Assembly of different length of polyubiquitins on the catalytic cysteine of E2 enzymes without E3 ligase; a novel application of non-reduced/reduced 2-dimensional electrophoresis

AbstractIn this study using non-reduced/reduced 2-dimensional electrophoresis (NR/R-2DE), we clearly demonstrated that E3-independent ubiquitination by Ube2K produced not only unanchored but also Ube2K-linked polyubiquitins through thioester and isopeptide bonds. E3-independent assembly of polyubiquitins on the catalytic cysteine of Ube2K strongly supports the possibility of ‘en bloc transfer’ for polyubiquitination. From the same analyses of E3-independent ubiquitination products by other E2s, we also found that different lengths of polyubiquitins were linked to different E2s through thioester bond; longer chains by Cdc34 like Ube2K, short chains by Ube2g2, and mono-ubiquitin by UbcH10. Our results suggest that E2s possess the different intrinsic catalytic activities for polyubiquitination

Variability of Response Time as a Predictor of Methylphenidate Treatment Response in Korean Children with Attention Deficit Hyperactivity Disorder

PURPOSE: Methylphenidate (MPH) is an effective medication for the treatment of attention deficit hyperactivity disorder (ADHD). However, about 30% of patients do not respond to or are unable to tolerate MPH. Based on previous findings, we hypothesized that great variability in response time (RT) among Korean children with ADHD on a computerized continuous performance attention test would be related to poor MPH treatment response. MATERIALS AND METHODS: Children (ages 6-18 years) with ADHD were recruited for a prospective 12-week, open-labeled, multicenter study to examine optimal dosage of OROS methylphenidate. Of the 144 subjects selected, 28 dropped out due to adverse events, medication noncompliance, or follow-up loss, and an additional 26 subjects with comorbid disorders were excluded from statistical analyses. We defined 'responders' as subjects who received a score of less than 18 on the attention deficit hyperactivity disorder rating scale (ARS; Korean version, K-ARS) and a score of 1 or 2 on the Clinical Global Impression-Improvement scale (CGI-I). RT variability was assessed with the ADHD diagnostic system (ADS). RESULTS: Fifty-nine (67%) subjects responded to MPH treatment. The non-responders showed greater RT variability at baseline (Mann Whitney U = 577.0, p < 0.01). Baseline RT variability was a significant predictor of MPH response (Nagelkerke R(2) = 0.136, p < 0.01). It predicted 94.9% of responder, 17.2% of non-responder and 69.3% of overall group. CONCLUSION: High RT variability may predict poor response to MPH treatment in children with ADHDope

Short-Term Effects of Combined Serial Casting and Botulinum Toxin Injection for Spastic Equinus in Ambulatory Children with Cerebral Palsy

PURPOSE: The purpose of this paper is to test the hypothesis that combination therapy of serial cast and botulinum toxin type A (BTX-A) injection can further enhance the effects of a BTX-A injection in ambulant children with cerebral palsy (CP) who have an equinus foot. MATERIALS AND METHODS: Children in group A (30 legs of 21 children) received a serial casting application after an injection of BTX-A, and children in group B (25 legs of 17 children) received only a BTX-A injection. Assessments were performed before the intervention and 1 month after the intervention. RESULTS: After the intervention, there were significant improvements in tone, dynamic spasticity, and passive range of motion (ROM) in both groups. However, the changes were greater in group A than in group B. Dimension D (standing) in Gross Motor Function Measure (GMFM)-66 was significantly improved in group A but not in group B. On the other hand, there were no significant changes in dimension E (walking, running, jumping) in GMFM-66 in either group. CONCLUSION: The results of our study suggest that a serial casting application after BTX-A injection can enhance the benefits of BTX-A injection in children with cerebral palsy.ope

Good Glycemic Control Is Associated with Better Survival in Diabetic Patients on Peritoneal Dialysis: A Prospective Observational Study

