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1.  Transplant physicians' perceptions of cord blood transplantation in Korea: a questionnaire survey 
Blood research  2014;49(4):228-233.
Background
Although bone marrow (BM) or mobilized peripheral blood (PB) is frequently used as the source of hematopoietic stem cells, hematopoietic stem cell transplantation (HSCT) using cord blood (CB) is gradually gaining popularity in many countries. However, BM or PB is still preferred over CB in Korea. Therefore, we tried to assess the awareness of CB transplantation (CBT) among domestic HSCT physicians and develop strategies for boosting its utilization by administering questionnaires to some of these physicians.
Methods
A direct questionnaire survey was conducted using the "Audience Response System" among 301 members who attended the annual meeting of the Korean Society of Blood and Marrow Transplantation. The data were analyzed for only 67 board certified physicians who were directly involved in HSCT activities.
Results
The poor outcomes resulting from insufficient experience in CBT was designated by the physicians as the main reason for the low domestic implementation of HSCT using CB. Other reasons identified in the survey were distrust in the quality and management of domestic CB and the high cost of obtaining CB.
Conclusion
Increasing the use of donated CB would foremost require increasing the inventory of donated CB containing a sufficient cell number for CBT and securing structured quality control of the CB banks. In addition, it would be necessary to minimize CB supply costs and continue to provide academic data, including CBT guidelines, so that clinicians could perform CBT with more confidence.
doi:10.5045/br.2014.49.4.228
PMCID: PMC4278003  PMID: 25548755
Cord blood; Utilization; Questionnaire
2.  Effects of GC7101, a Novel Prokinetic Agent on Gastric Motor Function: Ex Vivo Study 
Background/Aims
GC7101, an extract of Lonicera Flos, is a novel developing drug for reflux esophagitis and functional dyspepsia. However, the drug’s exact pharmacological mechanism of action remains unclear. This study assessed the effects of GC7101 on gastrointestinal (GI) motor function.
Methods
We used male guinea pigs to evaluate the effects of GC7101 on GI motility. The contraction of antral circular muscle in the presence of different doses of GC7101 was measured in a tissue bath. The prokinetic effects of GC7101 were tested using the charcoal transit assay from the pylorus to the most distal point of migration of charcoal mixture. To clarify the mechanism of action of GC7101, atropine, dopamine and the selective 5-hydroxytryptamine 4 receptor antagonist, GR113808 were used.
Results
The maximal amplitude of circular muscle contraction was induced by 5 mg mL−1 GC7101. The area under the curve of contraction was significantly increased at 5 mg mL−1 GC7101. Addition of 10−6 M atropine, 10−8 M dopamine or 10−7 M GR 113808 to GC7101 5 mg mL−1 decreased the amplitude and area under curve compared to GC7101 5 mg mL−1 alone. GC7101 accelerated GI transit in a dose dependent manner except 100 mg kg−1. Delayed GI transit caused by atropine, dopamine and GR 113808 was restored by GC7101 50 mg kg−1.
Conclusions
GC7101, an extract of Lonicera Flos, exerts a gastric prokinetic effect in guinea pig through cholinergic, antidopaminergic and serotonergic mechanisms. Therefore, GC7101 might be a novel drug for the treatment of functional dyspepsia.
doi:10.5056/jnm14010
PMCID: PMC4204422  PMID: 25273117
Functional dyspepsia; Gastrointestinal motility; Lonicera Flos; Prokinetic
3.  Efficacy and safety of tofacitinib for active rheumatoid arthritis with an inadequate response to methotrexate or disease-modifying antirheumatic drugs: a meta-analysis of randomized controlled trials 
Background/Aims
The aim of this study was to assess the efficacy and safety of tofacitinib (5 and 10 mg twice daily) in patients with active rheumatoid arthritis (RA).
Methods
A systematic review of randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib in patients with active RA was performed using the Medline, Embase, and Cochrane Controlled Trials Register databases as well as manual searches.
Results
Five RCTs, including three phase-II and two phase-III trials involving 1,590 patients, met the inclusion criteria. The three phase-II RCTs included 452 patients with RA (144 patients randomized to 5 mg of tofacitinib twice daily, 156 patients randomized to 10 mg of tofacitinib twice daily, and 152 patients randomized to placebo) who were included in this meta-analysis. The American College of Rheumatology 20% response rate was significantly higher in the tofacitinib 5- and 10-mg groups than in the control group (relative risk [RR], 2.445; 95% confidence interval [CI], 1.229 to 4.861; p = 0.011; and RR, 2.597; 95% CI, 1.514 to 4.455; p = 0.001, respectively). The safety outcomes did not differ between the tofacitinib 5- and 10-mg groups and placebo groups with the exception of infection in the tofacitinib 10-mg group (RR, 2.133; 95% CI, 1.268 to 3.590; p = 0.004). The results of two phase-III trials (1,123 patients) confirmed the findings in the phase-II studies.
