagia with both devices.
We retrospectively reviewed our experiences of single level ACDF with the CCP and Zero-P. From January 2011 to December 2013, 48 patients who had single level herniated intervertebral disc were operated on using ACDF, with CCP in 27 patients and Zero-P in 21 patients. Patients who received more than double-level ACDF or combined circumferential fusion were excluded. Age, operation time, estimated blood loss (EBL), pre-operative modified Japanese Orthopaedic Association (mJOA) scores, post-operative mJOA scores, achieved mJOA scores and recovery rate of mJOA scores were assessed. Prevertebral soft tissue thickness and postoperative dysphagia were analyzed on the day of surgery, and 2 weeks and 6 months postoperatively.
The Zero-P group showed same or favorable clinical and radiological outcomes compared with the CCP group. Postoperative dysphagia was significantly low in the Zero-P group.
Application of Zero-P may achieve favorable outcomes and reduce postoperative dysphagia in single level ACDF.
PMCID: PMC4200356  PMID: 25328646
Zero-profile; Prevertebral soft tissue swelling; Anterior cervical discectomy and fusion; ACDF; Dysphagia
30.  A Groove Technique for Securing an Electrode Connector on the Cranial Bone: Case Analysis of Efficacy 
A groove technique for securing an electrode connector was described as an alternative surgical technique in deep brain stimulation (DBS) surgery to avoid electrode connector-related complications, such as skin erosion, infection, and migration.
We retrospectively reviewed 109 patients undergoing one of two techniques; the standard technique (52 patients using 104 electrodes) and the groove technique (57 patients using 109 electrodes) for securing the electrode connector in DBS surgery, regardless of patient disease. In the standard percutaneous tunneling technique, the connector was placed on the vertex of the cranial surface. The other technique, so called the groove technique, created a groove (about 4 cm long, 8 mm wide) in the cranial bone at the posterior parietal area. Wound erosion and migration related to the connectors were compared between the two techniques.
The mean follow-up period was 73 months for the standard method and 46 months for the groove technique. Connector-related complications were observed in three patients with the groove technique and in seven patients with the standard technique. Wound erosion at the connector sites per electrode was one (0.9%) with the groove technique and six (5.8%) with the standard technique. This difference was statistically significant. The electrode connector was migrated in two patients with the groove technique and in one patient with the standard technique.
The groove technique, which involves securing an electrode using a groove in the cranial bone at the posterior parietal area, offers an effective and safe method to avoid electrode connector-related complications during DBS surgery.
PMCID: PMC4200360  PMID: 25328650
Deep brain stimulation; Connector; Complications
31.  Red Ginseng Extract Ameliorates Autoimmune Arthritis via Regulation of STAT3 Pathway, Th17/Treg Balance, and Osteoclastogenesis in Mice and Human 
Mediators of Inflammation  2014;2014:351856.
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation. Red ginseng is a steamed and dried Panax ginseng C.A. Meyer, which has been used as alternative medicine for thousands of years. This study was undertaken to investigate the effects of red ginseng extracts (RGE) on autoimmune arthritis in mice and humans and to delineate the underlying mechanism. RGE was orally administered three times a week to mice with arthritis. Oral administration of RGE markedly ameliorated clinical arthritis score and histologically assessed joint inflammation in mice with CIA. A significant reduction in STAT3 phosphorylation and a decrease in the number of Th17 cells were observed with RGE treatment. There was also a marked reduction in RANKL-induced osteoclastogenesis with treatment of RGE. The inhibitory effect of RGE on Th17 differentiation and osteoclastogenesis observed in mice was also confirmed in the subsequent experiments performed using human peripheral blood mononuclear cells. Our findings provide the first evidence that RGE can regulate Th17 and reciprocally promote Treg cells by inhibiting the phosphorylation of STAT3. Therefore, RGE can ameliorate arthritis in mice with CIA by targeting pathogenic Th17 and osteoclast differentiation, suggesting a novel therapy for treatment of RA.
