OBJECTIVES: The aim of this study was to develop a new prognostic classification for epithelial ovarian cancer (EOC) patients using gradient boosting (GB) and to compare the accuracy of the prognostic model with the conventional statistical method. METHODS: Information of EOC patients from Samsung Medical Center (training cohort, n=1,128) was analyzed to optimize the prognostic model using GB. The performance of the final model was externally validated with patient information from Asan Medical Center (validation cohort, n=229). The area under the curve (AUC) by the GB model was compared to that of the conventional Cox proportional hazard regression analysis (CoxPHR) model. RESULTS: In the training cohort, the AUC of the GB model for predicting second year overall survival (OS), with the highest target value, was 0.830 (95% confidence interval [CI]=0.802–0.853). In the validation cohort, the GB model also showed high AUC of 0.843 (95% CI=0.833–0.853). In comparison, the conventional CoxPHR method showed lower AUC (0.668 (95% CI=0.617–0.719) for the training cohort and 0.597 (95% CI=0.474–0.719) for the validation cohort) compared to GB. New classification according to survival probability scores of the GB model identified four distinct prognostic subgroups that showed more discriminately classified prediction than the International Federation of Gynecology and Obstetrics staging system. CONCLUSION: Our novel GB-guided classification accurately identified the prognostic subgroups of patients with EOC and showed higher accuracy than the conventional method. This approach would be useful for accurate estimation of individual outcomes of EOC patients.
Area Under Curve ; CA-125 Antigen ; Chungcheongnam-do ; Classification ; Cohort Studies ; Gynecology ; Humans ; Machine Learning ; Methods ; Obstetrics ; Ovarian Neoplasms ; Prognosis

BACKGROUND: Dermoscopy has been suggested as a useful tool for diagnosing various skin diseases. Recently, the possibility of using dermoscopy to predict the response to treatment has emerged. OBJECTIVE: The purpose of this study was to determine whether dermoscopic findings corresponded to clinical acne scar types. This study also aimed to discover which dermoscopic findings predict the response to acne scar treatment. METHODS: The dermoscopic findings of 39 participants undergoing atrophic acne scar treatment with fractional photothermolysis were evaluated. Patients were divided into two groups according to the duration of acne scar persistence. RESULTS: Patients with a relatively short duration of acne scar persistence usually achieved better treatment outcomes. Dermoscopic findings showed no obvious differences according to clinical acne scar type. But high hair follicle density can be considered a predictive factor of treatment effects. CONCLUSION: Our study indicated that acne scar improvements can be predicted by dermoscopically observing hair follicle density.
Acne Vulgaris* ; Cicatrix* ; Dermoscopy ; Hair Follicle ; Humans ; Pilot Projects* ; Skin Diseases

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates a wide variety of cellular functions, including cell growth, cellular differentiation, apoptosis, and wound healing. TGF-beta1, the prototype member of the TGF-beta superfamily, is well established as a central mediator of renal fibrosis. In chronic kidney disease, dysregulation of expression and activation of TGF-beta1 results in the relentless synthesis and accumulation of extracellular matrix proteins that lead to the development of glomerulosclerosis and tubulointerstitial fibrosis, and ultimately to end-stage renal disease. Therefore, specific targeting of the TGF-beta signaling pathway is seemingly an attractive molecular therapeutic strategy in chronic kidney disease. Accumulating evidence demonstrates that the multifunctionality of TGF-beta1 is connected with the complexity of its cell signaling networks. TGF-beta1 signals through the interaction of type I and type II receptors to activate distinct intracellular pathways. Although the Smad signaling pathway is known as a canonical pathway induced by TGF-beta1, and has been the focus of many previous reviews, importantly TGF-beta1 also induces various Smad-independent signaling pathways. In this review, we describe evidence that supports current insights into the mechanism and function of TGF-beta-activated kinase 1 (TAK1), which has emerged as a critical signaling molecule in TGF-beta-induced Smad-independent signaling pathways. We also discuss the functional role of TAK1 in mediating the profibrotic effects of TGF-beta1.
Apoptosis ; Extracellular Matrix Proteins ; Fibrosis ; Kidney ; Kidney Diseases ; Kidney Failure, Chronic ; MAP Kinase Kinase Kinases ; Negotiating ; Phosphotransferases ; Renal Insufficiency, Chronic ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Wound Healing

