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Naoyuki Akashi,1 Tomio Umemoto,1 Hodaka Yamada,2 Takayuki Fujiwara,3 Kei Yamamoto,1 Yousuke Taniguchi,1 Kenichi Sakakura,1 Hiroshi Wada,1 Shin-ichi Momomura,1 Hideo Fujita1 1Division of Cardiovascular Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan; 2Division of Endocrinology and Metabolism, Jichi Medical University Saitama Medical Center, Saitama, Japan; 3Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo, JapanCorrespondence: Tomio Umemoto, Division of Cardiovascular Medicine, Jichi Medical University Saitama Medical Center, 1-847 Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan, Tel +81-48-647-2111, Fax +81-48-648-5188, Email to-ume@omiya.jichi.ac.jpPurpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endothelial progenitor cells (EPCs) in peripheral blood circulation. However, the underlying mechanisms and effects on vascular endothelial function remain unclear. We evaluated whether the DPP-4 inhibitor teneligliptin increases circulating EPCs by inhibiting stromal-derived factor-1α (SDF-1α) and improves flow-mediated vascular dilatation (FMD) in type 2 diabetes mellitus patients with acute coronary syndrome (ACS) or its risk factors.Patients and Methods: This single-center, open-label, prospective, randomized controlled trial evaluated 17 patients (hemoglobin A1c ≤ 7.5% and peak creatinine phosphokinase < 2000 IU/mL) with ACS or a history of ACS or multiple cardiovascular risk factors. Metabolic variables of glucose and lipids, circulating EPCs, plasma DPP-4 activity, and SDF-1α levels, and FMD were evaluated at baseline and 28 ± 4 weeks after enrollment. Patients were randomly assigned to either the teneligliptin (n = 8) or control (n = 9) groups.Results: The DPP-4 activity (∆− 509.5 ± 105.7 vs ∆32.8 ± 53.4 μU/mL) and SDF-1α levels (∆− 695.6 ± 443.2 vs ∆11.1 ± 193.7 pg/mL) were significantly decreased after 28 weeks in the teneligliptin group than those in the control group. The number of EPCs showed an increasing trend in the teneligliptin treated group; albeit this did not reach statistical significance. Glucose and lipid levels were not significantly different between the groups before and after 28 weeks. However, FMD was significantly improved in the teneligliptin group when compared to the control group (∆3.8% ± 2.1% vs ∆− 0.3% ± 2.9%, P=0.006).Conclusion: Teneligliptin improved FMD through a mechanism other than increasing the number of circulating EPCs.Keywords: endothelial progenitor cell, teneligliptin, DPP-4 inhibitor, flow-mediated dilation, type 2 diabetes mellitus

Yoshiki Asai,1 Shunji Tsutsui,1 Noriko Yoshimura,2 Hiroshi Hashizume,1 Toshiko Iidaka,2 Chiaki Horii,2 Hiroshi Kawaguchi,3 Kozo Nakamura,4 Sakae Tanaka,5 Munehito Yoshida,1 Hiroshi Yamada1 1Department of Orthopedic Surgery, Wakayama Medical University, Wakayama, Japan; 2Department of Preventive Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; 3Department of Orthopedic Surgery, Tokyo Neurological Center, Tokyo, Japan; 4Department of Orthopedic Surgery, Towa Hospital, Tokyo, Japan; 5Department of Orthopedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, JapanCorrespondence: Shunji TsutsuiDepartment of Orthopedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, JapanTel +81-73-441-0645Fax +81-73-448-3008Email stsutsui1116@gmail.comPurpose: The demand for surgical correction in elderly patients with adult spinal deformity (ASD) has recently increased with the growth of the aging population. Age-related changes in spinopelvic sagittal alignment have been recently reported; thus, sagittal realignment should consider age-related changes. This study aimed to investigate the relationship between age-specific sagittal spinopelvic radiographic parameters and low back pain (LBP) to support the establishment of age-specific realignment targets for patients with ASD.Materials and Methods: A population-based cohort consisting of 1461 subjects (466 men and 995 women) was used. The participants were divided into five groups based on their age: (1) younger than 50 years, (2) 50– 59 years, (3) 60– 69 years, (4) 70– 79 years, and (5) 80 years and older. Standing lateral whole-spine radiographs were assessed to measure lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), and sagittal vertical axis (SVA). In addition, all participants were asked if they had LBP or not, using the following question: “Have you experienced LBP on most days during the past month and/or now?”.Results: The crucial parameter associated with LBP was the mismatch between PI and LL (PI-LL). The mean values of all the radiographic parameters increased with age. PI-LL and PT reached 11.5° and 25.6°, respectively, for women without LBP in the super-aged group (age > 80 years), which did not lie in the range of optimal values reported in the previous literature.Conclusion: A new optimal age-related target may be needed for the management of patients with ASD.Keywords: adult spinal deformity, spinopelvic sagittal alignment, low back pain, population-based cohort

