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Tomoki Nakamura,1 Kunihiro Asanuma,1 Motoshi Takao,2 Takashi Yamanaka,3 Hiroshi Koike,4 Toyofumi F Chen-Yoshikawa,5 Satoshi Tsukushi,6 Hiroaki Kuroda,7 Eiji Kozawa,8 Masaaki Sano,9 Hisaki Aiba,10 Ryoichi Nakanishi,11 Akihito Nagano,12 Kenji Yamada,13 Yoji Shido,14 Katsuhisa Kawanami,15 Yuya Izubuchi,16 Akihiro Sudo,1 Yoshihiro Nishida4,17 1Department of Orthopedic Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan; 2Department of Thoracic Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan; 3Department of Radiology, Mie University Graduate School of Medicine, Tsu, Mie, Japan; 4Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; 5Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; 6Department of Orthopedic Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan; 7Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan; 8Department of Orthopedic Surgery, Nagoya Memorial Hospital, Nagoya, Aichi, Japan; 9Department of Thoracic Surgery, Nagoya Memorial Hospital, Nagoya, Aichi, Japan; 10Department of Orthopedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan; 11Department of Oncology, Immunology and Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan; 12Department of Orthopedic Surgery, Gifu University Graduate School of Medicine, Gifu, Gifu, Japan; 13Department of Musculoskeletal Oncology, Okazaki City Hospital, Okazaki, Aichi, Japan; 14Department of Orthopedic Surgery, Hamamatsu Medical University, Hamamatsu, Sizuoka, Japan; 15Department of Orthopedic Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan; 16Department of Orthopedics and Rehabilitation Medicine, University of Fukui Faculty of Medical Sciences, Eiheiji, Fukui, Japan; 17Department of Rehabilitation, Nagoya University Hospital, Nagoya, Aichi, JapanCorrespondence: Tomoki NakamuraDepartment of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, JapanTel +81592315022Fax +81592315211Email tomoki66@med.mie-u.ac.jpPurpose: Here, we investigated the oncological outcomes of lung metastasectomy and/or radiofrequency ablation (RFA) of 92 patients with soft tissue sarcoma (STS) at nine institutions.Methods: The study cohort included 65 men and 27 women with a mean age of 59 years at the time of metastasis. The mean follow-up duration was 51 months. All patients underwent metastasectomy and/or RFA for lung metastasis.Results: The mean maximum size of the initial lung metastasis was 14.6 mm. At the initial evaluation, 41 patients had a single metastasis, whereas 51 patients had multiple metastases. The mean number of metastasectomies and/or RFA was 2 per patient. A total of 70 patients underwent lung metastasectomy, whereas the other 13 underwent lung RFA. The remaining nine patients underwent both RFA and metastasectomy. The 5-year post-metastatic survival rate was 52%. The patients who underwent complete treatment for the initial metastasis had better post-metastatic survival rates than those who underwent incomplete treatment. A univariate analysis of all possible prognostic factors for complete treatment confirmed the predictive value of disease-free interval, metastasis at initial presentation, distribution, tumor size, and number of lung metastases. Of the 92 patients, 74 underwent complete treatment for initial metastasis; in these patients, univariate and multivariate analyses showed that a smaller tumor size and single-lung metastasis were prognostic factors for superior post-metastatic survival. The patients with a smaller (< 11.5 mm) single metastasis had better post-metastasis survival. The 5-year post-metastatic survival rates were 89.9% for patients with a smaller (< 11.5 mm) single metastasis versus 22.7% for patients with larger (> 11.5 mm) and multiple metastases.Discussion: We propose that complete treatment for lung metastasis in patients with STS may improve post-metastatic survival rates. Furthermore, tumor number and size are important variables for clinical decision-making.Keywords: lung metastasis, metastasectomy, radiofrequency ablation, soft tissue sarcoma

Kanako Azuma,1 Takashi Kawaguchi,2 Takuhiro Yamaguchi,3 Sayuri Motegi,1 Kimito Yamada,4 Kenji Onda,5 Satoru Iwase,6 Sakae Unezaki,2 Hironori Takeuchi1 1Department of Pharmacy, Tokyo Medical University Hospital, Tokyo, Japan; 2Department of Practical Pharmacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; 3Division of Biostatistics, Tohoku University Graduate School of Medicine, Miyagi, Japan; 4Department of Breast Surgery, Tokyo Medical University Hospital, Tokyo, Japan; 5Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; 6Department of Emergency & Palliative Medicine, Faculty of Medicine, Saitama Medical University, Saitama, JapanCorrespondence: Takashi Kawaguchi Email tkawa@toyaku.ac.jpPurpose: The importance of shared decision-making (SDM) between physicians and patients is increasingly recognized. In Japan, patients have shown more willingness to participate in treatment if medical professionals provide sufficient information; however, relationships between physicians and patients have traditionally been asymmetric, with patients accepting information from physicians without discussion. To explore the benefits of SDM in cancer treatment, including confidence in treatment decisions, satisfaction with treatment, and trust in healthcare providers, this study developed Japanese versions of the Control Preference Scale (CPS) and Information Needs Questionnaire (INQ).Patients and Methods: Reliability and validity of the CPS and INQ were tested with 49 breast cancer patients.Results: The CPS showed good test–retest reliability (kappa coefficient: 0.61, weighted kappa coefficient: 0.61, Kendall’s tau coefficient: 0.61) and acceptable criterion validity. The INQ showed adequate consistency; the mean number of circular triads and coefficient of consistency were 3 (range 0– 19) and 0.9 (range 0.37– 1), respectively. Using the CPS and INQ to identify patients’ roles in decision-making and information needs, results further suggested that breast cancer patients in Japan want to participate in SDM. Medical issues, including disease spread and cure, were found to be of high interest, while social and psychological issues, including sexual attractiveness, genetic risk, and family impact, tended to be low.Conclusion: The Japanese CPS and INQ can be used to assess patients’ needs to improve care. Further, as patients’ information needs change along the care trajectory, these tools should be used throughout treatment.Keywords: shared decision-making, breast cancer, treatment option, control preference scale, information needs questionnaire