Conclusions
Tofacitinib at dosages of 5 and 10 mg twice daily was found to be effective in patients with active RA that inadequately responded to methotrexate or disease-modifying antirheumatic drugs, and showed a manageable safety profile.
doi:10.3904/kjim.2014.29.5.656
PMCID: PMC4164730  PMID: 25228842
Tofacitinib; Efficacy; Safety; Arthritis, rheumatoid
4.  Clinical utilization of cord blood over human health: experience of stem cell transplantation and cell therapy using cord blood in Korea 
Korean Journal of Pediatrics  2014;57(3):110-116.
Cord blood (CB) has been used as an important and ethical source for hematopoietic stem cell transplantation (SCT) as well as cell therapy by manufacturing mesenchymal stem cell, induced pleuripotential stem cell or just isolating mononuclear cell from CB. Recently, the application of cell-based therapy using CB has expanded its clinical utility, particularly, by using autologous CB in children with refractory diseases. For these purposes, CB has been stored worldwide since mid-1990. In this review, I would like to briefly present the historical development of clinical uses of CB in the fields of SCT and cell therapy, particularly to review the experiences in Korea. Furthermore, I would touch the recent banking status of CB.
doi:10.3345/kjp.2014.57.3.110
PMCID: PMC4000756  PMID: 24778692
Cord blood; Transplantation; Cell therapy
5.  Dacryocystocele on prenatal ultrasonography: diagnosis and postnatal outcomes 
Ultrasonography  2014;34(1):51-57.
Purpose:
To report the incidence of dacryocystoceles detected by prenatal ultrasonography (US) and their postnatal outcomes and to determine the factors associated with the postnatal persistence of dacryocystoceles at birth.
Methods:
We retrospectively reviewed the prenatal US database at our institution for the period between January 2012 and December 2013. The medical records of women who had fetuses diagnosed with dacryocystocel larger than 5 mm were reviewed for maternal age, gestational age (GA) at detection, size and side of the dacryocystoceles, delivery, and postnatal information, such as GA at delivery, delivery mode, and gender of the neonate.
Results:
A total of 49 singletons were diagnosed with a dacryocystocele on prenatal US, yielding an overall incidence of 0.43%. The incidence of dacryocystoceles was the highest at the GA of 27 weeks and decreased toward term. Of the 49 fetuses including three of undeter mined gender, 25 (54%) were female. The mean GA at first detection was 31.2 weeks. The dacryocystocele was unilateral in 29 cases, with a mean maximum diameter of 7 mm. Spontaneous resolution at birth was documented in 35 out of 46 neonates (76%), including six with prenatal resolution. Multivariate analysis demonstrated that GA at delivery was a significant predictor of the postnatal persistence of dacryocystoceles (P=0.045).
Conclusion:
The overall incidence of prenatal dacryocystoceles was 0.43%; the incidence was higher in the early third trimester and decreased thereafter. Prenatal dacryocystoceles resolved in 76% of the patients at birth, and the GA at delivery was a significant predictor of postnatal persistence.
doi:10.14366/usg.14037
PMCID: PMC4282226  PMID: 25475649
Fetus; Ultrasonography; Congenital abnormalities; Lacrimal duct obstruction
6.  Clinical characteristics of hemophagocytic lymphohistiocytosis following Kawasaki disease: differentiation from recurrent Kawasaki disease 
Blood research  2013;48(4):254-257.
Background
Our aim was to investigate the clinical pattern of hemophagocytic lymphohistiocytosis following Kawasaki disease (HLH-KD), to enable differentiation of HLH from recurrent or refractory KD and facilitate early diagnosis.
Methods
We performed a nationwide retrospective survey and reviewed the clinical characteristics of patients with HLH-KD, including the interval between KD and HLH, clinical and laboratory findings, treatment responses, and outcomes, and compared them with historical data for both diseases.
