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Yumi Suzuki, Takafumi Aoki, Akane Tomita, Tadahiro Mitsukawa, Yukiko Hama, Masakazu Yamada Department of Ophthalmology, Kyorin University School of Medicine, Mitaka, Tokyo, JapanCorrespondence: Yumi Suzuki, Email yumis@ks.kyorin-u.ac.jpPurpose: To evaluate the efficacy and safety of slanted bilateral lateral rectus recession (BLR-rec) for treating convergence insufficiency-type intermittent exotropia (CI-IXT) in children.Methods: In this retrospective cohort study, 26 patients aged < 16 years with CI-IXT who underwent BLR-rec between August 2016 and July 2021 with six months of follow-up data post-surgery were classified into slanted BLR-rec group (n = 14) and standard BLR-rec group (n = 12; equal-length recession of the upper and lower horns of the LR muscle). Surgical outcomes were compared between the groups.Results: In the slanted and standard groups, the preoperative distance exodeviation was 27.9 ± 5.5 and 30.8 ± 10.0 prism diopter (PD) (p = 0.63), near exodeviation was 41.1 ± 5.6 and 42.9 ± 9.2 PD (p = 0.75), and difference between near and distance deviation (N-D deviation difference) was 13.2 ± 3.2 and 12.1 ± 3.3 PD (p = 0.30), respectively. The ratio of postoperative and preoperative N-D deviation difference was compared between the slanted BLR and standard BLR groups at six months postoperatively. The results revealed that the ratio for slanted-BLR was 0.44 ± 0.19, and for standard-BLR was 0.84 ± 0.24. In the standard group, stereoacuity remained unchanged post-surgery compared to that pre-surgery, while the slanted group showed significant improvement (p < 0.05, Wilcoxon signed-rank test).Conclusion: Compared with the standard BLR-rec procedure, the slanted BLR-rec procedure reduced N-D deviation differences in CI-IXT, positively impacting gross stereopsis.Keywords: bilateral lateral rectus recession, convergence insufficiency-type intermittent exotropia, postoperative diplopia, consecutive esotropia, stereopsis

Yuji Watanabe,1,2 Hirohito Sano,3 Shuichi Konno,3 Yasuhiro Kamioka,1,4 Maya Hariu,1,2 Kazuki Takano,1,2 Mitsuhiro Yamada,3 Masafumi Seki1 1Division of Infectious Diseases and Infection Control, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai City, Miyagi, Japan; 2Laboratory for Clinical Microbiology, Tohoku Medical and Pharmaceutical University Hospital, Sendai City, Miyagi, Japan; 3Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai City, Miyagi, Japan; 4Division of Pharmacy, Tohoku Medical and Pharmaceutical University Hospital, Sendai City, Miyagi, JapanCorrespondence: Masafumi Seki, Division of Infectious Diseases and Infection Control, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-ku, Sendai City, Miyagi, 983-8612, Japan, Tel +81-22-259-1221, Fax +81-22-290-8956, Email m-seki@tohoku-mpu.ac.jp; seki@hosp.tohoku-mpu.ac.jpBackground: Exophiala dermatitidis is an environmental black fungus that rarely causes respiratory infections, yet its pathophysiological features and treatment regimens have not been established.Case Series: Two cases of exacerbations of chronic bronchitis and sinusitis due to E. dermatitidis infection in Japan are presented. Both patients were women, and non-tuberculous Mycobacterium (NTM) infection was suspected based on chest radiological findings, but E. dermatitidis was detected from bronchial lavage fluid and nasal mucus, respectively. Both cases were successfully treated by antifungal agents such as liposomal amphotericin B, voriconazole, and itraconazole, but clarithromycin, rifampicin, ethambutol, and sitafloxacin for NTM were not effective.Conclusion: E. dermatitidis can become a respiratory pathogen, especially in patients with chronic sinobronchial syndrome.Keywords: black fungus, bronchiectasis, rheumatoid arthritis, bronchoscope