Hideki Shibata, Takeshi Aoki, Tomotake Koizumi, Tomokazu Kusano, Tatsuya Yamazaki, Kazuhiko Saito, Takahito Hirai, Kodai Tomioka, Yusuke Wada, Tomoki Hakozaki, Yoshihiko Tashiro, Koji Nogaki, Kosuke Yamada, Kazuhiro Matsuda, Akira Fujimori, Yuta Enami, Masahiko Murakami Division of Gastroenterological and General Surgery, Department of Surgery, School of Medicine, Showa University, Tokyo, JapanCorrespondence: Takeshi AokiDivision of Gastroenterological and General Surgery, Department of Surgery, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, JapanTel +81-3-3784-8000Fax +81-3-3784-5835Email takejp@med.showa-u.ac.jpPurpose: Bile duct injury is one of the most serious complications of laparoscopic cholecystectomy. Intraoperative indocyanine green (ICG) cholangiography is a safe and useful navigation modality for confirming the biliary anatomy. ICG cholangiography is expected to be a routine method for helping avoid bile duct injuries.Patients and Methods: We examined 25 patients who underwent intraoperative cholangiography using ICG fluorescence. Two methods of ICG injection are used: intrabiliary injection (percutaneous transhepatic gallbladder drainage [PTGBD], gallbladder [GB] puncture and endoscopic nasobiliary drainage [ENBD]) at a dosage of 0.025 mg during the operation or intravenous injection with 2.5 mg ICG preoperatively.Results: There were 24 patients who underwent laparoscopic cholecystectomy and 1 patient who underwent hepatectomy. For laparoscopic cholecystectomy, the average operation time was 127 (50– 197) minutes, and estimated blood loss was 43.2 (0– 400) g. The ICG administration route was intravenous injections in 12 cases and intrabiliary injection in 12 cases (GB injection: 3 cases, PTGBD: 8 cases, ENBD:1 case). The course of the biliary tree was able to be confirmed in all cases that received direct injection into the biliary tract, whereas bile structures were recognizable in only 10 cases (83.3%) with intravenous injection. The postoperative hospital stay was 4.6 (3– 9) days, and no postoperative complications (Clavien–Dindo ≧IIIa) were observed. For hepatectomy, a tumor located near the left Glissonian pedicle was resected using a fluorescence image guide. Biliary structures were fluorescent without injury after resecting the tumor. No adverse events due to ICG administration were observed, and the procedure was able to be performed safely.Conclusion: ICG fluorescence imaging allows surgeons to visualize the course of the biliary tree in real time during cholecystectomy and hepatectomy. This is considered essential for hepatobiliary surgery to prevent biliary tree injury and ensure safe surgery.Keywords: indocyanine green fluorescent imaging, navigation surgery, near-infrared fluorescent cholangiography

Atsushi Miyamoto, Kazuhisa Asai, Hideaki Kadotani, Naomi Maruyama, Hiroaki Kubo, Atsuko Okamoto, Kanako Sato, Kazuhiro Yamada, Naoki Ijiri, Tetsuya Watanabe, Tomoya Kawaguchi Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, JapanCorrespondence: Kazuhisa AsaiDepartment of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-Machi, Abeno-ku, Osaka-City, Osaka 545-8585, JapanTel +81-6-6645-3916Fax +81-6-6646-6160Email kazuasai@med.osaka-cu.ac.jpPurpose: Sarcopenia, the loss of skeletal muscle mass and strength, is a common systemic consequence of chronic obstructive pulmonary disease (COPD) and is correlated with higher mortality. Ninjin’yoeito (NYT) is a Japanese herbal medicine used to treat athrepsia and anorexia and is reported to ameliorate weight loss and muscular dysfunction. Recent studies have shown that its crude components upregulate the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-related pathway, which is involved in skeletal muscle functions. Here, we examined whether NYT improves skeletal muscle complications by upregulating PGC-1α in COPD model mice.Materials and Methods: Mice were divided into four groups: control, NYT, smoking, and smoking + NYT. The smoking and smoking + NYT groups were exposed to cigarette smoke for 60 min once daily. The mice in the NYT and smoking + NYT groups were fed an NYT-containing diet (3% w/w). We performed cellular analysis of bronchoalveolar lavage fluid, assessed pulmonary morphological changes, examined the expression of PGC-1α mRNA and protein in the gastrocnemius and soleus muscle, measured the hindlimb muscle volume with micro-computed tomography, and determined the myofiber proportion in soleus muscle after 12 weeks.Results: Cigarette smoke exposure resulted in reduced skeletal muscle volume and slow-twitch muscle fibers and development of pulmonary emphysema. NYT feeding induced partial recovery of the damaged alveolar wall; however, NYT did not ameliorate smoke-induced alveolar enlargement. These findings revealed that NYT did not have sufficient efficacy in suppressing pulmonary emphysema. On the other hand, PGC-1α expression in muscle tissue of the NYT-fed mice increased significantly, resulting in suppression of smoke-induced loss of muscle mass and alteration in the muscle fiber distribution.Conclusion: NYT increases PGC-1α expression in the muscle of COPD model mice and is involved in suppressing cigarette smoke-induced muscle complications. NYT may be a novel preventive and therapeutic medication for muscular dysfunctions in COPD.Keywords: chronic obstructive pulmonary disease, sarcopenia, peroxisome proliferator-activated receptor γ coactivator-1α, Ninjin’yoeito, muscle dysfunction

Takashi Takeda,1 Kana Yoshimi,1 Keiko Yamada2,3 1Division of Women’s Health, Research Institute of Traditional Asian Medicine, Kindai University, Osaka 589-8511, Japan; 2Department of Psychology, McGill University, Montreal, Quebec H3A 1G1, Canada; 3Department of Anesthesiology and Pain Management, Juntendo University Faculty of Medicine, Tokyo 113-0033, JapanCorrespondence: Takashi TakedaDivision of Women’s Health, Research Institute of Traditional Asian Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, JapanTel + 81-72-366-0221 (Ext. 3393)Fax + 81-72-366-6661Email take@med.kindai.ac.jpPurpose: Premenstrual symptoms comprise a wide range of mood, behavioral, and physical symptoms occurring during the luteal phase. Perceived injustice is a belief linked to unfairness (ie, unnecessary suffering caused by illness). This study aimed to assess the validity and reliability of the Premenstrual Symptoms Questionnaire (PSQ), a patient-reported outcome measurement tool, and to examine the association between perceived injustice/perception of menstruation and premenstrual symptoms, as measured by the PSQ.Materials and Methods: Of 1388 female students, we analyzed 879 students with regular menstrual cycles who completed the PSQ, the premenstrual dysphoric disorder (PMDD) scale, the Somatic Symptom Scale-8 (SSS-8), and the Injustice Experience Questionnaire-chronic (IEQ-chr). First, the PSQ was examined for evidence of reliability and validity. Next, we used multiple regression and multivariate logistic regression to investigate the association between perceived injustice and premenstrual symptoms, using PSQ score as both a continuous variable and a dichotomous variable (premenstrual disorders or not). Moreover, the association between PSQ score and perceived menstruation was tested using student’s t-test and analysis of variance.Results: In terms of reliability, Cronbach’s α for PSQ score was 0.93. To assess structural validity, we used confirmatory factor analysis, which showed that the one-factor model and the two-factor model were a good fit. The PSQ showed good agreement with the PMDD scale. In terms of concurrent validity, PSQ total score correlated strongly with PMDD scale score, SSS-8 score, and IEQ-chr score (r = 0.88, 0.69, 0.57, respectively). IEQ-chr score predicted PSQ score (standardized regression coefficient = 0.53; P < 0.0001) and higher prevalence of premenstrual disorders (odds ratio: 1.15; 95% confidence interval: 1.12– 1.19). Negative perception of menstruation was associated with premenstrual symptoms.Conclusion: The PSQ showed sound psychometric properties among the adolescents in our sample. Perceived injustice and negative perception of menstruation were associated with premenstrual symptoms.Keywords: premenstrual syndrome, premenstrual disorders, injustice experience questionnaire-chronic, psychometric testing, validity

