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1.  Pes anserinus and anserine bursa: anatomical study 
Anatomy & Cell Biology  2014;47(2):127-131.
This study investigated the boundary of anserine bursa with the recommended injection site and shape on the insertion area of pes anserinus (PA), with the aim of improving clinical practice. Eighty six legs from 45 Korean cadavers were investigated. The mixed gelatin solution was injected to identify the shape of anserine bursa, and then the insertion site of the PA tendons was exposed completely and carefully dissected to identify the shape of the PA. The sartorius was inserted into the superficial layer and gracilis, and the semitendinosus was inserted into the deep layer on the medial surface of the tibia. The number of the semitendinosus tendons at the insertion site varied: 1 in 66% of specimens, 2 in 31%, and 3 in 3%. The gracilis and semitendinosus tendons were connected to the deep fascia of leg. Overall, the shape of the anserine bursa was irregularly circular. Most of the anserine bursa specimens reached the proximal line of the tibia, and some of the specimens reached above the proximal line of the tibia. In the medial view of the tibia, the anserine bursa was located posteriorly and superiorly from the tibia's midline, and it followed the lines of the sartorius muscle. The injection site for anserine bursa should be carried out at 20° from the vertical line medially and inferiorly, 15 or 20 mm deeply, and at the point of about 20 mm medial and 12 mm superior from inferomedial point of tibial tuberosity.
doi:10.5115/acb.2014.47.2.127
PMCID: PMC4076419  PMID: 24987549
Cadaver; Anserine bursa; Pes anserinus; Bursa injection
2.  A New Anti-c-Met Antibody Selected by a Mechanism-Based Dual-Screening Method: Therapeutic Potential in Cancer 
Molecules and Cells  2012;34(6):523-529.
c-Met, the high affinity receptor for hepatocyte growth factor (HGF), is one of the most frequently activated tyrosine kinases in many human cancers and a target for cancer therapy. However, inhibitory targeting of c-Met with antibodies has proven difficult, because most antibodies have intrinsic agonist activity. Therefore, the strategy for reducing the agonism is critical for successful development of cancer therapies based on anti-c-Met antibodies. Here we developed a mechanism-based assay method for rapid screening of anti-c-Met antibodies, involving the determination of Akt phosphorylation and c-Met degradation for agonism and efficacy, respectively. Using the method, we identified an antibody, F46, that binds to human c-Met with high affinity (Kd = 2.56 nM) and specificity, and induces the degradation of c-Met in multiple cancer cells (including MKN45, a gastric cancer cell line) with minimal activation of c-Met signaling. F46 induced c-Met internalization in both HGF-dependent and HGF-independent cells, suggesting that the degradation of c-Met results from antibody-mediated receptor internalization. Further-more, F46 competed with HGF for binding to c-Met, resulting in the inhibition of both HGF-mediated invasion and angiogenesis. Consistently, F46 inhibited the proliferation of MKN45 cells, in which c-Met is constitutively activated in an HGF-independent manner. Xenograft analysis revealed that F46 markedly inhibits the growth of subcutaneously implanted gastric and lung tumors. These results indicate that F46, identified by a novel mechanism-based assay, induces c-Met degradation with minimal agonism, implicating a potential role of F46 in therapy of human cancers.
doi:10.1007/s10059-012-0194-z
PMCID: PMC3887825  PMID: 23180291
Akt; anti-c-Met antibody; cancer therapy; c-Met; HGF
4.  Left Atrial Wall Dissection after Mitral Valve Replacement 
Left atrial dissection does occur, though rarely, after mitral valve surgery. A 68-year-old Korean female presented with moderate mitral stenosis, mild mitral regurgitation, moderate tricuspid regurgitation and mild aortic regurgitation. She was scheduled for mitral valve replacement and tricuspid annuloplasty. We experienced a left atrial dissection after weaning from cardiopulmonary bypass and decided not to repair it. The patient recovered uneventfully. We suggest that a specific type of left atrial dissection can be treated conservatively.
doi:10.4250/jcu.2013.21.3.145
PMCID: PMC3816166  PMID: 24198922
Atrium; Dissection; Mitral valve
5.  Interruption of bispectral index monitoring by nerve integrity monitoring during tympanoplasty -A case report- 
Korean Journal of Anesthesiology  2013;64(2):161-163.
