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Kuniaki Otsuka,1,2 Shougo Murakami,3 Kiyotaka Okajima,4 Koichi Shibata,1 Yutaka Kubo,5 Denis G Gubin,6– 8 Larry A Beaty,2 Germaine Cornelissen2 1Tokyo Women’s Medical University, Tokyo, Japan; 2Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN, USA; 3Department of Cardiovascular Medicine, Soseikai General Hospital, Kyoto, Japan; 4Cardiovascular Internal Medicine, Higashi Omiya General Hospital, Saitama, Japan; 5Department of Medicine, Machida Keisen Hospital, Tokyo, Japan; 6Laboratory for Chronobiology and Chronomedicine, Research Institute of Biomedicine and Biomedical Technologies, Medical University, Tyumen, 625023, Russia; 7Department of Biology, Medical University, Tyumen, 625023, Russia; 8Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Science, Tomsk, RussiaCorrespondence: Germaine Cornelissen, Halberg Chronobiology Center, University of Minnesota, MMC8609, 420 Delaware Street SE, Minneapolis, MN, 55455, USA, Email corne001@umn.edu.an Kuniaki Otsuka, Executive Medical Center, Totsuka Royal Clinic, Tokyo Women’s Medical University, Related Medical Facility, Sinjuku City, Tokyo, Japan, Email frtotk99@ba2.so-net.ne.jpBackground: Blood pressure (BP) variability is involved in the appraisal of threat and safety, and can serve as a potential marker of psychological resilience against stress. The relationship between biological rhythms of BP and resilience was cross-sectionally assessed by 7-day/24-hour chronobiologic screening in a rural Japanese community (Tosa), with focus on the 12-hour component and the “circadian-circasemidian coupling” of systolic (S) BP.Subjects and Methods: Tosa residents (N = 239, 147 women, 23– 74 years), free of anti-hypertensive medication, completed 7-day/24-hour ambulatory BP monitoring. The circadian-circasemidian coupling was determined individually by computing the difference between the circadian phase and the circasemidian morning-phase of SBP. Participants were classified into three groups: those with a short coupling interval of about 4.5 hours (Group A), those with an intermediate coupling interval of about 6.0 hours (Group B), and those with a long coupling interval of about 8.0 hours (Group C).Results: Residents of Group B who showed optimal circadian-circasemidian coordination had less pronounced morning and evening SBP surges, as compared to residents of Group A (10.82 vs 14.29 mmHg, P < 0.0001) and Group C (11.86 vs 15.21 mmHg, P < 0.0001), respectively. The incidence of morning or evening SBP surge was less in Group B than in Group A (P < 0.0001) or Group C (P < 0.0001). Group B residents showed highest measures of wellbeing and psychological resilience, assessed by good relation with friends (P < 0.05), life satisfaction (P < 0.05), and subjective happiness (P < 0.05). A disturbed circadian-circasemidian coupling was associated with elevated BP, dyslipidemia, arteriosclerosis and a depressive mood.Conclusion: The circadian-circasemidian coupling of SBP could serve as a new biomarker in clinical practice to guide precision medicine interventions aimed at achieving properly timed rhythms, and thereby resilience and wellbeing.Keywords: 7-day/24-hour chronobiologic screening, blood pressure, biological 12-hour rhythm, appropriate circadian-circasemidian coupling, circadian acrophase, 12-hour morning acrophase, morning blood pressure surge, evening blood pressure surge, human resilience, wellbeing

