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Mauricio Sato,1 Mariana Muniz,2 Luis Ricardo Coelho Ferreira3 1IDEL Institute, Dermatology Department, Curitiba, Brazil; 2Mariana Muniz Dermatologia, Dermatology Department, São Paulo, Brazil; 3Federal University of Parana, Radiology Department, Curitiba, BrazilCorrespondence: Mauricio Sato, IDEL Institute, Dermatology Department, Alameda Getúlio Vargas 4474, Curitiba, PR, 80240-041, Brazil, Tel +5541 99977-8475; +55413026-0778, Email mashmauricio@gmail.comAbstract: The mid-face has been rendered as the cornerstone of facial aesthetic improvement, since treating the mid-face has also beneficial effects on neighboring esthetic units and therefore should be one of the first areas to be assessed. Retaining ligaments (RL) bind soft tissue layers of the face to the underlying facial skeleton. It remains controversial whether RL suffers laxity with aging or if changes in 42 bone and other structures where ligaments are inserted lead to altered mechanical function of the latter. Enhancement of the supportive effect of the ligaments could help restore the soft tissues to their original anatomical positions and achieve a lifting effect. While injectable hyaluronic acid implants have been used to improve ligament support, calcium hydroxylapatite has one of the highest viscoelasticities when compared with other dermal fillers and can induce collagen synthesis, which could provide long-term laxity correction. In this preliminary report of a case series, our goal was to describe the use of calcium hydroxylapatite in different dilutions and combinations for different aging profiles to treat the midface as an alternative for hyaluronic acid injections and to describe the ultrasonographic behavior in the long run.Keywords: rejuvenation, retaining ligaments, calcium hydroxylapatite, hyaluronic acid, soft tissue repositioning, aging pattern

Makiko Komasawa,1,2 Kiyoko Saito,1 Miho Sato,3 Robert Tamale Ssekitoleko,4 Christopher Nsereko,5 Mitsuo Isono,6 Jesca Nantume,4 Myo Nyein Aung2 1Ogata Sadako Research Institute for Peace and Development, Japan International Cooperation Agency, Tokyo, Japan; 2Department of Global Health Research, Graduate School of Medicine, Juntendo University, Tokyo, Japan; 3School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan; 4College of Health Sciences, Makerere University, Kampala, Uganda; 5Department of Internal Medicine, Entebbe Regional Referral Hospital, Entebbe, Uganda; 6Department of Human Development, Japan International Cooperation Agency, Tokyo, JapanCorrespondence: Makiko Komasawa, Ogata Sadako Research Institute for Peace and Development, Japan International Cooperation Agency, 10-5, Ichigaya Honmura-cho, Shinjuku-ku, Tokyo, 162-8433, Japan, Tel +81-3-3269-2911, Fax +81-3-3269-2054, Email mkomasa@juntendo.ac.jpBackground: Coronavirus disease 2019 caused significant negative damage to the health status of populations and health systems globally. In Uganda, our previous study revealed that the strict Public Health and Social measures (PHSMs) and the closure of Entebbe Regional Referral Hospital (ERRH) led to missed healthcare access among the citizens in the Entebbe municipality. Limited studies, however, exist on the impact of the response measures on the local health systems. This study aims to explore the impacts of these measures on the local health service provision from the views of health facilities in Entebbe.Methods: We used a thematic framework method, grounded by the health systems resilience framework consisting of five components: (1) health service delivery; (2) medical products and technology; (3) health workforce; (4) public health functions; and (5) governance and financing. Key informant interviews with eight representatives from four private hospitals and four health centers were conducted from September to October 2022.Results: Fifteen themes and 25 subthemes were identified. With the closure of the ERRH and the strict PHSMs, the citizens faced various difficulties in accessing the needed health services. The facilities received an overwhelming number of patients and faced various challenges, such as a lack of medicine, healthcare workers, facility capacity, and no means to transfer patients. Nevertheless, the facilities made efforts to maintain the required services. Moreover, mobilizing vertical and horizontal actors through a flexible network, from the district health office to community health volunteers, helped to coordinate the medicines, transportation for both patients and healthcare workers, conduct patient tracking, etc.Conclusion: Our study suggested the importance of an integrated system of public health and health service delivery systems, the formalization of a vertical cooperative mechanism, and the introduction of public health insurance for strengthening resilient health systems. These insights may benefit other sub-Saharan cities.Keywords: public health and social measures, private hospital, health center, resilient health systems, universal health coverage, sub-Saharan Africa

