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Samiratu Mahazu,1,2 Isaac Prah,1,3 Yusuke Ota,1 Takaya Hayashi,3 Masato Suzuki,4 Mitsunori Yoshida,5 Yoshihiko Hoshino,5 Yukihiro Akeda,6 Toshihiko Suzuki,7 Tomoko Ishino,2 Anthony Samuel Ablordey,8 Ryoichi Saito1 1Department of Molecular Microbiology, Tokyo Medical and Dental University, Tokyo, Japan; 2Department of Parasitology and Tropical Medicine, Tokyo Medical and Dental University, Tokyo, Japan; 3Department of Molecular Virology, Tokyo Medical and Dental University, Tokyo, Japan; 4Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan; 5Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan; 6Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan; 7Department of Bacterial Pathogenesis, Tokyo Medical and Dental University, Tokyo, Japan; 8Department of Bacteriology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, GhanaCorrespondence: Anthony Samuel Ablordey; Ryoichi Saito, Email aablordey@noguchi.ug.edu.gh; r-saito.mi@tmd.ac.jpPurpose: Colistin is classified by the World Health Organization (WHO) as a critically important and last-resort antibiotic for the treatment of infections caused by carbapenem-resistant bacteria. However, colistin resistance mediated by chromosomal mutations or plasmid-linked mobilized colistin resistance (mcr) genes has emerged.Methods: Thirteen mcr-positive Aeromonas species isolated from water samples collected in Eastern Ghana were analyzed using whole-genome sequencing (WGS). Antimicrobial susceptibility was tested using the broth microdilution method. Resistome analysis was performed in silico using a web-based platform.Results: The minimum inhibitory concentration (MIC) of colistin for all except three isolates was > 4 μg/mL. Nine new sequence types were identified and whole-genome analysis revealed that the isolates harbored genes (mcr-3-related genes) that code for Lipid A phosphoethanolamine transferases on their chromosomes. BLAST analysis indicated that the amino acid sequences of the mcr-3-related genes detected varied from those previously reported and shared 79.04– 99.86% nucleotide sequence identity with publicly available mcr-3 variants and mcr-3-related phosphoethanolamine transferases. Analysis of the genetic context of mcr-3-related genes revealed that the genetic environment surrounding mcr-3-related genes was diverse among the different species of Aeromonas but conserved among isolates of the same species. Mcr-3-related-gene-IS-mcr-3-related-gene segment was identified in three Aeromonas caviae strains.Conclusion: The presence of mcr-3-related genes close to insertion elements is important for continuous monitoring to better understand how to control the mobilization and dissemination of antibiotic resistance genes.Keywords: Aeromonas spp, colistin, mcr-3-related gene, phosphoethanolamine transferases, whole genome analysis

Kazuhiko Watanabe,1,2 Hisamitsu Omori,3 Ayumi Onoue,3 Kenichi Kubota,4 Minoru Yoshida,4 Takahiko Katoh1 1Department of Public Health, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; 2Center for Research of the Aging Workforce, University of Occupational and Environmental Health, Fukuoka, Japan; 3Department of Laboratory Sciences in Environmental Hygiene and Public Health, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; 4Japanese Red Cross Kumamoto Health Care Center, Kumamoto, JapanCorrespondence: Hisamitsu Omori, Department of Laboratory Sciences in Environmental Hygiene and Public Health, Faculty of Life Sciences, Kumamoto University, 4-24-1 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan, Tel/Fax +81-96-373-5462, Email omorih@gpo.kumamoto-u.ac.jpPurpose: This study aimed to reveal the association between the osteoporosis self-assessment tool for Asians (OSTA) and airflow limitation (AL) in post-menopausal Japanese women.Participants and Methods: This cross-sectional study included 1580 participants undergoing a comprehensive health examination using spirometry and dual-energy X-ray absorptiometry. The OSTA was calculated by subtracting the age in years from the body weight (BW) in kilograms, and the result was multiplied by 0.2. The OSTA risk level was defined as low (>-1), moderate (− 4 to − 1), or high (

Teppei Hagino,1 Risa Hamada,2 Mai Yoshida,2 Eita Fujimoto,3 Hidehisa Saeki,2 Naoko Kanda1 1Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan; 2Department of Dermatology, Nippon Medical School, Tokyo, Japan; 3Fujimoto Dermatology Clinic, Funabashi, JapanCorrespondence: Teppei Hagino, Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan, Tel +81 476 99 1111, Fax +81 476 99 1911, Email teppei-hagino@nms.ac.jpPurpose: To investigate the therapeutic effectiveness and safety of Janus kinase 1 inhibitor upadacitinib in adolescent patients with atopic dermatitis (AD).Patients and Methods: This study examined therapeutic effectiveness and safety of upadacitinib for 39 Japanese adolescent patients (aged 12– 17 years) diagnosed with moderate-to-severe AD from August 2021 to January 2023. The patients were treated with upadacitinib 15 mg/day plus twice daily topical corticosteroids. Total eczema area and severity index (EASI) or EASI on head and neck, upper limbs, lower limbs, and trunk or for erythema, edema/papulation, excoriation, or lichenification, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and laboratory indexes were assessed at weeks 0, 4, and 12 of treatment. Treatment-emergent adverse events were recorded.Results: Total EASI or EASI on 4 anatomical sites or for 4 rash types, ADCT, and PP-NRS were significantly reduced at week 4 and 12 compared to week 0. The achievement rates at weeks 4 or 12 were 64.1% or 62.5% for EASI 75, 93.5% or 73.1% for ADCT < 7-point, and 80.6% or 60% for PP-NRS ≥ 4-point improvement, respectively, indicating their peak at week 4 and slight decrease at week 12. The percent reduction of EASI for excoriation was higher than that for lichenification or edema/papulation at week 4 or week 12, respectively. The percent reductions of EASI for erythema and edema/papulation on head and neck were lower than those on lower limbs at week 12. Total eosinophil counts (TEC) and IgE reduced at week 4 compared to week 0 while TARC, IgE, TEC, and LDH increased at week 12 compared to week 4.Conclusion: These results suggest therapeutic effectiveness and tolerability of upadacitinib and support its therapeutic usefulness for adolescent AD patients.Keywords: atopic dermatitis, upadacitinib, adolescent, effectiveness, safety