Keiko Yamada,1,2 Takatoshi Maeno,3 Shunji Kusaka,4 Jorge G Arroyo,2 Mitsunori Yamada5 1Department of Ophthalmology, Faculty of Medicine, Osaka University, Osaka, Japan; 2Department of Ophthalmology, Harvard University Beth Israel Deaconess Medical Center, Boston, MA, USA; 3Department of Ophthalmology, Toho University Sakura Medical Center, Chiba, Japan; 4Department of Ophthalmology, Faculty of Medicine, Kindai University, Osaka, Japan; 5Yamada Eye Clinic, Tokushima, JapanCorrespondence: Keiko Yamada Email meyamada@mb3.tcn.ne.jpPurpose: The peripheral adult human retina has been found to contain neuroepithelial stem cells. In this study, we examined the efficacy of an auto-transplant of peripheral retina into refractory macular holes (MH) from both anatomic and physiologic perspectives.Methods: The population consisted of four female patients aged 72, 82, 65 and 84 years (cases 1– 4, respectively) with persistent refractory MH status; internal limiting membrane (ILM) peeling (case 1), ILM transplant (case 2), and inverted ILM (cases 3 and 4 with myopic MH). In all our cases, retinal grafts were harvested beyond the equator from the far retinal periphery using curved horizontal scissors and gently moved toward the MH using a forceps. A 25-G manipulator with a silicone ball tip was used to tuck the trimmed graft into the MH, followed by fluid-air exchange and infusion of silicone oil, which was removed three months later.Results: Partial restoration and integration of the outer retinal layer were confirmed on an OCT-B scan imaging. The visual acuity (VA) was improved in all cases: 1.2 to 1.0 logMAR (case 1), 2.0 to 1.3 logMAR (case 2), 2.3 to 1.4 logMAR (case 3) and 2.0 to 1.0 logMAR (case 4). Microperimetry showed improved retinal sensitivity in every case. No intra- or post-operative complications were observed.Conclusion: Under pathological conditions, the Müller glia reportedly serves as a source of neuronal progenitor cells in regenerating retina, continuing to divide and migrate to the outer nuclear layer thus replacing lost photo-receptors. Although the histological findings remain unknown, the positive anatomic and physiologic outcomes of the auto-transplanted retinal flap in our series suggest that this technique may offer an effective option for treating recalcitrant MH. Further studies are warranted.Keywords: retina, macular hole, vitrectomy, stem cell, transplant; Müller glia

Hiroaki Kubo, Kazuhisa Asai, Kazuya Kojima, Arata Sugitani, Yohkoh Kyomoto, Atsuko Okamoto, Kazuhiro Yamada, Naoki Ijiri, Tetsuya Watanabe, Kazuto Hirata, Tomoya Kawaguchi Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, JapanCorrespondence: Kazuhisa AsaiDepartment of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-Ku, Osaka 545-8585, JapanTel +81 6 6645 3916Fax +81 6 6646 6160Email kazuasai@med.osaka-cu.ac.jpBackground: Oxidative stress is one of the important mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD). Irisin is a type of myokine secreted from the muscle during exercise and acts against oxidative stress via nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor with antioxidant properties. Here, we examined the emphysema suppressive effects of the exercise-irisin-Nrf2 axis in mice.Methods: Mice were divided into three groups, namely, the control, smoking, and exercise + smoking groups. All mice from the smoking and exercise + smoking groups were exposed to cigarette smoke once a day. The mice from the exercise + smoking group were adapted to a treadmill once a day. To investigate the Nrf2 cascade, after 12 weeks, serum irisin concentration and Nrf2 and heme oxygenase-1 (HO-1) expression in the lung homogenate were determined. To evaluate cigarette smoke-induced COPD, the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), mean linear intercept (MLI), and destructive index in the lung tissue were examined.Results: Serum irisin concentration and the expression levels of Nrf2 and HO-1 in the lung homogenate were significantly higher in mice from the exercise + smoking group than in those from the control and smoking groups. The proportion of neutrophils in the BALF was significantly lower in the exercise + smoking group than in the smoking group. The MLI and destructive index were also significantly smaller in mice from the exercise + smoking group than mice from the smoking group.Conclusion: Irisin secreted from the muscle during exercise may exert protective effects against oxidative stress via Nrf2 and HO-1, and ameliorate emphysema of cigarette smoke-induced COPD. The exercise-irisin-Nrf2 axis may serve as a novel target for COPD treatment.Keywords: chronic obstructive pulmonary disease, oxidative stress, exercise, irisin, nuclear factor erythroid 2-related factor 2, heme oxygenase-1

Ayako Kasai,1 Ayaka Ohta,1 Yuina Maeda,1 Kageto Yamada,2 Kazuyuki Tao,3 Ryoichi Saito1 1Department of Molecular Microbiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan; 2Department of Clinical Laboratory, Toho University Medical Center Omori Hospital, Ota-ku, Tokyo 143-8541, Japan; 3Radioisotope Center, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan Background: High-level macrolide-resistant Moraxella catarrhalis strains have been isolated; however, the underlying mechanism has not been well elucidated. We investigated the role of mutations in the 23S rRNA gene and the L4 and L22 ribosomal proteins using spontaneous erythromycin-resistant mutants and transformants. Materials and methods: The erythromycin-susceptible M. catarrhalis ATCC25238 and clinical isolate Mc19 were used as parental strains. To obtain spontaneous erythromycin-resistant mutants, in vitro stepwise selection was performed using brain–heart infusion agar plates containing various concentrations of erythromycin. The role of the mutations identified in the spontaneous mutants was validated using transformation experiments. Results: We obtained two spontaneous mutants with high-level resistance to erythromycin, S25-32-af10 and S19-256-af10, from ATCC25238 and Mc19, respectively. S25-32-af10 exhibited mutations of Q61R in L4 and Insertion98SRADRIS in L22. S19-256-af10 exhibited three C2611T-mutated alleles in the 23S rRNA gene and G65A in L4. Transformants with single mutations identified in S25-32-af10 or S19-256-af10 showed higher erythromycin and azithromycin minimum inhibitory concentrations (MICs) than those of each parental strain. However, transformants with multiple mutations identified in S25-32-af10 or S19-256-af10 showed macrolide MICs similar to those of each parental strain. Conclusion: Our results provide the first evidence suggesting that Q61R in L4 and Insertion98SRADRIS in L22 are involved in the synergistic acquisition of high-level resistance to both 14- and 15-member macrolides, and that C2611T in the 23S rRNA gene and G65A in L4 also synergistically contribute toward conferring high-level 14-member macrolide resistance to M. catarrhalis. Keywords: macrolide, Moraxella catarrhalis, ribosomal protein, 23S rRNA gene