Hiroaki Masuda,1,2 Daisuke Ishiyama,2 Minoru Yamada,2 Fumiko Iwashima,3 Yosuke Kimura,2 Yuhei Otobe,2 Naoki Tani,2 Mizue Suzuki,2 Hideki Nakajima1 1Department of Rehabilitation, Toshima Hospital, Tokyo Metropolitan Health and Hospitals Corporation, Tokyo, Japan; 2Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tokyo, Japan; 3Department of Endocrinology and Metabolism, Toshima Hospital, Tokyo Metropolitan Health and Hospitals Corporation, Tokyo, JapanCorrespondence: Hiroaki MasudaDepartment of Rehabilitation, Toshima Hospital, Tokyo Metropolitan Health and Hospitals Corporation, 33-1 Sakaecho, Itabashi-ku, Tokyo, 173-0015, JapanTel +81-3-5375-1234Fax +81-3-5944-3534Email hiroakimasuda15@gmail.comIntroduction: Increasing physical activity (PA) improves glycemic control in patients with type 2 diabetes mellitus (T2DM). However, whether long-term objectively measured PA is related to glycemic control remains unclear. The aim of this study was to investigate the relationship between long-term objectively measured PA and glycemic control in T2DM patients.Research Design and Methods: This prospective cohort study recruited T2DM patients admitted to a hospital-based diabetes management and education program. The primary outcome was glycemic control by hemoglobin A1c at 6 months after discharge. We defined poor glycemic control according to the Japanese Clinical Practice Guidelines. The PA was objectively measured using a three-axis accelerometer during 6 months’ period after discharge. The representative value of PA was the average daily steps during the measurement period and was divided into quartiles. To determine the relationship between the daily steps and poor glycemic control, we performed a multivariate logistic regression analysis.Results: Ninety-four participants were enrolled in the study. Their median age was 59 years, and 38 (40.0%) of them showed poor glycemic control. Multivariate logistic regression analysis showed that the first (Q1, ≤ 6106 steps/day) and second quartiles (Q2, 6107– 8258 steps/day) had significantly elevated risks of poor glycemic control compared to Q4 (≥ 10,542 steps/day), with odds ratios of 8.55 [95% confidence intervals (CI) =1.43– 51.23] and 15.62 (95% CI 2.63– 92.87), respectively.Conclusion: We found that lesser PA was significantly associated with poor glycemic control in T2DM patients. This finding may be beneficial for clinicians while providing long-term advice to diabetic patients.Keywords: glycemic control, long-term, physical activity, type 2 diabetes

Rie Tanaka,1 Akira Koarai,1 Mitsuhiro Yamada,1 Naoya Fujino,1 Tomohiro Ichikawa,1 Tadahisa Numakura,1 Katsuhiro Onodera,2 Yorihiko Kyogoku,1 Tsutomu Tamada,1 Motohiko Miura,3 Yoshiaki Minakata,4 Masakazu Ichinose,5 Hisatoshi Sugiura1 1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Department of Internal Medicine, Mizusawa Hospital, Oshu, Japan; 3Department of Respiratory Medicine, Tohoku Rosai Hospital, Sendai, Japan; 4Department of Respiratory Medicine, National Hospital Organization Wakayama Hospital, Wakayama, Japan; 5Academic Center, Osaki Citizen Hospital, Osaki, JapanCorrespondence: Akira KoaraiDepartment of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanTel +81-22-717-8539Fax +81-22-717-8549Email koarai@rm.med.tohoku.ac.jpBackground: Daily physical activity is reduced in patients with chronic obstructive pulmonary disease (COPD) and a reduced level of physical activity has been shown to be an important predictor for the prognosis, such as increased risk of exacerbation and mortality. However, there has not yet been a useful biomarker of the physical activity. In our previous cross-sectional study, we showed that the level of one of the possible myokines, which is an anti-aging factor, growth differentiation factor 11 (GDF11), was decreased in the plasma from patients with COPD and correlated with the physical activity. To clarify this relationship, we conducted a longitudinal evaluation of such factors.Patients and Methods: Twenty-four COPD patients were enrolled and prospectively followed. We measured the levels of plasma GDF11 and systemic inflammatory markers with immunoblotting or ELISA, respectively. We also evaluated lung function and daily physical activity using a triaxial accelerometer and the incidence of exacerbation.Results: The change in the plasma level of GDF11, but not systemic inflammatory markers, was positively correlated with the change in the physical activity in an intensity-dependent manner (between the change in the number of steps and GDF11; r = 0.41, p = 0.047). In the multiple regression analysis, the relationship was confirmed (β = 0.93, p < 0.001). In addition, patients who maintained their plasma level of GDF11 showed a significantly lower incidence in exacerbations of COPD than those with decreased levels of GDF11 (p = 0.041).Conclusion: The longitudinal change in the plasma level of GDF11 was positively correlated with the change in the daily physical activity in COPD. GDF11 could be a useful humoral factor that reflects the physical activity in COPD.Keywords: chronic obstructive pulmonary disease, physical activity, growth differentiation factor 11, exacerbation, longitudinal study