Masanori Kaji,1 Ho Namkoong,2 Genta Nagao,1 Shuhei Azekawa,1 Kensuke Nakagawara,1 Hiromu Tanaka,1 Atsuho Morita,1 Takanori Asakura,1,3,4 Hirofumi Kamata,1 Yoshifumi Uwamino,2,5 Mitsunori Yoshida,6 Koichi Fukunaga,1 Naoki Hasegawa2 1Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan; 3Department of Clinical Medicine (Laboratory of Bioregulatory Medicine), Kitasato University School of Pharmacy, Tokyo, Japan; 4Department of Respiratory Medicine, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan; 5Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan; 6Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, JapanCorrespondence: Ho Namkoong, Department of Infectious Diseases, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan, Tel + 3-3353-1211 61164, Fax + 3-3353-5958, Email hounamugun@gmail.comBackground: Mycobacterium abscessus (M. abscessus) is a rapidly growing bacterium (RGM) that causes refractory pulmonary and extrapulmonary infections. However, studies investigating pharyngeal and laryngeal M. abscessus infections are limited.Case Presentation: A 41-year-old immunocompetent woman complaining of bloody sputum was referred to our hospital. Although her sputum culture tested positive for M. abscessus subsp. abscessus, radiological findings were not indicative of pulmonary infection or sinusitis. Further diagnostic workup, including laryngeal endoscopy and positron emission tomography/computed tomography (PET/CT), confirmed the presence of nasopharyngeal M. abscessus infection. The patient was initially treated with intravenous amikacin, imipenem/cilastatin, azithromycin, and clofazimine for 28 days, after which the patient was provided with amikacin, azithromycin, clofazimine, and sitafloxacin for four months. After the completion of antibiotic therapy, the patient showed negative results on sputum smear and culture and normal findings on PET/CT and laryngeal endoscopy. Whole-genome sequencing of this strain revealed that it belonged to the ABS-GL4 cluster, which has a functional erythromycin ribosomal methylase gene, although it is not a major lineage in non-cystic fibrosis (CF) patients in Japan and Taiwan and in CF patients in European countries. We conducted a literature review and identified seven patients who developed pharyngeal/laryngeal non-tuberculous mycobacterium (NTM) infection. Four of the eight patients had a history of immunosuppressant use, including steroids. Seven of the eight patients responded well to their treatment regimens.Conclusion: Patients whose sputum culture tests are positive for NTM and who meet the diagnostic criteria for NTM infection but do not have intrapulmonary lesions should be evaluated for otorhinolaryngological infections. Our case series revealed that immunosuppressant use is a risk factor for pharyngeal/laryngeal NTM infection and that patients with pharyngeal/laryngeal NTM infections respond relatively well to antibiotic therapy.Keywords: pharyngeal NTM, laryngeal NTM, whole-genome sequencing

Hiroaki Ogata, Kachi Sha, Yasuaki Kotetsu, Aimi Enokizu-Ogawa, Katsuyuki Katahira, Akiko Ishimatsu, Kazuhito Taguchi, Atsushi Moriwaki, Makoto Yoshida Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, Fukuoka, JapanCorrespondence: Hiroaki Ogata, Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, 4-39-1 Yakatabaru, Minami-ku, Fukuoka, 811-1394, Japan, Tel +81-92-565-5534, Fax +81-92-566-0702, Email md105020@gmail.comPurpose: Similar to chronic obstructive pulmonary disease (COPD), the diffusing capacity of the lung (DLCO) might be decreased and associated with poor prognosis in preserved ratio impaired spirometry (PRISm), a clinical entity as a prodromal phase of COPD. The aims of the present study were to evaluate the distributions of DLCO and to assess the association between DLCO and mortality among subjects with PRISm.Patients and Methods: We conducted an observational cohort study at the National Hospital Organization Fukuoka National Hospital. We classified the 899 patients ≥ 40 years of age with an assessment of DLCO into five groups based on spirometry: preserved spirometry, PRISm, mild COPD, moderate COPD, and severe/very severe COPD. The prevalence of low DLCO (< 80% per predicted) was compared among the five groups. Using PRISm patients with follow-up data, we further investigated the association of low DLCO with all-cause mortality.Results: The prevalence of low DLCO in the PRISm group (58.8%) was significantly higher than that in the preserved-spirometry group (21.8%), the mild-COPD group (23.5%), and the moderate-COPD group (36.0%) (all P < 0.01), and it was comparable to that in the severe/very severe-COPD group (63.2%). The results remained unchanged after adjusting for potential confounders. Among the PRISm subjects, the overall survival rate was significantly lower in the low-DLCO group than in the preserved-DLCO group (P < 0.01). The multivariable-adjusted hazard ratio (HR) for all-cause mortality was significantly higher in the low-DLCO group than in the preserved-DLCO group (HR = 10.10 (95% confidence interval 2.33– 43.89)).Conclusion: Diffusing capacity was more impaired in PRISm subjects than in those with preserved spirometry or mild to moderate COPD. Regarding PRISm, low DLCO was a significant risk factor for all-cause mortality. Clinicians should assess DLCO in the management of PRISm to predict the future risk of overall death.Keywords: preserved ratio impaired spirometry, chronic obstructive pulmonary disease, diffusing capacity of the lungs, all-cause mortality

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

Koichiro Takahashi,1 Hiroki Tashiro,1 Ryo Tajiri,2 Ayako Takamori,2 Masaru Uchida,3 Go Kato,4 Yuki Kurihara,1 Hironori Sadamatsu,1 Takashi Kinoshita,5 Makoto Yoshida,6 Atsushi Kawaguchi,2,7 Shinya Kimura,1 Naoko Sueoka-Aragane,1 Tomotaka Kawayama5 On behalf of Saga-naïve COPD Physical Activity Evaluation (SCOPE) Study Investigator Group1Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan; 2Clinical Research Center, Saga University Hospital, Faculty of Medicine, Saga University, Saga, Japan; 3Division of Internal Medicine, Japan Community Health Care Organization Saga Central Hospital, Saga, Japan; 4Division of Respiratory Medicine, Saga Prefectural Medical Center Koseikan, Saga, Japan; 5Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan; 6Division of Respiratory Medicine, National Hospital Organization Fukuoka Hospital, Fukuoka, Japan; 7Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga, JapanCorrespondence: Koichiro TakahashiDivision of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, JapanEmail takahak@cc.saga-u.ac.jpBackground: Prolonged sedentary behavior is associated with worse prognosis in patients with chronic obstructive pulmonary disease (COPD). Our previous study found that first-line dual therapy with tiotropium/olodaterol significantly reduces sedentary time compared to tiotropium monotherapy in Japanese patients with treatment-naïve COPD, although the characteristics of responders to dual-therapy versus monotherapy for COPD are still unclear.Methods: Patients with treatment-naïve COPD were randomized to receive either tiotropium or tiotropium/olodaterol treatment for 12 weeks. Physical activity was assessed using a triaxle accelerometer for 2 weeks before and after treatment. This analysis focused on the change in sedentary time, indicated by physical activity of 1.0– 1.5 metabolic equivalents (METs), with stratification for the following factors: age, body mass index (BMI), pulmonary function, COPD assessment test (CAT), the 6-minute walk distance (6MWD), and physical activity level at study entry.Results: Thirty-five patients received tiotropium/olodaterol and 34 patients received tiotropium. In patients with lower inspiratory capacity at study entry, a significant reduction in sedentary time was observed in the tiotropium/olodaterol group compared with the tiotropium group (Tio: − 12.8 ± 13.5 min, Tio/Olo: − 65.1 ± 21.0 min, mean difference, − 52.2 min, 95% CI − 103.6 to 0.88, p = 0.046). In patients with a shorter duration of physical activity of ≥ 2 METs at study entry, a significant reduction of sedentary time was observed in the tiotropium/olodaterol group compared with the tiotropium group (Tio: − 3.3 ± 17.5 min, Tio/Olo: − 72.9 ± 23.1 min, mean difference, − 69.7 min, 95% CI − 128.7 to − 10.6, p = 0.02). There were no differences in terms of age, BMI, CAT score, 6MWD, FEV1, FVC, VC, and physical activity of 1.0– 1.5 METs and ≥ 3.0 METs.Conclusion: This study showed that COPD patients with lower inspiratory capacity or shorter active time of ≥ 2.0 METs at study entry are likely to exhibit significantly greater reduction in sedentary time with tiotropium/olodaterol treatment.Keywords: chronic obstructive pulmonary disease, physical activity, sedentary time, long-acting muscarinic antagonist, long-acting beta 2 agonist