Wakaho Hayashi,1,2 Hirohisa Suzuki,3 Nobuyuki Saga,1,2 Gosuke Arai,1,2 Reiko Igarashi,1,2 Takahiro Tokumasu,3 Haruhisa Ota,1,2 Hiroki Yamada,1,2 Osamu Takashio,1,2 Akira Iwanami1,2 1Department of Psychiatry, Showa University School of Medicine, Setagaya-ku, Tokyo 157-8577, Japan; 2Department of Psychiatry, Showa University Karasuyama Hospital, Setagaya-ku, Tokyo 157-8577, Japan; 3Department of Psychiatry, Showa University Northern Yokohama Hospital, Yokohama-shi, Kanagawa 224-8503, JapanCorrespondence: Wakaho HayashiDepartment of Psychiatry, Showa University Karasuyama Hospital, 6-11-11 Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, JapanTel +81-3-3300-5231Fax +81-3-3308-9710Email wakaho15@gmail.comPurpose: Although gender differences have been reported in various aspects of adult attention-deficit hyperactivity disorder (ADHD), such as prevalence, comorbidities, and social functioning, there have been few such studies conducted in Japan. Our research investigated gender differences in sociodemographic and clinical characteristics of adults with ADHD in a Japanese clinical sample. Due to unique Japanese cultural ideals and expectations of women’s behavior that are in opposition to ADHD symptoms, we hypothesized that women with ADHD experience more difficulties and present more dysfunctions than men. We tested the following hypotheses: first, women with ADHD have more comorbidities than men with ADHD; second, women with ADHD experience more social hardships than men, such as having less full-time employment and being more likely to be divorced.Patients and methods: The subjects were 335 outpatients with a DSM-5 ADHD diagnosis, who visited our ADHD specialty clinic at Showa University Karasuyama Hospital in central Tokyo between April 2015 and March 2016. Sociodemographic and clinical characteristics were collected, and gender differences were compared.Results: Results fully supported our hypotheses: women had a significantly higher psychiatric comorbidity rate, were significantly less likely to be a full-time employee, and were significantly more likely to be divorced than men with ADHD.Conclusion: Consistent with research in other countries, women with ADHD have greater impairments than men with ADHD in Japan. The importance of understanding gender differences of ADHD-diagnosed adults within a sociocultural context is highlighted.Keywords: ADHD, adults, gender difference, Japan

Kazunori Shinto,1 Akihito Minamide,1 Hiroshi Hashizume,1 Hiroyuki Oka,2 Ko Matsudaira,2 Hiroki Iwahashi,1 Yuyu Ishimoto,1 Masatoshi Teraguchi,1 Ryohei Kagotani,1 Yoshiki Asai,1 Shigeyuki Muraki,3 Toru Akune,4 Sakae Tanaka,5 Hiroshi Kawaguchi,6 Kozo Nakamura,7 Munehito Yoshida,1,8 Noriko Yoshimura,3,* Hiroshi Yamada1,* 1Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama City, Wakayama, Japan; 2Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; 3Department of Preventive Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; 4National Rehabilitation Center for Persons with Disabilities, Tokorozawa City, Saitama, Japan; 5Department of Orthopaedic Surgery, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; 6Tokyo Neurological Center, Minato-ku, Tokyo, Japan; 7Towa Hospital, Adachi-ku, Tokyo, Japan; 8Department of Orthopaedic Surgery, Sumiya Orthopaedic Hospital, Wakayama City, Wakayama, Japan*These authors contributed equally to this workCorrespondence: Hiroshi HashizumeDepartment of Orthopaedic Surgery, Wakayama Medical University, Wakayama City, 811-1 Kimiidera, Wakayama City, Wakayama 641-8510, JapanTel +81-73-441-0645Fax +81-73-448-3008Email hashizum@wakayama-med.ac.jpIntroduction: Facet effusion represents a magnetic resonance imaging finding suggesting accumulation of fluid in the facet joint, potentially predictive of lumbar spondylolisthesis and low back pain. However, its prevalence and epidemiological characteristics in the general population remain unclear, because previous studies only included patients or volunteers. The aim of the present study was to investigate the prevalence of facet effusion in the general population and to describe its potential relationship with spondylolisthesis and low back pain.Material and methods: Our study enrolled 808 participants from the Wakayama Spine Study who underwent magnetic resonance imaging investigations in supine position. Facet effusion was defined as a measurable, curvilinear, high-intensity signal within the facet joint, closely matching that of cerebrospinal fluid on the axial T2 images. We used standing lateral radiographs to diagnose L4 spondylolisthesis.Results: We found that the prevalence of facet effusion in the lumbar spine was 34.3%, which did not differ significantly between men and women (p=0.13) and did not tend to increase with age, either in men (p=0.81) or in women (p=0.65). Additionally, we found no significant association between facet effusion and low back pain (odds ratio, 1.04–1.49; 95% confidence interval, 0.57–2.64; p=0.17–0.85), or between facet effusion and L4 spondylolisthesis (odds ratio, 1.55; 95% confidence interval, 0.80–2.86; p=0.17). In a subset of participants with L4 spondylolisthesis, we also noted that facet effusion was not significantly associated with low back pain (odds ratio, 1.26; 95% confidence interval, 0.37–4.27; p=0.70).Discussion: This is the first study of facet effusion employing a population-based cohort, and the findings are thus expected to accurately describe the relationship between facet effusion and low back pain in the general population. We are planning a follow-up survey of the Wakayama Spine Study cohort to clarify the natural history of facet effusion and its relationship with clinical symptoms.Keywords: lumbar spine, facet effusion, low back pain, spondylolisthesis, epidemiology

