Validation of a Korean Version of the Short UPPS-P Impulsive Behavior Scale for Children.

OBJECTIVE: Impulsivity is a multifaceted construct that plays an important role in various problem behaviors in children and adolescents. The purpose of this study was to validate a Korean version of the short UPPS-P Impulsive Behavior Scale for Children. METHODS: Participants were 330 children (166 female) from 2 elementary schools in Korea and 94 attention deficit hyperactivity disorder (ADHD) children (23 female) from two major hospitals. The Korean short UPPS-P Impulsive Behavior Scale for Children (UPPS-P-C) (20 items), Child Behavior Checklist for Ages 6-18 (CBCL 6-18), and Barratt Impulsiveness Scale-11 (BIS-11) were administered. 107 children from the control group were retested 6 months later. RESULTS: Confirmatory factor analysis (CFA) conducted in the control group supported a 5-factor hierarchical model in which 1) positive and negative urgency factors are loaded on a higher-order factor of general urgency; 2) lack of perseveration and lack of premeditation factors are loaded on a higher-order factor of lack of conscientiousness; and 3) sensation seeking remained as a separate dimension. Reliability analysis demonstrated that the 5 factors of the Korean short UPPS-P-C had acceptable internal consistency and test-retest reliability. Lack of premeditation and lack of perseveration subscales showed significant correlations with measures of problem behaviors in CBCL and all the subscales were correlated with the BIS-11. The ADHD group showed significantly higher scores in lack of premeditation, lack of perseveration, positive urgency, and negative urgency subscales. CONCLUSION: This study indicates that the Korean version of short UPPS-P-C has adequate reliability and validity. It may be a valid tool to assess impulsivity of healthy children as well as ADHD.

Transient asystole during balloon dilation of the Eustachian tube: A case report.

RATIONALE: Neurally mediated reflexes can induce cardiac arrest during head and neck surgery through mechanisms including direct vagal stimulation, trigeminocardiac reflex, and baroreceptor reflex. Balloon dilation of the Eustachian tube (BDET) is a safe procedure without serious complications, including cardiac arrest. PATIENT CONCERNS: Transient asystole developed during BDET under general anesthesia in a 33-year-old woman as soon as the balloon in the Eustachian tube (ET) was inflated. DIAGNOSES: Monitoring records were reviewed. The asystolic period was recorded on the patient monitor as an event, which we recalled and printed. The asystole lasted for 13 seconds. INTERVENTIONS: The patient recovered sinus rhythm spontaneously after the balloon was deflated before resuscitation. The BDET was successfully performed after prophylaxis with vagolytic drugs. OUTCOMES: The patient recovered uneventfully after anesthesia. LESSONS: BDET, previously known to be a relatively safe procedure, induces asystole via balloon dilation. It is thought to be a neurally mediated vagal reflex, and both anesthesiologists and otologic physicians should pay proper attention to monitoring during the procedure.

Alleviation of abnormal synaptic neurotransmitter release by cell-permeable form of the truncated SNAP-25 upon transcutaneous delivery.

Abnormal releases of neurotransmitters result in movement disorders such as dystonia, chorea, tics, blepharospasm and wrinkle formation, and intra-muscular injection of Botulinum neurotoxin is widely used for the treatment of these complications. But it is potentially poisonous and must be intra-muscularly injected with precision by a well-trained physician. For novel therapeutic development with high safety profile and easy skin penetration for these complications, we generated Trans-X, a cell permeable form of the truncated SNAP-25 that is one of the SNARE complex for vesicle exocytosis of neuron. Upon topical administration, Trans-X efficiently penetrated through skin, reached the dermis layer and remained stable. Trans-X, which did not show any ocular or skin allergic sensitivity, can block the pre-synaptic neurotransmitter transport via acting as a competitive inhibitor of SNARE complex formation, and effectively induced muscle paralysis comparable to BOTOX(®) evaluated by measuring compound muscle action potential. Topical treatment of the facial skin with Trans-X in clinical study can prevent the wrinkle formation and improve the skin roughness. Therefore, our study suggests that Trans-X may be a convenient and effective medical and cosmetic treatment for local management of movement disorder without systemic toxicity.