Megumi Yoshida,1 Yoshikazu Yamaguchi,1 Mizuho Matsushita,1 Sayaka Tsuboi,1 Yoh Sugawara,1 Hajime Hayami,1 Joseph Tobias,2 Gaku Inagawa1 1Department of Anesthesiology, Yokohama Municipal Citizen‘s Hospital, Yokohama, Japan; 2Department of Anesthesiology & Pain Medicine, Nationwide Children’s Hospital and The Ohio State University, Columbus, OH, USACorrespondence: Megumi YoshidaYokohama Municipal Citizen’s Hospital, 1-1 Mitsuzawanishimachi, Kanagawa-ku, Yokohama, 221-0855, JapanTel +81 45 316-4580Fax +81 45 316-6580Email megu.m.y06@gmail.comAbstract: Tetanus is a potentially fatal infectious disease caused by the toxins produced by the anaerobic bacterium, Clostridium tetani. Of major concern during the perioperative care of these patients is control of muscle spasms, skeletal rigidity, and autonomic dysfunction. Several of the modern sedative and opioid agents including remifentanil have not been fully evaluated in managing tetanus. We present the intraoperative use of remifentanil in a 75-year-old woman with generalized tetanus who required anesthetic care during placement of a tracheostomy. The end-organ involvement of tetanus is presented, previous reports of anesthetic care reviewed, and the potential utility of remifentanil explored.Keywords: tetanus, tracheostomy, general anesthesia

Pham Duong Uyen Binh,1,2 Pham Le An,3 Nghia An Nguyen,3 Dan Van Nguyen,4 Giao Huynh,5 Harumi Gomi,2 Motofumi Yoshida2 1Department of Educational Quality Assurance, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Department of Social Medical Sciences, Graduate School of Medicine, International University of Health and Welfare, Tokyo, Japan; 3Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 4Faculty of Traditional Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 5Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, VietnamCorrespondence: Pham Duong Uyen BinhDepartment of Social Medical sciences, Graduate School of Medicine, International University of Health and Welfare, Tokyo, JapanTel +84 961156505Email p.d.uyenbinh@gmail.comPurpose: Health science students need to be professional to improve quality of care (QOC) in the current Vietnamese healthcare system. Therefore, we aim to evaluate medicine and traditional medicine (TM) students’ perception of the professional attributes relating to QOC for improving inter-disciplined professionalism training that promotes QOC in Vietnam.Methods: The cross-sectional study was carried on 2039 students of 6 years at the University of Medicine and Pharmacy at Ho Chi Minh City (HUMP) from the medical and TM faculty in March, 2021. The Vietnamese American Board of Internal Medicine (ABIM) questionnaire (2011) was used as the survey instrument. The confirmatory factor analysis (CFA) was performed to confirm the validity of the scale in TM students. Mean, Min–Max, standard deviation and sample paired t-test were performed for Likert scale. The one-way ANOVA was used for inferential statistics.Results: The CFA demonstrated the validity of the Vietnamese questionnaire in measuring 4 QOC-relating professional attributes, previously found in medical students for TM students. In both faculties and across academic years, students perceived self-awareness and ensuring QOC as the leading important attribute, while social duty and professional habit as the least important attribute. Contrasting with preclinical phase, students’ perception did not differ significantly between the two faculties in their clinical years (p > 0.05).Conclusion: TM students share universal QOC-relating professional traits with medical students. Moreover, exposure to clinical environment might increase inter-disciplined agreement on importance of these attributes. However, health sciences students’ underestimation of social duty and professional habit persists throughout 6 academic years. Hidden curriculum in clinical training such as specialist-centeredness might hinder the students’ improvement in perception of these traits. Therefore, these traits should strongly be emphasized in professionalism training to decrease the effects of hidden curriculum on them.Keywords: medical professionalism, quality of care, inter-disciplined professionalism

Kazuhiko Watanabe,1 Ayumi Onoue,2 Hisamitsu Omori,2 Kenichi Kubota,3 Minoru Yoshida,3 Takahiko Katoh1 1Department of Public Health, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; 2Department of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; 3Japanese Red Cross Kumamoto Health Care Center, Kumamoto, JapanCorrespondence: Hisamitsu OmoriDepartment of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, 4-24-1 Kuhonji, Chuo-ku Kumamoto, 862-0976, JapanTel/Fax +81-96-373-5462Email omorih@gpo.kumamoto-u.ac.jpPurpose: This study aimed to reveal the association between airflow limitation (AL) and carotid intima-media thickness (IMT) according to smoking status in Japan.Subjects and Methods: This cross-sectional study was performed in 2809 subjects, who underwent a comprehensive health examination with pulmonary function tests and carotid ultrasonographic measurement. AL was defined as forced expiratory volume in 1 s/forced vital capacity of < 0.7. The subjects were divided into the following four groups: never smokers without AL, never smokers with AL, former/current smokers without AL, and former/current smokers with AL. Mean IMT, the maximum measurable IMT value in the left and right common carotid arteries (IMT-C max), and mean IMT-C max were measured by carotid ultrasonography. The carotid wall thickness as defined as follows: IMT ≥ 1.1 mm (IMT1.1), IMT-C max ≥ 1.2 mm (IMTc1.2), and IMT-C max > 1.5 mm (IMTc1.5), based on each measured region. The association between AL and the carotid wall thickness according to smoking status was assessed by logistic regression analysis.Results: The mean carotid IMT and mean IMT-C max were significantly higher in never smokers with AL and former/current smokers with or without AL than in never smokers without AL. In logistic regression models adjusted for sex, age, body mass index, hypertension, dyslipidemia, hyperglycemia, physical activity, and alcohol consumption, the risk of carotid wall thickness (IMT1.1 [odds ratio {OR}: 1.55; 95% confidence interval {CI}: 1.07– 2.24]; IMTc1.2 [OR: 1.52; 95% CI: 1.03– 2.24]; IMTc1.5 [OR: 1.99; 95% CI: 1.15– 3.46]) were significantly higher in former/current smokers with AL than in never smokers without AL.Conclusion: The present results suggest that greater IMT and risk of carotid wall thickness were associated with AL and smoking experience.Keywords: chronic obstructive pulmonary disease, cardiovascular disease, comorbidity, atherosclerosis, airflow limitation, carotid intima-media thickness