Juichi Tonosu,1 Hiroyuki Oka,2,3 Kenichi Watanabe,1 Hiroaki Abe,1 Akiro Higashikawa,1 Koji Yamada,1 Takashi Kuniya,1 Koji Nakajima,1 Sakae Tanaka,3 Ko Matsudaira2,3 1Department of Orthopedic Surgery, Kanto Rosai Hospital, Kanagawa, Japan; 2Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; 3Department of Orthopedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan Background: There are no specific radiological findings for the diagnosis of sacroiliac joint-related pain. A diagnostic scoring system had been developed in 2017. The score comprised the sum of scores of six items. The score ranged from 0 to 9 points, and the cutoff was calculated as 4. Objective: To evaluate the validity of the diagnostic scoring system for sacroiliac joint-related pain. Patients and methods: The sacroiliac joint-related pain group (n=31) comprised patients diagnosed with sacroiliac joint-related pain based on patient history, physical findings, and responses to analgesic periarticular injection. In addition, it was confirmed that they had no other lumbar or hip joint diseases. The non-sacroiliac joint-related pain group (n=123) comprised patients with low back pain due to a reason other than sacroiliac joint-related pain. We evaluated scores for all subjects. We analyzed the differences in each item between both groups and performed receiver-operating characteristic curve analysis to evaluate the score validity. Results: There were no significant differences in patient characteristics between groups. There were significant differences for the following four of six items: one-finger test results (P

Anri Watanabe,1 Takashi Nakamae,1 Yuki Sakai,2 Seiji Nishida,1 Yoshinari Abe,1 Kei Yamada,3 Isao Yokota,4 Jin Narumoto1 1Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Neural Computation for Decision-Making, Advanced Telecommunications Research Institute International Brain Information Communication Research Laboratory Group, Kyoto, Japan; 3Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 4Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan Purpose: In recent years, a large number of studies have investigated obsessive–compulsive disorder (OCD) using diffusion-weighted images (DWIs) and have reported microstructural abnormalities in various regions, mainly the corpus callosum and cingulum. In the present study, we aimed to detect microstructural changes in the white matter using whole-brain tractography. Patients and methods: We obtained MRI data from 25 adult non-medicated OCD patients and 27 healthy controls. DWI data from MRI scans were analyzed by the automated probabilistic tractography method referred to as TRActs Constrained by UnderLying Anatomy (TRACULA). We investigated diffusivity parameters: fractional anisotropy, radial diffusivity (RD), axial diffusivity, and mean diffusivity in 18 major white matter tracts and examined indices to know which measurements in which fibers can predict the diagnosis of OCD. Results: Compared to healthy controls, OCD patients had significantly increased RD in the forceps major and a reduction of RD in the right cingulum angular (infracallosal) bundle. There was no correlation between these values and the clinical features. Conclusion: We found RD alterations in the forceps major and the right cingulum angular (infracallosal) bundle, which might be associated with myelination changes in the temporal and occipital regions in OCD. Our results suggest that the pathogenesis of OCD may include abonormality of myelination status in not only the fronto-striato-thalamic circuit but also the posterior and temporal regions. Keywords: tractography, radial diffusivity, forceps major, cingulum

Kumi Sakurada,1,* Takeshi Kozaru,2,* Kazuo Yamada,1 Masashi Nibuya,1 Kiyoshi Nagata,3 Eiji Suzuki1 1Department of Psychiatry, 2Department of Dermatology, 3Department of Environmental and Health Science, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan *These authors contributed equally to this work Abstract: A 73-year-old man, exhibiting psychomotor excitement after traumatic brain injury, developed allergic cutaneous eruptions and hepatic inflammation that did not resolve after the cessation of carbamazepine (CBZ). Fusing maculopapular erythema was observed in the face, neck, presternal region, and bilaterally in the forearms and feet. A drug-induced lymphocyte stimulation test revealed hypersensitivity to chlorpromazine (CPZ) and valproic acid (VPA), as well as to CBZ. The allergic reaction with eosinophilia to CPZ and VPA was suspected to have emerged following CBZ hypersensitivity, since previous treatment with CPZ and VPA prior to the introduction of CBZ had not been associated with adverse reactions earlier in the course of treatment. Recent studies have indicated linkages between severe CBZ hypersensitivity – but not mild CBZ hypersensitivity – and specific leukocyte antigens, HLA-B*1502 and HLA-A*3101, in Asian and European populations. The present case exhibited the HLA-B*4601 allele, which is associated with a high relative risk for the development of CBZ-induced maculopapular eruptions in Japanese and Han Chinese populations. Although cross-hypersensitivity among aromatic compounds, including CBZ and CPZ, is well-established, data regarding CBZ allergy-associated hypersensitivity to VPA are limited. In the present case, a cutaneous allergy to mianserin (a tetracyclic antidepressant) was also observed later in the course of treatment, suggesting additional cross-reactivity exists among aromatic psychotropic drugs. Thus, the association between the HLA-B*4601 allele and allergic reactions to VPA, aromatic psychotropic drugs, and CBZ should be further examined in future studies. Keywords: human leukocyte antigen, pharmacogenomics, maculopapular erythema, carbamazepine, chlorpromazine, valproic acid