Norichika Ueda,1 Mototaka Sato,1 Atsuki Matsukawa,1 Yuta Oki,2 Ryoya Mizuno,1 Mai Akiyama,1 Norihide Tei,1 Osamu Miyake1 1Department of Urology, Toyonaka Municipal Hospital, Toyonaka, Japan; 2Department of Urology, Osaka Rosai Hospital, Sakai, JapanCorrespondence: Mototaka Sato, Department of Urology, Toyonaka Municipal Hospital, 4-14-1 Shibahara-cho, Toyonaka, 560-8565, Japan, Tel +81-6-6843-0101, Fax +81-6-6858-3531, Email mototaka1022@yahoo.co.jpAbstract: Radiation-induced hemorrhagic cystitis is a refractory disease that can cause severe hematuria and bladder tamponade. Bladder tamponade due to radiation-induced hemorrhagic cystitis can often recur repeatedly and markedly reduce the quality of life. However, no blood test parameter has been studied yet regarding the prevention of bladder tamponade recurrence. An 84-year-old patient with a history of radiation therapy for cervical cancer was repeatedly hospitalized for bladder tamponade due to radiation-induced hemorrhagic cystitis. At each hospitalization, blood transfusions were performed to treat severe anemia as the first treatment, resulting in hematuria improvement, and the patient was discharged without invasive treatments such as transurethral coagulation. However, anemia developed gradually after each discharge. The anemia progression was obviously unrelated to macrohematuria because macrohematuria did not appear during that period. When the serum hemoglobin level decreased below the physiological range, bladder tamponade recurred. Based on these findings, we posited that the monitoring of the serum hemoglobin level could be useful to predict the occurrence of bladder tamponade. We hypothesized that if the serum hemoglobin level did not fall below the physiological range, bladder tamponade would not occur. We treated chronic anemia after determining its cause and kept serum hemoglobin levels within the physiological range. Since the treatment was initiated, bladder tamponade has not recurred in over 27 months. In this case, the monitoring of the serum hemoglobin level was useful to predict the occurrence of bladder tamponade due to radiation-induced hemorrhagic cystitis. By maintaining serum hemoglobin levels within the physiological range, we successfully prevented the recurrence of bladder tamponade due to radiation-induced hemorrhagic cystitis.Keywords: hematuria, blood tests, prevention, recurrence, monitoring

Daichi Tsukakoshi,1 Shuhei Yamamoto,1 Shuhei Takeda,1 Keisuke Furuhashi,1 Masaaki Sato2 1Department of Rehabilitation, Shinshu University Hospital, Matsumoto, Japan; 2Division of Occupational Therapy, School of Health Sciences, Shinshu University, Matsumoto, Nagano, JapanCorrespondence: Shuhei Yamamoto, Department of Rehabilitation, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan, Tel +81-263-37-2836, Fax +81-263-37-2835, Email syamamoto@shinshu-u.ac.jpAbstract: The purpose of this narrative review is to examine rehabilitation modalities for patients with heart failure and Frailty who require comprehensive intervention. Ischemic heart disease is the leading cause of death worldwide, accounting for 16% of global mortality. Due to population growing and aging, the total number of heart failure patients continues to rise, a condition known as the heart failure pandemic. Furthermore, frailty has been associated with an increased risk for heart failure and increased morbidity and mortality. The 2021 update of the 2017 ACC expert consensus decision pathway for optimization of HF treatment has become more concerning, citing frailty as one of the 10 most important issues associated with heart failure with reduced ejection fraction (HFrEF). Frailty and heart failure share common pathological mechanisms and are associated with poor clinical outcomes. Most studies of frailty in patients with heart failure primarily focus on physical frailty, and associations between psycho-psychological and social factors such as cognitive dysfunction and social isolation have also been reported. These results suggest that a more comprehensive assessment of frailty is important to determine the risk in patients with heart failure. Therefore, mechanisms of the three domains, including not only physical frailty but also cognitive, psychological, spiritual, and social aspects, should be understood. In addition to interventions in these three domains, nutritional and pharmacological interventions are also important and require tailor-made interventions for the widely varied conditions associated with heart failure and frailty. Although several studies have shown a relationship between frailty and prognosis in patients with heart failure, interventions to improve the prognosis have not yet been established. Further information is needed on frailty intervention by a multidisciplinary team to improve the prognosis.Keywords: frailty, heart failure, rehabilitation, cardiovascular diseases

