著者
Ohara Koji Mitsui Akio Mori Masahiro Onodera Yohei Shiotani Shinya Koyama Yukinori Orikasa Yuki Murakami Miwa Shimoda Keiji Mori Kazuhiro Fukunaga Toshiharu Arai Hajime Uchimoto Yoshiharu Ogumi Zempachi
出版者
Nature Publishing Group
雑誌
Scientific reports (ISSN:20452322)
巻号頁・発行日
vol.6, 2016-02-19
被引用文献数
107

次世代硫化物ガラス電解質の構造解明に成功 -複雑なガラス構造中のリチウムイオン伝導制御に期待-. 京都大学プレスリリース. 2016-02-22.The atomic and electronic structures of binary Li2S-P2S5 glasses used as solid electrolytes are modeled by a combination of density functional theory (DFT) and reverse Monte Carlo (RMC) simulation using synchrotron X-ray diffraction, neutron diffraction, and Raman spectroscopy data. The ratio of PSx polyhedral anions based on the Raman spectroscopic results is reflected in the glassy structures of the 67Li2S-33P2S5, 70Li2S-30P2S5, and 75Li2S-25P2S5 glasses, and the plausible structures represent the lithium ion distributions around them. It is found that the edge sharing between PSx and LiSy polyhedra increases at a high Li2S content, and the free volume around PSx polyhedra decreases. It is conjectured that Li(+) ions around the face of PSx polyhedra are clearly affected by the polarization of anions. The electronic structure of the DFT/RMC model suggests that the electron transfer between the P ion and the bridging sulfur (BS) ion weakens the positive charge of the P ion in the P2S7 anions. The P2S7 anions of the weak electrostatic repulsion would causes it to more strongly attract Li(+) ions than the PS4 and P2S6 anions, and suppress the lithium ionic conduction. Thus, the control of the edge sharing between PSx and LiSy polyhedra without the electron transfer between the P ion and the BS ion is expected to facilitate lithium ionic conduction in the above solid electrolytes.
著者
Kei KONDOH Ayman ATIBA Kiyoshi NAGASE Shizuko OGAWA Takashi MIWA Teruya KATSUMATA Hiroshi UENO Yuji UZUKA
出版者
公益社団法人 日本獣医学会
雑誌
Journal of Veterinary Medical Science (ISSN:09167250)
巻号頁・発行日
pp.14-0279, (Released:2015-04-04)
被引用文献数
1

In the present study, we compare a new carbon dioxide (CO2) absorbent, Yabashi lime® with a conventional CO2 absorbent, Sodasorb® as a control CO2 absorbent for Compound A (CA) and Carbon monoxide (CO) productions. Four dogs were anesthetized with sevoflurane. Each dog was anesthetized with four preparations, Yabashi lime® with high or low-flow rate of oxygen and control CO2 absorbent with high or low-flow rate. CA and CO concentrations in the anesthetic circuit, canister temperature, and carbooxyhemoglobin (COHb) concentration in the blood were measured. Yabashi lime® did not produce CA. Control CO2 absorbent generated CA and its concentration was significantly higher in low-flow rate than a high-flow rate. CO was generated only in low-flow rate groups, but there was no significance between Yabashi lime® groups and control CO2 absorbent groups. However, the CO concentration in the circuit could not be detected (≤5 ppm) and no change was found in COHb level. Canister temperature was significantly higher in low-flow rate groups than high-flow rate groups. Furthermore, in low-flow rate groups, the lower layer of canister temperature in control CO2 absorbent group was significantly higher than Yabashi lime® group. CA and CO productions are thought to be related to the composition of CO2 absorbent, flow rate, and canister temperature. Though CO concentration is equal, it might be safer to use Yabashi lime® with sevoflurane anesthesia in dogs than conventional CO2 absorbent at the point of CA production.
著者
Hiroaki Kisaka Dong Poh Chin Tetsuya Miwa Hiroto Hirano Sato Uchiyama Masahiro Mii Mayu Iyo
出版者
Japanese Society for Plant Biotechnology
雑誌
Plant Biotechnology (ISSN:13424580)
巻号頁・発行日
vol.40, no.4, pp.311-320, 2023-12-25 (Released:2023-12-25)
参考文献数
35