Koichiro Takahashi,1 Masaru Uchida,2 Go Kato,3 Ayako Takamori,4 Takashi Kinoshita,5 Makoto Yoshida,6 Ryo Tajiri,4 Keisuke Kojima,7 Hiroshi Inoue,8 Hiromi Kobayashi,9 Hironori Sadamatsu,1 Hiroki Tashiro,1 Masahide Tanaka,1 Shinichiro Hayashi,10 Atsushi Kawaguchi,4,11 Shinya Kimura,1 Naoko Sueoka-Aragane,1 Tomotaka Kawayama5 Saga-naïve COPD Physical Activity Evaluation (SCOPE) Study Investigator Group1Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan; 2Division of Internal Medicine, Japan Community Health Care Organization Saga Central Hospital, Saga, Japan; 3Division of Respiratory Medicine, Saga Prefectural Medical Center Koseikan, Saga, Japan; 4Clinical Research Center, Saga University Hospital, Faculty of Medicine, Saga University, Saga, Japan; 5Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan; 6Division of Respiratory Medicine, National Hospital Organization Fukuoka Hospital, Fukuoka, Japan; 7Division of Internal Medicine, Imari Arita Kyouritsu Hospital, Saga, Japan; 8Division of Internal Medicine, Karatsu Red Cross Hospital, Saga, Japan; 9Division of Respiratory Medicine, National Hospital Organization East Saga Hospital, Saga, Japan; 10Division of Internal Medicine, Kouhoukai Takagi Hospital, Fukuoka, Japan; 11Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga, JapanCorrespondence: Koichiro TakahashiDivision of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, JapanEmail takahak@cc.saga-u.ac.jpBackground: Comparative effects on physical activity of mono and dual bronchodilators remain unclear in patients with treatment-naïve chronic obstructive pulmonary disease (COPD). We sought to compare the changes in physical activity before and after tiotropium and tiotropium/olodaterol treatment in treatment-naïve COPD patients.Methods: A prospective, multicenter, randomized, open-labeled, and parallel interventional study was conducted. Eighty Japanese patients with treatment-naïve COPD were randomized to receive either tiotropium or tiotropium/olodaterol treatment for 12 weeks. Spirometry and dyspnea index were assessed, and COPD assessment test (CAT) and the 6-minute walk distance (6MWD) were conducted before and after treatment. Evaluation of physical activity was assessed by a triaxle accelerometer over a 2-week period before and after treatment.Results: There were no differences in the mean age (69.8 vs 70.4 years), body mass index (BMI) (22.5 vs 22.6 kg/m2) and mean % forced expiratory volume in 1 second (%FEV1) at baseline (61.5 vs 62.6%) between the two groups. Changes in FEV1 (mean±standard error, 242.8± 28.8 mL) and transient dyspnea index (TDI) (2.4± 0.3 points) before and after tiotropium/olodaterol treatment were greater than with tiotropium treatment (104.1± 31.9 mL, p< 0.01 and 1.5± 0.3, p=0.02, respectively). Changes in the duration of physical activity with 1.0– 1.5 metabolic equivalents (METs) estimated in the sedentary position following tiotropium/olodaterol treatment (− 38.7± 14.7 min) tended to be reduced more than with tiotropium treatment (− 4.6± 10.6 min) (p=0.06), although those with ≥ 2.0 METs numerically increased with both treatments (+10.8± 7.6 min for tiotropium/olodaterol vs +8.3± 7.6 min for tiotropium, p=0.82). Tiotropium/olodaterol treatment reduced the duration of physical activity with 1.0– 1.5 METs (regression coefficient, − 43.6 [95% CI − 84.1, − 3.1], p=0.04) in a multiple regression model adjusted for cofounding factors such as age, FEV1, total CAT scores, 6MWD, and TDI.Conclusion: This is the first study to report the impact of dual bronchodilator on physical activity in treatment-naïve COPD patients of Japanese with low BMI.Keywords: chronic obstructive pulmonary disease, physical activity, long-acting muscarinic antagonist, long-acting beta 2 agonist

Yuya Esaki, Yoshio Hirano, Ryo Kurobe, Yusuke Yasuda, Taneto Tomiyasu, Norihiro Suzuki, Tsutomu Yasukawa, Munenori Yoshida, Yuichiro Ogura Department of Ophthalmology & Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanCorrespondence: Yoshio HiranoDepartment of Ophthalmology & Visual Science, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-Cho, Mizuho-Ku, Nagoya 467-8601, JapanTel +81 52-8538251Fax +81 52-8419490Email yoshio.hirano@gmail.comPurpose: To classify microaneurysms (MAs) and investigate the relationships with retinal edema in eyes with branch retinal vein occlusion (BRVO).Study Design: Retrospective, observational, consecutive case series.Methods: Eyes with MAs due to BRVO that underwent optical coherence tomography angiography (OCTA) were enrolled. MAs on OCTA images were morphologically classified into six types: focal bulge, saccular, fusiform, mixed (saccular/fusiform), pedunculated, and irregular. The frequency, size, location, and relationships with retinal edema also were investigated.Results: Twenty-four eyes of 23 patients (12 men, 11 women; mean age, 68.0 years) were enrolled. A total of 244 MAs were detected on the OCTA images. The focal bulge and saccular types accounted for over 70% of all MAs. Smaller MAs such as the focal bulge or saccular type also were detected both at the edge of the nonperfused areas (NPAs) and in collateral vessels. In contrast, larger MAs such as the pedunculated or irregular types tended to form at the edges of the NPAs. Older age, the presence of MAs in the collateral vessels, and the absence of pedunculated type were independent predictive factors for retinal edema but not the MA size, or presence in the retinal deep capillary plexus. After treatment, the mean retinal thickness decreased significantly, but the mean MA size remained unchanged.Conclusion: OCTA enables morphologic classification, three-dimensional analysis, and investigation of the longitudinal changes of MAs with noninvasive volumetric quantification, leading to a better understanding of the pathology of MAs in eyes with BRVO.Keywords: microaneurysm, morphology, macular edema, optical coherence tomography angiography, branch retinal vein occlusion