Results
Twelve patients with HLH-KD, including 5 previously reported cases, were recruited. The median age was 6.5 years (range, 9 months-14.7 years). Eight patients were male and 4 were female. The median interval between the first episode of KD and the second visit with recurrent fever was 12 days (3-22 days). Of the 12 children, 2 were initially treated with intravenous IgG (IVIG) for recurrent KD when they presented at the hospital with recurrent fever. Eventually, 10 children received chemotherapy under an HLH protocol and 2 received supportive treatment. Two patients died of combined infections during chemotherapy, 1 was lost to follow up, and 9 remain alive. The overall survival rate at 4 years was 81.1% with a median follow up of 45.1 months.
Conclusion
A diagnosis of HLH-KD should be considered when symptoms similar to recurrent KD develop within 1 month of the first episode of KD. Our findings will help physicians differentiate between HLH and the recurrent form of KD.
doi:10.5045/br.2013.48.4.254
PMCID: PMC3894383  PMID: 24466549
Hemophagocytic lymphohistiocytosis; Kawasaki disease; Recurrent
7.  Meta-analysis of randomized controlled trials of bosentan for treatment of pulmonary arterial hypertension 
Background/Aims
We assessed the efficacy and safety of bosentan in patients with pulmonary arterial hypertension (PAH).
Methods
We surveyed randomized controlled trials (RCTs) of the efficacy and safety of bosentan in patients with PAH using MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manual searches. Meta-analysis of RCTs was performed to determine treatment efficacy and safety outcomes. Results are presented as odds ratios (ORs) or weighted mean differences (WMDs).
Results
Meta-analysis of seven RCTs including a total of 410 patients and 296 controls revealed that the 6-minute work distance was significantly higher in the bosentan group than in the placebo group (WMD, 46.19; 95% confidence interval [CI], 21.20 to 71.19; p = 2.9 × 10-5). Compared with the placebo, bosentan significantly reduced the mean pulmonary arterial pressure in patients with PAH (WMD, -6.026; 95% CI, -8.785 to -3.268, p = 1.8 × 10-6). The bosentan therapy group worsened less clinically than the placebo group (OR, 0.252; 95% CI, 0.140 to 0.454; p = 4.6 × 10-7). The incidence of serious adverse events did not differ between the bosentan and placebo groups (OR, 0.948; 95% CI, 0.556 to 1.614; p = 0.843). However, the results of the abnormal liver function test (LFT) were significantly higher in the bosentan group than in the placebo group (OR, 2.312; 95% CI, 1.020 to 5.241; p = 0.045).
Conclusions
This meta-analysis shows that bosentan can treat PAH effectively. However, bosentan increased the incidence of abnormal LFT results compared with the placebo.
doi:10.3904/kjim.2013.28.6.701
PMCID: PMC3846996  PMID: 24307846
Bosentan; Efficacy; Safety; Hypertension, pulmonary
8.  GM-CSF-loaded chitosan hydrogel as an immunoadjuvant enhances antigen-specific immune responses with reduced toxicity 
BMC Immunology  2014;15(1):48.
Background
The application of vaccine adjuvants has been vigorously studied for a diverse range of diseases in order to improve immune responses and reduce toxicity. However, most adjuvants have limited uses in clinical practice due to their toxicity.
Methods
Therefore, to reduce health risks associated with the use of such adjuvants, we developed an advanced non-toxic adjuvant utilizing biodegradable chitosan hydrogel (CH-HG) containing ovalbumin (OVA) and granulocyte-macrophage colony-stimulating factor (GM-CSF) as a local antigen delivery system.
Results
After subcutaneous injection into mice, OVA/GM-CSF-loaded CH-HG demonstrated improved safety and enhanced OVA-specific antibody production compared to oil-based adjuvants such as Complete Freund’s adjuvant (CFA) or Incomplete Freund’s adjuvant (IFA). Moreover, CH-HG system-mediated immune responses was characterized by increased number of OVA-specific CD4+ and CD8+ INF-γ+ T cells, leading to enhanced humoral and cellular immunity.
Conclusions
In this study, the improved safety and enhanced immune response characteristics of our novel adjuvant system suggest the possibility of the extended use of adjuvants in clinical practice with reduced apprehension about toxic side effects.
Electronic supplementary material
The online version of this article (doi:10.1186/s12865-014-0048-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s12865-014-0048-x
PMCID: PMC4201920  PMID: 25323934
Adjuvant; Chitosan; Hydrogel; Immune response
9.  Transient Receptor Potential Canonical Type 3 Channels Control the Vascular Contractility of Mouse Mesenteric Arteries 
PLoS ONE  2014;9(10):e110413.