Mihori Kita, Mami Kusaka, Hiroshi Yamada, Sachiyo Hama Department of Ophthalmology, National Organization Kyoto Medical Center, Kyoto, JapanCorrespondence: Mihori KitaDepartment of Ophthalmology, National Organization Kyoto Medical Center, 1-1 Mukouhata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555, JapanTel +81 75 641 9161Fax +81 75 643 4325Email mihorik@kuhp.kyoto-u.ac.jpPurpose: To assess the updated chandelier illumination-assisted scleral buckle procedures using a 3D visualization system.Subjects and methods: We report a single-center, retrospective, consecutive surgical case series of 18 eyes of 16 patients that underwent scleral buckle procedures combining the use of chandelier endoillumination, a noncontact wide-angle viewing system, an anti-drying contact lens, and a recently developed 3D visualization system. The mean age of the patients was 30.2 years, and the mean follow-up time was 11.3 months.Results: Retinal reattachment was achieved after the first surgery in all cases. There were no cases that required conversion of the 3D visualization to a conventional microscopic view. This updated chandelier-assisted scleral buckle procedure was successfully performed without any intraoperative or postoperative complications, except for the occurrence of postoperative diplopia in one case in which a supplementary radial buckle was used for a deep tear.Conclusion: The updated chandelier illumination-assisted scleral buckling surgery using a 3D visualization system appears to be a valuable and promising method for managing rhegmatogenous retinal detachment due to atrophic holes in lattice degeneration or ciliary tears in younger cases.Keywords: scleral buckling, chandelier illumination, wide-angle viewing system, 3D visualization system, retinal detachment, contact lens

Ayako Kato,1 Yuanying Li,1 Atsuhiko Ota,1 Hisao Naito,1 Hiroya Yamada,2 Takashi Nihashi,3 Yo Hotta,4 Chifa Chiang,5 Yoshihisa Hirakawa,5 Atsuko Aoyama,5,6 Koji Tamakoshi,7 Hiroshi Yatsuya1,51Department of Public Health, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 2Department of Hygiene, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 3Department of Radiology, Komaki City Hospital, Komaki, Aichi, Japan; 4Toyoda Gosei Co., Ltd, Medical and Hygiene Designing Department, Inazawa, Aichi, Japan; 5Department of Public Health and Health Systems, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; 6Nagoya University of Arts and Sciences, Nissin, Aichi, Japan; 7Department of Nursing, Nagoya University School of Health Sciences, Nagoya, Aichi, JapanObjective: An association between smoking and nonalcoholic fatty liver disease has been reported. However, objective quantification of intrahepatic fat via magnetic resonance spectroscopy (MRS) in relation to smoking has rarely been performed in previous studies. Moreover, the possible pathways via which smoking could induce ectopic fat accumulation have not yet been addressed. The current study aimed to examine the association between smoking status and intrahepatic fat quantity and explore the possible mediating effects of triglycerides (TG) and adiponectin.Subjects and methods: Magnetic resonance imager (MRI) spectra were analyzed to quantify intrahepatic fat in 45 men who were on average 62.3 years of age. Smoking status and alcohol intake were self-reported. Accelerometers were used to record daily total physical activity. Fasting blood TG and adiponectin levels were measured enzymatically. Differences in mean intrahepatic fat values according to smoking status were assessed using analysis of covariance.Results: A stepwise increase in mean intrahepatic fat was observed between never, former, and current smokers, respectively, independent of age, physical activity, alcohol intake, and body mass index (BMI) (P=0.005). Adjustment for TG and adiponectin significantly attenuated this association (P=0.074).Conclusion: Current smoking was significantly associated with increased intrahepatic fat, which may be a result of adipocyte dysfunction, manifested as high circulating TG concentrations and low adiponectin levels.Keywords: intrahepatic fat, cigarette smoking, adiponectin, triglycerides, cross-sectional study

