Description: Aims Atrial tachyarrhythmias (AT) commonly recur within the first 3 months after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF), and the influence of antiarrhythmic drugs (AADs) on the recurrences has not been fully elucidated. We sought to evaluate the efficacy of a 3-month lower-dose flecainide regime on early and late recurrences of ATs. Methods and results We randomly assigned 126 patients, who underwent RFCA for AF, to the flecainide group (150 or 100 mg/day according to their body weight) or to the control group receiving no AADs. The primary endpoint was any AT lasting for ≥30 s during the first 3 months and the secondary endpoint was a composite of ATs lasting for ≥24 h or requiring cardioversion or hospitalization during the same period. All AADs were stopped after the first 3 months and the late arrhythmia recurrences were also evaluated. The primary endpoint rates were 37 and 41% in the flecainide (143 ± 19 mg/day) and control groups, respectively (log-rank P = 0.76), and those of the secondary endpoint were 10 and 14%, respectively (log-rank P = 0.45). The estimated rates of maintaining sinus rhythm at 12 months after the first 3 months were 78 and 72%, in the flecainide and control groups, respectively (log-rank P = 0.68), and the rates were 51 and 90% in those with and without the primary endpoint, respectively (log-rank P 〈 0.001). Conclusion The 3-month lower-dose flecainide therapy after AF ablation did not reduce the early and late arrhythmia recurrences. The clinically significant ATs were also not prevented.

Description: Nature Photonics 8, 695 (2014). doi:10.1038/nphoton.2014.163 Authors: K. Nakagawa, A. Iwasaki, Y. Oishi, R. Horisaki, A. Tsukamoto, A. Nakamura, K. Hirosawa, H. Liao, T. Ushida, K. Goda, F. Kannari & I. Sakuma High-speed photography is a powerful tool for studying fast dynamics in photochemistry, spintronics, phononics, fluidics and plasma physics. Currently, the pump–probe method is the gold standard for time-resolved imaging, but it requires repetitive measurements for image construction and therefore falls short in probing non-repetitive or difficult-to-reproduce events. Here, we present a motion-picture camera that performs single-shot burst image acquisition without the need for repetitive measurements, yet with equally short frame intervals (4.4 trillion frames per second) and high pixel resolution (450 × 450 pixels). The principle of this method—‘motion picture femtophotography’—is all-optical mapping of the target's time-varying spatial profile onto a burst stream of sequentially timed photographs with spatial and temporal dispersion. To show the camera's broad utility we use it to capture plasma dynamics and lattice vibrational waves, both of which were previously difficult to observe with conventional methods in a single shot and in real time.

Description: Rationale: Inhibition of histone deacetylases (HDACs) results in attenuated development of hypertension in deoxycorticosterone acetate–induced hypertensive rats and spontaneously hypertensive rats. However, the molecular mechanism remains elusive. Objective: We hypothesized that HDAC inhibition attenuates transcriptional activity of mineralocorticoid receptor (MR) through its acetylation and prevents development of hypertension in deoxycorticosterone acetate–induced hypertensive rats. Methods and Results: Expression of MR target genes was measured by quantitative real-time polymerase chain reaction. Recruitment of MR and RNA polymerase II on promoters of target genes was analyzed by chromatin immunoprecipitation assay. Live cell imaging was performed for visualization of nuclear translocation of MR. MR acetylation was determined by Western blot with anti-acetyl-lysine antibody after immunoprecipitation with anti-MR antibody. Transcriptional activity of MR was determined by luciferase assay. For establishment of a hyperaldosteronism animal, Sprague-Dawley rats underwent uninephrectomy and received subcutaneous injection of 40 mg/kg per week of deoxycorticosterone acetate and drinking water containing 1% NaCl. Treatment with a HDAC class I inhibitor resulted in reduced expression of MR target genes in accordance with reduced recruitment of MR and RNA polymerase II on promoters of target genes. HDAC inhibition promoted MR acetylation, leading to decreased transcriptional activity of MR. Knockdown or inhibition of HDAC3 resulted in reduced expression of MR target genes induced by mineralocorticoids. Conclusions: These results indicate that HDAC inhibition attenuates transcriptional activity of MR through its acetylation and prevents development of hypertension in deoxycorticosterone acetate–induced hypertensive rats.