Hiroyoshi Machida,1 Sumito Inoue,1 Yoko Shibata,2 Tomomi Kimura,3 Takahito Ota,1 Yu Ishibashi,1 Hiroaki Murano,1 Kodai Furuyama,1 Sujeong Yang,1 Hiroshi Nakano,1 Kento Sato,1 Masamichi Sato,1 Takako Nemoto,1 Michiko Nishiwaki,1 Keiko Yamauchi,1 Akira Igarashi,1 Masafumi Watanabe1 1Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, Yamagata, Japan; 2Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan; 3Respiratory Medicine, Yamagata Saisei Hospital, Yamagata, JapanCorrespondence: Sumito InoueDepartment of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, JapanEmail sinoue@med.id.yamagata-u.ac.jpPurpose: Lung cancer is a serious complication in patients with chronic obstructive pulmonary disease (COPD) and accounts for approximately 15% of deaths in patients with COPD. However, with the exception of emphysema, few reports to date have been published on the factors that predict lung cancer development in COPD patients. It has been reported that patients with COPD develop lung cancer at a rate of 0.8% - 1.7%/year, but the incidence may be higher in the Japanese population. Therefore, we investigated the incidence of lung cancer and the lung cancer mortality rate in Japanese COPD patients, as well as factors that are associated with the development of lung cancer in COPD patients.Patients and Methods: We followed up 224 patients with stable COPD and performed CT examinations at least once per year. The incidence of lung cancer was recorded and data at enrollment were compared with data of the group that did not develop lung cancer.Results: Over a median follow-up period of 4.58 years, lung cancer was newly diagnosed in 19 patients; the incidence of lung cancer in this population was 1.85%/year. Patients who developed lung cancer had more severe emphysema assessed by CT and GOLD classification and were more likely to be current smokers than those who did not develop lung cancer. No other significant differences were observed between these two groups. Mortality was significantly increased in patients who developed lung cancer compared with those who did not.Conclusion: In COPD patients, the incidence of lung cancer is higher and the development of lung cancer worsens the prognosis; however, lung cancer development is unpredictable and attention should be paid to all patients. Annual CT screening is important for early detection of lung cancer.Keywords: chronic obstructive pulmonary disease, COPD, lung cancer, GOLD classification, current smoker, inhaled corticosteroid, ICS

Chihiro Kageyama,1 Mayu Sato,1 Hiroyuki Sakae,2 Yuka Obayashi,2 Yoshiro Kawahara,2 Takehiko Mima,3 Osamu Matsushita,3 Kenji Yokota,1 Motowo Mizuno,4 Hiroyuki Okada2 1Graduate School of Health Science, Medical Technology, Okayama University, Okayama 700-8558, Japan; 2Gastroenterology and Hepatology, Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan; 3Bacteriology, Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan; 4Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, 710-8602, Japan Background: Eradication effectively prevents Helicobacter pylori-associated diseases; however, H. pylori antibiotic resistance has increased throughout Japan and worldwide. This study aimed to assess rates of resistance to antibiotics; amoxicillin, clarithromycin and metronidazole in a University Hospital in Japan. Materials and methods: H. pylori (208 strains) were isolated from patients at the Okayama University Hospital in Japan. The minimum inhibitory concentrations (MIC) were determined using the mean values of the E-test to determine the antimicrobial susceptibilities of the strains. Sequencing and gene analysis were performed to analyze resistance genes to clarithromycin and amoxicillin. Results: Rates of amoxicillin, clarithromycin, and metronidazole resistance were 13%, 48%, and 49%, respectively. Genetic analysis indicated that the A2143G point mutation in 23S rDNA is closely associated with the MIC of clarithromycin. The MIC in amoxicillin-resistant strains increased with an increase in the number of PBP1A amino acids mutations. Conclusion: Genetic analysis for resistant strains is not clinically effective in cases of amoxicillin resistance. Numerous bacteria with already high antibiotic resistance rates have been isolated in large hospitals such as a University Hospital. For effective eradication therapy, MIC measurement should be considered via several methods. Keywords: Helicobacter pylori, resistance, clarithromycin, amoxicillin, University Hospital, genotype

Shinya Nakano,1,2 Yoshihisa Shoji,1,3 Kiichiro Morita,1,3 Hiroyasu Igimi,1,4 Mamoru Sato,1,3 Youhei Ishii,1 Akihiko Kondo,1 Naohisa Uchimura1,3 1Cognitive and Molecular Research Institute of Brain Diseases, Kurume University, Kurume, Japan; 2Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan; 3Department of Neuropsychiatry, Kurume University School of Medicine, Kurume, Japan; 4Department of Neuropsychiatry, Horikawa Hospital, Medical Corporation Association Horikawakai, Kurume, Japan Background: Tree-drawing test is used as a projective psychological test that expresses the abnormal internal experience in patients with schizophrenia (SZ). Despite the widely accepted view that the cognitive function is involved in characteristic tree-drawing in patients with SZ, no study has psychophysiologically examined it. The present study aimed to investigate the involvement of cognitive function during tree-drawing in patients with SZ. For that purpose, we evaluated the brain function in patients with SZ during a tree-drawing task by using near-infrared spectroscopy (NIRS) and compared them with those in healthy controls. Patients and methods: The subjects were 28 healthy controls and 28 patients with SZ. Changes in the oxygenated hemoglobin ([oxy-Hb]) concentration in both the groups during the task of drawing a tree imagined freely (free-drawing task) and the task of copying an illustration of a tree (copying task) were measured by using NIRS. Results: Because of the difference between the task conditions, [oxy-Hb] levels in controls during the free-drawing task were higher than that during the copying task at the bilateral frontal pole regions and left inferior frontal region. Because of the difference between the groups, [oxy-Hb] levels at the left middle frontal region, bilateral inferior frontal regions, bilateral inferior parietal regions, and left superior temporal region during the free-drawing task in patients were lower than that in controls. Conclusion: [oxy-Hb] during the tree-drawing task in patients with SZ was lower than that in healthy controls. Our results suggest that brain dysfunction in patients with SZ might be associated with their tree-drawing. Keywords: tree-drawing test, near-infrared spectroscopy, cognitive function, mnemonic retrieval, executive function, working memory, attention