We report that intraoperative NIM-2 monitoring devices can interfere with bispectral index monitoring. A 45-year-old male with chronic otits media underwent tympanolasty under general anesthesia with NIM-2 monitoring and bispectral index monitoring at our institution. And then, bispectral index monitoring was severely interrupted by facial nerve monitoring.
doi:10.4097/kjae.2013.64.2.161
PMCID: PMC3581786  PMID: 23459709
Bispectral index monitor; Facial nerve; Intraoperative monitoring; Tympanoplasy
6.  Subaortic Membrane Late after Surgical Correction of Tetralogy of Fallot 
We herein report a rare case of subaortic stenosis in association with a previous tetralogy of Fallot (TOF) surgical repair, which was not taken into account as a differential diagnosis. Echocardiography plays a pivotal role in identification of this rare combination. Therefore, echocardiography should be performed periodically during follow-up of patients with surgically corrected TOF. Given the clinical complications that can result from subaortic stenosis (i.e., aortic regurgitation and infective endocarditis), early and aggressive management of this rare combination should be performed.
doi:10.3904/kjim.2012.27.4.455
PMCID: PMC3529246  PMID: 23269888
Tetralogy of Fallot; Ventricular outflow obstruction; Echocardiography
7.  Subarachnoid Hemorrhage Mimicking Leakage of Contrast Media After Coronary Angiography 
Korean Circulation Journal  2012;42(3):197-200.
We report a patient who developed subarachnoid hemorrhage (SAH) just after coronary angiography (CAG) with non-ionic contrast media (CM) and minimal dose of heparin. The 55-year-old man had a history of acute ST elevation myocardial infarction that had been treated with primary percutaneous coronary intervention and was admitted for a follow-up CAG. The CAG was performed by the transradial approach, using 1000 U of unfractionated heparin for the luminal coating and 70 mL of iodixanol. At the end of CAG, he complained of nausea and rapidly became stuporous. Brain CT showed a diffusely increased Hounsfield unit (HU) in the cisternal space, similar to leakage of CM. The maximal HU was 65 in the cisternal space. No vascular malformations were detected on cerebral angiography. The patient partially recovered his mental status and motor weakness after 2 days. Two weeks later, subacute SAH was evident on magnetic resonance imaging. The patient was discharged after 28 days.
doi:10.4070/kcj.2012.42.3.197
PMCID: PMC3318092  PMID: 22493615
Subarachnoid hemorrhage; Iodixanol; Coronary angiography
8.  Compromised ventilation caused by tracheoesophageal fistula and gastrointestinal endoscope undergoing removal of disk battery on esophagus in pediatric patient -A case report- 
Korean Journal of Anesthesiology  2011;61(3):257-261.
Ingestion of disk batteries may have serious complications such as esophageal burn, perforation, and tracheoesophageal fistula, particularly when the battery is caught in the esophagus. Proper placement of the tracheal tube is critical when tracheoesophageal fistula was occurred from esophageal impaction the battery. Endoscopy of upper gastrointestinal tract in infants and children is an important and effective tool for the diagnosis and treatment of foreign body ingestion. But upper gastrointestinal endoscopy in infant and children has very high risk of tracheal compression and airway compromise. We present a case of ventilatory compromise during insertion of the upper gastrointestinal endoscopy in 16-month-old child with tracheoesophageal fistula secondary to disk battery ingestion.
doi:10.4097/kjae.2011.61.3.257
PMCID: PMC3198189  PMID: 22025950
Disk battery ingestion; Gastrointestinal endoscopy; Tracheoesophageal fistula; Ventilatory compromise
9.  Association between Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations and Susceptibility for Childhood Asthma in Korea 
Yonsei Medical Journal  2010;51(6):912-917.
Purpose
Classic cystic fibrosis is now known part of cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders. These include a wide spectrum, from multi-system disorders, such as cystic fibrosis, to mono-symptomatic conditions, such as chronic pancreatitis or congenital bilateral absence of the vas deferens. However, respiratory disease is considered typical for the multi system disorder, cystic fibrosis, and is the major cause of morbidity and mortality. The purpose of this study was to evaluate the potential effects of CFTR gene mutations in Korean children with asthma.