Description: Aims Ventricular tachycardia (VT) and ventricular fibrillation (VF) are not uncommon in patients hospitalized with acute heart failure (AHF). We sought to evaluate the efficacy of urgent radiofrequency catheter ablation (RFCA) for recurrent VT/VF during AHF decompensations. Methods and results The present study retrospectively analysed the data of 15 consecutive patients (69 ± 9 years, ischaemic heart disease in 10), who underwent urgent RFCA for frequent drug-refractory VT/VF episodes during an AHF decompensation with pulmonary congestion. The target arrhythmias were clinically documented monomorphic VTs in 10 patients, frequent premature ventricular contractions (PVCs) triggering VF in 4, and both in 1. The mean left ventricular ejection fraction was 26 ± 8%. The maximum number of arrhythmia episodes over 24 h was 9.1 ± 11.7. All RFCA sessions were completed without any major complications except for a temporary deterioration of pulmonary congestion in three patients (20%). Elimination and non-inducibility of the target arrhythmias were achieved in 13 patients (87%). Successful ablation site electrograms showed Purkinje potentials for all 5 PVCs triggering VF and 4 of 14 clinically documented monomorphic VTs (29%). Five patients (33%) underwent second sessions 10 ± 4 days after the first session for acute recurrences. Sustained VT/VF was completely suppressed during admission in 12 patients (80%), and the AHF ameliorated in 13 patients (93%). Twelve patients (80%) were discharged alive. Conclusion Urgent RFCA for drug-resistant sustained ventricular tachyarrhythmias during AHF decompensations would be an appropriate therapeutic option. Purkinje fibres can be ablation targets not only in those with PVCs triggering VF, but also in those with monomorphic VT.

Description: Objective Progressive muscular atrophy (PMA) is a clinical diagnosis characterised by progressive lower motor neuron (LMN) symptoms/signs with sporadic adult onset. It is unclear whether PMA is simply a clinical phenotype of amyotrophic lateral sclerosis (ALS) in which upper motor neuron (UMN) signs are undetectable. To elucidate the clinicopathological features of patients with clinically diagnosed PMA, we studied consecutive autopsied cases. Design Retrospective, observational. Setting Autopsied patients. Participants We compared clinicopathological profiles of clinically diagnosed PMA and ALS using 107 consecutive autopsied patients. For clinical analysis, 14 and 103 patients were included in clinical PMA and ALS groups, respectively. For neuropathological evaluation, 13 patients with clinical PMA and 29 patients with clinical ALS were included. Primary outcome measures Clinical features, UMN and LMN degeneration, axonal density in the corticospinal tract (CST) and immunohistochemical profiles. Results Clinically, no significant difference between the prognosis of clinical PMA and ALS groups was shown. Neuropathologically, 84.6% of patients with clinical PMA displayed UMN and LMN degeneration. In the remaining 15.4% of patients with clinical PMA, neuropathological parameters that we defined as UMN degeneration were all negative or in the normal range. In contrast, all patients with clinical ALS displayed a combination of UMN and LMN system degeneration. CST axon densities were diverse in the clinical PMA group, ranging from low values to the normal range, but consistently lower in the clinical ALS group. Immunohistochemically, 85% of patients with clinical PMA displayed 43-kDa TAR DNA-binding protein (TDP-43) pathology, while 15% displayed fused-in-sarcoma (FUS)-positive basophilic inclusion bodies. All of the patients with clinical ALS displayed TDP-43 pathology. Conclusions PMA has three neuropathological background patterns. A combination of UMN and LMN degeneration with TDP-43 pathology, consistent with ALS, is the major pathological profile. The remaining patterns have LMN degeneration with TDP-43 pathology without UMN degeneration, or a combination of UMN and LMN degeneration with FUS-positive basophilic inclusion body disease.

