著者
Kohei Tsuji Takuya Kobayakawa Takahiro Ishii Nobuyo Higashi-Kuwata Chika Azuma Kouki Shinohara Yutaro Miura Kenichi Yamamoto Soshi Nishimura Shin-ichiro Hattori Haydar Bulut Hiroaki Mitsuya Hirokazu Tamamura
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.71, no.12, pp.879-886, 2023-12-01 (Released:2023-12-01)
参考文献数
53

In the development of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs, its main protease (Mpro), which is an essential enzyme for viral replication, is a promising target. To date, the Mpro inhibitors, nirmatrelvir and ensitrelvir, have been clinically developed by Pfizer Inc. and Shionogi & Co., Ltd., respectively, as orally administrable drugs to treat coronavirus disease of 2019 (COVID-19). We have also developed several potent inhibitors of SARS-CoV-2 Mpro that include compounds 4, 5, TKB245 (6), and TKB248 (7), which possesses a 4-fluorobenzothiazole ketone moiety as a reactive warhead. In compounds 5 and TKB248 (7) we have also found that replacement of the P1-P2 amide of compounds 4 and TKB245 (6) with the corresponding thioamide improved their pharmacokinetics (PK) profile in mice. Here, we report the design, synthesis and evaluation of SARS-CoV-2 Mpro inhibitors with replacement of a digestible amide bond by surrogates (9–11, 33, and 34) and introduction of fluorine atoms in a metabolically reactive methyl group on the indole moiety (8). As the results, these compounds showed comparable or less potency compared to the corresponding parent compounds, YH-53/5h (2) and 4. These results should provide useful information for further development of Mpro inhibitors.
著者
Shang-Ju Wu Li-Wei Lo Fa-Po Chung Yenn-Jiang Lin Shih-Lin Chang Yu-Feng Hu Yu-Cheng Hsieh Cheng-Hung Li Ta-Chuan Tuan Tze-Fan Chao Jo-Nan Liao Chin-Yu Lin Ting-Yung Chang Ling Kuo Chih-Min Liu Shin-Huei Liu Cheng-I Wu Chi-Jen Weng Ming-Jen Kuo Guan-Yi Li Yu-Shan Huang Jose Antonio Bautista Yoon-Kee Siow Nguyen Dinh Son Ngoc Shih-Ann Chen
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-23-0364, (Released:2023-10-20)
参考文献数
25

Background: Circumferential pulmonary vein isolation (CPVI) has supplanted segmental PVI (SPVI) as standard procedure for atrial fibrillation (AF). However, there is limited evidence examining the efficacy of these strategies in redo ablations. In this study, we investigated the difference in recurrence rates between SPVI and CPVI in redo ablations for PV reconnection.Methods and Results: This study retrospectively enrolled 543 patients who had undergone AF ablation between 2015 and 2017. Among them, 167 patients (30.8%, including 128 male patients and 100 patients with paroxysmal AF) underwent redo ablation for recurrent AF. Excluding 26 patients without PV reconnection, 141 patients [90 patients of SPVI (Group 1) and 51 patients of CPVI (Group 2)] were included. The AF-free survival rates were 53.3% and 56.9% in Group 1 and Group 2, respectively (P=0.700). The atrial flutter (AFL)-free survival rates were 90% and 100% in Group 1 and Group 2, respectively (P=0.036). The ablation time was similar between groups, and there no major complications were observed.Conclusions: For redo AF ablation procedures, SPVI and CPVI showed similar outcomes, except for a higher AFL recurrence rate for SPVI after long-term follow-up (>2 years). This may be due to a higher probability of residual PV gaps causing reentrant AFL.
著者
Daisuke Nose Yuhei Shiga Ryou-u Takahashi Yuki Yamamoto Yasunori Suematsu Takashi Kuwano Makoto Sugihara Miyuki Kanda Hidetoshi Tahara Shin-ichiro Miura
出版者
The Japanese Circulation Society
雑誌
Circulation Reports (ISSN:24340790)
巻号頁・発行日
pp.CR-23-0038, (Released:2023-07-11)
参考文献数
52
被引用文献数
2