BACKGROUND: The effect of glycemic control after starting peritoneal dialysis (PD) on the survival of diabetic PD patients has largely been unexplored, especially in Asian population. METHODS: We conducted a prospective observational study, in which 140 incident PD patients with diabetes were recruited. Patients were divided into tertiles according to the means of quarterly HbA1C levels measured during the first year after starting PD. We examined the association between HbA1C and all-cause mortality using Cox proportional hazards models. RESULTS: The mean age was 58.7 years, 59.3% were male, and the mean follow-up duration was 3.5 years (range 0.4-9.5 years). The mean HbA1C levels were 6.3%, 7.1%, and 8.5% in the 1(st), 2(nd), and 3(rd) tertiles, respectively. Compared to the 1(st) tertile, the all-cause mortality rates were higher in the 2(nd) [hazard ratio (HR), 4.16; 95% confidence interval (CI), 0.91-18.94; p = 0.065] and significantly higher in the 3(rd) (HR, 13.16; 95% CI, 2.67-64.92; p = 0.002) tertiles (p for trend = 0.005), after adjusting for confounding factors. Cardiovascular mortality, however, did not differ significantly among the tertiles (p for trend = 0.682). In contrast, non-cardiovascular deaths, most of which were caused by infection, were more frequent in the 2(nd) (HR, 7.67; 95% CI, 0.68-86.37; p = 0.099) and the 3(rd) (HR, 51.24; 95% CI, 3.85-681.35; p = 0.003) tertiles than the 1(st) tertile (p for trend = 0.007). CONCLUSIONS: Poor glycemic control is associated with high mortality rates in diabetic PD patients, suggesting that better glycemic control may improve the outcomes of these patients

The submucosal fibrosis: what does it mean for colorectal endoscopic submucosal dissection?

Background/AimsEndoscopic submucosal dissection (ESD) allows removal of colorectal epithelial neoplasms en bloc regardless of size. Colorectal ESD is a difficult procedure because of technical difficulties and risks of complications. This study aimed to assess the relationship between ESD outcome and degree of submucosal fibrosis.MethodsPatients with colorectal tumors undergoing ESD and their medical records were reviewed retrospectively. The degree of submucosal fibrosis was classified into three types. The relationship between ESD outcome and degree of submucosal fibrosis was analyzed.ResultsESD was performed in 158 patients. Thirty-eight cases of F0 (no) fibrosis (24.1%) and 46 cases of F2 (severe) fibrosis (29.1%) were observed. Complete resection was achieved for 138 lesions (87.3%). Multivariate analysis demonstrated that submucosal invasion of tumor and histology of carcinoma were independent risk factors for F2 fibrosis. Severe fibrosis was an independent risk factor for incomplete resection.ConclusionsSevere fibrosis is an important factor related to incomplete resection during colorectal ESD. In cases of severe fibrosis, the rate of complete resection was low even when ESD was performed by an experienced operator. Evaluation of submucosal fibrosis may be helpful to predict the submucosal invasion of tumors and technical difficulties in ESD

High-Intensity Focused Ultrasound Therapy Versus Coblation for the Treatment of Inferior Turbinate Hypertrophy: A Clinical Trial

Objectives To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) therapy with coblation for the treatment of inferior turbinate hypertrophy (ITH). Methods In this randomized controlled clinical trial, 20 patients underwent inferior turbinate surgery, which consisted of either HIFU or coblation therapy. Efficacy, safety, and tolerability were evaluated by subjective symptom scores, acoustic rhinometry, and nasal endoscopy. Results The modified nasal obstruction symptom evaluation (NOSE) score and nasal obstruction visual analog scale (NO-VAS) significantly decreased in both groups 12 weeks postoperatively. The between-group differences in the evaluation scores were not statistically significant. On nasal endoscopy, the HIFU patients showed improvements in mucosal swelling sooner than the patients undergoing coblation therapy. Nasal crusting significantly increased in the patients undergoing coblation compared to the patients undergoing HIFU therapy until postoperative week 4. Mucosal preservation was superior in the HIFU patients. Although HIFU was less painful than coblation therapy during the procedure, the difference was not significant (4.9 vs. 6.3, P=0.143). The difference in global satisfaction between the two groups was not statistically significant, although satisfaction was slightly higher among the HIFU patients than among the coblation patients (4.6 vs. 4.1, P=0.393). Conclusion HIFU provided results similar to those of coblation therapy for patients with nasal obstruction due to ITH, but HIFU therapy caused less discomfort during the procedure. HIFU therapy appears to be a good noninvasive alternative to the current surgical modalities for ITH