Transient receptor potential canonical type 3 (TRPC3) channels are non-selective cation channels and regulate intracellular Ca2+ concentration. We examined the role of TRPC3 channels in agonist-, membrane depolarization (high K+)-, and mechanical (pressure)-induced vasoconstriction and vasorelaxation in mouse mesenteric arteries. Vasoconstriction and vasorelaxation of endothelial cells intact mesenteric arteries were measured in TRPC3 wild-type (WT) and knockout (KO) mice. Calcium concentration ([Ca2+]) was measured in isolated arteries from TRPC3 WT and KO mice as well as in the mouse endothelial cell line bEnd.3. Nitric oxide (NO) production and nitrate/nitrite concentrations were also measured in TRPC3 WT and KO mice. Phenylephrine-induced vasoconstriction was reduced in TRPC3 KO mice when compared to that of WT mice, but neither high K+- nor pressure-induced vasoconstriction was altered in TRPC3 KO mice. Acetylcholine-induced vasorelaxation was inhibited in TRPC3 KO mice and by the selective TRPC3 blocker pyrazole-3. Acetylcholine blocked the phenylephrine-induced increase in Ca2+ ratio and then relaxation in TRPC3 WT mice but had little effect on those outcomes in KO mice. Acetylcholine evoked a Ca2+ increase in endothelial cells, which was inhibited by pyrazole-3. Acetylcholine induced increased NO release in TRPC3 WT mice, but not in KO mice. Acetylcholine also increased the nitrate/nitrite concentration in TRPC3 WT mice, but not in KO mice. The present study directly demonstrated that the TRPC3 channel is involved in agonist-induced vasoconstriction and plays important role in NO-mediated vasorelaxation of intact mesenteric arteries.
doi:10.1371/journal.pone.0110413
PMCID: PMC4195735  PMID: 25310225
11.  Fetal tumors: prenatal ultrasonographic findings and clinical characteristics 
Ultrasonography  2014;33(4):240-251.
The incidence of fetal tumors has been increased due to generalization of prenatal evaluation and improvement of imaging techniques. The early detection of a fetal tumor and understanding of its imaging features are very important for fetal, maternal, and neonatal care. Ultrasonography is usually used for the detection and differential diagnosis of fetal tumors, and magnetic resonance imaging is increasingly being used as a complementary study. Many fetal tumors have different clinical and imaging features compared with pediatric tumors. Although several fetal tumors may mimic other common anomalies, some specific imaging features may carry early accurate diagnosis of fetal tumors, which may alter the prenatal management of a pregnancy and the mode of delivery, and facilitate immediate postnatal treatment.
doi:10.14366/usg.14019
PMCID: PMC4176115  PMID: 25116458
Fetus; Neoplasms; Congenital abnormalities; Ultrasonography
12.  Effect of Human Parathyroid Hormone on Hematopoietic Progenitor Cells in NOD/SCID Mice Co-Transplanted with Human Cord Blood Mononuclear Cells and Mesenchymal Stem Cells 
Yonsei Medical Journal  2012;54(1):238-245.
Purpose
We evaluated the effect of human parathyroid hormone (hPTH) on the engraftment and/or in vivo expansion of hematopoietic stem cells in an umbilical cord blood (UCB)-xenotransplantation model. In addition, we assessed its effect on the expression of cell adhesion molecules.
Materials and Methods
Female NOD/SCID mice received sublethal total body irradiation with a single dose of 250 cGy. Eighteen to 24 hours after irradiation, 1×107 human UCB-derived mononuclear cells (MNCs) and 5×106 human UCB-derived mesenchymal stem cells (MSCs) were infused via the tail vein. Mice were randomly divided into three groups: Group 1 mice received MNCs only, Group 2 received MNCs only and were then treated with hPTH, Group 3 mice received MNCs and MSCs, and were treated with hPTH.
Results
Engraftment was achieved in all the mice. Bone marrow cellularity was approximately 20% in Group 1, but 70-80% in the hPTH treated groups. Transplantation of MNCs together with MSCs had no additional effect on bone marrow cellularity. However, the proportion of human CD13 and CD33 myeloid progenitor cells was higher in Group 3, while the proportion of human CD34 did not differ significantly between the three groups. The proportion of CXCR4 cells in Group 3 was larger than in Groups 1 and 2 but without statistical significance.