Background: The utility of telomere G-tail length to predict coronary artery disease (CAD) remains controversial. CAD results from coronary artery narrowing due to cholesterol and lipid accumulation, augmented by inflammatory cells and other factors. This study explored the significance of telomere G-tail length in suspected CAD patients.Methods and Results: In all, 95 patients with suspected CAD or ≥1 cardiac risk factor underwent coronary computed tomography angiography (CCTA). We measured leukocyte telomere length and G-tail length using a hybrid protection method, and diagnosed the presence of CAD using CCTA. Associations between G-tail length and the presence of CAD, the number of stenosed coronary arteries, and brachial-ankle pulse wave velocity (baPWV) were analyzed. No significant difference was observed in G-tail length when comparing groups with or without CAD or statin treatment. However, in the non-statin group, G-tail length was significantly shorter in patients with 3-vessel disease compared with 1-vessel disease. Dividing the group using a baPWV of 1,300 cm/s, telomere G-tail length was significantly shorter in the high-risk (baPWV ≥1,300 cm/s) group.Conclusions: The clinical utility of telomere G-tail length as a CAD risk indicator seems limited. There was a trend for longer telomere G‐tail length in the statin‐treated group. Moreover, telomere G-tail length was reduced in patients at high-risk of cardiovascular events, aligning with the trend of a shortening in telomere G-tail length with CAD severity.
著者
Shin-ichiro Ohmura Yusuke Ohkubo Ryuhei Ishihara Yoshiro Otsuki Toshiaki Miyamoto
出版者
The Japanese Society of Internal Medicine
雑誌
Internal Medicine (ISSN:09182918)
巻号頁・発行日
vol.61, no.22, pp.3453-3457, 2022-11-15 (Released:2022-11-15)
参考文献数
28
被引用文献数
4

Coronavirus disease 2019 (COVID-19) vaccines have been delivered worldwide to prevent the spread of the disease, and almost all Japanese have received the mRNA vaccines "BNT162b2" (Pfizer-BioNTech) or "mRNA-1273" (Moderna). These vaccines have shown efficacy and safety with only minor adverse drug reactions. However, some patients develop severe adverse drug reactions, including autoimmune reactions. In addition, systemic vasculitis, mainly small-vessel vasculitis, following COVID-19 vaccination, has been reported. However, only a few investigators have reported medium-vessel vasculitis following vaccination. We herein report a case of medium-vessel vasculitis presenting with myalgia as the initial clinical manifestation following COVID-19 Moderna vaccination.
著者
Hiroyuki Tsutsui Shin-ichi Momomura Tohru Masuyama Yoshihiko Saito Issei Komuro Toyoaki Murohara Shintaro Kinugawa on behalf of CIBIS-J Investigators
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.83, no.6, pp.1269-1277, 2019-05-24 (Released:2019-05-24)
参考文献数
24
被引用文献数
6 10

Background: The comparative tolerability, efficacy, and safety of bisoprolol and carvedilol have not been established in Japanese patients with heart failure and reduced ejection fraction (HFrEF). Methods and Results: The CIBIS-J trial is a multicenter, open-label, non-inferiority randomized controlled trial of bisoprolol vs. carvedilol in 217 patients with HFrEF (EF ≤40%). The primary endpoint was tolerability, defined as reaching and maintaining the maximum maintenance dose (bisoprolol 5 mg/day or carvedilol 20 mg/day) during 48 weeks of treatment. The primary endpoint was achieved in 41.4% of patients in bisoprolol (n=111) and 42.5% in carvedilol (n=106) groups. The non-inferiority of tolerability of bisoprolol compared with carvedilol was not supported, however, neither β-blocker was superior with regard to tolerability. Heart rate (HR) decreased in both groups and its decrease from baseline was significantly greater in the bisoprolol group (20.3 vs. 15.4 beats/min at 24 week, P<0.05). Plasma B-type natriuretic peptide (BNP) levels decreased in both groups and the decrease was significantly greater in the carvedilol group (12.4 vs. 39.0 % at 24 weeks, P<0.05). Conclusions: There were no significant differences between bisoprolol and carvedilol in the tolerability of target doses in Japanese HFrEF patients. The clinical efficacy and safety were also similar despite the greater reduction in HR by bisoprolol and plasma BNP by carvedilol.
著者
Ju-Young Shin Kyu Rang Kim Yong Hee Lee
出版者
Meteorological Society of Japan
雑誌
SOLA (ISSN:13496476)
巻号頁・発行日
vol.18, pp.41-46, 2022 (Released:2022-03-18)
参考文献数
28