Hideyasu Yamada,1,2 Norihito Hida,2 Nobuyuki Hizawa1 1Department of Pulmonology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; 2Department of Respiratory Medicine, Hitachinaka General Hospital, Hitachi Ltd, Hitachinaka, Ibaraki, Japan Background: A large body of evidence suggests that long-acting β2-adrenoceptor agonist (LABA)/long-acting muscarinic antagonist (LAMA) combinations induce a strong synergistic bronchodilatory effect in human isolated airways. Moreover, a recent post hoc analysis demonstrated clinical synergism between LABAs and LAMAs, which induces a synergistic improvement not only in lung function but also in dyspnea in COPD patients. Aim: The aim of this study is to examine the baseline factors related to improvement in lung function or clinical symptoms that results from the administration of LAMA or LAMA/LABA and to compare the differences in improvement in lung function or clinical symptoms between LAMA and LAMA/LABA. Methods: Among 829 patients with COPD who were treated with LAMA or LAMA/LABA in our hospital, 112 patients (aged 40–89 years) matched the criteria. Of these 112 patients, 71 received LAMA (LAMA group) and 41 received LAMA/LABA (LAMA/LABA group) as the initial treatment. Various examination results such as lung function test values, symptom change, and frequency of exacerbations were compared between the two groups. Results: Compared with the monotherapy, the combination therapy significantly improved the FEV1, inspiratory capacity (IC), and total COPD assessment test (CAT) scores. Comparing the improvement in each domain of the CAT produced by the combination therapy with that of the monotherapy, larger improvements were found for the domains of going out and sleeping. The frequency of exacerbations during the 24 weeks was significantly lower in the combination therapy group than in the LAMA monotherapy group (P=0.034). Although no relationship was found between improvement in FEV1 and any pretreatment factors in the LAMA/LABA group, the improvement in the CAT score was strongly related to the baseline CAT score, smoking index, and air trapping index (P-value

Shusuke Hiragi,1,2 Hiroyuki Yamada,1 Tatsuo Tsukamoto,1,3 Kazuki Yoshida,4,5 Naoya Kondo,1 Takeshi Matsubara,1 Motoko Yanagita,1 Hiroshi Tamura,2 Tomohiro Kuroda2 1Department of Nephrology, Graduate School of Medicine, Kyoto University, 2Division of Medical Informatics and Administration Planning, Kyoto University Hospital, Kyoto, 3Department of Nephrology and Dialysis, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan; 4Department of Epidemiology, 5Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA Background: Acetaminophen (APAP) is frequently used for analgesia and is considered safer than nonsteroidal anti-inflammatory drugs (NSAIDs) for the kidneys. However, there is little epidemiological evidence of the association between APAP and acute kidney injury (AKI).Objectives: To examine the association between APAP and AKI using the self-controlled case series (SCCS) method, which is a novel strategy to control between-person confounders by comparing the risk and reference periods in each patient.Methods: We performed SCCS in 1,871 patients (39.9% female) who were administered APAP and subsequently developed AKI, by reviewing electronically stored hospital information system data from May 2011 to July 2016. We used conditional Poisson regression to compare each patient’s risk and reference period. As a time-varying confounder, we adjusted the status of liver and kidney functions, systemic inflammation, and exposure to NSAIDs.Results: We identified 5,650 AKI events during the 260,549 person-day observation period. The unadjusted incidences during the reference and exposure periods were 2.01/100 and 3.12/100 person-days, respectively. The incidence rate ratio adjusted with SCCS was 1.03 (95% confidence interval [CI]: 0.95–1.12). When we restricted endpoints as stage 2 AKI- and stage 3 AKI-level creatinine elevations, the incidence rate ratios were 1.20 (95% CI 0.91–1.58) and 1.20 (95% CI 0.62–2.31), respectively, neither of which was statistically significant.Conclusion: Our findings added epidemiological information for the relationship between APAP administration and AKI development. The results indicated scarce association between APAP and AKI, presumably supporting the general physicians’ impression that APAP is safer for kidney. Keywords: acetaminophen, acute kidney injury, adverse drug event, self-controlled case series, hospital information system

Mihori Kita, Mami Kusaka, Hiroshi Yamada, Sachiyo HamaDepartment of Ophthalmology, National Organization Kyoto Medical Center, Kyoto, JapanCorrespondence: Mihori KitaDepartment of Ophthalmology, National Organization Kyoto Medical Center, 1-1 Mukouhata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555, JapanTel +81 75 641 9161Fax +81 75 643 4325Email mihorik@kuhp.kyoto-u.ac.jpPurpose: To introduce a new three-dimensional (3D) endoscope system for vitrectomy.Subjects and methods: We report a single-center, retrospective, consecutive surgical case series of 391 eyes that underwent 25G hybrid vitrectomy. To create 3D endoscopic images, a 3D converter HD-3D-A was connected to a monocular endoscopic system.Results: The 3D endoscope system was successfully used to perform hybrid vitrectomy. No intra- or postoperative complications related to this system were encountered in any of the cases.Conclusion: This 3D endoscope system appears to be a valuable and promising tool for use in vitrectomy.Keywords: endoscope, 3D, vitrectomy, hybrid, wide-angle view