Hideyuki Imagawa,1 Saurabh P Nagar,2 William Montgomery,3 Tomomi Nakamura,1 Masayo Sato,1 Keith L Davis2 1Medical Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 2RTI Health Solutions, Research Triangle Park, NC, USA; 3Global Patient Outcomes and Real World Evidence, Eli Lilly Australia, NSW, Australia Objective: To describe the characteristics and medication treatment patterns of adult patients with attention-deficit/hyperactivity disorder (ADHD) prescribed atomoxetine in Japan. Materials and methods: A retrospective analysis of insurance claims data was conducted using the Japan Medical Data Center database. Adults (≥18 years) with ADHD who had ≥1 atomoxetine claim from January 1, 2013 to December 31, 2014, and ≥180 to ≤900 days of follow-up were included. First atomoxetine claim defined the index date. Patient characteristics included age, gender, and comorbid conditions. Treatment patterns assessed included rates of atomoxetine discontinuation, switching, persistence, adherence (assessed via the medication possession ratio), and use of concomitant medications. Results: A total of 457 adults met all the inclusion criteria. Mean (SD) age was 32.7 (10.4) years, and 61.0% of patients were male. Nearly 72.0% of the patients had at least one comorbid mental health condition in the baseline period; depression (43.8%) and insomnia (40.7%) were the most common mental health comorbidities. Most common physical comorbidities were chronic obstructive pulmonary disease (14.4%) and diabetes (12.9%). Non-ADHD-specific psychotropics were prescribed to 59.7% of patients during the baseline period and to 65.9% during the follow-up period; 6.6% were prescribed non-ADHD-specific psychotropics concomitantly with atomoxetine. Overall, 40.0% of adults discontinued atomoxetine during the entire follow-up period and 65.9% were persistent with atomoxetine therapy at 3 months post-index date. Mean (SD) atomoxetine medication possession ratio was 0.57 (0.25), and 25.4% switched to an alternative ADHD therapy; methylphenidate (22.4%) and non-ADHD-specific psychotropics (77.6%) were the most common medication alternatives. Nearly 8% augmented atomoxetine with methylphenidates, non-stimulants, or non-ADHD-specific psychotropics. Conclusion: In this observational study, a majority of adults with ADHD treated with atomoxetine were still persistent with therapy at 3 months post-index date, with one quarter switching to alternative ADHD therapy. High proportions of mental health comorbidities, along with high use of non-ADHD-specific psychotropic medications in both the baseline and follow-up periods, were observed among patients with ADHD prescribed atomoxetine. Keywords: ADHD, atomoxetine, treatment patterns, Japan, comorbidity, claims database, adherence, persistence

Ayano Otsuka,1 Yoshikazu Takaesu,1 Mitsuhiko Sato,1 Jiro Masuya,1 Masahiko Ichiki,1 Ichiro Kusumi,2 Takeshi Inoue1 1Department of Psychiatry, Tokyo Medical University, Tokyo, 2Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan Background: Recent studies have suggested that multiple factors interact with the onset and prognosis of major depressive disorders. In this study, we investigated how child abuse, affective temperaments, and interpersonal sensitivity are interrelated, and how they affect depressive symptoms in the general adult population. Subjects and methods: A total of 415 volunteers from the general adult population completed the Patient Health Questionnaire-9, the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire version, the Child Abuse and Trauma Scale, and the Interpersonal Sensitivity Measure, which are all self-administered questionnaires. Data were subjected to structural equation modeling (Mplus), and single and multiple regression analyses. Results: The effect of child abuse on depressive symptoms was mediated by interpersonal sensitivity and 4 affective temperaments, including depressive, cyclothymic, anxious, and irritable temperaments. In addition, the effect of these temperaments on depressive symptoms was mediated by interpersonal sensitivity, indicating the indirect enhancement of depressive symptoms. In contrast to these 4 temperaments, the hyperthymic temperament did not mediate the effect of child abuse on depressive symptoms; its effect was not mediated by interpersonal sensitivity. However, a greater hyperthymic temperament predicted decreased depressive symptoms and interpersonal sensitivity, independent of any mediation effect. Limitations: Because this is a cross-sectional study, long-term prospective studies are necessary to confirm its findings. Therefore, recall bias should be considered when interpreting the results. As the subjects were adults from the general population, the results may not be generalizable towards all patients with major depression. Conclusion: This study suggests that child abuse and affective temperaments affect depressive symptoms partly through interpersonal sensitivity. Interpersonal sensitivity may have a major role in forming the link between abuse, affective temperament, and depression. Keywords: child abuse, affective temperament, TEMPS-A, interpersonal sensitivity, depression, structural equation modeling