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

Binh PDU, An PL, Nguyen NA, et al. J Multidiscip Healthc. 2021;14:2229–2238. Table 4 Mean Scores of Professional Attributes Across Academic Years and Between Two Faculties Page 2231, Data Analysis section, first sentence, the text “Statistical analysis was performed using SPSS Statistics (SPSS Statistics Inc., Chicago, US) version 20.0” should read “Statistical analysis was performed using SPSS Statistics (SPSS Statistics Inc., Chicago, US) version 20.0 and STATA version 16.0”. Pages 2232 and 2234, Differences in Students’ Perception of Professional Attributes Relating to QOC Between the Two Faculties section, text has been deleted from paragraphs 2 and 3, the text should read as follows: “In both faculties, the trait Self-Awareness was reported as the most important attribute, the next being Quality of Care and Professional Habit in each year. Social Duty received the lowest mean scores, which made it the least important trait in both faculties almost at all years. Students’ perception in most attributes did not differ significantly between the two faculties in their clinical years (4th - 6th year). However, significant differences were found in the pre-clinical phase. 2nd year medical students 15significantly assigned higher scores for Self-Awareness and Social Duty over 2nd year TM students (t(356) = −3.12, p=0.002; t(356) = −3.53, p < 0.001).” Page 2235, errors have been found in Table 4. The correct Table 4 is shown in Download Article. Page 2236, Discussion section, left column, text has been deleted from paragraph 2, the text should read as follows: “This is the first study in Vietnam to reveal both Medical and TM students’ perceptions on QOC-relating to professional attributes. No differences were found between the faculties in the order of these 4 attributes, being from the most to the least important, which was Self-Awareness, Ensuring QOC, Professional Habit and Social Duty (Figure 1)”. Page 2237, Discussion section, paragraph 4, last sentence, the text “Last but not least, Professional Habit referring to collaboration should be emphasized for the junior TM students due to their extreme underestimation of this trait” should read “Last but not least, Professional Habit referring to collaboration should also be emphasized for the TM students due to their underestimation of this trait”. The authors apologize for these errors and state that these corrections do not change the scientific conclusions of the article in any way. Read the original article

Kentaro Machida,1,* Tomotaka Kawayama,2,* Masaharu Kinoshita,3,* Masakazu Ichinose,4 Tohru Tsuda,5 Shohei Takata,6 Hiroshi Koto,7 Makoto Yoshida,8 Yoshinori Ashihara,9 Masaru Kawashima,10 Hideaki Suna,10 Hiromasa Inoue1 1Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan; 2Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan; 3Nagata Hospital, Yanagawa 832-0059, Japan; 4Department of Respiratory Medicine, Tohoku University, Graduate School of Medicine, Sendai 980-8574, Japan; 5Kirigaoka Tsuda Hospital, Kitakyushu 802-0052 Japan; 6Division of Respiratory Medicine, National Hospital Organization Fukuoka-Higashi Medical Center, Koga 811-3195, Japan; 7Division of Respiratory Medicine, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka 815-8588, Japan; 8Division of Respiratory Medicine, National Hospital Organization Fukuoka Hospital, Fukuoka 811-1394, Japan; 9Division of Respiratory Medicine, Oita Nakamura Hospital, Oita 870-0022, Japan; 10ONO Pharmaceutical Co. Ltd., Osaka 541-8564, Japan*These authors contributed equally to this workCorrespondence: Hiromasa InoueDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, JapanTel +81 99 275 6481Fax +81 99 275 6482Email inoue-pulm@umin.netBackground: Although long-acting muscarinic receptor antagonists are central to the management of chronic obstructive pulmonary disease (COPD), inhaled medicines may have technical difficulty in some patients and adherence barriers.Methods: A multicenter, randomized, double-blind, placebo-controlled 3×3 crossover Phase II trial was performed to evaluate the efficacy and safety of oral administration of the antimuscarinic agent imidafenacin in patients with COPD. Twenty-seven male COPD patients with % forced expiratory volume in 1 s (FEV1) ≥30% and

Masanori Nakanishi,1 Yoshiaki Minakata,2 Rie Tanaka,3 Hisatoshi Sugiura,3 Hikaru Kuroda,4 Makoto Yoshida,5 Nobuyuki Yamamoto11Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan; 2Department of Respiratory Medicine, National Hospital Organization Wakayama Hospital, Wakayama, Japan; 3Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; 4Department of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, Asahikawa, Hokkaido, Japan; 5Department of Respiratory Medicine, National Hospital Organization Fukuoka Hospital, Fukuoka, JapanCorrespondence: Yoshiaki MinakataDepartment of Respiratory Medicine, National Hospital Organization Wakayama Hospital, 1138 Wada Mihama-cho, Hidaka-gun, Wakayama 644-0044, JapanTel +81 73 822 3256Fax +81 73 822 2126Email minakata.yoshiaki.qy@mail.hosp.go.jpPurpose: The improvement of physical activity in patients with COPD is an important issue. However, no standard for the recommended number of steps for patients with COPD has been determined. We conducted a retrospective observational study to create a simple standard equation for the daily step count, which makes it easier to determine whether each subject is attaining his/her predicted value or not.Patients and methods: Stable outpatients diagnosed with COPD whose physical activities had been measured using a triaxial accelerometer for more than 2 weeks were recruited from 5 institutes in Japan. Factors associated with the step count were detected by multivariate regression analysis. After the data were transformed to a normalized distribution, a multivariate linear regression equation was created using stepwise regression.Results: One hundred sixty-two patients aged 72.3 (7.2) years and of FEV1 %pred 59.2 (22.8) % were recruited. Among the parameters, age, mMRC dyspnea scale and inspiratory capacity (IC) were detected by the stepwise method. The created standard equation was “Step count = (−0.079×[age]−1.595×[mMRC]+2.078×[IC]+18.149)3,”. The correlations between the calculated values and the measured values were observed, and fixed, and proportional biases between them were also observed. When patients with