Materials and Methods
We selected 14 mutations identified in Korea and each of the 48 children with and without asthma were genotyped for the case-control study.
Results
No significant differences were found in genotype and allele frequencies of the 9 polymorphisms observed between the non-asthma and asthma groups. In a haplotype determination based on a Bayesian algorithm, 8 haplotypes were assembled in the 98 individuals tested. However, we also did not find any significant differences in haplotype frequencies between the non-asthma and asthma groups.
Conclusion
We have concluded that this study did not show any evidence in support of providing that CFTR genetic variations significantly contribute to the susceptibility of asthma in Korean children.
doi:10.3349/ymj.2010.51.6.912
PMCID: PMC2995957  PMID: 20879059
Cystic fibrosis transmembrane conductance regulator; asthma; children
10.  Peritoneal lymphomatosis: CT and PET/CT findings and how to differentiate between carcinomatosis and sarcomatosis 
Cancer Imaging  2013;13(2):162-170.
Abstract
Peritoneal lymphomatosis is a rare manifestation of lymphoma, seen most frequently with non-Hodgkin lymphoma, and it is important to be familiar with this condition, because early diagnosis directly affects the management of patients. This review illustrates the spectrum of imaging findings in peritoneal lymphomatosis, highlighting the use of positron emission tomography/computed tomography, showing common and uncommon subtypes of lymphoma associated with this entity, and how to differentiate it from peritoneal carcinomatosis and peritoneal sarcomatosis.
doi:10.1102/1470-7330.2013.0018
PMCID: PMC3629893  PMID: 23598428
Peritoneal lymphomatosis; extranodal lymphoma; peritoneal sarcomatosis; peritoneal carcinomatosis; positron emission tomography
11.  Molecular targeted therapies in non-GIST soft tissue sarcomas: what the radiologist needs to know 
Cancer Imaging  2013;13(2):197-211.
Abstract
Non-gastrointestinal stromal soft tissue sarcomas are uncommon neoplasms that have a dismal prognosis due to a high incidence of metastases and a poor response to conventional chemotherapy. The identification of characteristic genetic alterations in several of these tumors has opened the window for molecular targeted therapies in patients who have failed conventional chemotherapy. Imaging plays a critical role in assessing the response to these novel therapeutic agents. Just like the response of gastrointestinal stromal tumors to imatinib, the response of non-gastrointestinal stromal soft tissue sarcomas to molecular targeted drugs is better evaluated on imaging by alternate tumor response criteria such as the Choi criteria. In addition, these drugs are associated with distinct class-specific drug toxicities that can come to attention for the first time on imaging. The purpose of this article is to provide a primer for the radiologist on the various molecular targeted therapies in advanced/metastatic non-gastrointestinal stromal soft tissue sarcomas with emphasis on the role of imaging in assessing treatment response and complications.
doi:10.1102/1470-7330.2013.0022
PMCID: PMC3645342  PMID: 23649384
Soft tissue sarcomas; molecular targeted therapies; CT; MRI; PET/CT; drug toxicities
12.  Malignant abdominal rocks: where do they come from? 
Cancer Imaging  2013;13(4):527-539.
Abstract
For the radiologist, calcifications in an abdominal malignancy raise questions of both diagnostic and prognostic significance. Although certain cancers are well known to calcify, such as colorectal and ovarian, malignant abdominal calcifications actually arise from a wide variety of epithelial, mesenchymal, lymphoid, or germ cell neoplasms. The pathophysiology of calcification in abdominal malignancies is heterogeneous and incompletely understood. Calcifications may present primarily, in untreated tumors, or develop during treatment; the latter can occur in variable clinical settings. A basic understanding of the varied pathogenic etiology can assist the radiologist in assessing disease status. By presenting an assortment of calcified abdominal malignancies on computed tomography in varied clinical settings, we aim not only to inform the differential diagnosis, but also to clarify the prognosis of calcifications in abdominal malignancies.