Kazuki Ide,1 Hiroshi Yamada,1 Yohei Kawasaki,1 Marika Noguchi,1 Mamoru Kitagawa,1 Tsuyoshi Chiba,2 Yoshiyuki Kagawa,3 Keizo Umegaki2 1Department of Drug Evaluation & Informatics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 2Information Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, 3Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan Background: Dietary supplements are used by >50% of the adult population in Japan, and adverse events related to these products have been reported with their increased use. Thus, an efficient system to gather and report data on these adverse events is essential. To date, however, reporting has been limited. The aim of this study was to address this deficiency by exploring the routine reporting practices of the medical staff employed at clinics or pharmacies in Japan.Methods: We conducted a survey of the procedures used by the medical staff to report adverse events related to dietary supplement intake to public health centers in Japan. The survey was conducted in Japan between November 2015 and January 2016. Based on a sample size calculation, questionnaires were administered to 1,700 potential respondents (850 pharmacists and 850 physicians). The questionnaire inquired about the sociodemographic characteristics and dietary supplement-related adverse event-reporting practices.Results: The response rate was 34.7%, including 286 pharmacists and 304 physicians. Although >30% of the pharmacists and physicians had prior experience dealing with such adverse events,

Noriyuki Kanzaki,1 Yuta Otsuka,1 Takayuki Izumo,1 Hiroshi Shibata,1 Hideyuki Nagao,2 Keita Ogawara,3 Hiroshi Yamada,3 Seiji Miyazaki,3 Yutaka Nakamura3 1Institute for Health Care Science, Suntory Wellness Ltd, Seika-cho, Soraku-gun, Kyoto, Japan; 2Research Institute of Sports Medical Science, Tokai University, Hiratsuka, Kanagawa, Japan; 3School of Physical Education, Tokai University, Hiratsuka, Kanagawa, Japan Background: Previously, we demonstrated that glucosamine-containing supplementation was effective for improving locomotor functions, especially walking speed. However, the biomechanical mechanism of efficacy has not been elucidated. This study aimed to address this challenge in subjects with knee pain, using a motion capture system. Methods: An open label study was conducted in 30 Japanese subjects with knee pain. The subjects were administered a daily supplement containing 1,200 mg of glucosamine hydrochloride, 60 mg of chondroitin sulfate, 45 mg of type II collagen peptides, 90 mg of quercetin glycosides, 10 mg of imidazole peptides, 1 mg of proteoglycan, and 5 µg of vitamin D (GCQID). The intervention continued for 16 weeks. Efficacy for locomotor functions involving the knee joint was evaluated mainly using the Japanese Knee Osteoarthritis Measure (JKOM) and the 5-question Geriatric Locomotive Function Scale (GLFS-5). To examine the biomechanical mechanism of efficacy for locomotor functions, motions of subjects in a normal walking state were captured. Gait analysis was conducted and efficacy for gait parameters such as normal walking speed, stride length, cadence, and angle of soles was evaluated. Results: GCQID significantly improved total scores on the JKOM and GLFS-5. In gait analysis, normal walking speed, stride length, and angle of soles at the end of the stance phase were all significantly increased, but cadence did not change significantly during the intervention period. There were significant intercorrelations of changes in normal walking speed, stride length, and angle of soles at the end of the stance phase, and between changes in stride length and total JKOM score. Conclusion: A GCQID supplement may increase walking speed through increased stride length and angle of kicking from the ground during steps, which might be mainly associated with alleviated knee pain. Keywords: locomotive syndrome, GLFS-5, normal walking speed, stride length, toe angle

Kazuki Ide,1 Yohei Kawasaki,1 Hiroshi Yamada,1 Naohiko Masaki2 1Department of Drug Evaluation and Informatics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 2The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, JapanPurpose: The aims of this study were to investigate regional differences in hepatitis C virus (HCV) infection treatment with peginterferon and ribavirin in Japan and to develop and validate statistical models for analysis of regional differences, using generalized linear mixed models.Methods: Individuals with chronic HCV infection were identified from the Japanese Interferon Database (registered from December 2009 to April 2013). The total sustained virologic response rate and the rate in each prefecture were calculated. In the analysis using generalized linear mixed models, the following four models were constructed: 1) prefecture as a fixed effect, 2) prefecture and other confounding variables as fixed effects, 3) prefecture as a random effect, and 4) prefecture as a random effect and other confounding variables as fixed effects. The quality of the model fit was assessed using the Akaike information criterion and the Bayesian information criterion. All statistical analyses were performed using SAS Version 9.4 for Windows.Results: From 36 prefectures, 16,349 cases were recorded in the study period. Of these, 4,677 were excluded according to certain criteria. The total sustained virologic response rate was 59.9% (range, 43.9%–71.6%). The statistical model including prefecture as a random effect and other confounding variables as fixed effects showed the best fit based on the Akaike information criterion (13,830.92) and Bayesian information criterion (13,845.17).Conclusion: Regional differences may exist in HCV infection treatment in Japan. The model including prefecture as a random effect and other confounding variables as fixed effects was appropriate for analysis of such regional differences. Additional studies considering the medical situations of each patient would provide useful information that could contribute to improve and standardize HCV infection treatment. Keywords: hepatitis C virus, interferon, regional differences, nationwide database, generalized linear mixed model