Purpose Antithrombotic therapy could trigger diffuse alveolar hemorrhage (DAH), and there are several case reports of DAH that occurred during antithrombotic therapy (DAH-AT). However, little is known about the clinical features and outcomes of DAH-AT. The purpose of this study was to clarify the features and mortality of DAH-AT. Methods 76 consecutive patients with DAH who were admitted to our hospital between January 2003 and April 2014 were retrospectively reviewed to identify the clinical features and outcomes of DAH-AT. The primary outcome was 90-day mortality. Results Of the 76 patients with DAH, 39 patients (51 %) had DAH-AT, and 37 patients (49 %) had DAH that occurred with no antithrombotic therapy (DAH-NAT). Of the patients with DAH-AT, 25 (64 %) were taking aspirin, 14 (36 %) were taking warfarin, 5 (13 %) were taking clopidogrel sulfate, and 4 (10 %) were taking cilostazol. Pre-existing cardiac disease was present in 23 (59 %) DAH-AT cases and 5 (14 %) DAH-NAT cases. Logistic regression analysis was used to assess the effect of antithrombotic therapy on the mortality of DAH patients, and no significant difference in survival was seen with antithrombotic therapy (OR 1.18, 95 % CI 0.38-3.78). Conclusions Antithrombotic therapies had no effect on the 90-day mortality of DAH patients., Author(s): T. Otoshi[sup.1] , Y. Kataoka[sup.2] , A. Nakagawa[sup.1] , K. Otsuka[sup.1] , K. Tomii[sup.1] Author Affiliations: (1) Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojimaminami-cho, [...]

Yasushi Kono,1 Shota Fukuda,1 Akihisa Hanatani,2 Koki Nakanishi,2 Kenichiro Otsuka,2 Haruyuki Taguchi,1 Kenei Shimada2 1Department of Medicine, Osaka Ekisaikai Hospital, Osaka, Japan; 2Department of Internal Medicine and Cardiology, Osaka City University School of Medicine, Osaka, Japan Background: Remote ischemic conditioning (RIC) is a treatment modality that suppresses inflammation and improves endothelial function, which are factors involved in the pathogenesis of heart failure (HF) with reduced left ventricular ejection fraction. Coronary flow reserve (CFR) is a physiological index of coronary microcirculation and is noninvasively measured by transthoracic Doppler echocardiography (TTDE). This study aimed to investigate the effects of RIC on CFR in healthy subjects and patients with HF, through the assessment by TTDE. Methods: Ten patients with HF with left ventricular ejection fraction of less than 40%, and ten healthy volunteers were enrolled in this study. RIC treatment was performed twice a day for 1 week. Our custom-made RIC device was programmed to automatically conduct 4 cycles of 5 minutes inflation and 5 minutes deflation of a blood pressure cuff to create intermittent arm ischemia. CFR measurements and laboratory tests were examined before, and after 1 week of RIC treatment. Results: One week of RIC treatment was well tolerated in both groups. RIC treatment increased CFR from 4.0±0.9 to 4.6±1.3 (mean ± standard deviation) in healthy subjects (P=0.02), and from 1.9±0.4 to 2.3±0.7 in patients with HF (P=0.03), respectively. Systolic blood pressure in healthy subjects, and heart rate in HF patients decreased after RIC treatment (both P

Yasushi Kono,1 Shota Fukuda,1 Kenei Shimada,2 Koki Nakanishi,2 Kenichiro Otsuka,2 Tomoichiro Kubo,1 Satoshi Jissho,1 Haruyuki Taguchi,1 Junichi Yoshikawa,3 Minoru Yoshiyama21Department of Medicine, Osaka Ekisaikai Hospital, Nishi-ku, Osaka, Japan; 2Department of Internal Medicine and Cardiology, Osaka City University School of Medicine, Abeno-ku, Osaka, Japan; 3Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, JapanBackground: It has been reported that pitavastatin improves endothelial function faster than other statins. Recently introduced reactive hyperemia peripheral arterial tonometry (RH-PAT) provides objective and quantitative assessment of peripheral microvascular function.Purpose: This study aimed to investigate whether peripheral microvascular function improved 2 hours after pitavastatin in subjects with coronary artery disease (CAD) using RH-PAT, and the results were compared with those of rosuvastatin.Methods: This study included 94 subjects with CAD, assigned to a group given 2 mg of pitavastatin (n = 36), a group given 2.5 mg of rosuvastatin (n = 38), and a control group (n = 20). RH-PAT examinations were performed before and 2 hours after statin administration.Results: The RH-PAT index increased 2 hours after pitavastatin administration from 1.82 ± 0.45 to 2.16 ± 0.62 (P = 0.02), whereas there were no differences in the RH-PAT index in the rosuvastatin group (1.79 ± 0.71 to 1.91 ± 0.53, P = 0.09) and the control group (1.68 ± 0.36 to 1.84 ± 0.58, P = 0.4). No significant changes were observed at 2 hours in serum cholesterol levels in each group.Conclusion: The present study demonstrated that peripheral microvascular function improved 2 hours after a single clinical dose of pitavastatin, but not after rosuvastatin.Keywords: coronary artery disease, statin, microvascular function