Associations of reproductive factors with incidence of myocardial infarction and ischemic stroke in postmenopausal women: a cohort study

Background To assess the association between the reproductive factors of age at menarche, age at menopause, and reproductive span and the incidence of myocardial infarction (MI) and ischemic stroke (IS). Methods We used a population-based retrospective cohort study from the National Health Insurance Service database of Korea including a total of 1,224,547 postmenopausal women. Associations between age at menarche (≤ 12, 13–14 [reference], 15, 16, and ≥ 17years), age at menopause (< 40, 40–45, 46–50, 51–54 [reference], and ≥ 55years), and reproductive span (< 30, 30–33, 34–36, 37–40 [reference], and ≥ 41years) and the incidence of MI and IS were assessed by Cox proportional hazard models with adjustment for traditional cardiovascular risk factors and various reproductive factors. Results During a median follow-up of 8.4years, 25,181 MI and 38,996 IS cases were identified. Late menarche (≥ 16years), early menopause (≤ 50years), and short reproductive span (≤ 36years) were linearly associated with a 6%, 12–40%, and 12–32% higher risk of MI, respectively. Meanwhile, a U-shaped association between age at menarche and risk of IS was found, with a 16% higher risk in early menarche (≤ 12years) and a 7–9% higher risk in late menarche (≥ 16years). Short reproductive span was linearly associated with an increased risk of MI, whereas both shorter and longer reproductive spans were associated with an increased risk of IS. Conclusions This study demonstrated different patterns of association between age at menarche and incidence of MI and IS: a linear association for MI versus a U-shaped association for IS. Female reproductive factors in addition to traditional cardiovascular risk factors should be considered when assessing overall cardiovascular risk in postmenopausal women

Prognostic role of computed tomography analysis using deep learning algorithm in patients with chronic hepatitis B viral infection

Background/Aims The prediction of clinical outcomes in patients with chronic hepatitis B (CHB) is paramount for effective management. This study aimed to evaluate the prognostic value of computed tomography (CT) analysis using deep learning algorithms in patients with CHB. Methods This retrospective study included 2,169 patients with CHB without hepatic decompensation who underwent contrast-enhanced abdominal CT for hepatocellular carcinoma (HCC) surveillance between January 2005 and June 2016. Liver and spleen volumes and body composition measurements including subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and skeletal muscle indices were acquired from CT images using deep learning-based fully automated organ segmentation algorithms. We assessed the significant predictors of HCC, hepatic decompensation, diabetes mellitus (DM), and overall survival (OS) using Cox proportional hazard analyses. Results During a median follow-up period of 103.0 months, HCC (n=134, 6.2%), hepatic decompensation (n=103, 4.7%), DM (n=432, 19.9%), and death (n=120, 5.5%) occurred. According to the multivariate analysis, standardized spleen volume significantly predicted HCC development (hazard ratio [HR]=1.01, P=0.025), along with age, sex, albumin and platelet count. Standardized spleen volume (HR=1.01, P<0.001) and VAT index (HR=0.98, P=0.004) were significantly associated with hepatic decompensation along with age and albumin. Furthermore, VAT index (HR=1.01, P=0.001) and standardized spleen volume (HR=1.01, P=0.001) were significant predictors for DM, along with sex, age, and albumin. SAT index (HR=0.99, P=0.004) was significantly associated with OS, along with age, albumin, and MELD. Conclusions Deep learning-based automatically measured spleen volume, VAT, and SAT indices may provide various prognostic information in patients with CHB