Shusuke Yagi,1 Akira Takashima,1 Minoru Mitsugi,2 Toshihiro Wada,2 Junko Hotchi,1 Ken-ichi Aihara,3 Tomoya Hara,1 Masayoshi Ishida,1 Daiju Fukuda,4 Takayuki Ise,1 Koji Yamaguchi,1 Takeshi Tobiume,1 Takashi Iwase,1 Hirotsugu Yamada,1 Takeshi Soeki,1 Tetsuzo Wakatsuki,1 Michio Shimabukuro,4 Masashi Akaike,5 Masataka Sata11Department of Cardiovascular Medicine, Graduate School of Health Biosciences, University of Tokushima, Tokushima, 2Department of Internal Medicine, Shikoku Central Hospital, Shikokuchuo, 3Department of Medicine and Bioregulatory Sciences, 4Department of Cardio-Diabetes Medicine, 5Department of Medical Education, Graduate School of Health Biosciences, University of Tokushima, Tokushima, JapanBackground: Hypertension is one of the major risk factors for cardiovascular and cerebrovascular disease and mortality. Patients who receive insufficient doses of antihypertensive agents or who are poorly adherent to multidrug treatment regimens often fail to achieve adequate blood pressure (BP) control. The aim of this study was to determine the efficacy of an angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) combination tablet containing a regular dose of irbesartan (100 mg) and a high dose of amlodipine (10 mg) with regard to lowering BP and other risk factors for cardiovascular disease.Methods: We retrospectively evaluated data from 68 patients with essential hypertension whose treatment regimen was changed either from combination treatment with an independent ARB and a low-dose or regular-dose CCB or from a combination tablet of ARB and a low-dose or regular-dose CCB to a combination tablet containing amlodipine 10 mg and irbesartan 100 mg, because of incomplete BP control. Previous treatments did not include irbesartan as the ARB.Results: The combination tablet decreased systolic and diastolic BP. In addition, it significantly decreased serum uric acid, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol levels, independent of the BP-lowering effect. Treatment with the combination tablet did not affect serum triglycerides, plasma glucose, glycated hemoglobin, serum potassium or creatinine levels, or the urinary albumin excretion rate.Conclusion: The combination tablet containing amlodipine 10 mg and irbesartan 100 mg had a greater BP-lowering effect than an ARB and a low-dose or regular-dose CCB. In addition, the combination tablet had more favorable effects on serum uric acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels in patients with hypertension.Keywords: blood pressure, combination tablet, uric acid, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol

Hideyuki Shimizu,1 Minoru Takebayashi,2 Masayuki Tani,1 Hiroaki Tanaka,1 Bun Yamagata,1 Kenzo Kurosawa,1 Hiroki Yamada,1 Mitsugu Hachisu,3 Kazue Hisaoka-Nakashima,2 Mami Okada-Tsuchioka,2 Masaru Mimura,4 Akira Iwanami11Department of Neuropsychiatry, Showa University School of Medicine, Tokyo, Japan; 2Department of Psychiatry and Institute for Clinical Research, National Hospital Organization Kure Medical Center, Kure, Japan; 3Department of Clinical Psychopharmacy, Pharmacy School, Showa University, Tokyo, Japan; 4Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, JapanBackground: Recently, the sigma-1 receptor has been shown to play a significant role in the neural transmission of mood by regulating N-methyl-D-aspartate receptors. Additionally, the sigma-1 receptor has been reported to influence cognitive functions including learning and memory. In this study, we measured plasma sigma-1 receptor concentrations before and after antidepressant treatment in patients with late-life major depressive disorder (MDD) and explored whether changes in depressive status are related to sigma-1 receptor concentrations.Methods: The study participants were 12 subjects with late-life MDD diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. All of the participants were over 60 years old. Immediately prior to and 8 weeks after the start of treatment, sigma-1 receptor concentration and mental status, including depressive symptoms (Hamilton Depression Rating Scale; HAM-D), were measured. Treatment for depression was performed according to a developed algorithm based on the choice of treatments. We examined the association between changes in sigma-1 receptor concentration and HAM-D scores during antidepressant treatment. For the measurement of plasma sigma-1 receptor concentration, blood plasma samples were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Western blots were performed using a specific antibody that acts against the sigma-1 receptor, and the net densities of each band were quantified.Results: All participants showed improvement in depressive symptoms, which was indicated by a significant decrease in the HAM-D scores. The mean plasma sigma-1 receptor concentration also increased significantly following antidepressant treatment. However, no significant correlations were found between changes in plasma sigma-1 receptor concentration and changes in HAM-D scores.Conclusion: In this preliminary study, we demonstrated that the sigma-1 receptor concentration in plasma increases following antidepressant treatment in patients with late-life MDD. Further studies are warranted to confirm this finding with a larger number of patients.Keywords: sigma-1 receptor, late-life depression, depressive symptoms, antidepressant treatment