Masakazu Yamada,1 Yoshimune Hiratsuka,2 Tadashi Nakano,3 Yoshiyuki Kita,1 Tomoyuki Watanabe,3 Hiroshi Tamura,4,5 Ryo Kawasaki,6 Tetsuji Yokoyama,7 Shigeru Takano8 1Department of Ophthalmology, Kyorin University School of Medicine, Mitaka, Japan; 2Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan; 3Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan; 4Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan; 5Center for Innovative Research and Education in Data Science, Institute for Liberal Arts and Sciences, Kyoto University, Kyoto, Japan; 6Artificial Intelligence Center for Medical Research and Application, Osaka University Hospital, Suita, Japan; 7Department of Health Promotion, National Institute of Public Health, Wako, Japan; 8Japan Ophthalmologist Association, Tokyo, JapanCorrespondence: Masakazu Yamada Department of OphthalmologyKyorin University School of Medicine, Mitaka, JapanEmail yamadamasakazu@ks.kyorin-u.ac.jpBackground: The efficacy of vision screening for adults has not been well established. The present study aimed to investigate the prevalence of vision-threatening ocular diseases, including glaucoma, among subjects who participated in specific health checkups in Japan.Methods: This cross-sectional study included 1360 individuals who underwent comprehensive ophthalmic examinations at 16 ophthalmology clinics located in three municipalities. We surveyed the study participants using a questionnaire. The participants also underwent visual acuity and refraction tests, intraocular pressure tests, slit-lamp microscopy, fundus examinations, fundus photography, optical coherence tomography, and static perimetry.Results: The mean age of the subjects was 63.7 ± 8.7 years (range, 40– 74 years). Among the 1360 participants, 168 (12.4%) were diagnosed with glaucoma and 33 (2.4%) with preperimetric glaucoma. Cataracts were seen in 741 participants (54.5%), and 77 (5.7%) were diagnosed with clinically significant cataracts. Retinal diseases included macular degeneration (1.2%), diabetic retinopathy (1.0%), chorioretinal atrophy (0.5%), macular epiretinal membrane (2.9%), branch retinal vein occlusion (0.7%), and others (2.0%). Regarding the type of glaucoma, 93.5% of participants with glaucoma were diagnosed with open-angle glaucoma in a broad sense (81.0% with normal-tension glaucoma and 12.5% with primary open-angle glaucoma). Multivariate analysis showed that male sex, age, systemic comorbidities, and myopia were significant risk factors for open-angle glaucoma.Conclusion: Many adults with ocular diseases were screened by ophthalmic checkups. The addition of simultaneous ophthalmic checkups to specific health checkups could be an effective measure for the prevention of visual impairment in the older population.Keywords: cataract, glaucoma, ocular disease, prevalence, vision screening

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

Tadahiro Mitsukawa, Yumi Suzuki, Yosuke Momota, Shun Suzuki, Masakazu Yamada Department of Ophthalmology, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, JapanCorrespondence: Masakazu Yamada Email yamadamasakazu@ks.kyorin-u.ac.jpPurpose: We analyzed changes in the crystalline lens during accommodation and the effects of cycloplegics by swept-source anterior-segment optical coherence tomography (AS-OCT).Materials and Methods: Twenty healthy volunteers (7 males and 13 females, aged 22– 34 years), with no history of eye disease except for refractive errors, were recruited. Biometric parameters, including anterior chamber depth (ACD), lens thickness (LT), and anterior and posterior curvature of the lens (ACL and PCL), were measured using AS-OCT (CASIA2). The measurements were performed with or without an accommodative demand of 5.0 diopters (D). The same tests were repeated following the topical administration of 1% cyclopentolate or a compounding agent comprising 0.5% tropicamide and 0.5% phenylephrine.Results: The AS-OCT system was capable of simultaneous visualization of all optical components of the anterior segment in a single frame. ACD, LAC, and LPC decreased and LT increased significantly during 5.0 D accommodative stimulation in both eyes. Both cyclopentolate and tropicamide/phenylephrine eyedrops led to deeper ACD, thinner LT, and flatter LAC. There were no significant differences in all lens parameters despite having 5.0 D accommodative stimulation in both eyes with cycloplegia.Conclusion: Our results suggest that both tropicamide/phenylephrine and cyclopentolate eyedrops have enough cycloplegic effects in young adults.Keywords: accommodation, cycloplegics, lens, optical coherence tomography, refraction