PMCID: PMC4132415  PMID: 25147435
32.  An ethyl acetate fraction derived from Houttuynia cordata extract inhibits the production of inflammatory markers by suppressing NF-кB and MAPK activation in lipopolysaccharide-stimulated RAW 264.7 macrophages 
Houttuynia cordata Thunb. (Saururaceae) has been used in traditional medicine for treatment of inflammatory diseases. This study evaluated the anti-inflammatory effects of an ethyl acetate fraction derived from a Houttuynia cordata extract (HCE-EA) on the production of inflammatory mediators and the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.
To measure the effects of HCE-EA on pro-inflammatory cytokine and inflammatory mediator’s expression in RAW 264.7 cells, we used the following methods: cell viability assay, Griess reagent assay, enzyme-linked immunosorbent assay, real-time polymerase chain reaction and western blotting analysis.
HCE-EA downregulated nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin (IL-6) production in the cells, as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, HCE-EA suppressed nuclear translocation of the NF-κB p65 subunit, which correlated with an inhibitory effect on IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) phosphorylation. HCE-EA also attenuated the activation of MAPKs (p38 and JNK).
Our results suggest that the anti-inflammatory properties of HCE-EA may stem from the inhibition of pro-inflammatory mediators via suppression of NF-κB and MAPK signaling pathways.
PMCID: PMC4099023  PMID: 25012519
Houttuynia cordata; Inducible nitric oxide synthase; Cyclooxygenase-2; Nuclear factor-κB; Mitogen-activated protein kinase
33.  Prevalence of Systemic Lupus Erythematosus in South Korea: An Administrative Database Study 
Journal of Epidemiology  2014;24(4):295-303.
Systemic lupus erythematosus (SLE) is a rare autoimmune disease for which a population-based survey on the prevalence of the disease in South Korea has not yet been conducted. Our goal was to estimate the nationwide prevalence of SLE.
The International Classification of Diseases, Tenth Revision (ICD-10) code for SLE diagnosis—M32—was tentatively given when patients were suspected to have SLE before 2009. As such, the positive predictive value (PPV) of the M32 code shown in medical bills reflecting true SLE was uncertain. We attempted to estimate the prevalence of SLE in South Korea using national administrative database data from 2004–2006. We approximated the actual number of SLE patients by analyzing a list of SLE-coded patients provided by the National Health Insurance (NHI) and Health Insurance Review and Assessment Service. Prevalence was estimated by multiplying the PPV of the M32 diagnostic code by the number of patients receiving the code. The PPV was determined by three methods: direct investigation of the medical records of patients randomly selected from the SLE-coded patients list; assessment of all SLE patients treated at 56 selected hospitals in South Korea; and extrapolation from sub-groups at a single institute to the sub-groups of the national NHI data.
The estimated number of national SLE cases was between 9000 and 11 000, depending on the method of ascertainment, corresponding to a prevalence of 18.8–21.7 per 100 000 people.
This is the first report of a nationwide prevalence survey of SLE in South Korea. National databases may serve as a resource for epidemiologic studies of rare autoimmune diseases like SLE.
PMCID: PMC4074634  PMID: 24857955
systemic lupus erythematosus; prevalence; epidemiology
34.  The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods 
BMC Pulmonary Medicine  2014;14:109.
This paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases.
The participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child’s neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child’s genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim.
The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6 months and every year until 10 years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child’s exposure to environmental factors, maternal pre- and post-natal psychological stress, and the child’s neurodevelopment, nutritional status, and development of allergic and respiratory illnesses. The child’s microbiome, genes, epigenetics, plasma cytokine levels, and neuropsychological status, the microbiome of the residence, and the levels of indoor and outdoor pollutants are measured by standard procedures.
The COCOA study will improve our understanding of how individual genetic or environmental risk factors influence susceptibility to allergic disease and how these variables interact to shape the phenotype of allergic diseases.