Hidekazu Furuya,1 Tsuyoshi Kasama,1 Takeo Isozaki,1,2 Masayu Umemura,1 Kumiko Otsuka,1 Sakiko Isojima,1 Hiroyuki Tsukamoto,1 TakehiroTokunaga,1 Ryo Yanai,1 Ryo Takahashi11Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan; 2Department of Rheumatology,University of Michigan Medical School, Ann Arbor, MI, USAAbstract: Rheumatoid arthritis (RA) is a significant cause of work disability and job loss. The resulting economic burden experienced by patients has received considerable research attention. This research assesses the effect of tumor necrosis factor (TNF) antagonists (infliximab, etanercept) on the ability of RA patients living in Japan to work and participate in society. A total of 42 patients with active RA were enrolled and given biological therapy for 12 months (mo). Of these patients, 14 were employed full-time, 6 were employed part-time, and 22 were not employed. Twenty-six patients were given infliximab, and sixteen were given etanercept. The amount of domestic labor performed before the biologics served as a baseline and was assigned a value of 0%. After treatment with biologics, the productivity was evaluated using the visual analog scale (VAS; −100 to +100 mm). The administration of TNF antagonists to RA patients who exhibited an insufficient response to medical treatment significantly improved the Disease Activity Score 28 (DAS 28) after both 6 mo and 12 mo (P < 0.0001). A significant correlation was found between the improvement in their DAS 28 and improvements in their work situation (Productivity VAS) (P < 0.05). Of particular interest is the significant correlation between the values of baseline mHAQ and the percent changes of Productivity VAS that was observed after 6 mo and 12 mo (P < 0.05). Our findings indicate that medical treatment of RA with TNF antagonists improves the patients' ability to perform their jobs and housekeeping. Because loss of productivity is an important contributor to the indirect costs of RA, our findings are relevant for the pharmacoeconomic assessment of treatments.Keywords: rheumatoid arthritis, infliximab, etanercept, productivity, DAS28, mHAQ

Atomically thin two-dimensional transition-metal dichalcogenide materials with van der Waals integration provide various interesting optoelectronic characteristics that can be used to realize highly efficient flexible solar cells and photosensors. We previously reported in-plane lateral one-dimensional Schottky junctions (SJs) on few-atom-layer 2H-phase semiconductor-molybdenum disulfide by forming a 1T′-metal phase using laser beam (LB) irradiation and clarified their unique optoelectronic properties. Although the LB-derived 1T′/2H phase SJs provided efficient photocurrent generation, they had a large number of defects owing to the excess heat accumulation caused by the LB. Here, we observe partial electric hysteresis properties in photogenerated currents (Iphoto) on the SJs under reverse bias voltage regions and reveal that they are very sensitive to the voltage sweep direction and its switching (holding) time. The properties persist under dark ambient conditions for a few minutes, even after photo-irradiation is complete. The temperature dependence reveals that a defect-derived deep carrier trap-center, which is unique to the present 1T′ phase, can be the cause of these phenomena. A larger Iphoto and an increase in photogeneration efficiency are obtained by eliminating this trap center through thermal annealing. In contrast, it is expected that these hysteresis properties lead to atomically thin photo-memristor devices for opto-neuromorphic systems. [ABSTRACT FROM AUTHOR]