Shigeharu Yaginuma,1 Yoko Akune,2 Chika Shigeyasu,1,2 Yoji Takano,3 Masakazu Yamada1 1Department of Ophthalmology, Kyorin University School of Medicine, Tokyo 181-8611, Japan; 2Division for Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo 152-8902, Japan; 3Department of Ophthalmology, Kawasaki Municipal Ida Hospital, Kawasaki 211-0035, Japan Objectives: It is often hard to reach a definitive diagnosis of congenital alacrima because of the difficultly in proving the lack of lacrimal tissue. We report here the distinct tear protein profile in presumed congenital alacrima. Patients and methods: A 13-year-old girl with presumed congenital alacrima and 15 healthy volunteers aged 23–35 years were included in this study. Tears were collected using Schirmer strips, and tear protein analyses were performed. Tear samples were collected from the patient with alacrima before and after surgical punctal occlusion of both the upper and lower puncta, and tear protein extract was fractionated using HPLC. Lactoferrin and albumin concentrations in the tears were separately determined using ELISA. Results: The chromatogram in the patient greatly differed from that in normal subjects with low concentrations of secretory IgA, lipocalin-1, and lysozyme. ELISA results indicated that the tear fluid in the patient contained a high concentration of albumin but a minimal concentration of lactoferrin. Punctal occlusion improved the ocular surface findings, but major lacrimal protein concentrations remained low and tear albumin concentrations further increased. Conclusion: The tear protein profile of a patient with presumed congenital alacrima greatly differed from that of normal subjects. Tear protein analysis may be useful in making a diagnosis of congenital alacrima and in assessing the efficacy and mechanism of punctal occlusion. Keywords: alacrima, albumin, dry eye, lactoferrin, tears

Seiichi Kobayashi,1 Masakazu Hanagama,1 Masatsugu Ishida,1 Hikari Sato,1 Manabu Ono,1 Shinsuke Yamanda,1 Mitsuhiro Yamada,2 Hiroyuki Aizawa,1 Masaru Yanai1 1Department of Respiratory Medicine, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Miyagi, Japan; 2Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan Purpose: The GOLD report provides a framework for classifying COPD in a way that reflects its clinical impact and allows treatment recommendations. The GOLD 2017 proposes a new classification whereby patients are grouped as A–D according to their symptoms and history of exacerbations. However, the clinical characteristics and outcomes in these patients are not well documented.Patients and methods: In this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry. All patients with stable COPD were classified into the four groups defined by GOLD 2017. The patient demographics, clinical characteristics, number of exacerbations, and mortality rate during 1 year of follow-up were compared between the groups.Results: Four hundred and one patients with stable COPD were identified. There were 240 patients (59.9%) in group A, 122 (30.4%) in group B, 16 (4.0%) in group C, and 23 (5.7%) in group D. Patients in groups B, C, and D had ORs of 2.95, 3.92, and 5.45, respectively, for risk of exacerbation relative to group A. Groups C and D experienced exacerbations more frequently, including exacerbations leading to hospital admission, than groups A and B (both P

Rie Tanaka,1 Hisatoshi Sugiura,1 Mitsuhiro Yamada,1 Tomohiro Ichikawa,1 Akira Koarai,1 Naoya Fujino,1 Satoru Yanagisawa,1 Katsuhiro Onodera,1 Tadahisa Numakura,1 Kei Sato,1 Yorihiko Kyogoku,1 Hirohito Sano,1 Shun Yamanaka,1 Tatsuma Okazaki,1 Tsutomu Tamada,1 Motohiko Miura,2 Tsuneyuki Takahashi,3 Masakazu Ichinose1 1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan; 2Department of Respiratory Medicine, Tohoku Rosai Hospital, Aoba-ku, Sendai, Japan; 3Department of Internal Medicine, Tohoku Medical and Pharmaceutical University Wakabayashi Hospital, Wakabayashi-ku, Sendai, Japan Background: Growth differentiation factor 11 (GDF11) is reported to possess anti-aging and rejuvenating effects, including muscle regeneration and to be highly expressed in skeletal muscle. Recently, we demonstrated that the levels of plasma GDF11 were decreased in COPD. However, the effect of decreased circulating GDF11 in the pathophysiology of COPD remains unknown. The aim of this study is to investigate the association between the plasma GDF11 levels and various clinical parameters in patients with COPD. Patients and methods: Eighteen ex-smokers as control subjects and 70 COPD patients participated in the current study. We measured the levels of plasma GDF11 using immunoblotting, lung function, physical activity using a triaxial accelerometer, quadriceps strength, exercise capacity, and systemic inflammatory markers. We investigated the association between the levels of plasma GDF11 and these clinical parameters. Results: The levels of plasma GDF11 in the COPD patients had significant positive correlations with the data of lung function. Furthermore, the levels of plasma GDF11 were significantly correlated with the physical activity, quadriceps strength, and exercise capacity. Moreover, the levels of plasma GDF11 were significantly correlated with the data of inflammatory markers. Although various factors were related to GDF11, the multiple regression analysis showed that physical activity was significantly associated with the levels of plasma GDF11. Conclusion: Physical inactivity was significantly related to the decreased GDF11 levels in COPD, which might be useful for understanding the pathogenesis of COPD. Clarifying the relationships between the physical inactivity and GDF11 may reveal a potentially attractive therapeutic approach in COPD via increasing the plasma levels of GDF11. Keywords: physical activity, muscle strength, rejuvenating factor, COPD