Conclusion
We have demonstrated a positive effect of hPTH on stem cell proliferation and a possible synergistic effect of MSCs and hPTH on the proportion of human hematopoietic progenitor cells, in a xenotransplantation model. Clinical trials of the use of hPTH after stem cell transplantation should be considered.
doi:10.3349/ymj.2013.54.1.238
PMCID: PMC3521258  PMID: 23225826
Umbilical cord blood; parathyroid hormone; bone marrow niches
13.  Korean Type Distal Radius Anatomical Volar Plate System: A Preliminary Report 
Clinics in Orthopedic Surgery  2014;6(3):258-266.
Background
Distal radius fracture is the most common fracture of the upper extremity, and approximately 60,000 distal radius fractures occur annually in Korea. Internal fixation with an anatomical volar locking plate is widely used in the treatment of unstable distal radius fractures. However, most of the currently used distal radius anatomical plate systems were designed based on the anatomical characteristics of Western populations. Recently, the Korean-type distal radius anatomical volar plate (K-DRAVP) system was designed and developed based on the anatomical characteristics of the distal radius of Koreans. The purpose of this study was to evaluate the preliminary results of the new K-DRAVP system, and to compare its radiologic and functional results with those of the other systems.
Methods
From March 2012 to October 2012, 46 patients with acute distal radius fractures who were treated with the K-DRAVP system at three hospitals were enrolled in this study. Standard posteroanterior and lateral radiographs were obtained to assess fracture healing, and three radiographic parameters (volar tilt, radial inclination, and radial length) were assessed to evaluate radiographic outcomes. The range of motion and grip strength, the Gartland and Werley scoring system, and the disabilities of the arm, shoulder and hand (DASH) questionnaire were used to assess clinical and functional outcomes.
Results
All radiologic parameters were restored to normal values, and maintained without any loosening or collapse until the time of final follow-up. Grip strength was restored to 84% of the value for the unaffected side. The mean range of motion of the wrist at final follow-up was restored to 77%-95% of the value for the unaffected side. According to the Gartland and Werley scoring system, there were 16 excellent, 26 good, and 4 fair results. The mean DASH score was 8.4 points. There were no complications after surgery.
Conclusions
The newly developed K-DRAVP system could be used to restore and maintain good anatomical parameters, and provide good clinical outcomes with low complication rates. This system is a promising surgical option for the treatment of distal radius fractures in the Korean population.
doi:10.4055/cios.2014.6.3.258
PMCID: PMC4143511  PMID: 25177449
Radius; Distal radius fracture; Volar locking plate; Anatomical plate
14.  Examination of the Pronator Quadratus Muscle during Hardware Removal Procedures after Volar Plating for Distal Radius Fractures 
Clinics in Orthopedic Surgery  2014;6(3):267-272.
Background
It is not clear whether the pronator quadratus (PQ) muscle actually heals and provides a meaningful pronation force after volar plating for distal radius fractures (DRFs). We aimed to determine whether the length of the PQ muscle, which is dissected and then repaired during volar plating for a DRF, affects the forearm rotation strength and clinical outcomes.
Methods
We examined 41 patients who requested hardware removal after volar plating. We measured the isokinetic forearm rotation strength and clinical outcomes including grip strength, wrist range of motion, and disabilities of the arm, shoulder and hand (DASH) scores at 6 months after fracture fixation. During the hardware removal surgery, which was performed at an average of 9 months (range, 8.3 to 11.5 months) after fracture fixation, we measured the PQ muscle length.
Results
The average PQ muscle length was 68% of the normal muscle length, and no significant relationship was found between the PQ muscle length and the outcomes including isokinetic forearm rotation strength, grip strength, wrist range of motion, and DASH scores.
Conclusions
This study demonstrates that the length of the healed PQ muscle does not affect isokinetic forearm rotation strength and clinical outcomes after volar plating for DRFs. The results of this study support our current practice of loose repair of the PQ that is performed by most of the surgeons to prevent tendon irritation over the plate, and suggest that tight repair of the PQ is not necessary for achieving improved forearm function.
doi:10.4055/cios.2014.6.3.267
PMCID: PMC4143512  PMID: 25177450
Distal radius fracture; Volar plating; Pronator quadratus; Isokinetic strength
15.  Factors Associated with Postoperative Nausea and Vomiting in Patients Undergoing an Ambulatory Hand Surgery 
Clinics in Orthopedic Surgery  2014;6(3):273-278.