Mari Kawai,1 Shinji Kurata,1 Takuro Sanuki,2 Gaku Mishima,1 Kensuke Kiriishi,1 Toshihiro Watanabe,1 Yu Ozaki-Honda,1 Mizuki Yoshida,1 Ichiro Okayasu,1 Terumi Ayuse,3 Naomi Tanoue,3 Takao Ayuse1–31Department of Dental Anesthesia, Nagasaki University Hospital, Nagasaki, Japan; 2Nagasaki University Institute of Biomedical Sciences, Course of Medical and Dental Sciences, Dental Anesthesiology, Nagasaki, Japan; 3Department of Special Care Dentistry, Nagasaki University Hospital, Nagasaki, JapanBackground: Sevoflurane is generally the preferred anesthetic agent for general anesthesia in pediatric patients, due to its rapid induction and recovery characteristics. However, it has been recognized that a major complication is emergence agitation when awakening from general anesthesia. The aim of this study was to evaluate the occurrence rate of emergence agitation in the operating room and postoperative recovery area following intraoperative administration of midazolam to pediatric patients under general anesthesia.Patients and methods: One hundred and twenty pediatric patients undergoing dental treatment under sevoflurane anesthesia were enrolled in this study. The patients were divided into three groups (n=40 each in the 0.1 mg/kg midazolam, 0.05 mg/kg midazolam, and control with saline groups). Midazolam or saline was injected intravenously approximately 30 minutes before the end of the dental treatment. We used the Richmond Agitation and Sedation Scale (RASS) to assess the level of sedation and drowsiness at emergence phase in the operating room. We also used the Pediatric Anesthesia Emergence Delirium Scale (PAED) to assess the level of agitation and delirium at the full recovery phase from anesthesia in the recovery area.Results: At the emergence phase, the incidence of emergence agitation in the 0.1 mg/kg midazolam group was significantly lower than in the other groups (p=0.0010). At the recovery phase, there was no significant difference among the three groups. The odds ratio between PAED score and RASS score was 4.0 using logistic regression analysis. The odds ratio between PAED score and Disability was 2.5.Conclusion: Administration of a single dose of 0.1 mg/kg midazolam dose significantly decreases the incidence of severe emergence agitation at the emergence after sevoflurane anesthesia, but not at the recovery phase. Furthermore, the evaluation of sedative and agitation condition using RASS score at emergence from anesthesia is useful to predict occurrence of agitation in the recovery phase.Keywords: emergence agitation, sevoflurane anesthesia, pediatric patients, extreme non-cooperation against dental treatment

Mihoko Kawamura, Yoshio Hirano, Munenori Yoshida, Takeshi Mizutani, Kazuhiko Sugitani, Tsutomu Yasukawa, Yuichiro Ogura Department of Ophthalmology & Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Purpose: The aim of this study is to report the 6-month results after one intravitreal ranibizumab (IVR) injection followed by pro re nata dosing for macular edema (ME) after branch retinal vein occlusion.Patients and methods: The inclusion criteria included a minimal patient age of 18 years, 20 letters or more best-corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] score, 77 letters or less), and central retinal thickness (CRT) of 250 microns or more. The primary outcome measure was the mean BCVA change from baseline at month 6; the secondary outcomes were mean changes in CRT, residual ME, and microaneurysm formation.Results: Twenty patients were enrolled from March 2014 through October 2016 at Nagoya City University Hospital. The baseline mean ETDRS letters and CRT were 63.1 and 500 microns, respectively; mean time from symptom onset to initial therapy was 1.80 months; and mean ETDRS gain and CRT reduction were 15.2 letters and 230 microns, respectively. The percentages of patients with Snellen equivalent BCVAs of 20/40 (70 ETDRS letters) or better and 20/20 (85 ETDRS letters) were 90% and 15%, respectively. Residual ME and microaneurysms were observed in 85% and 35% of patients. Microaneurysm formation was associated with delayed initial therapy.Conclusion: Prompt initiation of IVR injection provided a better visual prognosis at month 6 and suppressed the microaneurysm formation. Keywords: branch retinal vein occlusion, macular edema, microaneurysm, ranibizumab, prompt treatment

Takeshi Terao,1 Atsuko Ishida,2 Toshifumi Kimura,3 Mitsuhiro Yoshida,4 Terufumi Hara2 1Department of Neuropsychiatry, Faculty of Medicine, Oita University, Oita, 2Post-Marketing Surveillance Department, 3MA Specialty & General Care Medicine Department, 4Biomedical Data Sciences Department, Development & Medical Affairs Division, GlaxoSmithKline K.K., Tokyo, Japan Background: A post-marketing surveillance (PMS) study was conducted with a 1-year observation period to assess the safety and efficacy of lamotrigine in routine clinical practice in patients with bipolar disorder (BD).Patients and methods: Central enrollment method was used to recruit patients diagnosed with BD who were being treated for the first time with lamotrigine to prevent the recurrence/relapse of BD mood episodes. Adverse drug reactions (ADRs) and recurrence/relapse were assessed. Improvement of mania and depression was also assessed using the Hamilton’s Rating Scale for Depression (HAM-D) and the Young Mania Rating Scale (YMRS) at treatment initiation, 4–6 months post treatment initiation, and 10–12 months post treatment initiation.Results: A total of 237/989 patients (24.0%) reported ADRs, most commonly rash (9.1%), and the incidence of serious ADRs was 3.3% (33/989 patients). Skin disorders occurred in 130 patients (13.1%), mostly within 8 weeks post treatment. A total of 237/703 patients (33.7%) experienced recurrence/relapse of mood episodes. The 25th percentile of the time to recurrence/relapse of mood episodes was 105 days. Remission of depression symptoms (HAM-D ≤7) occurred in 147/697 patients (21.1%) at treatment initiation, rising to 361 patients (67.4%) at 10–12 months post treatment. Remission of manic symptoms (YMRS ≤13) occurred in 615/676 patients (91.0%) at treatment initiation, rising to 500 patients (97.3%) at 10–12 months post treatment.Conclusion: The results of this PMS study suggest that lamotrigine is a well-tolerated and effective drug for preventing recurrence/relapse of BD in clinical practice. Keywords: lamotrigine, bipolar, mood episode, post-marketing surveillance study, safety, efficacy

Tetsuyuki Suetsugu,1,2 Aki Kato,1 Munenori Yoshida,1 Tsutomu Yasukawa,1 Akiko Nishiwaki,1,3 Norio Hasegawa,1 Hideaki Usui,1 Yuichiro Ogura1 1Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, 2Department of Ophthalmology, General Kamiiida Daiichi Hospital, 3Nishiwaki Eye Clinic, Nagoya, Aichi, Japan Purpose: We aimed to evaluate the prevalence of abnormal peripheral fundus autofluorescence (FAF) in wet age-related macular degeneration (AMD) using wide-field imaging instrument. Patients and methods: A retrospective, case-controlled study involving 66 eyes of 46 Japanese wet AMD patients and 32 eyes of 20 control patients was performed. Wide-field FAF images were obtained for typical AMD (37 eyes/28 patients), polypoidal choroidal vasculopathy (PCV) (22 eyes/20 patients), and retinal angiomatous proliferation (RAP) (seven eyes/four patients). Two masked ophthalmologists independently graded the images for mottled, granular, and nummular patterns. Main outcome measures were abnormal peripheral FAF frequencies and relative risks by disease subgroups and treatments. Results: Abnormal peripheral FAF patterns were found in 51.5% of wet AMD eyes compared with 18.8% of control eyes (P