Yasuhiro Ohkuma,1 Takaaki Hayashi,1 Tsutomu Sakai,1 Akira Watanabe,1 Hisashi Yamada,2 Masakazu Akahori,3 Takeshi Itabashi,3 Takeshi Iwata,3 Toru Noda,4 Hiroshi Tsuneoka11Department of Ophthalmology, 2Department of Molecular Genetics, Institute of DNA Medicine, The Jikei University School of Medicine, 3Division of Molecular and Cellular Biology, National Institute of Sensory Organs, 4Division of Ophthalmology, National Hospital Organization Tokyo Medical Center, Tokyo, JapanBackground: The purpose of this study was to investigate the association between ARMS2/HTRA1, CFH, and C3 gene polymorphisms and retinal angiomatous proliferation (RAP), an infrequent and severe form of exudative age-related macular degeneration, which is characterized by intraretinal neovascularization.Methods: Diagnosis of RAP was based on fundus photographs, images of fluorescein and indocyanine green angiographies, and optical coherence tomography findings. Six single nucleotide polymorphisms (SNPs), A69S (rs10490924) in ARMS2, rs11200638 in HTRA1, I62V (rs800292) in CFH, Y402H (rs1061170) in CFH, R80G (rs2230199) in C3, and rs2241394 in C3, were genotyped in eight Japanese patients with RAP.Results: The two SNPs in the ARMS2/HTRA1 were in complete linkage disequilibrium. The frequency of the risk T allele in ARMS2 (the risk A allele in HTRA1) was 93.8% in the RAP patients. The frequency of homozygosity for the risk genotype TT of ARMS2 (the risk genotype AA of HTRA1) was 87.5%. The frequency of the non-risk allele (A) of I62V was 100%. The frequencies of risk alleles of Y402H, R80G, and rs2241394 were 12.5%, 0%, and 18.8%, respectively.Conclusion: Our results suggest that the risk alleles of the ARMS2/HTRA1 SNPs may be associated with development of RAP and play a major role in the pathogenesis of intraretinal angiogenesis.Keywords: age-related macular degeneration, retinal angiomatous proliferation, single nucleotide polymorphisms, ARMS2/HTRA1 genes, components of the complement system

Yoshiko Kaneko, Yohei Yatagai, Hideyasu Yamada, Hiroki Iijima, Hironori Masuko, Tohru Sakamoto, Nobuyuki HizawaDepartment of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanAbstract: Recently, several genes and genetic loci associated with both asthma and chronic obstructive pulmonary disease (COPD) have been described as common susceptibility factors for the two diseases. In complex diseases such as asthma and COPD, a large number of molecular and cellular components may interact through complex networks involving gene–gene and gene–environment interactions. We sought to understand the functional and regulatory pathways that play central roles in the pathobiology of asthma and COPD and to understand the overlap between these pathways. We searched the PubMed database up to September 2012 to identify genes found to be associated with asthma, COPD, tuberculosis, or essential hypertension in at least two independent reports of candidate-gene associations or in genome-wide studies. To learn how the identified genes interact with each other and other cellular proteins, we conducted pathway-based analysis using Ingenuity Pathway Analysis software. We identified 108 genes and 58 genes that were significantly associated with asthma and COPD in at least two independent studies, respectively. These susceptibility genes were grouped into networks based on functional annotation: 12 (for asthma) and eleven (for COPD) networks were identified. Analysis of the networks for overlap between the two diseases revealed that the networks form a single complex network with 229 overlapping molecules. These overlapping molecules are significantly involved in canonical pathways including the “aryl hydrocarbon receptor signaling,” “role of cytokines in mediating communication between immune cells,” “glucocorticoid receptor signaling,” and “IL-12 signaling and production in macrophages” pathways. The Jaccard similarity index for the comparison between asthma and COPD was 0.81 for the network-level comparison, and the odds ratio was 3.62 (P < 0.0001) for the asthma/COPD pair in comparison with the tuberculosis/ essential hypertension pair. In conclusion, although the identification of asthma and COPD networks is still far from complete, these networks may be used as frameworks for integrating other genome-scale information including expression profiling and phenotypic analysis. Network overlap between asthma and COPD may indicate significant overlap between the pathobiology of these two diseases, which are thought to be genetically related.Keywords: COPD, asthma, network, common pathways, aryl hydrocarbon receptor signaling