Description: The Piwi–piRNA (PIWI-interacting RNA) complex (Piwi–piRISC) in Drosophila ovarian somatic cells represses transposons transcriptionally to maintain genome integrity; however, the underlying mechanisms remain obscure. Here, we reveal that DmGTSF1, a Drosophila homolog of gametocyte-specific factor 1 (GTSF1) (which is required for transposon silencing in mouse testes), is necessary for Piwi–piRISC to repress target transposons and neighboring genes. DmGTSF1 depletion affected neither piRNA biogenesis nor nuclear import of Piwi–piRISC. DmGTSF1 mutations caused derepression of transposons and loss of ovary follicle layers, resulting in female infertility. We suggest that DmGTSF1, a nuclear Piwi interactor, is an integral factor in Piwi–piRISC-mediated transcriptional silencing.

Description: Aims The antiarrhythmic effect of triple-site biventricular stimulation (Tri-V) is poorly understood. This study aims to evaluate the effect of cardiac resynchronization therapy (CRT) on ventricular arrhythmia (VA) with Tri-V using a single right ventricular (RV) and double left ventricular (LV) lead. Methods and results Over a period of 3.5 years, 58 consecutive patients with New York Heart Association class II–IV heart failure, an LV ejection fraction of ≤0.35, and a QRS interval of ≥120 ms were enrolled. Acute haemodynamic responses to dual-site biventricular stimulation (Bi-V) and Tri-V were evaluated by assigning patients to a Bi-V or Tri-V group. Electrocardiogram parameters [QT interval, JT interval, and transmural dispersion of repolarization (TDR)] were measured over time after CRT. Spontaneous VA detected by telemetry was reviewed and confirmed. During a mean follow-up of 481 days after implantation, VA occurred in 2 of 22 patients in the Tri-V group and 14 of 36 patients in Bi-V group. Triple-site biventricular stimulation was thus associated with a decreased VA risk ( P = 0.044). Multivariate Cox analysis showed that Tri-V pacing prevented arrhythmic events as compared with Bi-V pacing (hazard ratio, 0.13; 95% confidence interval, 0.029–0.610; P = 0.009). Ventricular repolarization indices at 6 months were significantly shortened in Tri-V compared with Bi-V (QTc, –23.6 vs. –14.1%, P = 0.008; JTc, –21.4 vs. –7.7%, P = 0.005; TDRc, –39.9 vs. –17.0%, P 〈 0.001). Conclusion Compared with Bi-V, Tri-V reduced VA during long-term follow-up. Improvements in repolarization parameters may result in antiarrhythmic effects.

Description: Chitin, a major component of fungal cell walls and invertebrate cuticles, is an exceedingly abundant polysaccharide, ranking next to cellulose. Industrial demand for chitin and its degradation products as raw materials for fine chemical products is increasing. A bacterium with high chitin-decomposing activity, Paenibacillus sp. strain FPU-7, was isolated from soil by using a screening medium containing α-chitin powder. Although FPU-7 secreted several extracellular chitinases and thoroughly digested the powder, the extracellular fluid alone broke them down incompletely. Based on expression cloning and phylogenetic analysis, at least seven family 18 chitinase genes were found in the FPU-7 genome. Interestingly, the product of only one gene ( chiW ) was identified as possessing three S-layer homology (SLH) domains and two glycosyl hydrolase family 18 catalytic domains. Since SLH domains are known to function as anchors to the Gram-positive bacterial cell surface, ChiW was suggested to be a novel multimodular surface-expressed enzyme and to play an important role in the complete degradation of chitin. Indeed, the ChiW protein was localized on the cell surface. Each of the seven chitinase genes ( chiA to chiF and chiW ) was cloned and expressed in Escherichia coli cells for biochemical characterization of their products. In particular, ChiE and ChiW showed high activity for insoluble chitin. The high chitinolytic activity of strain FPU-7 and the chitinases may be useful for environmentally friendly processing of chitin in the manufacture of food and/or medicine.

Description: Author(s): S. Ueda, Y. Iwasaki, Y. Uehara, and S. Ushioda The interlayer exchange coupling of the room-temperature-grown Fe/Si/Fe trilayer structure was studied by using spin-polarized secondary-electron microscopy. For the nominal Si spacer thickness in the 0.5–5.0 nm range, the interlayer exchange coupling between the Fe layers measured at room tempera... [Phys. Rev. B 83, 144424] Published Mon Apr 25, 2011