doi:10.1102/1470-7330.2013.0048
PMCID: PMC3864229  PMID: 24334568
Malignancy; calcifications; computed tomography; abdomen
13.  Conformational Substates of Myoglobin Intermediate Resolved by Picosecond X-ray Solution Scattering 
Conformational substates of proteins are generally considered to play important roles in regulating protein functions, but an understanding of how they influence the structural dynamics and functions of the proteins has been elusive. Here, we investigate the structural dynamics of sperm whale myoglobin associated with the conformational substates using picosecond X-ray solution scattering. By applying kinetic analysis considering all of the plausible candidate models, we establish a kinetic model for the entire cycle of the protein transition in a wide time range from 100 ps to 10 ms. Four structurally distinct intermediates are formed during the cycle, and most importantly, the transition from the first intermediate to the second one (B → C) occurs biphasically. We attribute the biphasic kinetics to the involvement of two conformational substates of the first intermediate, which are generated by the interplay between the distal histidine and the photodissociated CO.
doi:10.1021/jz4027425
PMCID: PMC3985870  PMID: 24761190
14.  Sub-100-ps structural dynamics of horse heart myoglobin probed by time-resolved X-ray solution scattering 
Chemical physics  2014;422:137-142.
Here we report sub-100-ps structural dynamics of horse heart myoglobin revealed by time-resolved X-ray solution scattering. By applying the time-slicing scheme to the measurement and subsequent deconvolution, we investigate the protein structural dynamics that occur faster than the X-ray temporal pulse width of synchrotrons (~100 ps). The singular value decomposition analysis of the experimental data suggests that two structurally distinguishable intermediates are formed within 100 ps. In particular, the global structural change occurring on the time scale of 70 ps is identified.
doi:10.1016/j.chemphys.2014.03.004
PMCID: PMC4323384
Time-resolved X-ray solution scattering; Time-slicing; Structural dynamics; Myoglobin
15.  Transcriptomic changes due to water deficit define a general soybean response and accession-specific pathways for drought avoidance 
BMC Plant Biology  2015;15:26.
Background
Among abiotic stresses, drought is the most common reducer of crop yields. The slow-wilting soybean genotype PI 416937 is somewhat robust to water deficit and has been used previously to map the trait in a bi-parental population. Since drought stress response is a complex biological process, whole genome transcriptome analysis was performed to obtain a deeper understanding of the drought response in soybean.
Results
Contrasting data from PI 416937 and the cultivar ‘Benning’, we developed a classification system to identify genes that were either responding to water-deficit in both genotypes or that had a genotype x environment (GxE) response. In spite of very different wilting phenotypes, 90% of classifiable genes had either constant expression in both genotypes (33%) or very similar response profiles (E genes, 57%). By further classifying E genes based on expression profiles, we were able to discern the functional specificity of transcriptional responses at particular stages of water-deficit, noting both the well-known reduction in photosynthesis genes as well as the less understood up-regulation of the protein transport pathway. Two percent of classifiable genes had a well-defined GxE response, many of which are located within slow-wilting QTLs. We consider these strong candidates for possible causal genes underlying PI 416937’s unique drought avoidance strategy.
Conclusions
There is a general and functionally significant transcriptional response to water deficit that involves not only known pathways, such as down-regulation of photosynthesis, but also up-regulation of protein transport and chromatin remodeling. Genes that show a genotypic difference are more likely to show an environmental response than genes that are constant between genotypes. In this study, at least five genes that clearly exhibited a genotype x environment response fell within known QTL and are very good candidates for further research into slow-wilting.
Electronic supplementary material
The online version of this article (doi:10.1186/s12870-015-0422-8) contains supplementary material, which is available to authorized users.
doi:10.1186/s12870-015-0422-8
PMCID: PMC4322458  PMID: 25644024
Drought stress; Canopy-wilting; Glycine max; RNA-Sequencing; Quantitative trait loci (QTL); Genotype x environment
16.  Phenotypic and Functional Analysis of HL-60 Cells Used in Opsonophagocytic-Killing Assay for Streptococcus pneumoniae 
Journal of Korean Medical Science  2015;30(2):145-150.