Kiyoka Enomoto,1–3 Tomonori Adachi,2–4 Keiko Yamada,5 Daisuke Inoue,2,6 Miho Nakanishi,7 Tomohiko Nishigami,2,8 Masahiko Shibata1,2 ¹Department of Pain Medicine, Osaka University Graduate School of Medicine, Suita, Japan; 2Center for Pain Management, Osaka University Hospital, Suita, Japan; 3Department of Anesthesiology, Interdisciplinary Pain Management Center, Shiga University of Medical Science Hospital, Otsu, Japan; 4Japan Society for the Promotion of Science (JSPS), Tokyo, Japan; 5Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Suita, Japan; 6Department of Occupational Therapy, Osaka College of Rehabilitation, Osaka, Japan; 7Department of Anesthesiology, Shiga University of Medical Science, Otsu, Japan; 8Department of Nursing and Physical Therapy, Konan Woman’s University, Kobe, Japan Purpose: To confirm the psychometric properties of the Athens Insomnia Scale (AIS) among Japanese chronic pain patients.Patients and methods: In total, 144 outpatients were asked to complete questionnaires comprising the AIS and other study measures. According to the original article, the AIS has 2 versions: the AIS-8 (full version) and the AIS-5 (brief version). To validate the AIS-8 and AIS-5 among chronic pain patients, we confirmed: 1) factor structure by confirmatory factor analysis; 2) internal consistency by Cronbach’s a; 3) test–retest reliability using with interclass correlation coefficients; 4) known-group validity; 5) concurrent validity; and 6) cut-off values by receiver operating characteristic analysis. In addition, semi-structured interviews were conducted to assess the participants’ sleep disturbance. If the participants had any sleep complaints, including difficulty in initiating sleep, difficulty in maintaining sleep, and early morning awakening, they were defined as insomnia symptoms.Results: A 2-factor model of the AIS-8 and 1-factor model of the AIS-5 demonstrated good fit. The AIS had adequate internal consistency and test–retest reliability. Patients with insomnia had a higher AIS score than those without insomnia. The sleep disturbance measured by the AIS was positively associated with pain intensity, disability, depression, anxiety, and pain catastrophizing, and negatively associated with pain-related self-efficacy. The cut-off values for detecting insomnia were estimated at 8 points in the AIS-8 and 4 points in the AIS-5.Conclusion: The AIS-8 and AIS-5 had adequate reliability and validity in chronic pain patients. Keywords: sleep disturbance, AIS, Japanese, insomnia symptom

Masao Ichiki,1 Hiroshi Wataya,2 Kazuhiko Yamada,3 Nobuko Tsuruta,4 Hiroaki Takeoka,1 Yusuke Okayama,1 Jun Sasaki,1 Tomoaki Hoshino3 1Department of Respiratory Medicine, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, 2Division of Internal Medicine, Saiseikai Fukuoka General Hospital, Fukuoka City, 3Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University, Kurume City, 4Department of Respiratory Medicine, Hamanomachi Hospital, Fukuoka City, Fukuoka, Japan Purpose: Diarrhea and oral mucositis induced by afatinib can cause devastating quality of life issues for patients undergoing afatinib treatment. Several studies have shown that hangeshashin-to (TJ-14) might be useful for chemotherapy-induced diarrhea and oral mucositis. In this study, we investigated the prophylactic effects of TJ-14 for afatinib-induced diarrhea and oral mucositis and minocycline for afatinib-induced skin rash.Patients and methods: First- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors have become the standard first-line treatment in patients with EGFR-mutated non-small cell lung cancer. The incidence of diarrhea was higher with afatinib than with gefitinib, and we conducted a single-arm Phase II study with afatinib. Patients who had previously undergone treatment with afatinib were ineligible. Both TJ-14 (7.5 g/day) and minocycline (100 mg/day) were administered simultaneously from the start of afatinib administration. The primary end point was the incidence of ≥ grade 3 (G3) diarrhea (increase of ≥7 stools/day over baseline) during the first 4 weeks of treatment. The secondary end points were the incidence of ≥ G3 oral mucositis (severe pain interfering with oral intake) and ≥ G3 skin toxicity (severe or medically significant but not immediately life-threatening).Results: A total of 29 patients (nine men and 20 women; median age, 66 years; performance status, 0/1/2: 18/10/1) were enrolled from four centers. Four patients had undergone prior treatment with chemotherapy, including gefitinib or erlotinib. In all, 20 (68.9%) patients and one (3.4%) patient had diarrhea of any grade and ≥ G3, respectively. One (3.4%) patient had ≥ G3 oral mucositis; no patients had ≥ G3 skin rash. A total of 18 (62%) of the 29 patients achieved a partial response.Conclusion: The present study indicated a trend in which TJ-14 reduced the risk of afatinib-induced diarrhea and minocycline reduced the risk of afatinib-induced skin rash. Keywords: epidermal growth factor receptor, hangeshashin-to, afatinib, adverse events

We present the requirements, design, and evaluation of the cryogenic continuously rotating half-wave plate (CHWP) for the Simons Observatory (SO). SO is a cosmic microwave background polarization experiment at Parque Astronómico de Atacama in northern Chile that covers a wide range of angular scales using both small (⌀0.42 m) and large (⌀6 m) aperture telescopes. In particular, the small aperture telescopes (SATs) focus on large angular scales for primordial B-mode polarization. To this end, the SATs employ a CHWP to modulate the polarization of the incident light at 8 Hz, suppressing atmospheric 1/f noise and mitigating systematic uncertainties that would otherwise arise due to the differential response of detectors sensitive to orthogonal polarizations. The CHWP consists of a 505 mm diameter achromatic sapphire HWP and a cryogenic rotation mechanism, both of which are cooled down to ∼50 K to reduce detector thermal loading. Under normal operation, the HWP is suspended by a superconducting magnetic bearing and rotates with a constant 2 Hz frequency, controlled by an electromagnetic synchronous motor. We find that the number of superconductors and the number of magnets that make up the superconducting magnetic bearing are important design parameters, especially for the rotation mechanism's vibration performance. The rotation angle is detected through an angular encoder with a noise level of 0.07 μrad s. During a cooldown process, the rotor is held in place by a grip-and-release mechanism that serves as both an alignment device and a thermal path. In this paper, we provide an overview of the SO SAT CHWP: its requirements, hardware design, and laboratory performance.

Hiroshi Fujimoto,1 Teruyuki Matsuoka,1 Yuka Kato,1 Keisuke Shibata,1 Kaeko Nakamura,1 Kei Yamada,2 Jin Narumoto1 1Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan Background and objective: Patients with Alzheimer’s disease (AD) are frequently unaware of their cognitive symptoms and medical diagnosis. The term “anosognosia” is used to indicate a general lack of awareness of one’s disease or disorder. The neural substrate underlying anosognosia in AD is unclear. Since anosognosia for memory disturbance might be an initial sign of AD, it is important to determine the neural correlates. This study was designed to investigate the characteristics and neural correlates of anosognosia for memory disturbance in patients with mild AD.Methods: The subjects were 49 patients with mild AD who participated in a retrospective cross-sectional study. None of the patients had been treated with cholinesterase inhibitors, memantine, or psychotropic drugs. All patients underwent magnetic resonance imaging (MRI). Anosognosia for memory disturbance was assessed based on the discrepancy between questionnaire scores of patients and their caregivers. Structural MRI data were analyzed to explore the association between anosognosia and brain atrophy, using a voxel-based approach. Statistical parametric mapping software was used to explore neural correlations. In image analysis, multiple regression analysis was performed to examine the relationship between anosognosia score and regional gray matter volume. Age, years of education, and total intracranial volume were entered as covariates.Results: The anosognosia score for memory disturbance was significantly negatively correlated with gray matter volume in the left superior frontal gyrus.Conclusion: The left superior frontal gyrus was involved in anosognosia for memory disturbance, while the medial temporal lobe, which is usually damaged in mild AD, was not associated with anosognosia. The left superior frontal gyrus might be an important region for anosognosia in mild AD. Keywords: anosognosia, Alzheimer’s disease, MRI, superior frontal gyrus