BACKGROUND: Abnormalities in the left atrial (LA) structure and function may develop in patients with paroxysmal atrial fibrillation (AF). We sought to determine the contribution of LA mechanical function, including LA stiffness, to AF by comparing patients with paroxysmal AF with normal control subjects, and to evaluate whether LA mechanical function and stiffness are related with the structural changes of LA. METHODS: Sixty-four paroxysmal AF patients (57 +/- 13 years, 59% male) were studied, using a speckle tracking echocardiography, and were compared with 34 age-, gender-, and left ventricular (LV) mass-matched controls (53 +/- 14 years, 61% male). LA volume indices, expansion index for reservoir function, active emptying fraction for contractile function, mitral annular velocities, and global longitudinal LA strain were measured. The ratio of E/e' to LA strain was used as an index of LA stiffness. RESULTS: Patients with paroxysmal AF had similar LV volume indices, ejection fraction, and diastolic function, when compared with that of the normal controls. However, paroxysmal AF patients showed increased LA volume indices and decreased LA reservoir function, but similar contractile function. LA stiffness was increased in patients with paroxysmal AF than in the control subjects (0.40 +/- 0.25 vs. 0.29 +/- 0.10, p = 0.002), and was related with LA volume indices and reservoir function. CONCLUSION: Patients with paroxysmal AF have decreased LA reservoir function and increased stiffness, in comparison with that of the control subjects. LA stiffness was significantly related with LA volume indices and reservoir function. LA stiffness can be used for the assessment of LA function in patients with paroxysmal AF.
Atrial Fibrillation ; Atrial Function, Left ; Echocardiography ; Humans ; Sprains and Strains ; Track and Field

PURPOSE: Missing cervical pathology after injury may lead to disability and influence long-term survival. Controversies continue to evolve concerning the initial screening methods used to predict cervical spine injury. Through a retrospective chart review, we attempted to analyze and propose factors predictive of cervical trauma. METHODS: Of all the patients who had visited the Emergency Department of Korea University, from January 2009 to December 2009, a retrospective review of the clinical records of the 217 patients who had undergone cervical spine computed tomography was done. We investigated whether we could predict the need for cervical spine computed tomography shortly after presentation in trauma patients by comparing the group with fractures and group without fractures and by finding risk factors showing significant differences between the two groups that might be used as guides in decision making. RESULTS: Of the 217 subjects who underwent cervical spine computed tomography scans, 33 were identified with fractures of the cervical spine while 184 were not. The most common mechanisms of trauma, in order, for those with fractures were falls, followed by traffic accidents. We found that the injury severity score, multiple injuries, a high-energy injury mechanism, neurologic deficit, and pain and tenderness of the cervical spine showed statistically significant differences between the two groups. CONCLUSION: Fractures of the cervical spine that are not observed with simple radiography occur with a relatively high frequency in trauma patients. Consideration should be given to the risk factors for cervical spine fracture, and if pertinent, cervical spine computed tomography should be performed with speed for early diagnosis of cervical spine fractures.
Accidents, Traffic ; Early Diagnosis ; Emergencies ; Humans ; Injury Severity Score ; Korea ; Mass Screening ; Multiple Trauma ; Neurologic Manifestations ; Retrospective Studies ; Risk Factors ; Spine