PMCID: PMC4099383  PMID: 24990471
Cohort study; Gene-environment interaction; Allergy; Microbiota; Nutritional Status; Psychologic stress
35.  Primary Benign Intraosseous Meningioma on 18F-FDG PET/CT Mimicking Malignancy 
We present a case of primary benign intraosseous meningioma in the sphenoid bone mimicking malignancy. A 44-year-old female patient who had a protruding right eye and headache came to our hospital. MRI showed a large, destructive, heterogeneously well-enhancing soft tissue mass in the right sphenoid bone suggesting malignancy. 18F-FDG PET/CT showed a hypermetabolic mass in the same site with an SUVmax of 9.1 The pathological diagnosis by surgery revealed that this tumor was a WHO grade I transitional meningioma. This case suggests that primary benign intraosseous meningioma may show high 18F-FDG uptake mimicking a malignancy.
PMCID: PMC4028472  PMID: 24900156
Benign meningioma; Sphenoid bone; PET/CT; 18F-Fluorodeoxyglucose
36.  Prognosis of early mucinous gastric carcinoma 
Little is known about the clinicopathological features of early mucinous gastric carcinoma (MGC). The purpose of this study was to compare the clinicopathological features and prognosis between patients with early MGC and those with early nonmucinous gastric carcinoma (NMGC).
We reviewed the records of 2,732 patients diagnosed with gastric carcinoma who were treated surgically. There were 14 patients (0.5%) with early MGC and 958 with early NMGC.
Early MGC patients had a higher prevalence of elevated type (71.4%) compared with early NMGC patients (29.5%). More early MGC patients had submucosal carcinoma, compared with early NMGC patients (78.6% vs. 64.1%). The overall 5-year survival of the patients with early MGC was 97.2% as compared with 92.7% for the patients with early NMGC (P < 0.01). The statistically significant prognostic parameters influencing the 5-year survival rate according to Cox's proportional hazard regression model were: age (risk ratio, 2.22; 95% confidence interval [CI], 1.62-3.04; P < 0.01); sex (risk ratio, 1.97; 95% CI, 1.42-2.73; P < 0.01); and lymph node metastases (risk ratio, 1.88; 95% CI, 1.28-2.77; P < 0.01).
Patients with early MGC had a better prognosis than those with early NMGC. Mucinous histology itself appears not to be an independent prognostic factor. Therefore, early detection is important for improving the prognosis for patients with gastric carcinoma regardless of tumor histology.
PMCID: PMC4091442  PMID: 25025020
Gastric neoplasm; Mucinous; Prognosis; Tumor histology
37.  Quantification of cerebral circulation and shunt volume in a tentorial dural arteriovenous fistula using two-dimensional phase-contrast magnetic resonance imaging 
Acta Radiologica Short Reports  2014;3(5):2047981614536559.
Venous hypertension is closely related to poor outcome of a dural arteriovenous fistula (DAVF). However, no direct measurements have been made of the shunt flow and impaired venous drainage that are suggestive of venous hypertension. We present a case of a 35-year-old man who presented with cerebral hemorrhage and underwent coil embolization for tentorial DAVF. Two-dimensional (2D) phase-contrast magnetic resonance imaging (MRI) was used to evaluate temporal changes in the flow volumes of the shunt and venous drainage between before and after embolization. The results demonstrated the feasibility of using 2D phase-contrast MRI to measure the shunt volume of a DAVF, which might be useful for assessing the improvement in cerebral circulation after embolization treatment.
PMCID: PMC4184434  PMID: 25298870
Tentorium; arteriovenous fistula; therapeutic embolization; blood flow velocity; cerebral vein; cine MRI
38.  Antioxidant activities and polyphenol content of Morus alba leaf extracts collected from varying regions 
Biomedical Reports  2014;2(5):675-680.