Yukari Sugiyama, Kazuhisa Asai, Kazuhiro Yamada, Yuko Kureya, Naoki Ijiri, Tetsuya Watanabe, Hiroshi Kanazawa, Kazuto Hirata Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan Background: Cigarette smoking-induced oxidant–antioxidant imbalance is a factor that contributes to the pathogenesis of COPD through epithelial cell apoptosis. Irisin is a skeletal muscle cell-derived myokine associated with physical activity. Irisin is also known to decrease oxidant-induced apoptosis in patients with diabetes mellitus. However, the correlation between irisin and emphysema in COPD and its role in epithelial cell apoptosis remains unknown. Subjects and methods: Forty patients with COPD were enrolled in this study. Pulmonary function tests and measurements of the percentage of low-attenuation area on high-resolution computed tomography images were performed, and the results were evaluated for correlation with serum irisin levels. The effect of irisin on cigarette-smoke extract-induced A549 cell apoptosis and the expression of Nrf2, a transcription factor for antioxidants, was also examined in vitro. Results: Serum irisin levels were significantly correlated with lung diffusing capacity for carbon monoxide divided by alveolar volume (r=0.56, P

Keiko Yamada,1,2 Ko Matsudaira,3,4 Eizaburo Tanaka,1,5 Hiroyuki Oka,3 Junji Katsuhira,3,6 Hiroyasu Iso1 1Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 2Center for Pain Management, Osaka University Hospital, Suita, Osaka, 3Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, Faculty of Medicine, The University of Tokyo, Tokyo, 4Japan Labour Health & Welfare Organization, Tokyo, 5Hyogo Institute for Traumatic Stress, Kobe, 6Department of Prosthetics & Orthotics and Assistive Technology, Faculty of Medical Technology, Niigata University of Health and Welfare, Niigata, Japan Background: Responses to early-life adversity may differ by sex. We investigated the ­sex-specific impact of early-life adversity on chronic pain, chronic multisite pain, and somatizing tendency with chronic pain. Methods: We examined 4229 respondents aged 20–79 years who participated in the Pain Associated Cross-Sectional Epidemiological Survey in Japan. Outcomes were: 1) chronic pain prevalence, 2) multisite pain (≥3 sites) prevalence, and 3) multiple somatic symptoms (≥3 symptoms) among respondents with chronic pain related to the presence or absence of early-life adversity. Multivariable-adjusted odds ratios (ORs) were calculated with 95% confidence intervals using a logistic regression model including age, smoking status, exercise routine, sleep time, body mass index, household expenditure, and the full distribution of scores on the Mental Health Inventory-5. We further adjusted for pain intensity when we analyzed the data for respondents with chronic pain. Results: The prevalence of chronic pain was higher among respondents reporting the presence of early-life adversity compared with those reporting its absence, with multivariable ORs of 1.62 (1.22–2.15, p

Tomoki Nakamura,1 Akihiko Matsumine,1 Satoshi Yamada,2 Satoshi Tsukushi,3,4 Katsuhisa Kawanami,5 Takatoshi Ohno,6 Hirohisa Katagiri,7 Hideshi Sugiura,3,8 Kenji Yamada,9 Yoshihisa Yamada,10 Akihiro Sudo,1 Yoshihiro Nishida4 1Department of Orthopaedic Surgery, Mie Graduate School of Medicine, Tsu-City, Mie, 2Department of Orthopedic Surgery, Graduate School of Medical Sciences, Nagoya City University, 3Department of Orthopedic Surgery, Aichi Cancer Center Hospital, 4Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 5Department of Orthopaedic Surgery, Aichi Medical University School of Medicine, Nagakute, 6Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, 7Division of Orthopaedic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi, Shizuoka, 8Department of Physical Therapy, Nagoya University Graduate School Medicine, Nagoya, 9Department of Orthopedic Surgery, Aichi Cancer Center, Aichi Hospital, Okazaki, 10Department of Orthopedic Surgery, Nagoya Memorial Hospital, Nagoya, Aichi, Japan Abstract: The oncological outcome after lung metastasis in patients with chondrosarcoma of the extremities has not been reported. Between June 2000 and June 2013, 179 patients with chondrosarcoma in the extremities were treated at eleven hospitals. Twenty consecutive patients (11.2%) developed lung metastases after initial treatment of primary chondrosarcoma in the extremities. We investigated the oncological outcome of 20 chondrosarcoma patients with lung metastasis. There were 14 males and six females with a mean age of 49 years. The mean duration between primary surgery and appearance of lung metastases was 34 months. The mean follow-up period was 48 months. We excluded patients with lung metastasis at the time of presentation from this study. At the final follow-up, four of 20 patients had no evidence of disease, four were alive with disease, and twelve had died of disease. The 3- and 5-year survival rates after lung metastasis were 51.5% and 45.7%, respectively. Tumor grade, extrapulmonary metastasis, and treatment for lung metastases including metastasectomy and radiofrequency ablation were identified by univariate analysis to be significant prognostic factors for oncological analysis. In conclusion, this study evaluated the oncological outcome in patients with chondrosarcoma of the extremities with lung metastasis. Although a large-scale study might be required to confirm the results of this study, we suggest that metastasectomy and/or radiofrequency ablation should be considered to improve postmetastatic survival. Keywords: chondrosarcoma, lung metastasis, radiofrequency ablation, metastasectomy, extremity