Differentiated HL-60 is an effector cell widely used for the opsonophagocytic-killing assay (OPKA) to measure efficacy of pneumococcal vaccines. We investigated the correlation between phenotypic expression of immunoreceptors and phagocytic ability of HL-60 cells differentiated with N,N-dimethylformamide (DMF), all-trans retinoic acid (ATRA), or 1α, 25-dihydroxyvitamin D3 (VitD3) for 5 days. Phenotypic change was examined by flow cytometry with specific antibodies to CD11c, CD14, CD18, CD32, and CD64. Apoptosis was determined by flow cytometry using 7-aminoactinomycin D. Function was evaluated by a standard OPKA against serotype 19F and chemiluminescence-based respiratory burst assay. The expression of CD11c and CD14 gradually increased upon exposure to all three agents, while CD14 expression increased abruptly after VitD3. The expression of CD18, CD32, and CD64 increased during differentiation with all three agents. Apoptosis remained less than 10% until day 3 but increased after differentiation by DMF or ATRA. Differentiation with ATRA or VitD3 increased the respiratory burst after day 4. DMF differentiation showed a high OPKA titer at day 1 which sustained thereafter while ATRA or VitD3-differentiated cells gradually increased. Pearson analysis between the phenotypic changes and OPKA titers suggests that CD11c might be a useful differentiation marker for HL-60 cells for use in pneumococcal OPKA.
Graphical Abstract
doi:10.3346/jkms.2015.30.2.145
PMCID: PMC4310939  PMID: 25653484
Opsonophagocytic-Killing Assay; Streptococcus pneumonia; HL-60; Differentiation
17.  Intestinal anti-inflammatory activity of Sasa quelpaertensis leaf extract by suppressing lipopolysaccharide-stimulated inflammatory mediators in intestinal epithelial Caco-2 cells co-cultured with RAW 264.7 macrophage cells 
BACKGROUND/OBJECTIVES
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Previously, Sasa quelpaertensis leaves have been shown to mediate anti-inflammation and anti-cancer effects, although it remains unclear whether Sasa leaves are able to attenuate inflammation-related intestinal diseases. Therefore, the aim of this study was to investigate the anti-inflammatory effects of Sasa quelpaertensis leaf extract (SQE) using an in vitro co-culture model of the intestinal epithelial environment.
MATERIALS/METHODS
An in vitro co-culture system was established that consisted of intestinal epithelial Caco-2 cells and RAW 264.7 macrophages. Treatment with lipopolysaccharide (LPS) was used to induce inflammation.
RESULTS
Treatment with SQE significantly suppressed the secretion of LPS-induced nitric oxide (NO), prostaglandin E2 (PGE2), IL-6, and IL-1β in co-cultured RAW 264.7 macrophages. In addition, expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α were down-regulated in response to inhibition of IκBα phosphorylation by SQE. Compared with two bioactive compounds that have previously been identified in SQE, tricin and P-coumaric acid, SQE exhibited the most effective anti-inflammatory properties.
CONCLUSIONS
SQE exhibited intestinal anti-inflammatory activity by inhibiting various inflammatory mediators mediated through nuclear transcription factor kappa-B (NF-kB) activation. Thus, SQE has the potential to ameliorate inflammation-related diseases, including IBD, by limiting excessive production of pro-inflammatory mediators.
doi:10.4162/nrp.2015.9.1.3
PMCID: PMC4317476
Sasa quelpaertensis; co-culture model; anti-inflammation; pro-inflammatory mediators
18.  Factors associated with nutrition label use among female college students applying the theory of planned behavior 
BACKGROUND/OBJECTIVES
Use of nutrition labels in food selection is recommended for consumers. The aim of this study is to examine factors, mainly beliefs explaining nutrition label use in female college students based on the Theory of Planned Behavior (TPB).
SUBJECTS/METHODS
The subjects were female college students from a university in Seoul, Korea. The survey questionnaire was composed of items examining general characteristics, nutrition label use, behavioral beliefs, normative beliefs, corresponding motivation to comply, and control beliefs. The subjects (n = 300) responded to the questionnaire by self-report, and data from 275 students were analyzed using t-test or χ2-test.