The biosynthetic pathway of Catharanthus roseus vinca alkaloids has a long research history, including not only identification of metabolic intermediates but also the mechanisms of inter-cellular transport and accumulation of biosynthesized components. Vinca alkaloids pathway begins with strictosidine, which is biosynthesized by condensing tryptamine from the tryptophan pathway and secologanin from the isoprenoid pathway. Therefore, increasing the supply of precursor tryptophan may enhance vinca alkaloid content or their metabolic intermediates. Many reports on the genetic modification of C. roseus use cultured cells or hairy roots, but few reports cover the production of transgenic plants. In this study, we first investigated a method for stably producing transgenic plants of C. roseus, then, using this technique, we modified the tryptophan metabolism system to produce transgenic plants with increased tryptophan content. Transformed plants were obtained by infecting cotyledons two weeks after sowing with Agrobacterium strain A13 containing a plant expression vector, then selecting with 1/2 B5 medium supplemented with 50 mg l−1 kanamycin and 20 mg l−1 meropenem. Sixty-eight regenerated plants were obtained from 4,200 cotyledons infected with Agrobacterium, after which genomic PCR analysis using NPTII-specific primers confirmed gene presence in 24 plants with a transformation rate of 0.6%. Furthermore, we performed transformation into C. roseus using an expression vector to join trpE8 and aroG4 genes, which are feedback-resistant mutant genes derived from Escherichia coli. The resulting transformed plants showed exactly the same morphology as the wild-type, albeit with a marked increase in tryptophan and alkaloids content, especially catharanthine in leaves.
著者
Kazunori Miwa Yan Guo Masayuki Hata Yoshinori Hirano Norio Yamamoto Tyuji Hoshino
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.897-905, 2023-12-01 (Released:2023-12-01)
参考文献数
40

Virtual screening with high-performance computers is a powerful and cost-effective technique in drug discovery. A chemical database is searched to find candidate compounds firmly bound to a target protein, judging from the binding poses and/or binding scores. The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infectious disease has spread worldwide for the last three years, causing severe slumps in economic and social activities. SARS-Cov-2 has two viral proteases: 3-chymotrypsin-like (3CL) and papain-like (PL) protease. While approved drugs have already been released for the 3CL protease, no approved agent is available for PL protease. In this work, we carried out in silico screening for the PL protease inhibitors, combining docking simulation and molecular mechanics calculation. Docking simulations were applied to 8,820 molecules in a chemical database of approved and investigational compounds. Based on the binding poses generated by the docking simulations, molecular mechanics calculations were performed to optimize the binding structures and to obtain the binding scores. Based on the binding scores, 57 compounds were selected for in vitro assay of the inhibitory activity. Five inhibitory compounds were identified from the in vitro measurement. The predicted binding structures of the identified five compounds were examined, and the significant interaction between the individual compound and the protease catalytic site was clarified. This work demonstrates that computational virtual screening by combining docking simulation with molecular mechanics calculation is effective for searching candidate compounds in drug discovery.
著者
Chih Chun WU Yasutsugu MIWA Makoto NAKATA James K CHAMBERS Kazuyuki UCHIDA Nobuo SASAKI
出版者
JAPANESE SOCIETY OF VETERINARY SCIENCE
雑誌
Journal of Veterinary Medical Science (ISSN:09167250)
巻号頁・発行日
pp.23-0230, (Released:2023-11-13)

A retrospective study involving 14 pet rabbits histopathologically diagnosed with malignant peripheral nerve sheath tumors (MPNSTs) was conducted. The age at diagnosis was 4–12 years, with a median age of 8.6 years. All rabbits had solid subcutaneous tumor masses in varied locations. Surgical excision of the tumors was performed in all cases. Recurrence was observed in 10 cases (71%), and postoperative metastasis to the lung was suspected in 4 cases (29%). The postoperative mean and median survival times were 11 months and 9 months, respectively. Hence, MPNSTs should be considered in the differential diagnosis for subcutaneous masses in rabbits and it is essential to inform the owners of the potentially high recurrence and metastasis rates.
著者
Shinji YAMASHITA Azusa MIWA Yu HINATA Koji URITA Kazuo MIYASHITA Mikio KINOSHITA
出版者
Center for Academic Publications Japan
雑誌
Journal of Nutritional Science and Vitaminology (ISSN:03014800)
巻号頁・発行日
vol.69, no.5, pp.382-387, 2023-10-31 (Released:2023-11-07)
参考文献数
28