Tsuyoto Harada, Ken Inada, Kazuo Yamada, Kaoru Sakamoto, Jun Ishigooka Department of Psychiatry, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan Objective: Patients often develop neuropsychiatric symptoms such as anxiety and agitation after they have started taking an antidepressant, and this is thought to be associated with a potentially increased risk of suicide. However, the incidence of antidepressant-induced jitteriness/anxiety syndrome has not been fully investigated, and little has been reported on its predictors. The aim of this study was to survey the incidence of antidepressant-induced jitteriness/anxiety syndrome and clarify its predictors in a natural clinical setting.Materials and methods: Between January 2009 and July 2012, we prospectively surveyed 301 patients who had not taken any antidepressants for 1 month before presentation, and who were prescribed antidepressants for 1 month after their initial visit. Patients were classified as developing antidepressant-induced jitteriness/anxiety syndrome if they experienced any symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, or mania during the first month.Results: Among the 301 patients, 21 (7.0%) developed antidepressant-induced jitteriness/anxiety syndrome. Major depressive disorder and a diagnosis of mood disorder in first-degree relatives of patients were significantly associated with induction of antidepressant-induced jitteriness/anxiety syndrome (odds ratio 10.2, P=0.001; odds ratio 4.65, P=0.02; respectively). However, there was no such relationship for sex, age, class of antidepressant, combined use of benzodiazepines, or diagnosis of anxiety disorder.Conclusion: The findings of this study suggest that major depressive disorder and a diagnosis of mood disorder in first-degree relatives may be clinical predictors of antidepressant-induced jitteriness/anxiety syndrome.Keywords: side effects, antidepressants, selective serotonin-reuptake inhibitors, tricyclic antidepressive agents, suicide

Yoshio Shimizu, Ayano Sonoda, Chieko Nogi, Yoko Ogushi, Reo Kanda, Saori Yamaguchi, Nao Nohara, Tatsuya Aoki, Kaori Yamada, Junichiro Nakata, Hiroaki Io, Atsushi Kurusu, Chieko Hamada, Satoshi Horikoshi, Yasuhiko Tomino Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan Introduction and objective: While pruritus is a common complication in hemodialysis patients, the pathophysiological mechanisms remain obscure. Recently, B-type (brain) natriuretic peptide (BNP) has been defined as an itch-selective neuropeptide in pruriceptive neurons in mice, and higher serum levels of BNP are frequently observed in hemodialysis patients. The objective of the present study was to evaluate the role of serum BNP in pruritus in patients undergoing hemodialysis. Patients and methods: The current cross-sectional study was performed on 43 patients undergoing maintenance hemodialysis. A visual analog scale (VAS) measuring the general severity of pruritus (values from 0 to 10, with higher values indicating more severe pruritus) in daytime and at night was self-reported by patients. Each patient's background and laboratory tests, including serum BNP in the post-hemodialysis period, were collected. The correlation between VAS and clinical parameters was evaluated. Results: Both daytime and nighttime VAS scores in diabetic patients were significantly less than those in nondiabetic patients. Multiple regression analysis revealed that pruritus in daytime was worsened by serum BNP (β=2.0, t=2.4, P=0.03), calcium (β=4.4, t=5.2, P

Keiko Yamada,1 Takatoshi Maeno,2 Mitsunori Yamada31Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Ophthalmology, Toho University Sakura Medical Center, Chiba, Japan; 3Yamada Eye Clinic, Tokushima, JapanPurpose: To verify the utility and preliminary safety of a 20-gauge silicone cannula for use with 20-gauge horizontal scissors delamination during microincision vitrectomy surgery (MIVS).Methods: Thirty-eight eyes in 35 consecutive patients with diabetic tractional retinal detachment, who underwent MIVS between April 2010 and March 2012 and were followed for 3–24 months, were retrospectively assessed using a chart review. Twenty-gauge scissors delamination through a silicone cannula, with an additional 20-gauge port as a hybrid, was primarily selected when treating thick and rigid fibrovascular membranes, including fluctuating vessels over the detached retina near the macula. The main outcome measures included the proportion of patients treated with this hybrid method, the postoperative visual acuity, and the incidence of complications.Results: Compared with the 26 eyes treated with MIVS only, 12 eyes (32%) required a hybrid technique with the use of 20-gauge instruments through a silicone cannula in addition to MIVS. Two patients underwent additional surgery. Temporary silicone oil tamponade was performed in one case of retinotomy and one case of schizophrenia. The mean visual acuity (logarithm of the minimum angle of resolution [logMAR]) improved from 1.43 ± 0.85 to 0.72 ± 0.47 at the last follow-up visit. No patients exhibited worsening of their visual acuity postoperatively. No sclerotomy-related complications were recorded during the intraoperative or postoperative periods.Conclusion: Hybrid MIVS combined with a 20-gauge silicone cannula for use with 20-gauge horizontal scissors in diabetic tractional retinal detachment eyes is useful and safe due to the reduced risk of sclerotomy-related retinal breaks. This procedure is a reasonable option when performing complex surgery for diabetic vitrectomy.Keywords: small gauge vitrectomy, cannulated vitrectomy system, cutter delamination, scissor delamination, 20-gauge instruments, sclerotomy retinal tears

Takashi Motegi,1,2 Rupert C Jones,3 Takeo Ishii,1,2 Kumiko Hattori,1,2 Yuji Kusunoki,1,2 Ryuko Furutate,2 Kouich Yamada,1,2 Akihiko Gemma,1 Kozui Kida1,2 1Divisions of Pulmonary Medicine, Infectious Disease, and Oncology, Department of Internal Medicine, 2Respiratory Care Clinic, Nippon Medical School, Tokyo, Japan; 3Respiratory Research Unit, Peninsula Medical School, Plymouth, UK Background: Prediction of future exacerbations of chronic obstructive pulmonary disease (COPD) is a major concern for long-term management of this disease. Aim: To determine which of three multidimensional assessment systems (the body mass index, obstruction, dyspnea, and exercise capacity [BODE] index; dyspnea, obstruction, smoking, exacerbations [DOSE] index; or age, dyspnea, obstruction [ADO] index) is superior for predicting exacerbations. Methods: This was a 2-year prospective cohort study of COPD patients. Pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council (MMRC) dyspnea scores, chest computed-tomography measurements, and body composition were analyzed, and predictions of exacerbation by the three assessment systems were compared. Results: Among 183 patients who completed the study, the mean annual exacerbation rate was 0.57 events per patient year, which correlated significantly with lower predicted forced expiratory volume in 1 second (FEV1) (P < 0.001), lower transfer coefficient of the lung for carbon monoxide (%DLco/VA) (P = 0.021), lesser 6MWD (P = 0.016), higher MMRC dyspnea score (P = 0.001), higher DOSE index (P < 0.001), higher BODE index (P = 0.001), higher ADO index (P = 0.001), and greater extent of emphysema (P = 0.002). For prediction of exacerbation, the areas under the curves were larger for the DOSE index than for the BODE and ADO indices (P < 0.001). Adjusted multiple logistic regression identified the DOSE index as a significant predictor of risk of COPD exacerbation. Conclusion: In this study, the DOSE index was a better predictor of exacerbations of COPD when compared with the BODE and ADO indices. Keywords: frequency of exacerbation, multidimensional assessment systems, DOSE index, BODE index

