Abrupt phase changes coupled with waning in amplitude of neural oscillation lead to phase-locking in the auditory evoked responses.

Neural oscillations on the human auditory cortex measured with the magnetoencephalography were band-pass filtered between 3 and 16 Hz and then divided into instantaneous phases and amplitudes by the Hilbert transformation. Spontaneously, the amplitudes fluctuated, i.e. waxed and waned; The phases rotated at around 6 Hz most of the time, but abruptly accelerated or decelerated when the amplitudes waned close to zero. After auditory stimuli, the amplitudes and the phases were coupled in the same way as spontaneously. Amounts and directions of the accelerations or decelerations were thereby specific so that the phases subsequently took mostly the same value, i.e. were locked, at around the time of N100 peaks in the auditory evoked responses. In short, the auditory evoked responses emerged from spontaneous oscillations by abrupt phase changes coupled with waning in amplitudes and phase-locking thereafter.

A Pilot Study Evaluating the Effectiveness and Safety of Daikenchuto (TJ-100) for the Treatment of Postoperative Abdominal Pain or Bloating in Patients Undergoing Hepatectomy: Study Protocol for a Randomized, Open, Controlled Trial.

This study is being performed to evaluate the effectiveness and safety of TJ-100 TSUMURA Daikenchuto (DKT) Extract Granules in preventing post-hepatectomy digestive symptoms, and to examine the effects of DKT on small intestinal mucosal atrophy using diamine oxidase (DAO) and glucagon-like peptide-2 (GLP-2) activities. This is a randomized, open, controlled trial using patients treated with usual care as the control group. Patients who meet the inclusion criteria are randomized to the study groups. Eligible patients are randomized to the DKT therapy group (DKT administration for 14 days postoperatively or until the day of discharge if a patient leaves the hospital less than 14 days after the surgery) or the usual care group (no administration of DKT (ratio 1:1). Using the NRS (numeric rating scale) as an indicator, we will attempt to show whether DKT is effective for abdominal pain and bloating after surgery by comparing both groups. We will also attempt to evaluate postoperative small intestinal mucosal atrophy using DAO and GLP-2 activities in the serum, and postoperative nutrient absorption using nutrient assessment indicators. This study is being conducted according to the CONSORT statement. A consent form was signed by all participants, and the study protocol has been approved by the Central Review Board and Local Ethics Committee (CRB7180001).

Tetrapeptides, as small-sized peptidic inhibitors; synthesis and their inhibitory activity against BACE1.

Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is known to be involved in the production of amyloid beta-peptide in Alzheimer's disease and is a major target for current drug design. We previously reported substrate-based peptidomimetics, KMI-compounds as potent BACE1 inhibitors. In this study, we designed and synthesized tetrapeptides as low molecular-sized inhibitors. These exhibited high potency against recombinant BACE1, with the highest IC(50) value of 34.6 nM from KMI-927.

Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis.

OBJECTIVE: Tissue hypoxia is closely associated with arthritis pathogenesis, and extracellular high mobility group box chromosomal protein 1 (HMGB-1) released from injured cells also has a role in arthritis development. This study was thus undertaken to investigate the hypothesis that extracellular HMGB-1 may be a coupling factor between hypoxia and inflammation in arthritis. METHODS: Concentrations of tumor necrosis factor alpha, interleukin-6, vascular endothelial growth factor, lactic acid, lactate dehydrogenase, and HMGB-1 were measured in synovial fluid (SF) samples from patients with inflammatory arthropathy (rheumatoid arthritis and pseudogout) and patients with noninflammatory arthropathy (osteoarthritis). The localization of tissue hypoxia and HMGB-1 was also examined in animal models of collagen-induced arthritis (CIA). In cell-based experiments, the effects of hypoxia on HMGB-1 release and its associated cellular events (i.e., protein distribution and cell viability) were studied. RESULTS: In SF samples from patients with HMGB-1-associated inflammatory arthropathy (i.e., samples with HMGB-1 levels >2 SD above the mean level in samples from patients with noninflammatory arthropathy), concentrations of HMGB-1 were significantly correlated with those of lactic acid, a marker of tissue hypoxia. In CIA models in which the pathologic phenotype could be attenuated by HMGB-1 neutralization, colocalization of HMGB-1 with tissue hypoxia in arthritis lesions was also observed. In cell-based experiments, hypoxia induced significantly increased levels of extracellular HMGB-1 by the cellular processes of secretion and/or apoptosis-associated release, which was much more prominent than the protein release in necrotic cell injury potentiated by oxidative stress. CONCLUSION: These findings indicate that tissue hypoxia and its resultant extracellular HMGB-1 might play an important role in the development of arthritis.

