再灌流後急性心筋梗塞患者におけるリバースリモデリングと非造影T1低信号梗塞コア

Background: Non-contrast T1 hypointense infarct cores (ICs) within infarcted myocardium detected using cardiac magnetic resonance imaging (CMR) T1 mapping may help assess the severity of left ventricular (LV) injury. However, because the relationship of ICs with chronic LV reverse remodeling (LVRR) is unknown, this study aimed to clarify it. Methods and Results: We enrolled patients with reperfused AMI who underwent baseline CMR on day-7 post-primary percutaneous coronary intervention (n=109) and 12-month follow-up CMR (n=94). Correlations between ICs and chronic LVRR (end-systolic volume decrease ≥15% at 12-month follow-up from baseline CMR) were investigated. We detected 52 (47.7%) ICs on baseline CMR by non-contrast-T1 mapping. LVRR was found in 52.1% of patients with reperfused AMI at 12-month follow-up. Patients with ICs demonstrated higher peak creatine kinase levels, higher B-type natriuretic peptide levels at discharge, lower LV ejection fraction at discharge, and lower incidence of LVRR than those without ICs (26.5% vs. 73.3%, P<0.001) at follow-up. Multivariate logistic regression analysis showed that the presence of ICs was an independent and the strongest negative predictor for LVRR at 12-month followup (hazard ratio: 0.087, 95% confidence interval: 0.017–0.459, P=0.004). Peak creatine kinase levels, native T1 values at myocardial edema, and myocardial salvaged indices also correlated with ICs. Conclusions: ICs detected by non-contrast-T1 mapping with 3.0-T CMR were an independent negative predictor of LVRR in patients with reperfused AMI.博士（医学）・乙第1529号・令和5年3月15

心不全を合併した心房細動患者のカテーテルアブレーション後の長期予後 : 左室駆出率に基づいた心不全のサブタイプ間における比較

Aims: Heart failure (HF) prognosis has been reported similar in patients with preserved vs. reduced left ventricular ejection fraction (LVEF). This study compared the long-term prognosis of HF patients undergoing radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). Methods and results: Among 5010 patients undergoing RFCA in Kansai Plus AF registry, 656 patients (13.1%) with a documented history of HF were enrolled in the study before RFCA. The primary endpoint was a composite of all-cause death, HF hospitalization, and stroke or systemic embolism. Patients with reduced (<40%), mid-range (40-49%), and preserved (≥50%) LVEF were 98 (14.9%), 107 (16.3%), and 451 (68.8%) patients, respectively. The prevalence of ischaemic heart disease and cardiomyopathies was higher among patients with reduced as compared with preserved LVEF (27.6% vs. 10.0%, P < 0.05 and 36.7% vs. 15.3%, P < 0.05, respectively). The median follow-up period was 2.9 years. The 3-year cumulative risk for the primary endpoint was higher in patients with reduced LVEF (32.7%) compared to those with mid-range (11.7%) or preserved (11.6%) LVEF (P < 0.001). Reduced LVEF was the most significant independent risk factor for primary endpoint (hazard ratio, 2.83; 95% confidence interval 1.74-4.61, P < 0.001). The 3-year arrhythmia recurrence rate was similar among the groups (48.2%, 42.8%, and 47.3%, respectively, P = 0.75). Conclusion : This study raises hypothesis that patients with HFrEF and AF had approximately three times higher risk for a composite of all-cause death, HF hospitalization, and stroke or systemic embolism after AF ablation compared with patients with HFmrEF or HFpEF.博士（医学）・甲第802号・令和3年12月21日Copyright: © Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021.This is a pre-copyedited, author-produced version of an article accepted for publication in Europace following peer review. The version of record "Europace Online ahead of print (2021 Aug 31;euab201) is available online at: https://doi.org/10.1093/europace/euab201.発行元が定める登録猶予期間終了の後、本文を登録予定（2022.08

Characterization of the novel mutant A78T-HERG from a long QT syndrome type 2 patient: Instability of the mutant protein and stabilization by heat shock factor 1

Background:The human ether-a-go-go-related gene (HERG) encodes the α-subunit of rapidly activating delayed-rectifier potassium channels. Mutations in this gene cause long QT syndrome type 2 (LQT2). In most cases, mutations reduce the stability of the channel protein, which can be restored by heat shock (HS). Methods: We identified the novel mutant A78T-HERG in a patient with LQT2. The purpose of the current study was to characterize this mutant protein and test whether HS and heat shock factors (HSFs) could stabilize the mutant protein. A78T-HERG and wild-type HERG (WT-HERG) were expressed in HEK293 cells and analyzed by immunoblotting, immunoprecipitation, immunofluorescence, and whole-cell patch clamping. Results: When expressed in HEK293 cells, WT-HERG gave rise to immature and mature forms of the protein at 135 and 155 kDa, respectively. A78T-HERG gave rise only to the immature form, which was heavily ubiquitinated. The proteasome inhibitor MG132 increased the expression of immature A78T-HERG and increased both the immature and mature forms of WT-HERG. WT-HERG, but not A78T-HERG, was expressed on the plasma membrane. In whole-cell patch clamping experiments, depolarizing pulses evoked E4031-sensitive HERG channel currents in cells transfected with WT-HERG, but not in cells transfected with A78T-HERG. The A78V mutant, but not A78G mutant, remained in the immature form similarly to A78T. Maturation of the A78T-HERG protein was facilitated by HS, expression of HSF-1, or exposure to geranyl geranyl acetone. Conclusions: A78T-HERG was characterized by protein instability and reduced expression on the plasma membrane. The stability of the mutant was partially restored by HSF-1, indicating that HSF-1 is a target for the treatment for LQT2 caused by the A78T mutation in HERG