BACKGROUND AND OBJECTIVES: The objective of this study was to determine whether long-term exercise training will improve age-related cardiac metabolic derangement using proton magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Young and old male Fischer 344 rats were assigned to sedentary controls groups {young control (YC) group-3 months of age: YC, n=10; old control (OC) group-22 months of age: OC, n=10}, and an exercise training group (OT, n=5). After 12-week of treadmill exercise training, MR spectroscopy at 4.7 T was performed to assess myocardial energy metabolism: measurements of myocardial creatine-to-water ratio (Scr/Sw) were performed using the XWIN-NMR software. RESULTS: Exercise capacity was 14.7 minutes greater in OT than that in OC (20.1+/-1.9 minutes in OT, 5.4+/-2.3 minutes in OC; p<0.001). The 12-week exercise training rendered the old rats a maximum exercise capacity matching that of untrained YC rats (17.9+/-1.5 minutes in YC, 20.1+/-1.9 minutes in OT; p>0.05). The creatine-to-water ratios in the interventricular septa of YC did not differ significantly from that of OT (0.00131+/-0.00025 vs. 0.00127+/-0.00031; p=0.37). However, OC showed significant reduction in creatine-to-water ratio compared to OT (0.00096+/-0.00025 vs. 0.00127+/-0.00031; p<0.001). Mean total creatine concentrations in the myocardium were similar between YC and OT (13.3 +/-3.6 vs. 11.5+/-4.1 mmol/kg wet weight; p=0.29). In contrast, the mean total creatine concentration of OC was significantly reduced compared to OT (6.8+/-3.2 vs. 11.5+/-4.1 mmol/kg wet weight; p=0.03). CONCLUSION: Our findings suggest that long-term exercise training in old rats induced prevention of age-related deterioration in myocardial metabolism.
Animals ; Creatine ; Humans ; Magnetic Resonance Spectroscopy ; Magnetics ; Magnets ; Male ; Myocardium ; Protons ; Rats ; Spectrum Analysis

KIOM-79, a mixture of ethanol extracts from four herbs (parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix), has been developed for the potential therapeutic application to diabetic symptoms. Because screening of unexpected cardiac arrhythmia is compulsory for the new drug development, we investigated the effects of KIOM-79 on the action potential (AP) and various ion channel currents in cardiac myocytes. KIOM-79 decreased the upstroke velocity (Vmax) and plateau potential while slightly increased the duration of action potential (APD). Consistent with the decreased Vmax and plateau potential, the peak amplitude of Na+ current (INa) and Ca2+ current (ICa,L) were decreased by KIOM-79. KIOM-79 showed dual effects on hERG K+ current; increase of depolarization phase current (Idepol) and decreased tail current at repolarization phase (Itail). The increase of APD was suspected due to the decreased Itail. In computer simulation, the change of cardiac action potential could be well simulated based on the effects of KIOM-79 on various membrane currents. As a whole, the influence of KIOM-79 on cardiac ion channels are minor at concentrations effective for the diabetic models (0.1-10 microg/mL). The results suggest safety in terms of the risk of cardiac arrhythmia. Also, our study demonstrates the usefulness of the cardiac computer simulation in screening drug-induced long-QT syndrome.
Action Potentials/*drug effects ; Animals ; Cell Line ; Computer Simulation ; Female ; Ginger/chemistry ; Humans ; Ion Channels/*physiology ; Long QT Syndrome/diagnosis ; Male ; Membrane Potentials/drug effects/physiology ; Myocytes, Cardiac/*drug effects/physiology ; Patch-Clamp Techniques ; Plant Extracts/*pharmacology ; Pueraria/chemistry ; Purkinje Fibers/drug effects/physiology ; Rabbits ; Rats ; Rats, Sprague-Dawley