Tadashi Nakano,1 Motoko Kawashima,2 Yoshimune Hiratsuka,3 Hiroshi Tamura,4,5 Koichi Ono,6 Akira Murakami,3 Kazuo Tsubota,2 Masakazu Yamada7,8 1Department of Ophthalmology, Jikei University School of Medicine, 2Department of Ophthalmology, Keio University School of Medicine, 3Department of Ophthalmology, Juntendo University Graduate School of Medicine, Tokyo, 4Department of Ophthalmology & Visual Sciences, Kyoto University, 5Division of Medical Information Technology & Administration Planning, Kyoto University Hospital, Kyoto, 6Department of Ophthalmology, Juntendo Tokyo Koto Geriatric Medical Center, 7National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, 8Department of Ophthalmology, Kyorin University, Tokyo, Japan Background: The purpose of the present study was to assess the vision-related quality of life (QOL) of visually impaired patients using the Japanese 11-item National Eye Institute Visual Function Questionnaire (VFQ-J11). Comparisons with the 25-item version (VFQ-25) and the EuroQoL Index using a large group of patients with various degrees of impairments and various causative diseases were performed.Methods: A total of 232 visually impaired Japanese patients were recruited from six ophthalmology departments in Japan. Information on ophthalmic findings and patient backgrounds was collected, and information on QOL and utility assessments was collected from the patients by means of survey questionnaires.Results: The average age of patients was 69.6±14.3 years. Both the vision-related QOL scores (VFQ-25 composite and VFQ-J11) were significantly associated with better and worse visual acuity (VA) in visually impaired subjects (all P

Makiko Saita,1 Takayuki Ikeda,1,2 Masahiro Yamada,1,3 Katsuhiko Kimoto,4 Masaichi Chang-Il Lee,5 Takahiro Ogawa1 1Division of Advanced Prosthodontics, Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, CA, USA; 2Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, Yokosuka, Japan; 3Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan; 4Department of Prosthodontics and Oral Rehabilitation, 5Yokosuka-Shonan Disaster Health Emergency Research Center and ESR Laboratories, Kanagawa Dental University Graduate School of Dentistry, Yokosuka, Japan Background: Although biomimetic apatite coating is a promising way to provide titanium with osteoconductivity, the efficiency and quality of deposition is often poor. Most titanium implants have microscale surface morphology, and an addition of nanoscale features while preserving the micromorphology may provide further biological benefit. Here, we examined the effect of ultraviolet (UV) light treatment of titanium, or photofunctionalization, on the efficacy of biomimetic apatite deposition on titanium and its biological capability.Methods and results: Micro-roughed titanium disks were prepared by acid-etching with sulfuric acid. Micro-roughened disks with or without photofunctionalization (20-minute exposure to UV light) were immersed in simulated body fluid (SBF) for 1 or 5 days. Photofunctionalized titanium disks were superhydrophilic and did not form surface air bubbles when immersed in SBF, whereas non-photofunctionalized disks were hydrophobic and largely covered with air bubbles during immersion. An apatite-related signal was observed by X-ray diffraction on photofunctionalized titanium after 1 day of SBF immersion, which was equivalent to the one observed after 5 days of immersion of control titanium. Scanning electron microscopy revealed nodular apatite deposition in the valleys and at the inclines of micro-roughened structures without affecting the existing micro-configuration. Micro-roughened titanium and apatite-deposited titanium surfaces had similar roughness values. The attachment, spreading, settling, proliferation, and alkaline phosphate activity of bone marrow-derived osteoblasts were promoted on apatite-coated titanium with photofunctionalization.Conclusion: UV-photofunctionalization of titanium enabled faster deposition of nanoscale biomimetic apatite, resulting in the improved biological capability compared to the similarly prepared apatite-deposited titanium without photofunctionalization. Photofunctionalization-assisted biomimetic apatite deposition may be a novel method to effectively enhance micro-roughened titanium surfaces without altering their microscale morphology. Keywords: nanotechnology, dental and orthopedic implants, superhydrophilic, hydrocarbon, osseointegration