Background
Patients undergoing ambulatory surgery under general anesthesia experience considerable levels of postoperative nausea and vomiting (N/V) after their discharge. However, those complications have not been thoroughly investigated in hand surgery patients yet. We investigated factors associated with postoperative N/V in patients undergoing an ambulatory hand surgery under general anesthesia and determined whether patients' satisfaction with this setting is associated with postoperative N/V levels.
Methods
We prospectively evaluated 200 consecutive patients who underwent ambulatory hand surgeries under general anesthesia to assess their postoperative N/V visual analogue scale (VAS) levels during the first 24 hours after surgery and their satisfaction with an ambulatory surgery setting. Potential predictors of postoperative N/V were; age, sex, body mass index, smoking behavior, a history of postoperative N/V after previous anesthesia or motion sickness, preoperative anxiety level and the duration time of anesthesia. We conducted multivariate analyses to identify factors associated with postoperative N/V levels. We also conducted multivariate logistic regression analyses to determine whether the N/V levels are associated with the patients' satisfaction with this setting. Here, potential predictors for satisfaction were sex, age, postoperative pain and N/V.
Results
Postoperative N/V were associated with a non-smoking history, a history of motion sickness and a high level of preoperative anxiety. Twenty-two patients (11%) were dissatisfied with the ambulatory setting and this dissatisfaction was independently associated with moderate (VAS 4-7) and high (VAS 8-10) levels of postoperative N/V and with a high level (VAS 8-10) of postoperative pain.
Conclusions
Although most of the patients were satisfied with the ambulatory surgery setting, moderate to high levels of N/V were associated with dissatisfaction of patients with this setting, suggesting a need for better identifying and managing those patients at risk. The information regarding risk factors for N/V could help in preoperative patient consultation regarding an ambulatory hand surgery under general anesthesia.
doi:10.4055/cios.2014.6.3.273
PMCID: PMC4143513  PMID: 25177451
Ambulatory hand surgery; Nausea; Vomiting; Satisfaction
16.  Thromboembolic events identified during diagnosis of germ cell tumors in 2 children 
The Korean Journal of Hematology  2012;47(3):233-236.
We describe 2 cases in which radiographic evidence of thromboembolic events was obtained during germ cell tumor diagnosis. There was no evidence of coagulation factor abnormalities or contributory procedures or drugs in either patient. We used anticoagulation therapy for thrombolysis in one patient, but in the other, the thromboembolism resolved spontaneously.
doi:10.5045/kjh.2012.47.3.233
PMCID: PMC3464343  PMID: 23071481
Thromboembolism; Germ cell tumor; Chemotherapy
17.  Enactment of a Law for Governmental Support of the Use of Cord Blood, and Ethical Issues 
In Korea, cord blood banking projects have been developed since 1996, and the 1st successful cord blood transplant was performed in 1998. Recently, “Cord Blood Management and Research Act” was legislated in 2010, and has been come into effect on July 1st, 2011. This review focuses the backgrounds, aims, and legislation process as well as principal articles in this act.
PMCID: PMC3840985  PMID: 24298360
Cord blood; Act
18.  Roles of protein arginine methylation in DNA damage signaling pathways 
Cell Cycle  2011;10(9):1343-1344.
doi:10.4161/cc.10.9.15379
PMCID: PMC3117038  PMID: 21445011
BRCA1; p300; CARM1; DNA damage; protein methylation; p21; Gadd45; cell cycle; apoptosis; cancer
19.  Triple disruption of the superior shoulder suspensory complex 
The superior shoulder suspensory complex (SSSC) is an extremely important structure composed of a ring of bone and soft tissues at the superior aspect of the shoulder. Double disruption leads to instability of the construct and usually requires operative treatment. Triple disruption of the SSSC is extremely rare and is encountered in high-energy trauma cases often in association with other injuries. The authors experienced a case of triple disruption involving the acromion, coracoid process, and acromioclavicular separation. This type of SSSC disruption is unlikely to have been caused by a single impact and is rather caused by multiple impacts during one traumatic event.
doi:10.4103/0973-6042.96999
PMCID: PMC3391788  PMID: 22787337
Superior shoulder suspensory complex; SSSC; triple disruption
20.  Healthcare Decision Support System for Administration of Chronic Diseases 
Healthcare Informatics Research  2014;20(3):173-182.
Objectives
A healthcare decision-making support model and rule management system is proposed based on a personalized rule-based intelligent concept, to effectively manage chronic diseases.