RESULTS
The results showed that 37.8% of subjects were nutrition label users. Three out of 15 behavioral beliefs differed significantly by nutrition label use. Nutrition label users agreed more strongly on the benefits of using nutrition labels including 'comparing and selecting better foods' (P < 0.001), 'selecting healthy foods' (P < 0.05). The negative belief of 'annoying' was stronger in non-users than in users (P < 0.001). Three out of 7 sources (parents, siblings, best friend) were important in nutrition label use. Twelve out of 15 control beliefs differed significantly by nutrition label use. These included beliefs regarding constraints of using nutrition labels (e.g., time, spending money for healthy foods) and lack of nutrition knowledge (P < 0.001). Perceived confidence in understanding and applying the specifics of nutrition labels in food selection was also significantly related to nutrition label use (P < 0.001).
CONCLUSIONS
This study found that the beliefs, especially control beliefs, suggested in the TPB were important in explaining nutrition label use. To promote nutrition label use, nutrition education might focus on increasing perceived control over constraints of using nutrition labels, acquiring skills for checking nutrition labels, as well as the benefits of using nutrition labels and receiving support from significant others for nutrition label use.
doi:10.4162/nrp.2015.9.1.63
PMCID: PMC4317482
Nutrition label; factors; beliefs; theory of planned behavior; college students
19.  Surgical Results of Third or More Cardiac Valve Operation 
Background
We evaluated operative outcomes after third or more cardiac operations for valvular heart disease, and analyzed whether pericardial coverage with artificial membrane is helpful for subsequent reoperation.
Methods
From 2000 to 2012, 149 patients (male: female=70: 79; mean age at operation, 57.0±11.3 years) underwent their third to fifth operations for valvular heart disease. Early results were compared between patients who underwent their third operation (n=114) and those who underwent fourth or fifth operation (n=35). Outcomes were also compared between 71 patients who had their pericardium open during the previous operation and 27 patients who had artificial membrane coverage.
Results
Intraoperative adverse events occurred in 22 patients (14.8%). Right atrium (n=6) and innominate vein (n=5) were most frequently injured. In-hospital mortality rate was 9.4%. Total cardiopulmonary bypass time (225±77 minutes vs. 287±134 minutes, p=0.012) and the time required to prepare aortic cross clamp (209±57 minutes vs. 259±68 minutes, p<0.001) increased as reoperations were repeated. However, intraoperative event rate (13.2% vs. 20.0%), in-hospital mortality (9.6% vs. 8.6%) and postoperative complications were not statistically different according to the number of previous operations. Pericardial closure using artificial membrane at previous operation was not beneficial in reducing intraoperative events (25.9% vs. 18.3%) and shortening operation time preparing aortic cross clamp (248±64 minutes vs. 225±59 minutes) as compared to no-closure.
Conclusion
Clinical outcomes of the third or more operations for valvular heart disease were acceptable in terms of intraoperative adverse events and in-hospital mortality rates. There were no differences in the incidence of intraoperative adverse events, early mortality and postoperative complications between third cardiac operation and fourth or more.
doi:10.5090/kjtcs.2015.48.1.25
PMCID: PMC4333857
Reoperation; Sternum; Pericardium; Outcomes; Valve disease
20.  An Unusual Presentation of Schwannoma in the Interatrial Space 
We report the case of a 69-year-old woman who was diagnosed with intracardiac schwannoma without symptoms. Preoperative echocardiography and cardiac magnetic resonance imaging showed a mass attached to the interatrial septum. The initial diagnosis was a myxoma or a bronchogenic cyst. The tumor was successfully excised under cardiopulmonary bypass. However, the pathology of the excised tumor was consistent with schwannoma. We suggest that cardiovascular surgeons consider schwannoma to be a possible differential diagnosis for a mass close to the interatrial septum.
doi:10.5090/kjtcs.2015.48.1.95
PMCID: PMC4333859
Atrium; Heart neoplasms; Schwannoma (neurolemmoma)
21.  Dual Conical Conducting Filament Model in Resistance Switching TiO2 Thin Films 
Scientific Reports  2015;5:7844.