Natsuko Nakamura,1 Kunihiko Akiyama,1,2 Chika Shigeyasu,1,3 Masakazu Yamada1,31Division for Vision Research, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, 2Department of Ophthalmology, National Tokyo Medical Center, Tokyo, 3Department of Ophthalmology, Kyorin University School of Medicine, Mitaka, JapanPurpose: The aim of the study described here was to report the outcomes of surgery for orbital fat prolapse by conjunctival fixation to the sclera.Patients and methods: Twenty-three consecutive eyes of 19 patients with orbital fat prolapse were retrospectively reviewed. All cases were treated with the same simple procedure without resection through conjunctival incision: fixation of conjunctiva to the sclera with interrupted sutures of 10-0 nylon in two rows located approximately 12–14 mm posterior to the limbus. These sutures formed an embankment to keep the prolapsed fat posteriorly. Postoperative results were determined by slit-lamp examination and recurrence of prolapse was defined as the presence of orbital fat anterior to the embankment.Results: During the mean follow-up period of 19 months (range: 1-59 months), one case experienced recurrence which required further surgery. None of the other cases experienced recurrence, and there were no intraoperative or postoperative complications.Conclusion: Conjunctival fixation to the sclera was a simple and effective surgical technique for orbital fat prolapse, with less invasion compared to the conventional method that requires conjunctival incision.Keywords: surgical technique, herniation, orbital fat, conjunctiva, suture, 10-0 nylon

Tamotsu Ishizuka,1,2 Takeshi Hisada,2 Yosuke Kamide,2 Haruka Aoki,2 Kaori Seki,2 Chisato Honjo,1 Hiroyuki Sakai,1 Maiko Kadowaki,1 Yukihiro Umeda,1 Miwa Morikawa,1 Masaki Anzai,1 Shingo Ameshima,1 Takeshi Ishizaki,1 Kunio Dobashi,2 Masanobu Yamada,2 Motoyasu Kusano3 1Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 2Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Maebashi, Japan Background: Losing the sense of smell, which suggests eosinophilic rhinosinusitis, is a subjective symptom, sometimes reported in asthmatic patients taking controller medication. Upper abdominal symptoms, suggesting gastroesophageal reflux disease (GERD) or functional dyspepsia, occur also in these patients. However, the relationship between these symptoms, concomitant with asthma, and the intensity of eosinophilic airway inflammation remains obscure. Objective: To assess the symptoms of asthma and rhinosinusitis, and to examine the relationship between the symptoms and bronchial inflammation, a new questionnaire, the G scale, was developed. To investigate the effects of GERD, dyspepsia, and rhinosinusitis on asthma symptoms and bronchial inflammation, the symptoms of asthma and rhinosinusitis obtained by the G scale, upper abdominal symptoms obtained by the modified F scale, a questionnaire for GERD and dyspepsia, and fractional exhaled nitric oxide (FeNO) were analyzed. Methods: A prospective, observational study was performed in four hospitals in Gunma prefecture, and a retrospective analysis was done using data obtained from five hospitals in Gunma prefecture and Fukui prefecture, Japan. A total of 252 patients diagnosed as having asthma participated in the prospective study. Results: The frequency of daytime phlegm or losing the sense of smell had a positive correlation with FeNO levels in asthmatic patients taking controller medication. Upper abdominal symptoms, as well as symptoms suggesting rhinitis, were well correlated with asthma symptoms. However, neither upper abdominal symptoms nor rhinitis symptoms increased FeNO levels, which reflect eosinophilic airway inflammation during treatment for asthma. On the other hand, the degree of upper abdominal symptoms or dyspepsia symptoms had a weak but significant negative correlation with FeNO levels. Conclusion: Daytime phlegm and losing the sense of smell suggest that eosinophilic airway inflammation persists, despite anti-inflammatory therapy, in patients with asthma. Although rhinitis and GERD made the subjective symptoms of asthma worse, they did not seem to enhance eosinophilic airway inflammation. Keywords: asthma symptoms, FeNO, rhinosinusitis, GERD, dyspepsia