Determining the thresholds for risk assessment is critical for the successful implementation of thermal health warning systems. A risk assessment methodology with multiple thresholds must be developed to provide detailed warning information to the public and decision makers. This study developed a new methodology to identify multiple thresholds for different risk levels for heat or cold wave events by considering simultaneously impact on public health. A new objective function was designed to optimize segmented Poisson regression, which relates public health to temperature indicators. Thresholds were identified based on the values of the objective functions for all threshold candidates. A case study in identifying thresholds for cold and heat wave events in Seoul, South Korea, from 2014 to 2018, was conducted to evaluate the appropriateness of the proposed methodology. Daily minimum or maximum air temperature, mortality, and morbidity data were used for threshold identification and evaluation. The proposed methodology can successfully identify multiple thresholds to simultaneously represent different risk levels. These thresholds show comparable performance to those using the relative frequency approach.
著者
Ju-Young Shin Kyu Rang Kim Yong Hee Lee
出版者
Meteorological Society of Japan
雑誌
SOLA (ISSN:13496476)
巻号頁・発行日
pp.2022-007, (Released:2022-01-26)

Determining the thresholds for risk assessment is critical for the successful implementation of thermal health warning systems. A risk assessment methodology with multiple thresholds must be developed to provide detailed warning information to the public and decision makers. This study developed a new methodology to identify multiple thresholds for different risk levels for heat or cold wave events by considering simultaneously impact on public health. A new objective function was designed to optimize segmented Poisson regression, which relates public health to temperature indicators. Thresholds were identified based on the values of the objective functions for all threshold candidates. A case study in identifying thresholds for cold and heat wave events in Seoul, South Korea, from 2014 to 2018, was conducted to evaluate the appropriateness of the proposed methodology. Daily minimum or maximum air temperature, mortality, and morbidity data were used for threshold identification and evaluation. The proposed methodology can successfully identify multiple thresholds to simultaneously represent different risk levels. These thresholds show comparable performance to those using the relative frequency approach.
著者
Natsuko SUGIURA Kazuhiko OCHIAI Toshiaki YAMAMOTO Takuya KATO Yoshi KAWAMOTO Toshinori OMI Shin-ichi HAYAMA
出版者
JAPANESE SOCIETY OF VETERINARY SCIENCE
雑誌
Journal of Veterinary Medical Science (ISSN:09167250)
巻号頁・発行日
vol.82, no.4, pp.479-482, 2020 (Released:2020-04-09)
参考文献数
29
被引用文献数
1

We analyzed the genotypes of three pregnant females and their litters to investigate the phenomenon of multiple paternity in wild raccoon dogs (Nyctereutes procyonoides) using 17 microsatellite markers. If a female has mated with only one male during estrus, then the maximum number of paternal alleles will not exceed two among littermates with the same father. The results revealed two out of three litters had three or four paternal alleles at one or five microsatellite loci. Therefore, the female had mated with more than one male during estrus. To the best of our knowledge, the present study is the first to report the possibility of multiple paternity in wild raccoon dogs.
著者
Shin Fukui Akihiko Murata
出版者
Meteorological Society of Japan
雑誌
SOLA (ISSN:13496476)
巻号頁・発行日
vol.17, pp.207-212, 2021 (Released:2021-11-25)
参考文献数
40