Morus alba leaf (MAL), also known as Mori folium when used as a herbal medicine, has traditionally been used in Chinese medicine to treat diabetes, protect the liver and lower blood pressure. In the present study, MAL was collected from various regions in Korea and the antioxidant activity, total polyphenol contents and main flavonoid contents was investigated. MAL were collected from various areas in Korea and extracted with methanol. The total polyphenol contents were evaluated based on the Folin-Ciocalteu method using a spectrophotometer. The antioxidant activities were determined by a 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay method. The identification and quantification of three main polyphenol constituents was performed using high-performance liquid chromatography/diode array detection analysis. The total polyphenol contents of the MAL extracts varied between 23.2 and 55.4 mg gallic acid equivalent/g. The radical scavenging activity (SC50) of the MAL extracts ranged between 584 and 139 μg/ml. Three flavonol compounds (rutin, isoquercitrin and astragalin) were identified as main polyphenol constituents. These contents varied from 0.68–12.7, 0.69–9.86 and 0.05–3.55 mg/g, respectively. The average of the total was 9.52 mg/g, which was similar to that of commercial MAL extracts (10.58 mg/g). Among the three flavonol compounds, isoquercitrin showed the highest content (5.68 mg/g) followed by rutin (3.1 mg/g) and astragalin (2.4 mg/g). In the present study, the radical scavenging activity, polyphenol content and flavonol content of MAL were significantly different according to growing area. These three flavonol compounds were identified as main constituents of MAL in this study, and are known to have various biological activities, as well as strong antioxidant activities. Therefore, the sum of these three flavonol compounds was indicated as a good marker for the quality control of Mori folium.
PMCID: PMC4106594  PMID: 25054010
Morus alba leaf; Mori folium; antioxidant; polyphenol; QC markers
39.  The Positive Effects of One-Hour Intravenous Administration of Bortezomib on Peripheral Neuropathy in Multiple Myeloma Patients 
BioMed Research International  2014;2014:237698.
Bortezomib-induced peripheral neuropathy (BiPN) in multiple myeloma (MM) patients is a common and serious side effect. Currently, it has been reported that subcutaneous (SC) administration of bortezomib decreases the incidence of BiPN as compared to standard intravenous (IV) bolus injection without any differences in efficacy. However, there are reports of severe injection site reaction following SC administration of bortezomib. The aim of this study was to evaluate the response rate and incidence of BiPN following one-hour IV infusion of bortezomib. The data was retrospectively collected from MM patients who had been treated with IV administration of bortezomib for one hour. Twenty-three patients were evaluated (median age 72 years, 13 males). The median number of treatment cycles was 5 (range 2–10). The cumulative bortezomib dose was 26.0 mg/m2 (14.3–66.3) and percent of actual per expected cumulative dose was 90% (50–100). The overall response (complete response plus partial response) rate was 65%. The incidence of BiPN was 57% (n = 13) and incidence of severe neuropathy was 4% (n = 1). One-hour IV infusion of bortezomib was an effective regimen for MM with reduced incidence of severe BiPN. This route of administration of bortezomib could be an alternative mode of delivery for patients with severe injection site reactions following SC administration.
PMCID: PMC4065765  PMID: 24995276
40.  Clinical characteristics and treatment outcome of acute myeloid leukemia in elderly patients in Korea: a retrospective analysis 
Blood research  2014;49(2):95-99.
The clinical characteristics of elderly patients with AML differ from those of younger patients, resulting in poorer survival and treatment outcomes. We analyzed retrospectively the clinical data of AML patients 65 years old and above to describe patients' characteristics and treatment patterns, and to define meaningful prognostic factors of survival in the Korean population.
Basic patients' characteristics, clinical outcomes according to treatments, and prognostic factors associated with survival and treatment intensity were examined in a total of 168 patients diagnosed in 5 institutes between 1996 and 2012 as having AML.
Herein, 84 patients (50.0%) received high-intensity regimens (HIR), 18 (10.7%) received low-intensity regimens (LIR), and 66 (39.3%) received supportive care (SC) only. The median survival of all patients was 4.5 months; and median survival times with HIR, LIR, and SC were 6.8 months, 10.2 months, and 1.6 months, respectively. Median survival times with HIR and LIR were significantly longer than that with SC (P<0.0001 and P=0.006, respectively). Multivariate analysis identified age, Eastern Cooperative Oncology Group-performance status (ECOG-PS), hemoglobin (Hb) level, and serum creatinine (Cr) level as statistically significant prognostic factors for survival. In the HIR group, prognostic factors for survival were ECOG-PS, Hb level, and C-reactive protein level.