Hiroharu Kamioka,1 Kiichiro Tsutani,2 Minoru Yamada,3 Hyuntae Park,4 Hiroyasu Okuizumi,5 Koki Tsuruoka,6 Takuya Honda,7 Shinpei Okada,8 Sang-Jun Park,8 Jun Kitayuguchi,9 Takafumi Abe,9 Shuichi Handa,5 Takuya Oshio,10 Yoshiteru Mutoh111Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, Japan; 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; 3Kyoto University Graduate School Research, Kyoto, Japan; 4Department of Functioning Activation, National Center for Geriatrics and Gerontology, Aichi, Japan; 5Mimaki Onsen (Spa) Clinic, Tomi, Nagano, Japan; 6Graduate School of Social Services, Japan College of Social Work, Tokyo, Japan; 7Japanese Society for the Promotion of Science, Tokyo, Japan; 8Physical Education and Medicine Research Foundation, Tomi, Nagano, Japan; 9Physical Education and Medicine Research Center Unnan, Shimane, Japan; 10Social Welfare Service Corporation CARE-PORT MIMAKI, Tomi, Nagano, Japan; 11The Research Institute of Nippon Sport Science University, Tokyo, JapanObjective: The objective of this review was to summarize evidence for the effectiveness of music therapy (MT) and to assess the quality of systematic reviews (SRs) based on randomized controlled trials (RCTs).Study design: An SR of SRs based on RCTs.Methods: Studies were eligible if they were RCTs. Studies included were those with at least one treatment group in which MT was applied. We searched the following databases from 1995 to October 1, 2012: MEDLINE via PubMed, CINAHL (Cumulative Index of Nursing and Allied Health Literature), Web of Science, Global Health Library, and Ichushi-Web. We also searched all Cochrane Database and Campbell Systematic Reviews up to October 1, 2012. Based on the International Classification of Diseases, 10th revision, we identified a disease targeted for each article.Results: Twenty-one studies met all inclusion criteria. This study included 16 Cochrane reviews. As a whole, the quality of the articles was very good. Eight studies were about "Mental and behavioural disorders (F00-99)"; there were two studies on "Diseases of the nervous system (G00-99)" and "Diseases of the respiratory system (J00-99)"; and there was one study each for "Endocrine, nutritional and metabolic diseases (E00-90)", "Diseases of the circulatory system (I00-99)", and "Pregnancy, childbirth and the puerperium (O60)". MT treatment improved the following: global and social functioning in schizophrenia and/or serious mental disorders, gait and related activities in Parkinson's disease, depressive symptoms, and sleep quality.Conclusion: This comprehensive summary of SRs demonstrated that MT treatment improved the following: global and social functioning in schizophrenia and/or serious mental disorders, gait and related activities in Parkinson's disease, depressive symptoms, and sleep quality. MT may have the potential for improving other diseases, but there is not enough evidence at present. Most importantly, no specific adverse effect or harmful phenomenon occurred in any of the studies, and MT was well tolerated by almost all patients.Keywords: ICD-10, schizophrenia, mental disorders, Parkinson's disease, depression, sleep

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

Masakazu Yamada, Yoshinobu Mizuno, Chika ShigeyasuNational Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, JapanBackground: The purpose of this study was to evaluate the impact of dry eye on work productivity of office workers, especially in terms of presenteeism.Methods: A total of 396 individuals aged ≥20 years (258 men and 138 women, mean age 43.4 ± 13.0 years) were recruited through an online survey. Data from 355 responders who did not have missing values were included in the analysis. They were classified into the following four groups according to the diagnostic status and subjective symptoms of dry eye: a definite dry eye group; a marginal dry eye group; a self-reported dry eye group; and a control group. The impact of dry eye on work productivity was evaluated using the Japanese version of the Work Limitations Questionnaire. The cost of work productivity loss associated with dry eye and the economic benefits of providing treatment for dry eye were also assessed.Results: The degree of work performance loss was 5.65% in the definite dry eye group, 4.37% in the marginal dry eye group, 6.06% in the self-reported dry eye group, and 4.27% in the control group. Productivity in the self-reported dry eye group was significantly lower than that in the control group (P < 0.05). The annual cost of work productivity loss associated with dry eye was estimated to be USD 741 per person.Conclusion: Dry eye impairs work performance among office workers, which may lead to a substantial loss to industry. Management of symptoms of dry eye by providing treatment may contribute to improvement in work productivity.Keywords: burden of disease, dry eye, presenteeism, quality of life

Yoshinobu Mizuno, Masakazu Yamada, Chika ShigeyasuDivision for Vision Research, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, JapanOn behalf of The Dry Eye Survey Group, National Hospital Organization of JapanBackground: This study was performed to estimate the annual direct cost incurred by dry eye patients, which includes expenses for treatment and drugs, as well as the cost of punctal plugs.Methods: The study group consisted of 118 dry eye patients aged 20 years or older who visited any of the 15 medical care facilities that participated in this prospective cohort dry eye study. We estimated annual direct costs from outpatient medical records and survey questionnaires obtained from patients. Results: Of the total patients enrolled, 10 were men and 108 women, and their average age was 64.1 ± 11.2 years. The number of hospital visits made by patients was 5.8 ± 3.6 per year. Among those who used ophthalmic solutions, the numbers of bottles used per year were as follows: 32.1 ± 20.8 bottles of hyaluronic acid ophthalmic solution (87 patients), 53.1 ± 42.2 bottles of artificial tears (40 patients), and 33.2 ± 23.2 bottles of over-the-counter eyedrops (15 patients). In patients with punctal plugs, 4.1 ± 3.9 plugs were used annually. The annual drug cost was 32,000 ± 21,675 Japanese yen (323 ± 219 US dollars). The clinical cost was 16,318 ± 9961 Japanese yen (165 ± 101 US dollars). The total direct costs including punctal plug treatment amounted to 52,467 ± 38,052 Japanese yen (530 ± 384 US dollars). Conclusion: Although treatment modalities for dry eye in Japan were different from those in the US and in European countries, the direct cost of dry eye patients in Japan was comparable with that reported in those countries. Considering the high prevalence of dry eye, the direct cost of this chronic condition may be significant.Keywords: burden of disease, cost, dry eye, eyedrops, quality of life