Perilla oil is a valuable food source of α-linolenic acids. However, its high reactivity with oxygen shortens its shelf-life after opening. This study investigated the antioxidative profiles of 15 plant materials, including herbs, and examined methods to suppress the oxidation of perilla oil using these plant materials. These plant materials had wide ranges of phenolic, carotenoid, and chlorophyll contents. They exhibit radical scavenging activities and suppress lipid peroxidation, which show highly positive correlations with the phenolic contents. Dipping most of the plant materials examined in perilla oil suppressed its oxidation, and the peroxide values of the oil mixtures indicated a negative correlation with the carotenoid and chlorophyll contents of the plant materials. The leaves of Angelica, Astragalus, and Thyme herbs exhibited the same effect as that of ascorbyl palmitate, which was used as a positive control after 8 wk of incubation in the dark. The suppression of lipid peroxidation was found to be related to the herbal contents of carotenoids and chlorophylls, rather than phenols. Hence, herbal leaves can suppress the oxidation of perilla oil in the dark. The oxidation of n-3 polyunsaturated fatty acids could be suppressed effectively by utilizing plant materials with abundant carotenoids and chlorophylls.
著者
Osamu Katsuta Katsuhiko Shinomiya Takaharu Mochizuki Chinami Kikkawa Miwa Yoshimi Toshimi Ikuse
出版者
JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY
雑誌
Journal of Toxicologic Pathology (ISSN:09149198)
巻号頁・発行日
vol.21, no.4, pp.239-241, 2008 (Released:2009-01-14)
参考文献数
9
被引用文献数
2 5

A unique conjunctive stricture was observed in the eye of a male 17-week-old Japanese White rabbit (Kbl:JW). The conjunctival membrane had proliferated centripetally and covered a large portion of the cornea. However, the membrane did not adhere to the cornea. Histopathologically, the inner epithelium of the conjunctival membrane appeared flattened, while the outer epithelium had become stratified and squamous. Goblet cells were observed on both sides of the epithelium. The lamina propria consisted of well-developed, vascularized collagen fiber. Myxoid change was seen near the tip of the membrane. In animals, these conjunctival membranes have been reported in a few dwarf rabbits, dogs and horses and have had various different terms applied to them due to their unknown etiology. Based on the conventions of human ophthalmology, such lesions should be regarded as pseudopterygia. Therefore, the present case was diagnosed as involving a pseudopterygium. The centripetal proliferation of the conjunctival membrane may be a characteristic finding in animal cases. Our goal is to encourage accumulation of such cases by researchers and practitioners working in the field of toxicology.
著者
Kento TAKAHARA Tomoru MIWA Takashi IWAMA Masahiro TODA
出版者
The Japan Neurosurgical Society
雑誌
NMC Case Report Journal (ISSN:21884226)
巻号頁・発行日
vol.10, pp.185-189, 2023-12-31 (Released:2023-06-26)
参考文献数
27

The occipital transtentorial approach (OTA), which is often applied for superior cerebellar lesions, has an inevitable risk of homonymous hemianopsia due to the retraction of the occipital lobe. The endoscopic approach provides increased visibility of the surgical field due to the wide-angled panoramic view and is minimally invasive in approaching deep brain lesions compared to the conventional microscopic approach. However, little is known regarding endoscopic OTA for the removal of cerebellar lesions. We experienced a case of a hemangioblastoma in the paramedian superior surface of the cerebellum that was successfully treated with endoscopic OTA combined with gravity retraction while avoiding postoperative visual dysfunction.A 48-year-old woman was diagnosed with a hemangioblastoma in the superior surface of the cerebellum. She underwent tumor removal with endoscopic OTA combined with gravity retraction of the occipital lobe instead of using brain retractors. The narrower space was sufficient for surgical manipulation with a panoramic view obtained by endoscopy. The simultaneous observation of the lesion with both an endoscope and a microscope revealed the superiority of infratentorial visualization with an endoscope. Gross total removal was achieved with no postoperative complications, including visual dysfunction.Endoscopic OTA may reduce the risk of postoperative visual dysfunction because of its minimally invasive nature, which is enhanced when combined with gravity retraction. Additionally, the panoramic view of the endoscope allows favorable visualization of an infratentorial lesion, which is otherwise hidden partly by the tentorium. The use of endoscopy is compatible with OTA, and endoscopic OTA could be an option for superior cerebellar lesions for avoiding visual dysfunction.
著者
Kazunori Miwa Yan Guo Masayuki Hata Norio Yamamoto Tyuji Hoshino
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.5, pp.360-367, 2023-05-01 (Released:2023-05-01)
参考文献数
39
被引用文献数
4