Even in elderly AML patients, an intensive treatment regimen could be beneficial with careful patient selection. Further prospective studies designed to identify specific prognostic factors are required to establish an optimal treatment strategy for elderly AML patients.
PMCID: PMC4090344  PMID: 25025010
Acute myeloid leukemia; Survival; Prognosis; Chemotherapy; Elderly
41.  Extremely Efficient Liquid Exfoliation and Dispersion of Layered Materials by Unusual Acoustic Cavitation 
Scientific Reports  2014;4:5133.
Layered materials must be exfoliated and dispersed in solvents for diverse applications. Usually, highly energetic probe sonication may be considered to be an unfavourable method for the less defective exfoliation and dispersion of layered materials. Here we show that judicious use of ultrasonic cavitation can produce exfoliated transition metal dichalcogenide nanosheets extraordinarily dispersed in non-toxic solvent by minimising the sonolysis of solvent molecules. Our method can also lead to produce less defective, large graphene oxide nanosheets from graphite oxide in a short time (within 10 min), which show high electrical conductivity (>20,000 S m−1) of the printed film. This was achieved by adjusting the ultrasonic probe depth to the liquid surface to generate less energetic cavitation (delivered power ~6 W), while maintaining sufficient acoustic shearing (0.73 m s−1) and generating additional microbubbling by aeration at the liquid surface.
PMCID: PMC4038810  PMID: 24875584
42.  Clinical and Genetic Aspects in Twelve Korean Patients with Adrenomyeloneuropathy 
Yonsei Medical Journal  2014;55(3):676-682.
This study was designed to investigate the characteristics of Korean adrenomyeloneuropathy (AMN) patients.
Materials and Methods
We retrospectively selected 12 Korean AMN patients diagnosed by clinical analysis and increased plasma content of very long chain fatty acids.
All 12 patients were men. Patient ages at symptom onset ranged from 18 to 55 years. Family history was positive in two patients. The phenotype distributions consisted of AMN without cerebral involvement in seven patients, AMN with cerebral involvement in two patients, and the spinocerebellar phenotype in three patients. Nerve conduction studies revealed abnormalities in four patients and visual evoked tests revealed abnormalities in three patients. Somatosensory evoked potential tests revealed central conduction defects in all of the tested patients. Spinal MRI showed diffuse cord atrophy or subtle signal changes in all 12 patients. Brain MRI findings were abnormal in six of the nine tested patients. These brain abnormalities reflected the clinical phenotypes. Mutational analysis identified nine different ABCD1 mutations in 10 of 11 tested patients. Among them, nine have been previously reported and shown to be associated with various phenotypes; one was a novel mutation.
In conclusion, the present study is the first to report on the clinical and mutational spectrum of Korean AMN patients, and confirms various clinical presentations and the usefulness of brain MRI scan.
PMCID: PMC3990087  PMID: 24719134
Adrenoleukodystrophy; adrenomyeloneuropathy; ataxia; very long chain fatty acid; ABCD1
43.  Silencing of KIF14 interferes with cell cycle progression and cytokinesis by blocking the p27Kip1 ubiquitination pathway in hepatocellular carcinoma 
Although it has been suggested that kinesin family member 14 (KIF14) has oncogenic potential in various cancers, including hepatocellular carcinoma (HCC), the molecular mechanism of this potential remains unknown. We aimed to elucidate the role of KIF14 in hepatocarcinogenesis by knocking down KIF14 in HCC cells that overexpressed KIF14. After KIF14 knockdown, changes in tumor cell growth, cell cycle and cytokinesis were examined. We also examined cell cycle regulatory molecules and upstream Skp1/Cul1/F-box (SCF) complex molecules. Knockdown of KIF14 resulted in suppression of cell proliferation and failure of cytokinesis, whereas KIF14 overexpression increased cell proliferation. In KIF14-silenced cells, the levels of cyclins E1, D1 and B1 were profoundly decreased compared with control cells. Of the cyclin-dependent kinase inhibitors, the p27Kip1 protein level specifically increased after KIF14 knockdown. The increase in p27Kip1 was not due to elevation of its mRNA level, but was due to inhibition of the proteasome-dependent degradation pathway. To explore the pathway upstream of this event, we measured the levels of SCF complex molecules, including Skp1, Skp2, Cul1, Roc1 and Cks1. The levels of Skp2 and its cofactor Cks1 decreased in the KIF14 knockdown cells where p27Kip1 accumulated. Overexpression of Skp2 in the KIF14 knockdown cells attenuated the failure of cytokinesis. On the basis of these results, we postulate that KIF14 knockdown downregulates the expression of Skp2 and Cks1, which target p27Kip1 for degradation by the 26S proteasome, leading to accumulation of p27Kip1. The downregulation of Skp2 and Cks1 also resulted in cytokinesis failure, which may inhibit tumor growth. To the best of our knowledge, this is the first report that has identified the molecular target and oncogenic effect of KIF14 in HCC.