The resetting behaviors of Pt/TiO2/Pt resistive switching (RS) cell in unipolar RS operations were studied in detail through an experiment and by modeling. The experiment showed that the apparently highly arbitrary resetting current-voltage (I–V) curves could be grouped into three types: normal, delayed, and abnormal behaviors. A dual conical conducting filament (CF) model was conceived, and their electrothermal behaviors were analytically described from the heat-balance and charge-transport equations. The almost spontaneous resetting behavior of the normal reset could be easily understood from the mutually constructive interference effect between the Joule heating and temperature-dependent resistance effect along the CF. The delayed reset could be explained by the time-dependent increase in the reset voltage during the rest process, which was most probably induced in the more conical-shaped CF. The abnormal reset could be understood from the temporal transfer of oxygen ions near the kink positions of the two different-diameter portions of the more cylindrical CFs, which temporally decreases the overall resistance immediately prior for the actual reset to occur. The accuracy of the dual conical CF model was further confirmed by adopting a more thorough electrothermal simulation package, COMSOL.
doi:10.1038/srep07844
PMCID: PMC4297972  PMID: 25598439
22.  Identification of Intermediate- to High-Risk Papillary Thyroid Carcinoma Patients Who May Be Safely Managed without the Performance of Delayed Stimulated Thyroglobulin Measurements following Total Thyroidectomy and Radioactive Iodine Therapy 
Background. The measurement of stimulated thyroglobulin (sTg) after total thyroidectomy and remnant radioactive iodine (RAI) ablation is the gold standard for monitoring disease status in patients with papillary thyroid carcinomas (PTCs). The aim of this study was to determine whether sTg measurement during follow-up can be avoided in intermediate- and high-risk PTC patients. Methods. A total of 346 patients with PTCs with an intermediate or high risk of recurrence were analysed. All of the patients underwent total thyroidectomy as well as remnant RAI ablation and sTg measurements. Preoperative and postoperative parameters were included in the analysis. Results. Among the preoperative parameters, age below 45 years and preoperative Tg above 19.4 ng/mL were significant risk factors for predicting detectable sTg during follow-up. Among the postoperative parameters, thyroid capsular invasion, lymph node metastasis, and ablative Tg above 2.9 ng/mL were independently correlated with a detectable sTg range. The combination of ablative Tg less than 2.9 ng/mL with pre- and postoperative independent risk factors for detectable sTg increased the negative predictive value for detectable sTg up to 98.5%. Conclusions. Based on pre- and postoperative parameters, a substantial proportion of patients with PTCs in the intermediate- and high-risk classes could avoid aggressive follow-up measures.
doi:10.1155/2015/318916
PMCID: PMC4306371  PMID: 25649811
23.  Safety and immunogenicity of a freeze-dried, Vero cell culture-derived, inactivated Japanese encephalitis vaccine (KD-287, ENCEVAC®) versus a mouse brain-derived inactivated Japanese encephalitis vaccine in children: a phase III, multicenter, double-blinded, randomized trial 
Background
Although mouse brain-derived, inactivated Japanese encephalitis vaccines (JE-MBs) have been successfully used for a long time, potential rare neurological complications have prompted the development of a Vero cell culture-derived inactivated vaccine (JE-VC). In a phase III clinical study, we aimed to compare the safety and immunogenicity of a JE-VC, KD-287 with a JE-MB, JEV-GCC, in children.
Methods
In this multicenter, double-blinded, randomized controlled trial, the study population consisted of 205 healthy Korean children aged 12–23 months. Each subject was subcutaneously vaccinated with either KD-287 or JEV-GCC twice at an interval of 2 weeks and then vaccinated once 12 months after the second vaccination. Neutralizing antibodies were measured by the plaque reduction neutralization test using the homologous and heterologous, as a post hoc analysis, challenge virus strains.
Results
The three-dose regimen of KD-287 showed a comparable safety profile with JEV-GCC except higher incidence of fever after the first dose (30.4% and 14.7%, respectively). Most of the fever was mild degree (61.3% and 66.7%, respectively). KD-287 fulfilled the non-inferiority criteria for seroconversion rate (SCR) and geometric mean titer (GMT) of the neutralizing antibody, which were the primary endpoints, at 4 weeks after the third vaccination (95% CI: −1.00, 3.10 for the SCR difference and 10.8, 17.6 for the GMT ratio). The SCRs of KD-287 were all 100% and the GMTs were higher in the KD-287 group than in the JEV-GCC group after the second vaccination and before and after the third vaccination (GMT ratio: 5.59, 20.13, and 13.79, respectively, p < 0.001 in all). GMTs were higher in the KD-287 group in the heterologous analysis also (GMT ratio: 4.05, 5.15, and 4.19, respectively, p < 0.001 in all).