Computational screening is one of the fundamental techniques in drug discovery. Each compound in a chemical database is bound to the target protein in virtual, and candidate compounds are selected from the binding scores. In this work, we carried out combinational computation of docking simulation to generate binding poses and molecular mechanics calculation to estimate binding scores. The coronavirus infectious disease has spread worldwide, and effective chemotherapy is strongly required. The viral 3-chymotrypsin-like (3CL) protease is a good target of low molecular-weight inhibitors. Hence, computational screening was performed to search for inhibitory compounds acting on the 3CL protease. As a preliminary assessment of the performance of this approach, we used 51 compounds for which inhibitory activity had already been confirmed. Docking simulations and molecular mechanics calculations were performed to evaluate binding scores. The preliminary evaluation suggested that our approach successfully selected the inhibitory compounds identified by the experiments. The same approach was applied to 8820 compounds in a database consisting of approved and investigational chemicals. Hence, docking simulations, molecular mechanics calculations, and re-evaluation of binding scores including solvation effects were performed, and the top 200 poses were selected as candidates for experimental assays. Consequently, 25 compounds were chosen for in vitro measurement of the enzymatic inhibitory activity. From the enzymatic assay, 5 compounds were identified to have inhibitory activities against the 3CL protease. The present work demonstrated the feasibility of a combination of docking simulation and molecular mechanics calculation for practical use in computational virtual screening.
著者
Motohiro INOUE Miwa NAKAJIMA Megumi ITOI
出版者
The Japanese Society of Balneology, Climatology and Physical Medicine
雑誌
日本温泉気候物理医学会雑誌 (ISSN:00290343)
巻号頁・発行日
vol.78, no.3, pp.187-194, 2015-05-13 (Released:2015-05-26)
参考文献数
14
被引用文献数
2

Background: The relaxing phenomenon induced by acupuncture on hypertonic muscle has not clearly been demonstrated. We studied whether acupuncture stimulation on the hypertonic muscle model induce relaxation. Methods: A rat model of hypertonia was created by inducing tetanic contraction in the triceps surae muscles of 21 Wistar rats (male, 12 weeks) with four electrical stimulations (80 Hz, 5 mA, 5 min.), with a 2 min. interval between each stimulation. The rats were randomly divided into two test groups: 1. Untreated group (N = 12), 2. Group treated with acupuncture stimulation of the triceps surae muscle (N = 9). Rats in the untreated group received no therapeutic treatment after the model was created. Acupuncture was performed within 5 min. after the model was created. Evaluations were taken before and 5 min., 1, 2 and 3 days after tetanic contraction was induced. The rats were anaesthetized and a tension sensor for measuring static and dynamic muscle tension was used to determine triceps surae muscle stretching tension during passive dorsal flexion of the foot (30°, 40°, 50°).Results: In both groups, at each of the angles of passive dorsal flexion, there was a significant increase in stretching tension 5 min. after inducing tetanic contraction compared to before induction, and statistics showed recovery to pre-induced tetanic contraction values after 1 day and thereafter. Compared to the untreated group, however, values 5 min. after induced tetanic contraction tended to be lower in the group treated with acupuncture stimulation.Conclusions: Compared to the untreated group, stretching tension values 5 min. after inducing tetanic contraction tended to be lower in the acupuncture group. This could be due to acupuncture stimulation causing changes in blood flow in the lower leg, including muscle tissue, resulting in reuptake of calcium by the sarcoplasmic reticulum, and/or the influence acupuncture on reducing lower leg edema. Acupuncture stimulation could also have an action on the γ fibers and Ib fibers associated with continuous muscle tonus and muscle relaxation.
著者
Yoshiro MIWA
出版者
Graduate School of Economics, The University of Tokyo
雑誌
経済学論集 (ISSN:00229768)
巻号頁・発行日
vol.79, no.3, pp.33-77, 2013-10-01 (Released:2022-03-25)
参考文献数
31