Echocardiographic predictors of left ventricular function and clinical outcomes after successful mitral valve repair: conventional two-dimensional versus speckle-tracking parameters.

BACKGROUND: We aimed to compare conventional echocardiographic versus speckle tracking-derived parameters in predicting postoperative left ventricular (LV) dysfunction and clinical outcomes after successful mitral valve repair in patients with mitral regurgitation. METHODS: In 147 consecutive patients in sinus rhythm with severe MR, two-dimensional echocardiography and speckle-tracking imaging for global longitudinal, circumferential, and radial strains and strain rates were performed within 30 days before successful mitral valve repair. Echocardiography was repeated within 7 days in all patients, and more than 3 months after surgery in 112 patients. Clinical events were evaluated for 21±17 months. RESULTS: Multivariate linear regression analysis showed that preoperative LV systolic dimension (p=0.004) and volume (p=0.001) were independent determinants of immediate postoperative LV ejection fraction. Preoperative LV end-systolic dimension (p=0.004), LV ejection fraction (p=0.017), and circumferential strain (p=0.029) were independent predictors of late follow-up LV ejection fraction. By Cox regression analysis, preoperative end-systolic LV dimension (hazard ratio 1.26 for every 1 mm, 95% confidence interval 1.11 to 1.44, p<0.001) was the only predictor of hospital admission for heart failure. The best cutoff values of LV end-systolic dimension (≥41 mm) and volume (≥85 mL) for predicting postoperative severe LV dysfunction (ejection fraction<0.35) identified patients at high risk for event-free survival, but those of speckle-tracking parameters did not. CONCLUSIONS: Preoperative LV remodeling parameters, such as LV end-systolic dimension and volume, are superior to speckle tracking-derived deformation parameters in predicting LV dysfunction and clinical events after successful mitral valve repair in patients with severe mitral regurgitation.

Qualitative and quantitative differences in the intensity of Fas-mediated intracellular signals determine life and death in T cells.

Fas stimulation has been reported to promote the activation and proliferation of T lymphocytes, but the intracellular signalling pathways that mediate non-apoptotic responses to Fas are poorly defined. To distinguish between the activation signalling and the death-inducing pathway downstream of Fas, we generated a novel T cell line expressing a chimeric hCD8-FasC protein and found that stimulation with the anti-CD8 antibodies induced tyrosine phosphorylation of TCR-proximal proteins, activation of Raf-1/ERK, p38 and JNK, and increased expression of CD69, Fas, and Fas ligand. Stimulation of hCD8-FasC-induced activation of an atypical NF-kappaB pathway, partial cleavage of caspases, and increased expression of TRAF1, FLIP(L) and FLIP(S), thereby protecting T cells from FasL-mediated apoptosis. The proliferative response transmitted through hCD8-FasC chimeric receptors was converted into death signals when cells were stimulated, resulting in increased expression of IL-2 and Nur77 and increased caspase cleavage. Surprisingly, both the enhanced expression of FLIP(L) and FLIP(S) and the complete inhibition of FLIP(S) expression were functionally associated with cell death induction. These findings imply that Fas is able to trigger intracellular signalling events driving both apoptosis and activation of T cells but that cell fate is determined by quantitative and qualitative differences in intracellular signalling following Fas stimulation.

Tumor necrosis factor-alpha potentiates RhoA-mediated monocyte transmigratory activity in vivo at a picomolar level.