Conclusions
This study suggests that the KD-287, a JE-VC is as safe as and may be more effective than the licensed MB-derived vaccine. KD-287 could thus be useful as a second-generation vaccine and substitute for the current JE-MB vaccine in Korean children.
Trial registration
ClinicalTrials.gov: NCT01150942
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-014-0744-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-014-0744-4
PMCID: PMC4296691  PMID: 25567119
Japanese encephalitis; Vaccine; Vero cells; Clinical trial
24.  Optimization of Naltrexone Diclofenac Codrugs for Sustained Drug Delivery Across Microneedle-Treated Skin 
Pharmaceutical research  2013;31(1):10.1007/s11095-013-1147-8.
Purpose
The purpose of this work was to optimize the structure of codrugs for extended delivery across microneedle treated skin. Naltrexone, the model compound was linked with diclofenac, a nonspecific cyclooxygenase inhibitor to enhance the pore lifetime following microneedle treatment and develop a 7 day transdermal system for naltrexone.
Methods
Four different codrugs of naltrexone and diclofenac were compared in terms of stability and solubility. Transdermal flux, permeability and skin concentration of both parent drugs and codrugs were quantified to form a structure permeability relationship.
Results
The results indicated that all codrugs bioconverted in the skin. The degree of conversion was dependent on the structure, phenol linked codrugs were less stable compared to the secondary alcohol linked structures. The flux of naltrexone across microneedle treated skin and the skin concentration of diclofenac were higher for the phenol linked codrugs. The polyethylene glycol link enhanced solubility of the codrugs, which translated into flux enhancement.
Conclusion
The current studies indicated that formulation stability of codrugs and the flux of naltrexone can be enhanced via structure design optimization. The polyethylene glycol linked naltrexone diclofenac codrug is better suited for a 7 day drug delivery system both in terms of stability and drug delivery.
doi:10.1007/s11095-013-1147-8
PMCID: PMC3870048  PMID: 23943543
codrugs; drug delivery; microneedle; stability; transdermal
25.  Doenjang, a Fermented Korean Soybean Paste, Inhibits Lipopolysaccharide Production of Gut Microbiota in Mice 
Journal of Medicinal Food  2014;17(1):67-75.
Abstract
Doenjang has been reported to exhibit antioxidant, fibrinolytic, antimutagenic, anticancer, and antiobesity effects. In our preliminary study, doenjang decreased fecal lipopolysaccharide (LPS) levels in mice. Therefore, we investigated the effect of doenjang on the composition of gut microbiota in mice. Treatment with doenjang significantly increased the number of bifidobacteria cultured in BL media, compared with mice not treated with doenjang. However, doenjang decreased the number of Enterobacteriaceae cultured in DHL media. Doenjang significantly suppressed the β-glucuronidase activity, but did not influence α-/β-glucosaminidase and α-/β-glucosidase activities. When gut microbiota in mice treated with or without doenjang was analyzed by pyrosequencing, doenjang induced a significant modulation of the populations of the dominant gut microbiota. At the phylum level, doenjang treatment resulted in a significant decrease of Firmicutes and an increase of Bacteroidetes, which led to a decrease in the Firmicutes to Bacteroidetes ratio in gut microbiota. At the family level, the number of Ruminococcaceae and Lachnospiraceae were significantly decreased, while the number of Odoribacter_f was increased in doenjang-treated mice. Of colonic tight junction proteins, occludin, ZO-1, and claudin-1 in mice, occludin alone was significantly increased by treatment with doenjang. Although treatment with doenjang seemed to suppress NF-κB activation, it was not significant. Doenjang significantly suppressed tumor necrosis factor-α expression, whereas it did not influence interleukin (IL)-1β and IL-6 expression. However, doenjang increased IL-10 expression. Based on these findings, doenjang may promote gut health by regulating gut microbiota and its LPS concentrations and suppressing harmful enzyme production.
doi:10.1089/jmf.2013.3073
PMCID: PMC3901390  PMID: 24456356
doenjang; gut microbiota; inflammation; lipopolysaccharide

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