William Montgomery,1 Masayo Sato,2 Yasuo Nagasaka,2 Jeffrey Vietri3 1Global Patient Outcomes & Real World Evidence, Eli Lilly Australia Pty Ltd., West Ryde, Australia; 2Medical Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 3Kantar Health, Horsham, PA, USA Background: Few data are available that provide estimates of the economic impact of chronic lower back pain (CLBP) in Japan. The current study estimated the patient burden and the direct and indirect medical costs associated with CLBP in Japan using data from a large cross-sectional patient survey. CLBP was hypothesized to be associated with a considerable burden of illness and a large economic impact.Methods: Study participants completed the Japan National Health and Wellness Survey in 2014, which included measures of health-related quality of life (HRQoL), work impairment, impairment to daily activities, and healthcare service use. Data from those reporting CLBP (N=392) were contrasted against those from matched controls without back pain, using age and sex-adjusted models.Results: CLBP patients reported significantly lower HRQoL relative to matched controls. Age- and sex-adjusted models estimated mean annual per patient direct and indirect costs attributable to CLBP to be ¥1,820,297 ($15,239 or €12,551) and ¥1,479,899 ($12,389 or €10,203), respectively, with the majority of direct costs related to hospital expenses (¥1,584,759, which is equivalent to $13,267 and €10,927). In estimating the economic impact of CLBP on society, the CLBP respondents were estimated to include 1,508,524 individuals when extrapolated to the Japanese population (815,461 of them employed). Ultimately, this represented approximately ¥1.2 trillion ($10 billion and €8.3 billion) per year in lost productivity at the time of this study.Conclusion: This study of patients with CLBP in Japan has shown it to be associated with a significant burden on patients and to have a considerable negative impact on the Japanese economy primarily driven by lost productivity. Further research on the effectiveness of interventions to improve the outcomes of those with CLBP is warranted. Keywords: indirect costs, direct costs, work impairment, healthcare resource use, quality of life

Chihiro Oda,1,2 Toshiyuki Yamamoto,3 Yutaka Fukumoto,4 Keigo Nakayama,1 Masako Sato,1 Miho Murata,3 Yoko Kobayashi1 1Department of Physical Rehabilitation, National Center Hospital, National Center of Neurology and Psychiatry, 2Department of Rehabilitation Medicine, Showa University School of Medicine, 3Department of Neurology, 4Department of Dentistry, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan Background: We developed, and examined the reliability and validity of, a Japanese version of the Dysphagia Handicap Index (DHI; DHI-J), which is a self-reported measure to assess the quality of life (QOL) of individuals with dysphagia. Participants and methods: The DHI-J was developed via the back-translation method: the DHI was translated into Japanese and then translated back into English by a native English speaker. The back translation was discussed with and approved by the DHI’s lead author. A total of 229 patients (119 males, 110 females; median age: 66 years) who underwent videofluorography at our hospital between January and December 2013 and 65 controls (23 males, 42 females; median age: 44 years) were included in the study. All the subjects completed the DHI-J and self-reported their dysphagia severity. Twenty-three patients repeated the procedure 1 week later. Patients’ swallowing function was classified as “normal”, “moderately impaired”, or “severely impaired”, and the DHI-J total scores were compared between the severity groups. Results: The internal consistency of the DHI-J was high (Cronbach’s α=0.95), as was the test–retest reliability of the 23 patients who answered the questionnaire twice (intraclass correlation coefficient =0.98, P

Mototsugu Fukaya,1 Kenji Sato,2 Takahiro Yamada,2 Mitsuko Sato,3 Shigeki Fujisawa,4 Satoko Minaguchi,5 Hajime Kimata,6 Haruhiko Dozono7 1Tsurumai Kouen Clinic, Nagoya, 2Department of Dermatology, Hannan Chuo Hospital, 3Sato Pediatric Clinic, Osaka, 4Fujisawa Dermatology Clinic, Tokyo, 5Ageofutatsunomiya Clinic, Saitama, 6Kimata Hajime Clinic, Osaka, 7Dozono Medical House, Kagoshima, Japan Abstract: Topical corticosteroids (TCS) are regarded as the mainstay treatment for atopic dermatitis (AD). As AD has a tendency to heal naturally, the long-term efficacy of TCS in AD management should be compared with the outcomes seen in patients with AD not using TCS. However, there are few long-term studies that consider patients with AD not using TCS. We designed a prospective multicenter cohort study to assess the clinical outcomes in patients with AD who did not use TCS for 6 months and then compared our results with an earlier study by Furue et al which considered AD patients using TCS over 6 months. Our patients’ clinical improvement was comparable with the patients described in Furue’s research. In light of this, it is reasonable for physicians to manage AD patients who decline TCS, as the expected long-term prognosis is similar whether they use TCS or not. Keywords: atopic dermatitis, topical corticosteroids, topical steroid addiction