For more than half a century, inventory investment has attracted wide attention as a major cause of shortterm macroeconomic fluctuations, and the mechanisms involved have been the focus of many major studies. Yet microeconomists and business people familiar with corporate behavior have frequently expressed misgivings about the enterprise.Using Japanese quarterly GDP inventory investment statistics both by commodity and by category, 1994~2010, I investigate the nature of quarterly inventory statistics and the inventory investment behavior, and draw two conclusions. First, statisticians estimate the quarterly statistics under severe time constraints, and their resulting figures incorporate seasonal variations which dominate the quarterly fluctuations. This fluctuation mostly disappears in annual data. Secondly, when I examine the inventory variation after the Lehman Shock in the autumn of 2008, I find neither a notable increase in inventory stock nor a long-run stock adjustment process. Given the size of this unforeseen exogenous shock, most observers expected a large inventory stock accumulation to follow. That the accumulation did not follow suggests that the focus on inventory variation may be misplaced.For inventory investment data estimation, Japan is an ideal OECD country, with generous statistics availability. The conclusions of this research, drawn from the quarterly GDP inventory statistics, will stimulate the interest both in the study of inventory data in other countries focusing on its estimation process and source statistics, and in the great variety of inventory investment. At the same time, the conclusions pose a grave implication not only for re-evaluation of the literature in inventory investment variations but also for other research topics in macroeconomics like monetary transmission mechanisms including “financial accelerator” theory.
著者
Yuta Nakamura Ichiro Horie Kengo Kanetaka Susumu Eguchi Seiko Nakamichi Ryoko Hongo Miwa Takashima Atsushi Kawakami Norio Abiru
出版者
The Japan Endocrine Society
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
pp.EJ22-0224, (Released:2022-07-26)

The postoperative increase in glucagon-like peptide-1 (GLP-1) is the main factor to improve glucose metabolism following sleeve gastrectomy (SG) in obese patients with type 2 diabetes. We investigated whether the β-cell responsiveness to an injection of exogenous GLP-1 in the preoperative period could determine the postoperative glucose tolerance in 18 patients underwent SG. In the preoperative period, a regular oral glucose tolerance test (OGTT) and an exenatide-challenge during OGTT (Ex-OGTT) were performed to evaluate the β-cell function and its responsiveness to GLP-1. The postoperative glucose tolerance was evaluated by another regular OGTT performed at 3 months after SG. The significant decrease in glucose levels with enhanced secretions of insulin and GLP-1 was observed in OGTT at 3 months after SG. The area under the curve of glucose from 0 to 120 minutes (AUC glucose0–120 min) and the insulinogenic index (I.I.) in OGTT at 3 months post-SG were significantly improved compared to those in preoperative period, but comparable with those in Ex-OGTT. AUC glucose0–120 min and I.I. in OGTT at 3 months post-SG were significantly correlated with not only those in Ex-OGTT, but also those in the preoperative regular OGTT. Conversely, the correlations calculated by the Spearman’s ρ were stronger in the latter than the former. This exenatide-challenge protocol might be useful to estimate glucose tolerance and insulin secretion after SG, however, it may be insufficient to improve predictability of a patient who is likely to achieve a significant benefit on glucose metabolism from receiving SG.
著者
Chinami Matsumoto Hitomi Sekine Miwa Nahata Sachiko Mogami Katsuya Ohbuchi Naoki Fujitsuka Hiroshi Takeda
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
pp.b22-00171, (Released:2022-04-08)
参考文献数
68
被引用文献数
7