Masahiro Yamada*, Takeshi Ueno*, Naoki Tsukimura, Takayuki Ikeda, Kaori Nakagawa, Norio Hori, Takeo Suzuki, Takahiro OgawaLaboratory of Bone and Implant Sciences, The Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, Los Angeles, CA, USA *These authors contributed equally to this workAbstract: The mechanism by which hydroxyapatite (HA)-coated titanium promotes bone–implant integration is largely unknown. Furthermore, refining the fabrication of nanostructured HA to the level applicable to the mass production process for titanium implants is challenging. This study reports successful creation of nanopolymorphic crystalline HA on microroughened titanium surfaces using a combination of flame spray and low-temperature calcination and tests its biological capability to enhance bone–implant integration. Sandblasted microroughened titanium implants and sandblasted + HA-coated titanium implants were subjected to biomechanical and histomorphometric analyses in a rat model. The HA was 55% crystallized and consisted of nanoscale needle-like architectures developed in various diameters, lengths, and orientations, which resulted in a 70% increase in surface area compared to noncoated microroughened surfaces. The HA was free from impurity contaminants, with a calcium/phosphorus ratio of 1.66 being equivalent to that of stoichiometric HA. As compared to microroughened implants, HA-coated implants increased the strength of bone–implant integration consistently at both early and late stages of healing. HA-coated implants showed an increased percentage of bone–implant contact and bone volume within 50 µm proximity of the implant surface, as well as a remarkably reduced percentage of soft tissue intervention between bone and the implant surface. In contrast, bone volume outside the 50 µm border was lower around HA-coated implants. Thus, this study demonstrated that the addition of pure nanopolymorphic crystalline HA to microroughened titanium not only accelerates but also enhances the level of bone–implant integration and identified the specific tissue morphogenesis parameters modulated by HA coating. In particular, the nanocrystalline HA was proven to be drastic in increasing osteoconductivity and inhibiting soft tissue infiltration, but the effect was limited to the immediate microenvironment surrounding the implant.Keywords: osseointegration, dental and orthopedic implant, nanotechnology, bone–implant integration, HA, calcium phosphate

Ken Ishizaki*, Yoshihiko Sugita*, Fuminori Iwasa, Hajime Minamikawa, Takeshi Ueno, Masahiro Yamada, Takeo Suzuki, Takahiro OgawaLaboratory for Bone and Implant Sciences, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, Los Angeles, CA, USA*Authors contributed equally to this workBackground: The independent role of the surface chemistry of titanium in determining its biological properties is yet to be determined. Although titanium implants are often in contact with muscle tissue, the interaction of muscle cells with titanium is largely unknown. This study tested the hypotheses that the surface chemistry of clinically established microroughened titanium surfaces could be controllably varied by coating with a minimally thin layer of TiO2 (ideally pico-to-nanometer in thickness) without altering the existing topographical and roughness features, and that the change in superficial chemistry of titanium is effective in improving the biological properties of titanium.Methods and results: Acid-etched microroughened titanium surfaces were coated with TiO2 using slow-rate sputter deposition of molten TiO2 nanoparticles. A TiO2 coating of 300 pm to 6.3 nm increased the surface oxygen on the titanium substrates in a controllable manner, but did not alter the existing microscale architecture and roughness of the substrates. Cells derived from rat skeletal muscles showed increased attachment, spread, adhesion strength, proliferation, gene expression, and collagen production at the initial and early stage of culture on 6.3 nm thick TiO2-coated microroughened titanium surfaces compared with uncoated titanium surfaces.Conclusion: Using an exemplary slow-rate sputter deposition technique of molten TiO2 nanoparticles, this study demonstrated that titanium substrates, even with microscale roughness, can be sufficiently chemically modified to enhance their biological properties without altering the existing microscale morphology. The controllable and exclusive chemical modification technique presented in this study may open a new avenue for surface modifications of titanium-based biomaterials for better cell and tissue affinity and reaction.Keywords: nanotechnology, orthopedic implants, molten TiO2 nanoparticles, surface chemistry