This study statistically investigated sensitivities of simulated precipitation to horizontal resolution of a regional climate model, instead of focusing on particular cases. We performed long-term integrations of models with horizontal grid spacings of 20, 5, 2, 1, and 0.5 km over Kyushu in the Baiu seasons of 2009-2020. The 2-km grid model improves simulated precipitation to the 5-km grid models with and without cumulus parameterization. Further decreasing the gird spacing from 2 km to 1 and 0.5 km reduces the dependency of the frequency biases on intensities of hourly precipitation and mitigates the excessive concentration of heavy precipitation in small scale, approaching that of the radar/raingauge analysis. The features of individual deep moist convections, specifically the horizontal scale of updrafts, the representation of downdrafts, and the number of convections, start to converge when the grid spacing is reduced from 1 to 0.5 km. The results suggest models with grid spacing of 1 km or less are needed to resolve deep moist convections and to represent the resulting precipitations. The 2-km grid models can partly resolve the deep moist convections, but their effective resolution is still insufficient, requiring some parameterizations to simulate convective precipitations appropriately.
著者
Syuichi Itahashi Junichi Kurokawa Toshimasa Ohara Itsushi Uno Shin-ichi Fujita
出版者
Meteorological Society of Japan
雑誌
SOLA (ISSN:13496476)
巻号頁・発行日
vol.17, pp.184-190, 2021 (Released:2021-10-14)
参考文献数
44
被引用文献数
1

Precipitation chemistry was observed at the remote background site at Ryori, Ofunato in northeastern Japan, from 1976 to 2011 as the part of World Meteorological Organization-Global Atmospheric Watch (WMO-GAW). During this period, anthropogenic emissions in East Asia varied widely, which affected the precipitation chemistry. The precipitation amount also affects the wet deposition amount. Thus, to eliminate the effect of the precipitation amount, we used the ratio of nitrate (NO3−) to non-sea-salt sulfate (nss-SO42−) concentration in precipitation on an equivalent basis (Ratio). The historical trend of NO3− and nss-SO42− concentrations in precipitation was not clear; however, Ratio showed a strong increase in the 1990s, a sudden drop in 2001, and an increase again after 2007. Based on the analysis of the historical emission dataset, the increases in Ratio during the 1990s and after 2007 were attributed to anthropogenic emission changes in Japan and China. The drop in Ratio in 2001 was explained by the massive SO2 release from Miyakejima volcano from mid-August 2000, rather than by anthropogenic emissions. The 36-year historical record analysis of precipitation chemistry at Ryori detected both anthropogenic and natural emission changes and indicated the transition from local to transboundary air pollution in Japan.
著者
Tetsuaki Ban Shin-ichiro Fujiwara Rui Murahashi Hirotomo Nakajima Takashi Ikeda Sae Matsuoka Yumiko Toda Shin-ichiro Kawaguchi Shoko Ito Takashi Nagayama Kento Umino Daisuke Minakata Hirofumi Nakano Kaoru Morita Masahiro Ashizawa Chihiro Yamamoto Kaoru Hatano Kazuya Sato Ken Ohmine Yoshinobu Kanda
出版者
The Japanese Society of Internal Medicine
雑誌
Internal Medicine (ISSN:09182918)
巻号頁・発行日
pp.8184-21, (Released:2021-09-11)
参考文献数
19
被引用文献数
2

Objective Peripherally inserted central catheters (PICCs) are widely used in patients with hematologic malignancies. However, the risks of PICC-related complications during chemotherapy for acute myeloid leukemia (AML) are not fully understood. Methods We conducted a retrospective review of 128 adult patients with AML who received induction therapy by way of PICC insertion between 2012 and 2019. Results The median duration of PICC insertion was 30 days. The incidence rate of catheter-related bloodstream infection (CRBSI) was 2.4% at 30 days, and women were more likely to suffer from CRBSI than men. Local reactions at the insertion site were observed in 56 patients; however, these events did not predict CRBSI. The incidence rates of catheter-related thrombosis (CRT) were 1.6% at 30 days. Obesity put patients at an increased risk for CRT. Unexpected PICC removal occurred in 59 patients, and women were at a higher risk of catheter removal than men. Conclusion Low PICC-related complication rates, possibly associated with high rates of catheter removal, were observed during intensive chemotherapy for AML. Women and obese patients require careful monitoring of their PICC. Procedures to achieve appropriate PICC removal without increasing the complication rate need to be considered.
著者
酒井 奈緒美 小倉(青木) 淳 森 浩一 Chu Shin Ying 坂田 善政
出版者
日本音声言語医学会
雑誌
音声言語医学 (ISSN:00302813)
巻号頁・発行日
vol.56, no.1, pp.1-11, 2015 (Released:2015-04-08)
参考文献数
19
被引用文献数
5 1