Muscle atrophy is commonly observed during cisplatin chemotherapy, leading to a reduced quality of life in cancer patients. Reduced skeletal muscle mass caused by cisplatin treatment results from the activation of ubiquitin ligases–Atrogin-1 and MuRF1, but the precise mechanisms are poorly understood. In this study, we investigated the possible involvement of mitochondrial dysfunction, including reactive oxygen species (ROS) generation and ATP production, in cisplatin-induced muscle atrophy. Skeletal C2C12 myotubes were treated with cisplatin, and gene and protein expression were evaluated. Mitochondrial mass, membrane potential, and ROS levels were measured using fluorescent dyes. Mitochondrial respiratory function, ATP production rates, and glycolytic capacity were also analyzed using an extracellular flux analyzer. Metabolomic analyses were performed using gas chromatography-tandem mass spectrometry. Cisplatin treatment reduced myosin heavy chain expression by activating the ubiquitin-proteasome system. Increased ROS production was observed after cisplatin treatment, followed by significant changes in apoptosis-related gene expression and decrease in mitochondrial mass, membrane potential, respiration, and ATP production. Glycolytic capacity and TCA cycle metabolite levels were reduced with cisplatin treatment. Mitochondria-targeted antioxidant mitoquinone mesylate prevented up-regulation of Atrogin-1 gene expression and restored myosin heavy chain levels, accompanied by a decrease in ROS generation, but not mitochondrial ATP production. We concluded that cisplatin-induced myotube atrophy was associated with mitochondrial dysfunction. Reducing ROS generation, rather than promoting ATP production, could be a useful therapeutic strategy for preventing cisplatin-induced muscle atrophy.
著者
Ryosuke Murai Yuichi Kawase Tomohiko Taniguchi Takeshi Morimoto Kazushige Kadota Masanobu Ohya Takenobu Shimada Takeshi Maruo Yasushi Fuku Tatsuhiko Komiya Kenji Ando Michiya Hanyu Norio Kanamori Takeshi Aoyama Koichiro Murata Tomoya Onodera Fumio Yamazaki Takeshi Kitai Yutaka Furukawa Tadaaki Koyama Makoto Miyake Chisato Izumi Yoshihisa Nakagawa Kazuo Yamanaka Hirokazu Mitsuoka Manabu Shirotani Masashi Kato Shinji Miki Hiroyuki Nakajima Yutaka Hirano Shunichi Miyazaki Toshihiko Saga Sachiko Sugioka Shintaro Matsuda Mitsuo Matsuda Tatsuya Ogawa Kazuya Nagao Tsukasa Inada Shogo Nakayama Hiroshi Mabuchi Yasuyo Takeuchi Hiroki Sakamoto Genichi Sakaguchi Keiichiro Yamane Hiroshi Eizawa Mamoru Toyofuku Takashi Tamura Atsushi Iwakura Mitsuru Ishii Masaharu Akao Kotaro Shiraga Eri Minamino-Muta Takao Kato Moriaki Inoko Koji Ueyama Tomoyuki Ikeda Yoshihiro Himura Akihiro Komasa Katsuhisa Ishii Kozo Hotta Yukihito Sato Keiichi Fujiwara Yoshihiro Kato Ichiro Kouchi Yasutaka Inuzuka Shigeru Ikeguchi Senri Miwa Chiyo Maeda Eiji Shinoda Junichiro Nishizawa Toshikazu Jinnai Nobuya Higashitani Mitsuru Kitano Yuko Morikami Shouji Kitaguchi Kenji Minatoya Takeshi Kimura on behalf of the CURRENT AS Registry Investigators
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.86, no.3, pp.427-437, 2022-02-25 (Released:2022-02-25)
参考文献数
26
被引用文献数
3

Background:The clinical significance of concomitant mitral regurgitation (MR) has not been well addressed in patients with severe aortic stenosis (AS).Methods and Results:We analyzed 3,815 patients from a retrospective multicenter registry of severe AS in Japan (CURRENT AS registry). We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategy (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death or heart failure hospitalization. At baseline, moderate/severe MR was present in 227/1,197 (19%) patients with initial AVR strategy and in 536/2,618 (20%) patients with a conservative strategy. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR, regardless of the initial treatment strategy (25.2% vs. 14.4%, P<0.001 in the initial AVR strategy, and 63.3% vs. 40.7%, P<0.001 in the conservative strategy). After adjusting confounders, moderate/severe MR was not independently associated with higher risk for the primary outcome measure in the initial AVR strategy (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.67–1.83, P=0.69), and in the conservative strategy (HR 1.13, 95% CI 0.93–1.37, P=0.22).Conclusions:Concomitant moderate/severe MR was not independently associated with higher risk for the primary outcome measure regardless of the initial treatment strategy.