OBJECTIVE: The serum level of tumor necrosis factor-alpha (TNF-alpha) is in the picomolar range under inflammatory conditions. We investigated whether these picomolar levels of TNF-alpha directly modulate the functional activities of circulating monocytes. METHODS AND RESULTS: In THP-1 monocytes treated with TNF-alpha (1 to 100 pmol/L/30 minutes), cytosolic RhoA small GTPase rapidly translocated to the plasma membrane via functionally active ezrin/radixin/moesin (ERM) complex, a cytoskeletal linker, and subsequent actin polymerization through NF-kappaB activation. The threonine phosphorylation of ERM was accomplished by the activation of TNF receptor type I (TNFRI) and signaling pathways involving PI3K and an atypical PKC; ie, PKCzeta. The TNF-alpha-treated monocytes (10 pmol/L) displayed more potent and prolonged generation of GTP-bound RhoA in response to secondary stimulation with RhoA-activating monocyte chemoattractant protein-1 (MCP-1). Clearly, human circulating monocytes preconditioned by 10 pmol/L TNF-alpha augmented MCP-1-mediated chemotaxis and firm adhesion on VCAM-1 and ICAM-1 in vitro and ex vivo. The elevation of serum TNF-alpha (>5 pmol/L within 16 hours), which was introduced by intraperitoneal injection of mouse-specific TNF-alpha to C57/BL6 mice, enhanced the number of CD80+ monocytes transmigrating to the JE/MCP-1-injected intraperitoneal space. CONCLUSIONS: Picomolar concentrations of TNF-alpha in the bloodstream may prime the RhoA-dependent activities of circulating monocytes to enhance recruitment to active inflammatory foci.

Proteomic profiling of cellular proteins interacting with the hepatitis C virus core protein.

Hepatitis C virus (HCV) is a causative agent of chronic hepatitis and hepatocellular carcinoma. The core protein of HCV packages the viral RNA genome to form a nucleocapsid. In addition to its function as a structural protein, core protein is involved in regulation of cellular transcription, virus-induced transformation, and pathogenesis. To gain insights into cellular functions of the core protein by identification of cellular proteins interacting with the core protein, we employed a proteomic approach. Hepatocytes soluble cytoplasmic proteins were applied to the core proteins immobilized on Ni-nitrilotriacetic resin and total bound cellular proteins were resolved by 2-DE. Analyses of interacting proteins by matrix-assisted laser desorption/ionization-time of flight mass spectrometry allowed identification of 14 cellular proteins binding to the core protein. These proteins include DEAD-box polypeptide 5, similar in function to a known protein identified previously by yeast two-hybrid screening and 13 newly identified cellular proteins. Interestingly, nine protein spots were identified as intermediate microfilament proteins, including cytokeratins (five spots for cytokeratin 8, two for cytokeratin 19, and one for cytokeratin 18) and vimentin. Cytokeratin 8 and vimentin, which were previously shown to be involved in the infection processes of other viruses, were further analyzed to confirm their in vivo interactions with the core protein by immunoblotting and immunofluorescence microscopy. We discuss the functional implications of the interactions of the core protein with newly identified cellular proteins in HCV infection and pathogenesis.

Musical training-induced functional reorganization of the adult brain: functional magnetic resonance imaging and transcranial magnetic stimulation study on amateur string players.

We used the combined technique of functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to observe changes that occur in adult brains after the practice of stringed musical instruments. We carried out fMRI on eight volunteers (aged 20-22 years): five novices and three individuals who had discontinued practice for more than 5 years. The motor paradigm contained a repetitive lift-abduction/fall-adduction movement of the left/right little finger, carried out with maximum efforts without pacing. The sensory paradigm was to stimulate the same little finger using a string. In parallel to the fMRI acquisition, TMS motor maps for the little finger were obtained using a frameless stereotactic neuronavigation system. After the baseline study, each participant began to learn a stringed instrument. Newly developed fMRI activations for the left little finger were observed 6 months after practice at multiple brain regions including inferior parietal lobule, premotor area (PMA), left precuneus, right anterior superior temporal gyrus, and posterior middle temporal gyrus. In contrast, new activations were rarely observed for the right little finger. The TMS study revealed new motor representation sites for the left little finger in the PMA or supplementary motor area (SMA). Unexpectedly, TMS motor maps for the right little finger were reduced significantly. Among new fMRI activations for sensory stimuli of the left little finger, the cluster of highest activation was located in the SMA. Collectively, these data provide insight into orchestrated reorganization of the sensorimotor and temporal association cortices contributing to the skillful fingering and musical processing after the practice of playing stringed instruments.