The antinucleon-nuclei annihilation cross sections at low energies were systematically measured at CERN in the 80’s and 90’s with the LEAR facility and later with the Antiproton Decelerator. Unfortunately only few data exist for very low energy antiprotons (p

The interaction of very low energy antiprotons (ps) and antineutrons (ns) with nuclei is interesting for its influence on both fundamental cosmology and nuclear physics. Measuring the annihilation cross section of antimatter on matter can help in solving the universe matter-antimatter puzzle and could give relevant hints in the definition of strong interaction model parameters as well. The ASACUSA collaboration recently measured the antiproton-carbon annihilation cross section at 5.3 MeV of kinetic energy of the incoming antiproton. The experimental apparatus consisted in a vacuum chamber containing thin foils (~0.7-1 μm) of carbon crossed by a bunched beam of antiprotons from the CERN Antiproton Decelerator (AD). The fraction of antiprotons annihilating on the target nucleons gives origin to charged pions which can be detected and counted by segmented scintillators placed outside the chamber. This work describes the experimental details of the apparatus and the technique to perform the cross section measurements.

The antinucleon-nuclei annihilation cross section at very low energy has been measured at the LEAR facility (CERN) during the 80’s and 90’s and recently at the Antiproton Decelerator. The results have raised some interesting questions that still need answers. The ASACUSA collaboration performed an experiment to measure the σann of 100 MeV/c antiprotons on carbon target and the preliminary results are presented here.

Until 2009, three high-power, over 1MW each, 77GHz gyrotrons have been installed and applied to the LHD experiment. In addition, a 154GHz gyrotron of 1MW was installed in 2012. The 77GHz gyrotrons suffer gradual increases of internal pressure during long-pulse operation delivering power to LHD. To mitigate the problem, quasi-steady operation by combination of on-off operations of the 77GHz gyrotrons was performed. Applying two 77GHz gyrotrons alternately with intervals of two minutes and an 84GHz gyrotron continuously, a 30 min. long-pulse discharge with the line average electron density ne_ave of 0.7×1019m−3 and the central electron temperature Te0 of 1.7keV was achieved by the time average injection power Pinj of 260kW in 2012, showing significant progress in sustained density from the former 65 min. discharge with ne_ave of 0.15×1019m−3 and Te0 of 1.7keV by Pinj of 110kW of 84GHz wave. In 2013, one of the 77GHz gyrotron was improved to furnish a sub-window to remove stray radiation inside the tube. And the new 154GHz gyrotron was applied to the long-pulse discharge experiment. Using three gyrotrons: 154, the improved and an existing 77GHz with Pinj of 340kW in total, higher temperature plasma having steep temperature gradient typical for internal transport barrier, with ne_ave of 1.1×1019m−3 and Te0 of 3.5keV was quite stably sustained for 325s.

The ASACUSA (Atomic Spectroscopy and Collisions Using Slow Antiprotons) collaboration is currently attempting to observe a laser-induced resonant transition of antiprotonic helium atoms at wavelength of 1154.9 nm. Motivations to observe this transition and a nanosecond near-infrared laser prepared for this work are presented.

The indentation properties of pure aluminum (99.9%, 3N aluminum) and high purity aluminum (99.999%, 5N aluminum) with respect to the strain rate dependence of strength are experimentally investigated in order to clarify the effect of strain rate on the micro-indentation test. A micro-indentation test using a Berkovich indenter was performed at loading rates of 0.7, 7, and 70 mN/s. In all of the specimens, the indenter was loaded to a maximum value of 1200 mN, and then was maintained for 30 s. In the 3N specimen, the dependence of the loading rate on the load was slight at loading rates of 0.7 and 7 mN/s, whereas the load at the loading rate of 70 mN/s was higher than the loads at loading rates of 0.7 and 7 mN/s. On the other hand, the load for the 5N specimen increased with the increasing loading rate. Thus, the effect of the loading rate on the load-displacement curve for the 3N and 5N specimens was similar to the strain rate dependence of strength for theses metals. In addition, the micro-indentation test was demonstrated to be strongly affected by high strain rate at a loading rate of 70 mN/s.

A case report published in the Scandinavian Journal of Rheumatology discusses the efficacy of plasma exchange in a 53-year-old female with anti-Ro52 and anti-MDA5 antibody-positive dermatomyositis and progressive interstitial lung disease. The patient presented with skin manifestations and ILD, leading to emergency admission. Treatment with triple therapy and plasma exchange resulted in remission, highlighting the potential benefits of this combination therapy in refractory cases. Further research is needed to validate these findings and explore the role of plasma exchange in similar cases. [Extracted from the article]