Methods
A Web service was built using a standard message transfer protocol for interoperability of personal health records among healthcare institutions. An intelligent decision service is provided that analyzes data using a service-oriented healthcare rule inference function and machine-learning platform; the rules are extensively compiled by physicians through a developmental user interface that enables knowledge base construction, modification, and integration. Further, screening results are visualized for the self-intuitive understanding of personal health status by patients.
Results
A recommendation message is output through the Web service by receiving patient information from the hospital information recording system and object attribute values as input factors. The proposed system can verify patient behavior by acting as an intellectualized backbone of chronic diseases management; further, it supports self-management and scheduling of screening.
Conclusions
Chronic patients can continuously receive active recommendations related to their healthcare through the rule management system, and they can model the system by acting as decision makers in diseases management; secondary diseases can be prevented and health management can be performed by reference to patient-specific lifestyle guidelines.
doi:10.4258/hir.2014.20.3.173
PMCID: PMC4141131  PMID: 25152830
Clinical Decision Support Systems; Expert Systems; Knowledge Bases; Personal Health Records; Chronic Disease
21.  Early-onset Childhood Sarcoidosis with Incidental Multiple Enchondromatosis 
The triad of rash, arthritis, and uveitis seems to be characteristic for early-onset childhood sarcoidosis. We describe an interesting case of early-onset childhood sarcoidosis coexisting enchondromatosis, which clinically masquerade as Langerhans cell histiocytosis. A 33 months old girl presented with skin rash, subcutaneous nodules with polyarthritis, and revealed the involvement of lymph nodes as well as spleen during work-up. She also presented with multiple osteolytic lesions which pathologically proven enchondromatosis. Oral prednisone was prescribed at 2 mg/kg/day for 2 months until when subcutaneous nodules and joint swellings almost disappeared, and then slowly tapered over a period of 5 months. We report an unusual case of early-onset childhood sarcoidosis presented with osteolytic bone lesions which were irrelevant to sarcoidosis.
doi:10.3346/jkms.2012.27.1.96
PMCID: PMC3247783  PMID: 22219622
Sarcoidosis; Polyarthritis; Enchondromatosis; Nodule; Childhood
22.  A Multi-Classifier Based Guideline Sentence Classification System 
Healthcare Informatics Research  2011;17(4):224-231.
Objectives
An efficient clinical process guideline (CPG) modeling service was designed that uses an enhanced intelligent search protocol. The need for a search system arises from the requirement for CPG models to be able to adapt to dynamic patient contexts, allowing them to be updated based on new evidence that arises from medical guidelines and papers.
Methods
A sentence category classifier combined with the AdaBoost.M1 algorithm was used to evaluate the contribution of the CPG to the quality of the search mechanism. Three annotators each tagged 340 sentences hand-chosen from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) clinical guideline. The three annotators then carried out cross-validations of the tagged corpus. A transformation function is also used that extracts a predefined set of structural feature vectors determined by analyzing the sentential instance in terms of the underlying syntactic structures and phrase-level co-occurrences that lie beneath the surface of the lexical generation event.
Results
The additional sub-filtering using a combination of multi-classifiers was found to be more effective than a single conventional Term Frequency-Inverse Document Frequency (TF-IDF)-based search system in pinpointing the page containing or adjacent to the guideline information.
Conclusions
We found that transformation has the advantage of exploiting the structural and underlying features which go unseen by the bag-of-words (BOW) model. We also realized that integrating a sentential classifier with a TF-IDF-based search engine enhances the search process by maximizing the probability of the automatically presented relevant information required in the context generated by the guideline authoring environment.
doi:10.4258/hir.2011.17.4.224
PMCID: PMC3259557  PMID: 22259724
Knowledge Bases; Data Mining; Natural Language Processing
23.  NMR Characterization of the Interaction of the Endonuclease Domain of MutL with Divalent Metal Ions and ATP 
PLoS ONE  2014;9(6):e98554.
MutL is a multi-domain protein comprising an N-terminal ATPase domain (NTD) and C-terminal dimerization domain (CTD), connected with flexible linker regions, that plays a key role in DNA mismatch repair. To expand understanding of the regulation mechanism underlying MutL endonuclease activity, our NMR-based study investigated interactions between the CTD of MutL, derived from the hyperthermophilic bacterium Aquifex aeolicus (aqMutL-CTD), and putative binding molecules. Chemical shift perturbation analysis with the model structure of aqMutL-CTD and circular dichroism results revealed that tight Zn2+ binding increased thermal stability without changing secondary structures to function at high temperatures. Peak intensity analysis exploiting the paramagnetic relaxation enhancement effect indicated the binding site for Mn2+, which shared binding sites for Zn2+. The coexistence of these two metal ions appears to be important for the function of MutL. Chemical shift perturbation analysis revealed a novel ATP binding site in aqMutL-CTD. A docking simulation incorporating the chemical shift perturbation data provided a putative scheme for the intermolecular interactions between aqMutL-CTD and ATP. We proposed a simple and understandable mechanical model for the regulation of MutL endonuclease activity in MMR based on the relative concentrations of ATP and CTD through ATP binding-regulated interdomain interactions between CTD and NTD.