General characterization of Antarctic micrometeorites collected by the 39th Japanese Antarctic Research Expedition: Consortium studies of JARE AMMs (III)

From November 1998 to January 1999,the 39th Japanese Antarctic Research Expedition (JARE-39) undertook Japanese first large-scale collection of Antarctic micrometeorites (AMMs), with sizes larger than 10μm, at the Meteorite Ice Field around the Yamato Mountains in Antarctica (at three different locations, for a total of 24 collection sites). The number of collected AMMs larger than 40μm is estimated to be about 5000. Here we present the general characterization (i.e., micro-morphology and surface chemical composition using SEM/EDS) of &acd;810 AMMs chosen from 5 of the 24 sites. Additionally, the mineral composition of 61 out of 810 AMMs was determined by Synchrotron X-ray radiation. Preliminary results on mineralogical and chemical compositions show similarities with that of previous studies, even though a pronounced alteration of some AMMs is noticed. A correlation is found between the Mg/Si ratio at the sample\u27s surfaces of unmelted AMMs and the age of snow/ice in which the AMMs are embedded

Thermal neutron fluence measurement by Cadmium differential method at laser-driven neutron source

We generated high-energy neutrons by (d, n) and (p, n) reactions on a Be target with protons and deuterons that were accelerated up to 30 and 10 MeV/u, respectively, by laser-plasma interactions. Thermal neutrons were subsequently generated through deceleration by a small moderator with conjunction on the Be target. Here we report the measurements on the thermal neutron fluence using the activation method with/without Cd filters. The unstable isotopes of 198Au, 56Mn, 60Co, and 181Hf were produced through (n, γ) reactions by a single laser shot. The nuclear reaction rates were evaluated by measurring the γ-rays emitted from these unstable isotopes. The thermal neutron fluences from the four nuclides are consistent within their experimental uncertainties. The fluence is evaluated to be (2.2±0.4)×105 neutrons/cm2 at the distance of approximately 9-mm at 90◦ against the laser axis. The present result shows that the method to generate thermal neutrons from a compact neutron source with a diamater of 44 mm and length of 46 mm is expected to be a useful tool for various nuclear experiments

High Flux Neutrons Provided by a Laser driven Neutron Source and its Application to Nuclear Astrophysics

We demonstrated that (n, 2n) and (n, gamma) reactions are induced by a high-flux pulse of fast neutrons provided from a Laser-driven Neutron Source (LDNS). Several kinds of metal targets are exposed to the fast neutrons with energies of approximately 10-20 MeV. As a result, 180Hfm,181Hf, 56Mn, 198Au, and 60Co are produced by (n, gamma) reactions. Furthermore, unstable isotopes such as 54Mn, 58Co, 175Hf, and 196Au are produced by (n, 2n) reactions. We evaluate the neutron fluence and energy spectrum using the activation method in conjunction with a time-of-flight (TOF) method.The 16th international symposium on nculei in cosmo

Direct evaluation of high neutron density environment using (n,2n) reaction induced by laser-driven neutron source

We demonstrated that (n, 2n) and (n, gamma) reactions are induced by a high-flux pulse of fast neutrons provided from a Laser-driven Neutron Source (LDNS). The maximum energy of the broadband neutrons reaches a few tens MeV. Several kinds of metal targets are exposed to the fast neutrons. As a result, unstable isotopes such as 54Mn, 58Co, 175Hf, and 196Au are produced by (n, 2n) reactions and 180Hfm,181Hf, 56Mn, 198Au, and 60Co are produced by (n, gamma) reactions. We evaluate the neutron fluence and energy spectrum using the activation method in conjunction with a time-of-flight (TOF) method. The present scheme provides a method to evaluate high density neutrons seen in stellar environments, which are expected to be generated from future LDNSs

Non-destructive inspection of water or high-pressure hydrogen gas in metal pipes by the flash of neutrons and X-rays generated by laser

Low-energy neutrons in the thermal and epithermal energy regions are a powerful probe to inspect water or high pressure hydrogen gas because of their large scattering cross-sections with protons. Laser-driven neutron source, whichis able to simultaneously emit different types of radiations such as X-rays, can be used for neutron and X-ray radiography in the same laser shot. In the present paper, we report the demonstration of non-destructive inspection for H2Oinside of a stainless steel pipe using a laser driven thermal neutron source, where water and stainless containers are detected by neutrons and X-rays, respectively. The simulation result indicates that this method is also able to measure accurately the hydrogen density in high-pressure hydrogen gas in metal containers