Nitrosylation of b2-Tubulin Promotes Microtubule Disassembly and Differentiated Cardiomyocyte Beating in Ischemic Mice

BACKGROUND@#Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. @*METHODS@#Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of b2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. @*RESULTS@#Tyr-NO-b2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-b2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. @*CONCLUSION@#This is the first discovery of a new target molecule of NO, b2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-b2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.

Patterns and Persistence of Pharmacotherapy for Children and Adolescents with Attention Deficit Hyperactivity Disorder in South Korea

OBJECTIVE: This study aimed to assess treatment persistence in Korean children and adolescents with attention deficit hyperactivity disorder (ADHD) and the factors influencing their adherence to ADHD pharmacotherapy. METHODS: The study included patients between 6 and 18 years of age with ADHD who were taking various formulations of methylphenidate and atomoxetine on June 1, 2014. Patients were dichotomized as “persistent” or “non-persistent”, depending on whether they continued ADHD therapy for 6 months (therapy persistence). We also investigated if the patients were taking the same medication(s) as before and also classified the patients as “medication persistent” or “non-persistent”. Patient' characteristics were correlated with therapy persistence and medication persistence. Multiple logistic regression analyses were performed to assess potential risk factors for treatment persistence. RESULTS: Overall, 3,317 patients were included in the analysis. A majority of patients were taking stimulants (82.0%), 16.2% were taking non-stimulants and 1.8% were taking a combination therapy of stimulants and non-stimulants. After 6 months, 2,290 patients (69.0%) continued to take medication for ADHD with 1,953 patients taking the same medication(s) as 6 months previously. Common positive factors for therapy persistence and medication persistence were identified as younger age, retardation, and developmental delay, and long-acting formulations of methylphenidate as either monotherapy or in a combination therapy may be used. CONCLUSION: ADHD medications were proven to improve academic performance and social skills of children. Collaboration between patients, parents, school staffs, and prescribers is required to improve the persistent use of ADHD medications.

Verification of a computer-aided replica technique for evaluating prosthesis adaptation using statistical agreement analysis

PURPOSE: The purpose of this study was to evaluate the reliability of computer-aided replica technique (CART) by calculating its agreement with the replica technique (RT), using statistical agreement analysis. MATERIALS AND METHODS: A prepared metal die and a metal crown were fabricated. The gap between the restoration and abutment was replicated using silicone indicator paste (n = 25). Gap measurements differed in the control (RT) and experimental (CART) groups. In the RT group, the silicone replica was manually sectioned, and the marginal and occlusal gaps were measured using a microscope. In the CART group, the gap was digitized using optical scanning and image superimposition, and the gaps were measured using a software program. The agreement between the measurement techniques was evaluated by using the 95% Bland-Altman limits of agreement and concordance correlation coefficients (CCC). The least acceptable CCC was 0.90. RESULTS: The RT and CART groups showed linear association, with a strong positive correlation in gap measurements, but without significant differences. The 95% limits of agreement between the paired gap measurements were 3.84% and 7.08% of the mean. The lower 95% confidence limits of CCC were 0.9676 and 0.9188 for the marginal and occlusal gap measurements, respectively, and the values were greater than the allowed limit. CONCLUSION: The CART is a reliable digital approach for evaluating the fit accuracy of fixed dental prostheses.

A Clinical Study of Acute Symptomatic Seizures in Children

PURPOSE: To determine the incidence, etiology, sex, age, seizure type and prognosis of acute symptomatic seizures in children and evaluate the hypothesis that acute symptomatic status epilepticus(SE) is associated with an increased risk of subsequent unprovoked seizure compared with the risk of acute syrnptomatic seizure without SE. METHODS: Five hundred and sixty-eight convulsive children visited the Pediatric Department of Chungbuk National University Hospital from February 1991 to February 1999. Of these, 109 patients were determined as acute symptomatic seizure, and their medical record were reviewed. RESULTS: One hundred and nine children(59#boys, 50#girls) had acute symptomatic seizures, the ratio of male to female and the ages at the onset of first seizure were 1.18: 1 and 1.58+/-2.53 years, respectively. Causes of acute symptomatic seizure in order of frequency were acute gastroenteritis(33.0%), encephalopathy(31.2%), metabolic/toxic disturbance(19.3%), CNS infection (11.0%), brain trauma(2.8%), cerebrovascular disease(1.8%) and CNS tumor(0.9%). At six months of follow-up, the incidence of a first unprovoked seizure was 28.4% for children with acute symptomatic seizure, 67.6% for those with encephalopathic cause, 44% for those with structural cause, and O% for those with metabolic cause. At six months of follow-up, the risk of a first unprovoked seizure was significantly greater for those with acute symptornatic seizure with SE(100%) than without SE(22%). CONCLUSION: The leading causes of acute syrnptomatic seizures were acute gastroenteritis. Age-specific incidence was highest in the group aged 0-12 rnonths. The incidence of subsequent un-provoked seizure was highest in the group of encephalopathy. The risk for subsequent un-provoked seizure was greater for those with SE than for those without SE and for those with abnormal EEG and abnormal findings of neuroimage.