Minako Sato,1 Shotaro Chubachi,1 Mamoru Sasaki,1 Mizuha Haraguchi,1 Naofumi Kameyama,1 Akihiro Tsutsumi,1 Saeko Takahashi,1 Hidetoshi Nakamura,1,2 Koichiro Asano,3 Tomoko Betsuyaku1 1Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, 2Department of Respiratory Medicine, Saitama Medical University, Saitama, 3Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan Background: Patients with COPD might not report mild exacerbation. The frequency, risk factors, and impact of mild exacerbation on COPD status are unknown. Objectives: The present study was performed to compare features between mild exacerbation and moderate or severe exacerbation in Japanese patients with COPD. Patients and methods: An observational COPD cohort was designed at Keio University and affiliated hospitals to prospectively investigate the management of COPD comorbidities. This study analyzes data only from patients with COPD who had completed annual examinations and questionnaires over a period of 2 years (n=311). Results: Among 59 patients with mild exacerbations during the first year, 32.2% also experienced only mild exacerbations in the second year. Among 60 patients with moderate or severe exacerbations during the first year, 40% also had the same severity of exacerbation during the second year. Findings of the COPD assessment test and the symptom component of the St George’s Respiratory Questionnaire at steady state were worse in patients with mild exacerbations than in those who were exacerbation free during the 2-year study period, although the severity of the ratio of predicted forced expiratory volume in 1 second did not differ between them. Severe airflow limitation (the ratio of predicted forced expiratory volume in 1 second

Noriko Nishikawa,1 Satoshi Ishiko,2 Ikuko Yamaga,1 Miho Sato,3 Akitoshi Yoshida1 1Department of Ophthalmology, 2Department of Medicine and Engineering Combined Research Institute, Asahikawa Medical University, Asahikawa, 3Department of Ophthalmology, Hamamatsu University School of Medicine, Hamamatsu, Japan Purpose: To assess the role of distance stereoacuity using the System Chart SC-1600 Pola (SC) to evaluate intermittent exotropia (IXT).Methods: Stereoacuity testing was performed in 28 children with IXT and 25 age-matched control subjects using the SC test, the distance Randot stereotest for distance, and the Titmus stereotest for near stereoacuity. Ocular alignment control was defined using the revised Newcastle Control Score (NCS). The correlations between the stereotests and NCS were evaluated using Spearman’s correlation test.Results: Distance stereoacuity was better in both groups when using the SC test than when using the distance Randot stereotest (median: patients with IXT, 90 arcsec and 400 arcsec; control, 60 arcsec and 100 arcsec; P

Ryo Fujiki,1,2 Kiichiro Morita,1,2 Mamoru Sato,1,2 Yuji Yamashita,1,2 Yusuke Kato,1,2 Yohei Ishii,2 Yoshihisa Shoji,1,2 Naohisa Uchimura1 1Department of Neuropsychiatry, Kurume University, 2Cognitive and Molecular Research Institute of Brain Diseases, Kurume University School of Medicine, Kurume-City, Japan Abstract: Neuroimaging studies have been conducted using word generation tasks and have shown greater hypofrontality in patients with schizophrenia compared with healthy subjects. In this study, we compared the characteristics of oxygenated hemoglobin changes involved in both phonological and categorical verbal fluency between 35 outpatients with schizophrenia and 35 healthy subjects during a Japanese “shiritori” task using single-event-related near-infrared spectroscopy. During this task, the schizophrenic patients showed significantly smaller activation in the prefrontal cortex area than the controls. In addition, a significant positive correlation was obtained between oxygenated hemoglobin changes (prefrontal cortex area, inferior parietal area) and the severity of positive psychiatric symptoms. It is possible that hypofrontality of patients may be a diagnostic assistance tool for schizophrenia, and that the relationship between activation and positive syndrome scores may be of help in predicting functional outcome in patients. Keywords: word production task, single-event-related near-infrared spectroscopy, schizophrenia, hypofrontality, biological marker