吃音のある成人が抱える困難を,WHOの国際生活機能分類のモデルに基づき4つのセクションから包括的に評価する質問紙(Overall Assessment of the Speaker's Experience of Stuttering: OASES; Yaruss and Quesal, 2006)を日本語に訳し(日本語版OASES試案),吃音のセルフヘルプグループの活動に参加している成人30名に対して実施した.対象者の傾向として,①吃音に対する感情・行動・認知面に比較的大きな困難を感じる者が多い,②日常生活上の具体的なコミュニケーション場面における困難や生活の質の低下などは比較的小さい,③総合の重症度評定は軽度から中等度であることが示された.OASES自体に関しては,項目数の多さ,選択肢の表現や質問意図のわかりづらさなど,臨床場面にて使用するには問題となる点も認められたが,セクション間における平均得点の相違や,セクション間における平均得点の相関の高さが先行研究と一致し,海外と共通の尺度として有用であることが示された.
著者
Norikazu MATSUOKA Shin-ichi SAWAGUCHI Kenji YOSHIKAWA
出版者
The Association of Japanese Geographers
雑誌
地理学評論 (ISSN:13479555)
巻号頁・発行日
vol.77, no.5, pp.276-300, 2004-04-01 (Released:2008-12-25)
参考文献数
62
被引用文献数
11 18

This report overviews observations on periglacial geomorphology in central Spitsbergen, which have been undertaken by the Japanese geomorphological groups. Focus is given to permafrost-related processes, including solifluction, thermal contraction cracking and pingo growth. Annual freeze-thaw action dominates the ground, resulting in extensive occurrence of solifluction and shallow landslides on soil slopes. Solifluction shows low surface velocity but large volumetric transport, which respectively reflects infrequent diurnal frost creep and deep movement. The latter partly originates from plug-like flow in the basal active layer, where permafrost temperature is low and muddy sediment is thick. Non-sorted polygons with a wide range of diameters develop on lowlands. In colder inland terrains, large polygons (>7m) have ice wedges, whereas smaller polygons have only soil wedges or cracks confined to the active layer. Significant ice-wedge cracking occurs during rapid and intensive cooling in midwinter. In warmer coastal terrains, ice wedges are not common even below large polygons, because higher winter temperature can produce only shallow cracks. Open-system pingos occur in valley bottoms and near shores. Some pingos are still growing under a low artesian pressure fed by constant supply of sub-permafrost water. Following lateral river erosion, a new frost mound emerged at a side of a pingo, reaching 3m high during three years. The observations demonstrate that central Spitsbergen is situated in a High Arctic but relatively warm permafrost environment. The transitional condition between cold and warm permafrost allows diverse periglacial features to coexist within a small area. Even minor climatic change can switch the two thermal regimes, affecting significantly the type and magnitude of periglacial processes.
著者
Miho Nishitani-Yokoyama Hiroyuki Daida Kazunori Shimada Akiko Ushijima Keisuke Kida Yuji Kono Yasuhiko Sakata Masatoshi Nagayama Yutaka Furukawa Nagaharu Fukuma Keijiro Saku Shin-ichiro Miura Yusuke Ohya Youichi Goto Shigeru Makita for the Japanese Association of Cardiac Rehabilitation (JACR) Registration Committee
出版者
The Japanese Circulation Society
雑誌
Circulation Reports (ISSN:24340790)
巻号頁・発行日
vol.2, no.12, pp.715-721, 2020-12-10 (Released:2020-12-10)
参考文献数
25
被引用文献数
2