Masayo Kimura, Miho Nozaki, Munenori Yoshida, Yuichiro Ogura Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Purpose: Optical coherence tomography angiography (OCTA) is a newly developed technology which allows us to reconstruct the three-dimensional chorioretinal vasculature without dye injection. OCTA is a noninvasive, rapid, and reproducible method to assess retinal ischemia. However, one of its limitations is the size of scanning area. A novel yet simple technique to expand the scan length on optical coherence tomography has been reported as an extended field imaging (EFI) technique. It involves imaging the posterior pole through trial frames fitted with a +20 diopter lens. We applied this technique to OCTA to evaluate retinal vein occlusion.Materials and methods: Ten eyes of nine patients with retinal vein occlusion were studied. The average age was 69.0 years (range: 49–93 years). We obtained OCTA images by using RTVue XR Avanti OCT with AngioVue®. The images of OCTA with scan size of 8×8 mm were obtained with and without EFI, and then they were compared.Results: OCTA with EFI technique was performed successfully in all eyes. The nonperfusion area was well defined in superficial capillary plexus layer. The images with EFI were able to capture the larger area of the fundus by an average of 188.5% than those without EFI. The posterior pole inside the vascular arcade was well covered with this technique. The area of the fundus imaged by OCTA with EFI technique was even larger than that of fluorescein angio­graphy using Heidelberg Retina Angiograph 2, which captured a 30° field.Conclusion: Our results suggested that OCTA with EFI technique is very useful to evaluate the retinal ischemia in retinal vein occlusion. Keywords: optical coherence tomography angiography, OCTA, retinal vein occlusion, RVO, nonperfusion area, wide-field imaging, extended field imaging, EFI

Sheena Hunt,1 Mayumi Yoshida,2 Catherine EJ Davis,2 Nicholas S Greenhill,2 Paul F Davis21Promisia Integrative Ltd, Wellington, New Zealand; 2Trinity Bioactives Ltd, Wellington, New ZealandPurpose: To investigate the ability of a commercial extract from the medicinal plant Artemisia annua to modulate production of the cytokine, tumor necrosis factor-alpha (TNF-α), and the cyclooxygenase (COX) inflammatory marker, prostaglandin E2 (PGE2) in activated neutrophils. Methods: Neutrophils were harvested from rat whole blood and cultured in the presence of plant extract or control samples. Neutrophils, except unactivated control cells, were activated with 10 µg/mL lipopolysaccharide (LPS). The cells were cultured with a range of different concentrations of the A. annua extracts (400–1 µg/mL) and artemisinin (200 and 100 µg/mL) and the supernatants were then tested by enzyme-linked immunosorbent assay (ELISA) for the concentrations of TNF-α and PGE2. Each sample was assayed in triplicate. Positive controls with an inhibitor were assayed in triplicate: chloroquine 2.58 and 5.16 µg/mL for TNF-α, and ibuprofen 400 µg/mL for PGE2. An unsupplemented group was also assessed in triplicate as a baseline control.Results: Neutrophils were stimulated to an inflammatory state by the addition of LPS. A. annua extract significantly inhibited TNF-α production by activated neutrophils in a dose-dependent manner. There was complete inhibition by the A. annua extract at 200, 100, and 50 µg/mL (all P≤0.0003). At A. annua extract concentrations of 25, 10, and 5 µg/mL, TNF-α production was inhibited by 89% (P0.05). Concentrations of 400, 200, and 100 µg/mL A. annua extract significantly inhibited PGE2 production by 87% (P=0.0128), 91% (P=0.0017), and 93% (P=0.0114), respectively.Conclusion: An extract of A. annua was shown to be a potent inhibitor of TNF-α and a strong inhibitor of PGE2 production in activated neutrophils at the concentrations tested. Further studies are warranted with this promising plant extract.Keywords: in vitro, TNF-α, COX-2, PGE2, artemisinin, Arthrem

Satoshi Ota, Miho Nozaki, Shuichiro Hirahara, Tomoaki Hattori, Munenori Yoshida, Yuichiro Ogura Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Abstract: We experienced a case of retinopathy of prematurity that was successfully treated with pattern scan laser. Pattern scan laser treatment should be considered as one treatment option for Retinopathy of Prematurity. Keywords: retinopathy of prematurity, PASCAL, slit-lamp delivery

High precision measurements of the ground state hyperfine structure (HFS) of muonium is a stringent tool for testing bound-state quantum electrodynamics (QED) theory, determining fundamental constants of the muon magnetic moment and mass, and searches for new physics. Muonium is the most suitable system to test QED because both theoretical and experimental values can be precisely determined. Previous measurements were performed decades ago at LAMPF with uncertainties mostly dominated by statistical errors. At the J-PARC Muon Science Facility (MUSE), the MuSEUM collaboration is planning complementary measurements of muonium HFS both at zero and high magnetic field. The new high-intensity muon beam that will soon be available at H-Line will provide an opportunity to improve the precision of these measurements by one order of magnitude. An overview of the different aspects of these new muonium HFS measurements, the current status of the preparation for high-field measurements, and the latest results at zero field are presented.

Masao Yoshida,1,* Akira Meguro,2,* Atsushi Yoshino,2 Naoko Nomura,2 Eiichi Okada,3 Nobuhisa Mizuki21Department of Public Health, Kyorin University School of Medicine, Mitaka, Tokyo, Japan; 2Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan; 3Okada Eye Clinic, Yokohama, Kanagawa, Japan*These authors contributed equally to this workPurpose: Polymorphisms in the insulin-like growth factor 1 (IGF1) gene were previously associated with high or extreme myopia in Caucasian and Chinese populations. In the present study, we investigated whether IGF1 polymorphisms are associated with high myopia in a Japanese population.Methods: A total of 446 Japanese patients with high myopia (≤–9.00 diopters) and 481 Japanese healthy controls (+1.50 diopters to –1.50 diopters) were recruited. We genotyped seven tagging single-nucleotide polymorphisms (SNPs) in IGF1 and assessed allelic and haplotypic diversity in cases and controls.Results: There were no statistically significant differences in the allele frequencies of IGF1 SNPs and genotypes between cases and controls (P>0.05). However, the A allele of rs5742629 and the G allele of rs12423791 were associated with a moderately increased risk of high myopia (odds ratio [OR] =1.20 and OR =1.21, respectively) with borderline statistical significance (P=0.0502, corrected P (Pc) =0.21 and P=0.064, Pc=0.29, respectively). The haplotype consisting of the A allele of rs5742629 and the G allele of rs12423791 was marginally associated with the risk of high myopia (P=0.041; OR =1.21); this association was not significant after correction (Pc=0.19).Conclusion: We found that the IGF1 SNPs are not significantly associated with high myopia in our Japanese population. Our results are in contrast to a previous study in which extreme myopia cases had significantly higher frequencies of the G allele of rs5742629 and the C allele of rs12423791 than controls. Therefore, the IGF1 SNPs may not be important factors for susceptibility to high myopia in all populations. Further genetic studies are needed to elucidate the possible contributions of the IGF1 region to the development of high myopia.Keywords: high myopia, IGF1, association study, polymorphism