Saeko Fujiwara,1 Etsuro Hamaya,2 Masayo Sato,2 Peita Graham-Clarke,3 Jennifer A Flynn,2 Russel Burge41Hiroshima Atomic Bomb Casualty Council, Hiroshima, Japan; 2Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan; 3Global Health Outcomes, Eli Lilly Australia, Sydney, NSW, Australia; 4Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USAPurpose: To systematically review the literature describing the efficacy, effectiveness, and safety of raloxifene for postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia).Materials and methods: Medline via PubMed and Embase was systematically searched using prespecified terms. Retrieved publications were screened and included if they described randomized controlled trials or observational studies of postmenopausal Japanese women with osteoporosis or osteopenia treated with raloxifene and reported one or more outcome measures (change in bone mineral density [BMD]; fracture incidence; change in bone-turnover markers, hip structural geometry, or blood–lipid profile; occurrence of adverse events; and change in quality of life or pain). Excluded publications were case studies, editorials, letters to the editor, narrative reviews, or publications from non-peer-reviewed journals; multidrug, multicountry, or multidisease studies with no drug-, country-, or disease-level analysis; or studies of participants on dialysis.Results: Of the 292 publications retrieved, 15 publications (seven randomized controlled trials, eight observational studies) were included for review. Overall findings were statistically significant increases in BMD of the lumbar spine (nine publications), but not the hip region (eight publications), a low incidence of vertebral fracture (three publications), decreases in markers of bone turnover (eleven publications), improved hip structural geometry (two publications), improved blood–lipid profiles (five publications), a low incidence of hot flushes, leg cramps, venous thromboembolism, and stroke (12 publications), and improved quality of life and pain relief (one publication).Conclusion: Findings support raloxifene for reducing vertebral fracture risk by improving BMD and reducing bone turnover in postmenopausal Japanese women with osteoporosis or osteopenia. Careful consideration of fracture risk and the risk–benefit profile of antiosteoporosis medications is required when managing patients with osteoporosis.Keywords: bone density, fractures, osteoporotic, Japan, osteoporosis, raloxifene

Mototsugu Fukaya,1 Kenji Sato,2 Mitsuko Sato,3 Hajime Kimata,4 Shigeki Fujisawa,5 Haruhiko Dozono,6 Jun Yoshizawa,7 Satoko Minaguchi8 1Tsurumai Kouen Clinic, Nagoya, 2Department of Dermatology, Hannan Chuo Hospital, Osaka, 3Sato Pediatric Clinic, Osaka, 4Kimata Hajime Clinic, Osaka, 5Fujisawa Dermatology Clinic, Tokyo, 6Dozono Medical House, Kagoshima, 7Yoshizawa Dermatology Clinic, Yokohama, 8Department of Dermatology, Kounosu Kyousei Hospital, Saitama, Japan Abstract: The American Academy of Dermatology published a new guideline regarding topical therapy in atopic dermatitis in May 2014. Although topical steroid addiction or red burning skin syndrome had been mentioned as possible side effects of topical steroids in a 2006 review article in the Journal of the American Academy of Dermatology, no statement was made regarding this illness in the new guidelines. This suggests that there are still controversies regarding this illness. Here, we describe the clinical features of topical steroid addiction or red burning skin syndrome, based on the treatment of many cases of the illness. Because there have been few articles in the medical literature regarding this illness, the description in this article will be of some benefit to better understand the illness and to spur discussion regarding topical steroid addiction or red burning skin syndrome. Keywords: topical steroid addiction, atopic dermatitis, red burning skin syndrome, rebound, corticosteroid, eczema

Ryo Fujiki,1,2 Kiichiro Morita,1,2 Mamoru Sato,1,2 Yuji Kamada,1,2 Yusuke Kato,1,2 Masayuki Inoue,2 Yoshihisa Shoji,1,2 Naohisa Uchimura1 1Department of Neuropsychiatry, Kurume University School of Medicine, Kurume-City, Japan; 2Cognitive and Molecular Research Institute of Brain Diseases, Kurume University School of Medicine, Kurume-City, Japan Abstract: Schizophrenia has been associated with a deficit of the prefrontal cortex, which is involved in attention, executive processes, and working memory. The Trail Making Test (TMT) is administered in two parts, TMT-A and TMT-B. It is suggested that the difference in performance between part A and part B reflects executive processes. In this study, we compared the characteristics of hemodynamic changes during TMT tasks between 14 outpatients with schizophrenia and 14 age- and gender-matched healthy control subjects. Using multichannel near-infrared spectroscopy, we measured relative changes in oxygenated hemoglobin concentration, which reflects brain activity of the prefrontal cortex during this task. In both tasks, patients showed significantly smaller activation than controls and, in an assessment of executive functions, a subtraction of oxygenated hemoglobin (oxy-Hb) changes during TMT-A from those of TMT-B showed a decrease in cerebral lateralization and hypoactivity in patients. There was a significant negative correlation between oxy-Hb changes and the severity of psychiatric symptoms. These findings may characterize disease-related features, suggesting the usefulness of oxy-Hb change measurement during TMT tasks for assessing functional outcomes in schizophrenic patients. Keywords: Trail Making Test, multichannel near-infrared spectroscopy, schizophrenia, prefrontal cortex, executive function

