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Left ventricular (LV) diastolic dysfunction is increasingly common in heart failure with preserved ejection fraction (HFpEF), and new drug therapy is desired. We recently reported that dantrolene (DAN) attenuates pressure-overload induced hypertrophic signaling through stabilization of tetrameric structure of cardiac ryanodine receptor (RyR2). Because cardiac hypertrophy substantially affects LV diastolic properties, we investigated the effect of DAN on LV diastolic properties in mineralocorticoid-salt–induced hypertensive rat model exhibiting the HFpEF phenotype.Male Sprague-Dawley (SD) rats (8 weeks old) received an uninephrectomy (UNX), subcutaneous implantation of a 200 mg pellet of deoxycorticosterone acetate (DOCA), and 0.9% NaCl water (UNX + DOCA-salt). UNX, a control pellet, and water without NaCl served as controls (UNX control). The effect of oral administration of 100 mg/kg/d DAN was examined in UNX control and UNX + DOCA-salt groups (UNX + DAN and UNX + DOCA-salt + DAN).UNX + DOCA-salt treatment resulted in mild hypertension. Chronic administration of DAN to UNX + DOCA-salt rats (UNX + DOCA-salt + DAN) did not affect blood pressure. DAN treatment increased the mitral annular early relaxation velocity in the UNX + DOCA-salt group. The size of cardiomyocytes increased in the UNX + DOCA-salt group, whereas the increase was suppressed by DAN treatment. LV fibrotic area was significantly smaller in the UNX + DOCA-salt + DAN group than in the UNX + DOCA-salt group (2.0 ± 0.2% vs 4.0 ± 0.4%). The LV chamber stiffness significantly increased in the UNX + DOCA-salt group, whereas the increase was suppressed by DAN treatment. DAN treatment normalized the CaM-RyR2 interaction and inhibited aberrant Ca2+ release.DAN improved left ventricular diastolic properties with respect to both myocardial relaxation and chamber stiffness. DAN may be a new treatment option for HFpEF. more...

ABSTRACT Leptospirosis is a zoonotic disease caused by infection with pathogenic leptospires. Consistent with recent studies by other groups, leptospires were isolated from 89 out of 110 (80.9%) soil or water samples from varied locations in the Philippines in our surveillance study, indicating that leptospires might have a life cycle that does not involve animal hosts. However, despite previous work, it has not been confirmed whether leptospires multiply in the soil environment under various experimental conditions. Given the fact that the case number of leptospirosis is increased after flood, we hypothesized that waterlogged soil, which mimics the postflooding environment, could be a suitable condition for growing leptospires. To verify this hypothesis, pathogenic and saprophytic leptospires were seeded in the bottles containing 2.5 times as much water as soil, and bacterial counts in the bottles were measured over time. Pathogenic and saprophytic leptospires were found to increase their number in waterlogged soil but not in water or soil alone. In addition, leptospires were reisolated from soil in closed tubes for as long as 379 days. These results indicate that leptospires are in a resting state in the soil and are able to proliferate with increased water content in the environment. This notion is strongly supported by observations that the case number of leptospirosis is significantly higher in rainy seasons and increased after flood. Therefore, we reached the following conclusion: environmental soil is a potential reservoir of leptospires. IMPORTANCE Since research on Leptospira has focused on pathogenic leptospires, which are supposed to multiply only in animal hosts, the life cycle of saprophytic leptospires has long been a mystery. This study demonstrates that both pathogenic and saprophytic leptospires multiply in the waterlogged soil, which mimics the postflooding environment. The present results potentially explain why leptospirosis frequently occurs after floods. Therefore, environmental soil is a potential reservoir of leptospires and leptospirosis is considered an environment-borne as well as a zoonotic disease. This is a significant report to reveal that leptospires multiply under environmental conditions, and this finding leads us to reconsider the ecology of leptospires. more...

Disasters such as the magnitude-9 Great East Japan Earthquake occur periodically. We considered this experience while developing measures against a predicted earthquake in the Nankai Trough. This report includes a summary of 10 disastrous infectious diseases for which a countermeasures seminar was held. Thirty-five speakers from twenty-one organizations performed the lectures. Besides infectious diseases, conference topics also included disaster prevention and mitigation methods. In addition, the development of point-of-care tests, biomarkers for diagnosis, and severity assessments for infectious diseases were introduced, along with epidemics of infectious diseases affected by climate. Of the 28 pathogens that became a hot topic, 17 are viruses, and 14 out of these 17 (82%) are RNA viruses. Of the 10 seminars, the last 2 targeted only COVID-19. It was emphasized that COVID-19 is not just a disaster-related infection but a disaster itself. The first seminar on COVID-19 provided immunological and epidemiological knowledge and commentary on clinical practices. During the second COVID-19 seminar, vaccine development, virological characteristics, treatment of respiratory failure, biomarkers, and human genetic susceptibility for infectious diseases were discussed. Conducting continuous seminars is important for general infectious controls. more...

Public transportation is becoming increasingly important in regions where the residential population is decreasing. In Japan, many regional transportation systems are experiencing financial challenges. It is difficult for fixed-route transportation systems to operate at a surplus when serving only local resident users. We consider one of the problems of these regional public transport systems to be the lack of information on the Internet about regional public transportation routes. For people who are unfamiliar with the region, such as inbound tourists, there is no easy way to conduct a route search. In this paper, we describe our efforts to build a fundamental database of the regional public transportation provided by municipalities and to publish this data for those conducting route searches on the Internet. Specifically, we converted fundamental data regarding regional public transportation to the feed of the General Transit Feed Specification-Japan (GTFS-JP), which is based on the Google GTFS, as formulated by the Ministry of Land in Japan. Then we encouraged municipalities to publish these transit data to enable route searches on Google Maps and other domestic-content providers. more...