PMCID: PMC4044675  PMID: 24854087
cell cycle; cytokinesis; hepatocellular carcinoma; KIF14; p27kip1; ubiquitination
44.  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
45.  Electrically Robust Metal Nanowire Network Formation by In-Situ Interconnection with Single-Walled Carbon Nanotubes 
Scientific Reports  2014;4:4804.
Modulation of the junction resistance between metallic nanowires is a crucial factor for high performance of the network-structured conducting film. Here, we show that under current flow, silver nanowire (AgNW) network films can be stabilised by minimizing the Joule heating at the NW-NW junction assisted by in-situ interconnection with a small amount (less than 3 wt%) of single-walled carbon nanotubes (SWCNTs). This was achieved by direct deposition of AgNW suspension containing SWCNTs functionalised with quadruple hydrogen bonding moieties excluding dispersant molecules. The electrical stabilisation mechanism of AgNW networks involves the modulation of the electrical transportation pathway by the SWCNTs through the SWCNT-AgNW junctions, which results in a relatively lower junction resistance than the NW-NW junction in the network film. In addition, we propose that good contact and Fermi level matching between AgNWs and modified SWCNTs lead to the modulation of the current pathway. The SWCNT-induced stabilisation of the AgNW networks was also demonstrated by irradiating the film with microwaves. The development of the high-throughput fabrication technology provides a robust and scalable strategy for realizing high-performance flexible transparent conductor films.
PMCID: PMC3999447  PMID: 24763208
46.  Ultra-High Performance, High-Temperature Superconducting Wires via Cost-effective, Scalable, Co-evaporation Process 
Scientific Reports  2014;4:4744.
Long-length, high-temperature superconducting (HTS) wires capable of carrying high critical current, Ic, are required for a wide range of applications. Here, we report extremely high performance HTS wires based on 5 μm thick SmBa2Cu3O7 − δ (SmBCO) single layer films on textured metallic templates. SmBCO layer wires over 20 meters long were deposited by a cost-effective, scalable co-evaporation process using a batch-type drum in a dual chamber. All deposition parameters influencing the composition, phase, and texture of the films were optimized via a unique combinatorial method that is broadly applicable for co-evaporation of other promising complex materials containing several cations. Thick SmBCO layers deposited under optimized conditions exhibit excellent cube-on-cube epitaxy. Such excellent structural epitaxy over the entire thickness results in exceptionally high Ic performance, with average Ic over 1,000 A/cm-width for the entire 22 meter long wire and maximum Ic over 1,500 A/cm-width for a short 12 cm long tape. The Ic values reported in this work are the highest values ever reported from any lengths of cuprate-based HTS wire or conductor.
PMCID: PMC3994444  PMID: 24752189
47.  Body Mass Index and Mortality in Korean Intensive Care Units: A Prospective Multicenter Cohort Study 
PLoS ONE  2014;9(4):e90039.
The level of body mass index (BMI) that is associated with the lowest mortality in critically ill patients in Asian populations is uncertain. We aimed to examine the association of BMI with hospital mortality in critically ill patients in Korea.