KIOM-79, a mixture of ethanol extracts from four herbs (parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix), has been developed for the potential therapeutic application to diabetic symptoms. Because screening of unexpected cardiac arrhythmia is compulsory for the new drug development, we investigated the effects of KIOM-79 on the action potential (AP) and various ion channel currents in cardiac myocytes. KIOM-79 decreased the upstroke velocity (Vmax) and plateau potential while slightly increased the duration of action potential (APD). Consistent with the decreased Vmax and plateau potential, the peak amplitude of Na+ current (INa) and Ca2+ current (ICa,L) were decreased by KIOM-79. KIOM-79 showed dual effects on hERG K+ current; increase of depolarization phase current (Idepol) and decreased tail current at repolarization phase (Itail). The increase of APD was suspected due to the decreased Itail. In computer simulation, the change of cardiac action potential could be well simulated based on the effects of KIOM-79 on various membrane currents. As a whole, the influence of KIOM-79 on cardiac ion channels are minor at concentrations effective for the diabetic models (0.1-10 microg/mL). The results suggest safety in terms of the risk of cardiac arrhythmia. Also, our study demonstrates the usefulness of the cardiac computer simulation in screening drug-induced long-QT syndrome.
Action Potentials/*drug effects ; Animals ; Cell Line ; Computer Simulation ; Female ; Ginger/chemistry ; Humans ; Ion Channels/*physiology ; Long QT Syndrome/diagnosis ; Male ; Membrane Potentials/drug effects/physiology ; Myocytes, Cardiac/*drug effects/physiology ; Patch-Clamp Techniques ; Plant Extracts/*pharmacology ; Pueraria/chemistry ; Purkinje Fibers/drug effects/physiology ; Rabbits ; Rats ; Rats, Sprague-Dawley

BACKGROUND/AIMS: Immune thrombocytopenic purpura (ITP) is an autoimmune disease that is mediated by anti-platelet antibodies. Based on the pathogenesis of ITP we evaluated the efficacy of intravenous anti-D immunoglobulin for adult chronic ITP. METHODS: Fourteen patients (4 without splenectomy and 10 with splenectomy) with refractory chronic ITP were treated with 50-70 microgram/kg of intravenous anti-D immunoglobulin only once. Treatment effects were evaluated by measuring the platelet counts and hemoglobin levels. RESULTS: Five patients (36%) showed a response; improvement in the platelet count lasted for on average 7 days (range: 2~24 days). There were no serious adverse effects. CONCLUSION: Anti-D immunoglobulin, which is associated with an Fc receptor blockade, appeared to be safe and effective for the treatment of adults with chronic ITP. Further studies are needed to confirm these findings and define further potentially effective treatment protocols with intravenous anti-D immunoglobulin.
Adult ; Antibodies ; Autoimmune Diseases ; Clinical Protocols ; Hemoglobins ; Humans ; Immunoglobulins ; Isoantibodies ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; Receptors, Fc ; Rho(D) Immune Globulin ; Splenectomy

The layers of keratinocytes form an acid mantle on the surface of the skin. Herein, we investigated the effects of acidic pH on the membrane current and [Ca2+](c) of human primary keratinocytes from foreskins and human keratinocyte cell line (HaCaT). Acidic extracellular pH (pHe< or =5.5) activated outwardly rectifying Cl- current (I(Cl,pH)) with slow kinetics of voltage-dependent activation. I(Cl,pH) was potently inhibited by an anion channel blocker 4,4`-diisothiocyanostilbene-2,2`-disulphonic acid (DIDS, 73.5% inhibition at 1micrometer). I(Cl,pH) became more sensitive to pHe by raising temperature from 24degrees C to 37degrees C. HaCaT cells also expressed Ca2+ -activated Cl- current (I(Cl,Ca)), and the amplitude of I(Cl,Ca) was increased by relatively weak acidic pHe (7.0 and 6.8). Interestingly, the acidic pHe (5.0) also induced a sharp increase in the intracellular [Ca2+] (delta[Ca2+](acid)) of HaCaT cells. The delta[Ca2+](acid) was independent of extracellular Ca2+, and was abolished by the pretreatment with PLC inhibitor, U73122. In primary human keratinocytes, 5 out of 28 tested cells showed delta[Ca2+](acid). In summary, we found I(Cl,pH) and delta[Ca2+](acid) in human keratinocytes, and these ionic signals might have implication in pathophysiological responses and differentiation of epidermal keratinocytes.
Cell Line ; Estrenes ; Foreskin ; Humans ; Hydrogen-Ion Concentration ; Keratinocytes ; Kinetics ; Membranes ; Pyrrolidinones ; Skin