Background:Cardiac rehabilitation (CR) is categorized as a Class I recommendation in guidelines for the management of patients with acute coronary syndrome (ACS); however, nationwide studies on CR in patients with ACS remain limited in Japan.Methods and Results:The Japanese Association of Cardiac Rehabilitation (JACR) Registry is a nationwide, real-world database for patients participating in CR. From the JACR Registry database, we analyzed 924 patients participating in Phase II CR in 7 hospitals between September 2014 and December 2016. The mean age of patients was 65.9±12.0 years, and 80% were male. The prevalence of ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and unstable angina pectoris (UAP) was 58%, 9%, and 33%, respectively. The prevalence of hypertension, diabetes, dyslipidemia, current smoking, and a family history was 55%, 27%, 67%, 21%, and 10%, respectively. Among the entire CR cohort at baseline, 96%, 78%, and 92% were treated with aspirin, β-blockers, and statins, respectively. After CR, the values of body mass index, the lipid profile, and exercise capacity significantly improved in the STEMI, NSTEMI and UAP groups.Conclusions:In the JACR Registry, a high rate of guideline-recommended medications at baseline and improvements in both coronary risk factors and exercise capacity after CR were observed in patients with ACS.
著者
Yosuke Hata Osamu Iida Mitsutoshi Asai Masaharu Masuda Shin Okamoto Takayuki Ishihara Kiyonori Nanto Takashi Kanda Takuya Tsujumura Shota Okuno Yasuhiro Matsuda Mitsuyoshi Takahara Toshiaki Mano
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.57711, (Released:2020-07-23)
参考文献数
11
被引用文献数
12

Aim: The latest Global Vascular Guidelines (GVG) recommend assessing the 2-year mortality risk in patients with chronic limb-threatening ischemia (CLTI) before revascularization. This study aimed to reveal whether the Wound, Ischemia and foot Infection (WIfI) classification, developed originally as a risk assessment tool for limb prognosis, would be useful in predicting the 2-year mortality risk in patients with CLTI in the era of GVG and WIfI. Methods: We retrospectively analyzed 849 patients with CLTI who were primarily treated with endovascular therapy (EVT) between April 2010 and December 2016. The impact of baseline characteristics, including the WIfI classification on mortality risk, was investigated using the Cox proportional hazards regression model. Results: During a mean follow-up of 19.3 months, 243 deaths were observed. The 2-year mortality rate was 32.3%. Multivariate analysis demonstrated that WIfI classification stages (p=0.037), in addition to male sex (p=0.010), age (p<0.001), non-ambulatory status (p<0.001), body mass index (p=0.002), and hemodialysis (p <0.001), were independent predictors for an increased risk of mortality, while the Rutherford classification was not. Conclusions: WIfI classification stages were independently associated with mortality risk in patients with CLTI undergoing EVT, while the Rutherford classification was not. The WIfI classification would be a practical tool for planning the revascularization strategy in CLTI treatment.
著者
西尾 悠佑 石川 信一 ニシオ ユウスケ イシカワ シンイチ Nishio Yusuke Ishikawa Shin-ichi
出版者
心理臨床科学編集委員会
雑誌
心理臨床科学 = Doshisha Clinical Psychology : therapy and research (ISSN:21864934)
巻号頁・発行日
vol.6, no.1, pp.43-52, 2016-12-15

研究動向本稿の目的は,心理的ウェルビーイング(PsychologicalWell-Being:PWB)および,ウェルビーイング療法(Well-BeingTherapy:WBT)についてレビューすることであった。まず先行研究を概観したところ,PWBはさまざまな精神疾患との関係性が示されており,PWBの向上が精神疾患の改善に有効であることが示唆された。次に,WBTのこれまでのエビデンスを概観したところ,WBTは認知行動療法(CognitiveBehaviorTherapy:CBT)に追加されて実施されることが多いとわかった。しかし,CBT単独の実施より,CBTにWBTを追加した方が,効果が高いかについては,今後検討していく必要性があげられた。最後にWBTでは"肯定的な側面の否定や割り引き"という思考の誤りを扱っている可能性が推察された。そのためWBTの介入により,この思考の誤りが変化しているかについて検討する余地がある。