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

Early deprivation induces competitive subordinance in C57BL/6 male mice

Rodent models have been widely used to investigate the impact of early life stress on adult health and behavior. However, the social dimension has rarely been incorporated into the analysis due to methodological limitations. This study characterized the effects of neonatal social isolation (early deprivation, ED) on adult C57BL/6 mouse behavior in a social context using our recently developed behavioral test protocols for group-housed mice. During the first two postnatal weeks, half of the pups per dam were separated from their dam and littermates for 3. h per day (ED group). Post weaning, ED and control pups were electronically tagged and co-housed. At 12. weeks, the mixed cohorts were transferred to IntelliCages, equipped with computer-controlled operant chambers. Access to the chambers was used as an index to analyze novel object response, behavioral flexibility, and competitive dominance with minimal experimenter intervention. In general, ED had greater effects on males; ED males exhibited reduced body weight, increased novelty response, and were subordinate to control littermates when competing for reward access. Male ED mice also demonstrated mildly impaired reversal learning. Analyzing gene expression changes in brain regions controlling emotion, stress, spatial memory, and executive function revealed reduced BDNF and c-Fos in hippocampal CA1, enhanced c-Fos in the basolateral amygdala, reduced Map2 while enhanced HSD11β2 in prefrontal cortex of ED males. In male mice, it was suggested that neonatal social isolation results in sustained changes in social behavior with altered function of limbic and frontal cortices

A pristine record of outer Solar System materials from asteroid Ryugu’s returned sample

Volatile and organic-rich C-type asteroids may have been one of the main sources of Earth’s water. Our best insight into their chemistry is currently provided by carbonaceous chondritic meteorites, but the meteorite record is biased: only the strongest types survive atmospheric entry and are then modified by interaction with the terrestrial environment. Here we present the results of a detailed bulk and microanalytical study of pristine Ryugu particles, brought to Earth by the Hayabusa2 spacecraft. Ryugu particles display a close compositional match with the chemically unfractionated, but aqueously altered, CI (Ivuna-type) chondrites, which are widely used as a proxy for the bulk Solar System composition. The sample shows an intricate spatial relationship between aliphatic-rich organics and phyllosilicates and indicates maximum temperatures of ~30 °C during aqueous alteration. We find that heavy hydrogen and nitrogen abundances are consistent with an outer Solar System origin. Ryugu particles are the most uncontaminated and unfractionated extraterrestrial materials studied so far, and provide the best available match to the bulk Solar System composition

Acceleration of the Deamination of Cytosine through Photo-Crosslinking

Herein, we report the major factor for deamination reaction rate acceleration, i.e., hydrophilicity, by using various 5-substituted target cytosines and by carrying out deamination at high temperatures. Through substitution of the groups at the 5′-position of the cytosine, the effect of hydrophilicity was understood. It was then used to compare the various modifications of the photo-cross-linkable moiety as well as the effect of the counter base of the cytosine to edit both DNA and RNA. Furthermore, we were able to achieve cytosine deamination at 37 °C with a half-life in the order of a few hours

Advances in boron neutron capture therapy (BNCT) at kyoto university - From reactor-based BNCT to accelerator-based BNCT

First online: 28 July 2015At the Kyoto University Research Reactor Institute (KURRI), a clinical study of boron neutron capture therapy (BNCT) using a neutron irradiation facility installed at the research nuclear reactor has been regularly performed since February 1990. As of November 2014, 510 clinical irradiations were carried out using the reactor-based system. The world’s first accelerator-based neutron irradiation system for BNCT clinical irradiation was completed at this institute in early 2009, and the clinical trial using this system was started in 2012. A shift of BCNT from special particle therapy to a general one is now in progress. To promote and support this shift, improvements to the irradiation system, as well as its preparation, and improvements in the physical engineering and the medical physics processes, such as dosimetry systems and quality assurance programs, must be considered. The recent advances in BNCT at KURRI are reported here with a focus on physical engineering and medical physics topics

Effects of Long-Term Treatment with Ranirestat, a Potent Aldose Reductase Inhibitor, on Diabetic Cataract and Neuropathy in Spontaneously Diabetic Torii Rats

We evaluated ranirestat, an aldose reductase inhibitor, in diabetic cataract and neuropathy (DN) in spontaneously diabetic Torii (SDT) rats compared with epalrestat, the positive control. Animals were divided into groups and treated once daily with oral ranirestat (0.1, 1.0, 10 mg/kg) or epalrestat (100 mg/kg) for 40 weeks, normal Sprague-Dawley rats, and untreated SDT rats. Lens opacification was scored from 0 (normal) to 3 (mature cataract). The combined scores (0–6) from both lenses represented the total for each animal. DN was assessed by measuring the motor nerve conduction velocity (MNCV) in the sciatic nerve. Sorbitol and fructose levels were measured in the lens and sciatic nerve 40 weeks after diabetes onset. Cataracts developed more in untreated rats than normal rats (P<0.01). Ranirestat significantly (P<0.01) inhibited rapid cataract development; epalrestat did not. Ranirestat significantly reversed the MNCV decrease (40.7 ± 0.6 m/s) in SDT rats dose-dependently (P<0.01). Epalrestat also reversed the prevented MNCV decrease (P<0.05). Sorbitol levels in the sciatic nerve increased significantly in SDT rats (2.05 ± 0.10 nmol/g), which ranirestat significantly suppressed dose-dependently, (P<0.05, <0.01, and <0.01); epalrestat did not. Ranirestat prevents DN and cataract; epalrestat prevents DN only