Norio Watanabe,1,2 Keiko Yamamura,3 Yusuke Suzuki,4 Hiroyuki Umegaki,4 Katsuro Shigeno,5 Ryo Matsushita,1 Yoshimichi Sai,1 Ken-ichi Miyamoto,1 Kiyofumi Yamada61Department of Clinical Pharmacy, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Ishikawa, Japan; 2Department of Pharmacy, Hashima Municipal Hospital, Hashima, Gifu, Japan; 3Department of Clinical Pharmacy, School of Pharmacy, Aichi Gakuin University, Nagoya, Aichi, Japan; 4Department of Community Healthcare and Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; 5Department of Pharmacy Practice and Sciences, School of Pharmacy, Aichi Gakuin University, Nagoya, Aichi, Japan; 6Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Aichi, JapanAim: Donepezil is widely used to delay the progression of cognitive dysfunction in patients with Alzheimer's disease (AD), but the efficacy of pharmacotherapy is often reduced by poor adherence to medication. In order to improve adherence by providing information about AD and the significance of pharmacotherapy, the Donepezil Outpatient Consultation Service (DOCS) was set up. The influence of this service on medication persistence was assessed in the present study.Methods: Among outpatients starting donepezil therapy, we enrolled 59 patients between April 2008 and September 2010 before establishment of the DOCS (non-DOCS group) and 52 patients between October 2010 and March 2012 who attended the DOCS (DOCS group). Each patient's and their caregiver's understanding about the clinical features of AD and pharmacotherapy with donepezil were also assessed. Their understanding was compared before and after the DOCS, and the 1-year medication persistence rate and the reasons for discontinuation were also investigated.Results: The 1-year medication persistence rate was significantly higher in the DOCS group than in the non-DOCS group (73.1% vs 49.2%, P = 0.008). We examined the association of medication persistence with age, sex, clinical dementia rating, living alone, and attending the DOCS. As a result, medication persistence was significantly higher in patients attending the DOCS. The main reasons for discontinuation of donepezil were transfer elsewhere (11) and gastrointestinal side effects (5) in the non-DOCS group, and transfer (9) and gastrointestinal side effects (3) in the DOCS group. The overall score for understanding was 2.5 ± 1.7 before attending the DOCS and it increased significantly to 5.7 ± 0.7 afterward (P < 0.001).Conclusion: The DOCS consultation provided by hospital pharmacists for AD patients and their caregivers improved understanding about the clinical features of dementia and provided pharmacological knowledge about antidementia drugs, leading to better adherence to pharmacotherapy that could maximize its effect.Keywords: Alzheimer's disease, cholinesterase inhibitors, consultation, donepezil, patient knowledge, pharmacists

Ryuko Furutate1, Takeo Ishii1,2, Ritsuko Wakabayashi1, Takashi Motegi1,2, Kouichi Yamada1,2, Akihiko Gemma2, Kozui Kida1,21Respiratory Care Clinic, Nippon Medical School, Kudan-Minami, Chiyoda-ku, Tokyo, Japan; 2Department of Internal Medicine, Division of Pulmonary Medicine, Infectious Diseases and Oncology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo, JapanBackground: Previous studies have suggested links between chronic obstructive pulmonary disease (COPD), cardiovascular disease, and abdominal obesity. Although abdominal visceral fat is thought to be associated with cardiovascular risk factors, the degree of visceral fat accumulation in patients with COPD has not been directly studied. The aim of this study was to investigate the abdominal visceral fat accumulation and the association between visceral fat and the severity and changes in emphysema in COPD patients.Methods: We performed clinical and laboratory tests, including pulmonary function, dyspnea score, and the six-minute walking test in COPD patients (n = 101) and control, which included subjects with a smoking history but without airflow obstruction (n = 62). We used computed tomography to evaluate the abdominal visceral fat area (VFA), subcutaneous fat area (SFA), and the extent of emphysema.Results: The COPD group had a larger VFA than the control group. The prevalence of non-obese subjects with an increased VFA was greater in the Global Initiative for Chronic Obstructive Lung Disease Stages III and IV than in the other stages of COPD. The extent of emphysema was inversely correlated with waist circumference and SFA. However, VFA did not decrease with the severity of emphysema. VFA was positively correlated with the degree of dyspnea.Conclusion: COPD patients have excessive visceral fat, which is retained in patients with more advanced stages of COPD or severe emphysema despite the absence of obesity.Keywords: abdominal obesity, chronic obstructive pulmonary disease, emphysema, visceral fat

We report an improved measurement of the degree-scale cosmic microwave background B-mode angular-power spectrum over 670 deg2 sky area at 150 GHz with Polarbear. In the original analysis of the data, errors in the angle measurement of the continuously rotating half-wave plate, a polarization modulator, caused significant data loss. By introducing an angle-correction algorithm, the data volume is increased by a factor of 1.8. We report a new analysis using the larger data set. We find the measured B-mode spectrum is consistent with the ΛCDM model with Galactic dust foregrounds. We estimate the contamination of the foreground by cross-correlating our data and Planck 143, 217, and 353 GHz measurements, where its spectrum is modeled as a power law in angular scale and a modified blackbody in frequency. We place an upper limit on the tensor-to-scalar ratio r < 0.33 at 95% confidence level after marginalizing over the foreground parameters.

Coherent spin fluctuation was detected in the photoinduced Mott insulator-metal transition in perovskite cobalt oxide by using 3 optical-cycle infrared pulse. Such coherent spin fluctuation is driven by the perovskite distortion changing orbital gap.

Abstract The histopathology of periodontal ligament of the mouse subjected to mechanical stress was studied. Immunohistochemical expressions of HSP27 and pHSP27 were examined. Experimental animals using the maxillary molars of ddY mouse by Waldo method were used in the study. A separator was inserted to induce mechanical stress. After 10 minutes, 20 minutes, 1 hour, 3 hours, 9 hours and 24 hours, the regional tissues were extracted, fixed in 4% paraformaldehyde and 0.05 M phosphate-buffered fixative solution. Paraffin sections were made for immunohistochemistry using HSP27 and p-HSP27. In the control group, the periodontal ligament fibroblasts expressed low HSP27 and p-HSP27. However, in the experimental group, periodontal ligament fibroblasts expressed HSP27 10 minutes after mechanical load application in the tension side. The strongest expression was detected 9 hours after inducing mechanical load. p-HSP27 was also expressed in a time-dependent manner though weaker than HSP27. The findings suggest that HSP27 and p-HSP27 were expressed for the maintenance of homeostasis of periodontal ligament by the activation of periodontal ligament fibroblasts on the tension side. It also suggests that these proteins act as molecular chaperones for osteoblast activation and maintenance of homeostasis.

Droplet microfluidics has become a powerful tool in precision medicine, green biotechnology, and cell therapy for single-cell analysis and selection by virtue of its ability to effectively confine cells. However, there remains a fundamental trade-off between droplet volume and sorting throughput, limiting the advantages of droplet microfluidics to small droplets (