doi:10.1371/journal.pone.0098554
PMCID: PMC4047009  PMID: 24901533
24.  Responsiveness of the Korean Version of the Michigan Hand Outcomes Questionnaire after Carpal Tunnel Release 
Clinics in Orthopedic Surgery  2014;6(2):203-207.
Background
The Korean version of the Michigan Hand Outcomes Questionnaire (K-MHQ) was recently validated; however, the questionnaire's responsiveness as well as the degree to which the instrument is sensitive to change has not been thoroughly evaluated in a specific condition in Koreans. We evaluated the responsiveness of the K-MHQ in a homogenous cohort of patients with carpal tunnel syndrome (CTS) and we compared it with that of the Korean version of the Disability of the Arm, Shoulder, and Hand Questionnaire (K-DASH), which was found to have a large degree of responsiveness after carpal tunnel release for Korean patients with CTS.
Methods
Thirty-seven patients with CTS prospectively completed the K-MHQ and the K-DASH before and 6 months after surgery. The responsiveness statistics were assessed for both the K-MHQ and the K-DASH by using the standardized response mean (SRM), which was defined as the mean change of the original scores after surgery divided by the standard deviation of the change.
Results
All domains of the K-MHQ significantly improved after carpal tunnel release (p < 0.001). The SRM for all scales but one (the aesthetics scale) showed large responsiveness of ≥ 0.8. The aesthetics scale showed medium responsiveness of 0.6. The combined function/symptom scale of the K-DASH significantly improved after surgery (p < 0.001). The SRM of the K-DASH revealed large responsiveness of 0.9.
Conclusions
The K-MHQ was found to have a large degree of responsiveness after carpal tunnel release for Korean patients with CTS, which is comparable not only to the K-DASH, but also to the original version of the MHQ. The region-specific K-MHQ can be useful for outcomes research related to carpal tunnel surgery, especially for research comparing CTS with various other hand and wrist health conditions.
doi:10.4055/cios.2014.6.2.203
PMCID: PMC4040382  PMID: 24900903
Responsiveness; K-MHQ; K-DASH; Carpal tunnel syndrome
25.  Efficacy and Safety of Monthly 150 mg Oral Ibandronate in Women with Postmenopausal Osteoporosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials 
Background/Aims
The aim of this study was to assess the efficacy and safety of monthly oral 150 mg ibandronate in women with postmenopausal osteoporosis (PMO).
Methods
A systematic review and meta-analysis were performed to determine treatment efficacy and safety outcomes between monthly oral 150 mg ibandronate and weekly 70 mg alendronate, daily 2.5 mg ibandronate, and a placebo.
Results
Eight randomized controlled trials were included in this systematic review and meta-analysis. Once-monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, showing increased bone mineral density (BMD) in both the lumbar spine and total hip. Pooled data from two cross-over trials showed that significantly more women with PMO preferred once-monthly ibandronate therapy to once-weekly alendronate therapy (relative risk [RR], 2.422; 95% confidence interval [CI], 2.111 to 2.825; p < 1 × 10-8) and found the monthly ibandronate regimen more convenient than the weekly alendronate regimen (RR, 3.096; 95% CI, 2.622 to 3.622; p < 1 × 10-8). Monthly 150 mg ibandronate therapy resulted in a significantly higher change in BMD of the lumbar spine than with the placebo. A once monthly 150 mg regimen produced greater increases in lumbar spine, total hip, femoral neck, and trochanter BMD than daily treatment, with a similar incidence of adverse events between the groups.
Conclusions
Once monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, and patients strongly preferred the convenience of monthly ibandronate over weekly alendronate. Monthly 150 mg ibandronate was superior to, and as well tolerated as, the daily treatment.
doi:10.3904/kjim.2011.26.3.340
PMCID: PMC3192207  PMID: 22016595
Ibandronic acid; Efficacy; Safety; Osteoporosis; Review

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