The extracellular matrix (eCM) of articular cartilage has several functions that are unique to joints. Although a technique for transplanting cultured chondrocytes has already been introduced, it is difficult to collect intact eCM when using enzymes to harvest samples. Temperature-responsive culture dishes have already been clinically applied in the fields of myocardial and corneal transplantation. Earlier studies have shown that a sheet of cultured cells with intact eCM and adhesive factors can be harvested using such culture dishes, which allow the surface properties of the dish to be reversibly altered by changing the temperature. Human chondrocytes were subjected to enzymatic digestion and then were seeded in temperature-responsive culture dishes. A sheet of chondrocytes was harvested by only reducing the temperature after the cultured cells reached confluency. A real-time PCR analysis of the chondrocyte sheets confirmed that type II collagen, aggrecan, and fibronectin were present. These results suggested that, although chondrocytes undergo dedifferentiation in a monolayer culture, multilayer chondrocyte sheets grown in a similar environment to that of three-dimensional culture may be able to maintain a normal phenotype. A histological examination suggested that multilayer chondrocyte sheets could thus prevent the loss of proteoglycans because the area covered by the sheets was well stained by safranin-O. The present experiments suggested that temperature-responsive culture dishes are useful for obtaining cultured chondrocytes, which may then be clinically employed as a substitute for periosteal patches because such sheets can be applied without a scaffold.

Total cross section for the double neutral pion photoproduction off the proton is presented in the incident photon energy range of 0.58 to 1.15 GeV. The data were accumulated in the years 2009–2010, recorded by a 4π EM calorimeter at ELPH, named FOREST. The number of recorded events obtained during this period is 1.6×109 for a hydrogen target. Two neutral pions are reconstructed via detecting their decay products, four gammas (2π0 → 4γ). Compared to the previous results obtained by other groups, our data are in good agreement with theirs within error bars.

We have collected the first physics data of an experimental search for the simplest kaonic nuclear bound state, “K− pp”, by the 3He(K− n) reaction at J-PARC. We confirmed that our spectrometer system works as designed and observed clear peak structure composed of the quasi-elastic K−“n” → K−n and the charge-exchange K−“p” → ¯̅K0n reactions in the forward neutron spectrum.

In the J-PARC E15 experiment, a K− pp search was performed via the 3He(K−, n) reaction at 1.0 GeV/c. A forward-going neutron is detected by a neutron counter with 15 m flight length, and decay particles from K− pp are simultaneously measured by a cylindrical detector system that surrounds a liquid 3He target system. In March and May, 2013, we carried out the first physics data-taking with 5×109 incident kaons on the 3He target, and we have obtained a preliminary exclusive analysis result of 3He(K−, Λp)n reaction.

Abstract We aimed to evaluate the subcutaneous tissue reaction to a newly-developed MgO Sealer for root canals. We injected the experimental material and three existing control materials into the dorsal area of 43 male ddY mice. One week and 12 weeks after embedding, the tissue surrounding the embedding sites was removed and histopathological examination was performed. The results demonstrate that the basic histopathological reaction is the formation of fibrous capsules consisting of granulation tissue around the experimental and control embedded materials. Based on our results, we believe that the newly-developed MgO Sealer is as safe as the existing control materials and can be considered for dental use as a root canal sealer.

Abstract We examined change of Runx2 and ALP expression in mouse tooth pulp which exposed to teeth separation experiment by immunohistochemistry as a model for conservative dentistry treatment. 8-week-old 36 male ddY mice were used and wedge was inserted between upper 1st and 2nd molars. The wedge was removed 30 minutes as well as 3 hours after the insertion and the samples were prepared extending up to 1 week of time period for regular histopathological and immunohistochemical examinations for ALP and Runx2 expression. The opposite sides without wedge insertion were taken as controls. In the control group pulp, weak expressions of Runx2 and ALP in the vessel endothelial cells as well as the pulp cells were revealed, suggesting the appearance of these genes upon mechanical stress induced by mastication and tongue pressure etc. On the other hand in the experiment group, Runx2 expression increased both in 30-minute and 3-hour teeth separation group. The expression became maximum at 24 hours. Then it gradually decreased and became similar level with the control group at 1-week after the wedge insertion. Similarly ALP expression increased after the wedge insertion and was maximum at 24 hours and then gradually decreased to the levels similar with the control group. These results suggest that when immunohistochemical expression of Runx2 as well as ALP was used as an index, no severe damage occur upon clinical application of wedge insertion.