Masaki Yoshida1, Junzo Kudoh2, Yukio Homma3, Kazuki Kawabe41Department of Medical Informatics, 2Department of Urology, Japan Labor Health and Welfare Organization, Kumamoto Rosai Hospital, Kumamoto, Japan; 3Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 4Tokyo Teishin Hospital, Tokyo, JapanAbstract: Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS associated with BPH. Mainstays in the treatment of male LUTS and clinical BPH are the α1-adrenergic receptor antagonists. Silodosin is a new α1-adrenergic receptor antagonist that is selective for the α1A-adrenergic receptor. By antagonizing α1A-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the lower urinary tract. Since silodosin has greater affinity for the α1A-adrenergic receptor than for the α1B-adrenergic receptor, it minimizes the propensity for blood pressure-related adverse effects caused by α1B-adrenergic receptor blockade. In the clinical studies, patients receiving silodosin at a total daily dose of 8 mg exhibited significant improvements in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving placebo. Silodosin showed early onset of efficacy for both voiding and storage symptoms. Furthermore, long-term safety of silodosin was also demonstrated. Retrograde or abnormal ejaculation was the most commonly reported adverse effect. The incidence of orthostatic hypotension was low. In conclusion, silodosin, a novel selective α1A-adrenergic receptor antagonist, was effective in general and without obtrusive side effects. This review provides clear evidence in support of the clinical usefulness of silodosin in the treatment of LUTS associated with BPH.Keywords: α1A-adrenoceptor antagonist, silodosin, selective, benign prostatic hyperplasia, lower urinary tract symptoms

Our understanding of physics at very early Universe, as early as 10−35 s after the Big Bang, relies on the scenario known as the inflationary cosmology. Inflation predicts a particular polarization pattern in the cosmic microwave background, known as the B-mode yet the strength of such polarization pattern is extremely weak. To search for the B-mode of the polarization in the cosmic microwave background, we are constructing an off-axis rotating telescope to mitigate systematic effects as well as to maximize the sky coverage of the observation. We will discuss the present status of the GroundBIRD telescope.

We present two results of a search for MeV-scale neutrino and anti-neutrino events correlated with gravitational wave events/candidates and large solar flares with KamLAND. The KamLAND detector is a large-volume neutrino detector using liquid scintillator, which is located at 1 km underground under the top of Mt. Ikenoyama in Kamioka, Japan. KamLAND has multiple reaction channels to detect neutrinos. Electron antineutrino can be detected via inverse-beta decay with 1.8 MeV neutrino energy threshold. All flavors of neutrinos can be detected via neutrino-electron scattering without neutrino energy threshold. KamLAND has continued the neutrino observation since 2002 March. We use the data set of 60 gravitational waves provided by the LIGO/Virgo collaboration during their second and third observing runs and search for coincident electron antineutrino events in KamLAND. We find no significant coincident signals within a ±500 s timing window from each gravitational wave and present 90% C.L. upper limits on the electron antineutrino fluence between 108–1013 cm−2 for neutrino energies of 1.8–111 MeV. For a solar-flare neutrino search at KamLAND, we determine the timing window using the solar X-ray data set provided by the GOES satellite series from 2002 to 2019 and search for the excess of coincident event rate on the all-flavor neutrinos. We find no significant event rate excess in the flare time windows and get 90% C.L. upper limits on the fluence of neutrinos of all flavors (electron anti-neutrinos) between 1010–1013 cm−2 (108–1013 cm−2) for neutrino energies in the energy range of 0.4–35 MeV.

We report on a search for electron antineutrinos ( ) from astrophysical sources in the neutrino energy range 8.3-30.8 MeV with the KamLAND detector. In an exposure of 6.72 kton-year of the liquid scintillator, we observe 18 candidate events via the inverse beta decay reaction. Although there is a large background uncertainty from neutral current atmospheric neutrino interactions, we find no significant excess over background model predictions. Assuming several supernova relic neutrino spectra, we give upper flux limits of 60-110 cm-2 s-1 (90% confidence level, CL) in the analysis range and present a model-independent flux. We also set limits on the annihilation rates for light dark matter pairs to neutrino pairs. These data improve on the upper probability limit of 8B solar neutrinos converting into , (90% CL) assuming an undistorted shape. This corresponds to a solar flux of 60 cm-2 s-1 (90% CL) in the analysis energy range.

We report the result of a search for neutrinos in coincidence with solar flares from the GOES flare database. The search was performed on a 10.8 kton-year exposure of KamLAND collected from 2002 to 2019. This large exposure allows us to explore previously unconstrained parameter space for solar flare neutrinos. We found no statistical excess of neutrinos and established 90% confidence level upper limits of 8.4 × 107 cm-2 (3.0 × 109 cm-2) on the electron antineutrino (electron neutrino) fluence at 20 MeV normalized to the X12 flare, assuming that the neutrino fluence is proportional to the X-ray intensity.

We have performed a multi-color photo-polarimetric monitoring of 45 optical-bright blazars since 2007.3C 454.3, which is one of the brightest blazars in the gamma-ray sky, is one of targets of its project. We have made photo-polarimetric monitorings since July 2007. The object showed violent variation in its flux and polarization. In particular, four large-amplitude outbursts in 2007, 2008, 2009 and 2010 are remarkable. In each outburst, we observed a significant rise in the polarization degree. We calculated structure functions of the total flux and polarization from the 4-year monitoring data. In this time, we estimate the systematic and statistical errors of its structure functions. We adopt these errors when we estimate the break time-scales. The break time-scale of the total flux in 3C 454.3 is longer than that of the polarization. We also calculate the structure functions from total flux and polarization of the 15 blazars which are high-frequency monitored, and estimate the break time-scales. Most of estimated break time-scales of the total fluxes are longer than that of the polarization. From these results, it is indicated that the break time-scale of the total flux is reflected to the larger-amplitude and longer variation, like the outburst. However, the break time-scale of the polarization is related to the time-scale of the day-scale flares.