We conducted a prospective multicenter cohort study of 3,655 critically ill patients in 22 intensive care units (ICUs) in Korea. BMI was categorized into five groups: <18.5, 18.5 to 22.9, 23.0 to 24.9 (the reference category), 25.0 to 29.9, and ≥30.0 kg/m2.
The median BMI was 22.6 (IQR 20.3 to 25.1). The percentages of patients with BMI<18.5, 18.5 to 22.9, 23.0 to 24.9, 25.0 to 29.9, and ≥30.0 were 12, 42.3, 19.9, 22.4, and 3.3%, respectively. The Cox-proportional hazard ratios with exact partial likelihood to handle tied failures for hospital mortality comparing the BMI categories <18.5, 18.5 to 22.9, 25.0 to 29.9, and ≥30.0 with the reference category were 1.13 (0.88 to 1.44), 1.03 (0.84 to 1.26), 0.96 (0.76 to 1.22), and 0.68 (0.43 to 1.08), respectively, with a highly significant test for trend (p = 0.02).
A graded inverse association between BMI and hospital mortality with a strong significant trend was found in critically ill patients in Korea.
PMCID: PMC3991578  PMID: 24747262
48.  Predictors of high score patient-reported barriers to controlling cancer pain: a preliminary report 
Pain is one of the most common and devastating symptoms in cancer patients, and misunderstandings on the patient’s part can cause major obstacles in pain management.
We evaluated factors associated with patient’s high barrier score to managing cancer-associated pain by having 201 patients complete the Korean Barriers Questionnaire II, the Brief Pain Inventory—Korean, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Korean Beck Depression Inventory. The Pain Management Index (PMI) was also assessed.
The patients were from nine oncology clinics in university hospitals and a veterans’ hospital in South Korea. The median pain score (0–10 scale) was 4, with a median percentage of pain improvement during the last 24 h of 70 %. A total of 150 patients (75 %) received strong opioids, and 177 (88 %) achieved adequate analgesia (positive PMI). Mean scores ± SD for the Barriers Questionnaire II ranged from 1.5 ± 1 to 2.8 ± 1.1, with the harmful effects subscale the highest. In the multiple regression model, depression was significantly associated with total barrier score to pain management (p < 0.0001). Pain reduction was significantly associated with the fatalism subscale.
Depression was associated with high barrier score in patients with cancer pain. Management of cancer pain should include screening for depression, and management of depression could reduce patient-reported barriers to pain management.
PMCID: PMC3881357  PMID: 23151648
Cancer; Depression; Pain management
49.  Primary Bronchial Granular Cell Tumor in an Adult Male 
We report a rare case of granular cell tumor arising in the left lower lobe (LLL) bronchus with secondary obstructive change in a 60-year-old male. The patient was found to have a nodule in the LLL on a computed tomography scan, three months prior to his presentation to the Asan Medical Center. Bronchoscopic biopsies revealed a granular cell tumor. After undergoing LLL lobectomy with bronchoplasty, the patient has not experienced any tumor recurrence.
PMCID: PMC4000886  PMID: 24782979
Granular cell tumor; Bronchial tumor
50.  Parkinsonism as late sequela of organophosphate intoxication 
Delayed morphologic and metabolic change of organophosphate intoxication is rarely reported than those of acute episode. The patient was a 52-year-old woman who had a history of acute organophosphate intoxication, which paralyzed her for one week when she was 25 years old. She recovered slowly to near normal after one year. After 22 years of the acute episode, tremor developed in 2007 followed by bradykinesia, rigidity, and postural instabilities. Brain MRI showed linear atrophy in bilateral striatal area and multiple cysts in anterior caudate nucleus. F-18 fluorodeoxyglucose positron emission tomography revealed multiple hypometabolic areas in bilateral striatum, cerebellar hemisphere, and occipital area.
PMCID: PMC4013729  PMID: 24812459
Cerebellum; F-18 positron-emission tomography; metabolism; organophsphate; parkinsonism; striatum

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