A model for the mechanism of generating the auditory evoked field.

The auditory evoked potentials and fields, recorded with electro- and magneto-encephalography, respectively, have the prominent peak at the latency of about 100 ms, named N100(m). The mechanism for generating the peak is not yet fully elucidated, however. Firstly, this study reviewed empirical results on the mechanism that had been previously published by the same author. The results showed that phases of the ongoing oscillations at around 6 Hz above the auditory cortex are locked with respect to onsets of the auditory stimuli during the period of N100 m, and also that powers of the oscillations are increased during the same period. Taking into account these results as well as another evidence that the peak arises from multiple sources within the auditory cortex, a model for the mechanism of generating the auditory N100 m was proposed. The model assumed several oscillators in the auditory cortex, whose phases were locked during the period of N100 m, but not locked at other periods. Computer simulation validated the model. The model could represent a starting point for further experiment and simulation.

A neuromagnetic analysis of the mechanism for generating auditory evoked fields.

Averaged and non-averaged neuromagnetic responses to repetitive transients of sound were analyzed in the frequency and time domains. It was found that ongoing oscillations between 3 and 16 Hz are relevant to the generation of auditory evoked fields (AEF). First, phases of the oscillation were locked at around the timings of N100m, but randomly distributed from trial to trial at the other timings. Secondly, amplitudes of the oscillation were larger on average at around the timings of N100m than at the other timings, although the amplitudes fluctuated from trial to trial with almost the same standard deviations throughout the periods of observation. Thirdly, spatial distributions of the oscillatory activities were often reduced to an equivalent current dipole in the auditory cortex at around the timings of N100m, but seldom reduced at the other timings. An explanation of these results would be to suppose several oscillators within the cortex whose phases are locked at around the timings of N100m, but fluctuated randomly at the other timings.

P wave signal-averaged electrocardiography predicts recurrence of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome who underwent successful catheter ablation: a prospective study.

INTRODUCTION: Paroxysmal atrial fibrillation (PAF) frequently occurs in patients with Wolff-Parkinson-White (WPW) syndrome. Catheter ablation of the accessory pathway eliminates PAF in some patients, but PAF frequently recurs in other patients. The present study was designed to determine prospectively whether P wave signal-averaged electrocardiography (P-SAECG) predicts the recurrence of PAF after successful ablation in patients with WPW syndrome. METHODS AND RESULTS: Forty-six patients with WPW syndrome who had episodes of PAF were prospectively followed. SAECG recording was performed on day 7 after successful ablation of the accessory pathway at study entry. Abnormal P-SAECG for the prediction of recurrence of PAF was defined as a filtered P wave duration > 130 msec. Eleven patients had an abnormal P-SAECG (group 1), whereas 35 patients (group 2) did not. The two groups did not differ in terms of gender, age, left atrial dimension, and atrial vulnerability as determined by electrophysiologic study. During follow-up (40 +/- 19 months), the recurrence of PAF was noted in 10 (91%) of 11 patients in group 1, whereas it was observed in only 2 (6%) of 35 patients in group 2. Kaplan-Meier analysis revealed that the recurrence of PAF was significantly more frequent in group 1 than in group 2 (log rank test, P < 0.0001). By multivariate analysis, filtered P wave duration >130 msec was an independent predictor of recurrence of PAF after ablation (Chi-square = 21.5, P < 0.0001). CONCLUSION: The results of this study indicate that P-SAECG may be useful for identifying patients at risk for recurrence of PAF after successful ablation of WPW syndrome.