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Taku Yamada,1 Taketomo Kikuchi,1 Sachiko Nagasu,2,3 Kayoko Hashimoto,4 Eri Furukawa,4 Hirokazu Matsumoto,1 Kazuki Tsutsumi,1 Toshimitsu Tanaka,2,5 Miho Kugishima,3 Takumi Kawaguchi,5 Fumihiko Fujita,3 Kyouko Higuchi,1 Keisuke Miwa2 1Department of Pharmacy, Kurume University Hospital, Kurume, Fukuoka, Japan; 2Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Kurume, Fukuoka, Japan; 3Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan; 4Department of Nursing, Kurume University Hospital, Kurume, Fukuoka, Japan; 5Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, JapanCorrespondence: Keisuke Miwa, Multidisciplinary Treatment Cancer Center, Kurume University Hospital, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan, Tel +81-942-31-7566, Fax +81-942-34-0709, Email miwa_keisuke@kurume-u.ac.jpPurpose: Elastomeric infusion pumps are widely used in colorectal cancer chemotherapy. However, no studies to date have investigated patient preferences regarding different infusion pump types.Patients and Methods: Twenty patients with unresectable colorectal cancer undergoing chemotherapy were initially treated with a portable hard-shelled continuous infusion pump, followed by a soft-shelled continuous infusion pump. The respondents used a numerical rating scale (0– 10) to rate their comfort when using each pump, their ease of carrying it, the pump size and shape, its weight, their ease of reading its memory, and their overall satisfaction with it. They were then asked to determine which pump they would ultimately prefer.Results: In terms of comfort, significantly higher user satisfaction was reported for the soft-shelled pump during the daytime and when going out (P < 0.001, P < 0.001, respectively). For pump portability, size, shape, and weight, the soft-shelled type also outperformed the hard-shelled one (P < 0.001, P=0.0011, P < 0.001, respectively). However, the hard-shelled pump scored significantly better in terms of ease of viewing memory (P < 0.001). Overall satisfaction was significantly higher for the soft-shelled pump than the hard-shelled type (P=0.0095). Finally, 13 patients (65%) indicated that they would prefer a soft-shelled pump for their next treatment, while only one patient (5%) preferred a hard-shelled alternative. A preference for soft-shelled pump was observed, particularly in female patients and those with a body mass index of < 22 kg/m2.Conclusion: The selection of portable elastomeric infusion pumps should consider the preferences of patients with colorectal cancer, as these devices have the potential to enhance their quality of life.Keywords: colorectal cancer, chemotherapy, infusion pump, elastomeric infusion pump, portable infusion pump, patient preference

Soichiro Hanada,1,&ast; Masato Muraki,1,&ast; Yoshiyuki Kawabata,1 Kazuya Yoshikawa,1 Toshiyuki Yamagata,1 Tadao Nagasaki,1 Yushiro Ohara,2 Naoki Oiso,2 Hisako Matsumoto,3 Yuji Tohda4 1Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital, Ikoma, Nara, Japan; 2Department of Dermatology, Kindai University Nara Hospital, Ikoma, Nara, Japan; 3Department of Respiratory Medicine and Allergology, Kindai University Hospital, Osakasayama, Osaka, Japan; 4Kindai University Hospital, Osakasayama, Osaka, Japan&ast;These authors contributed equally to this workCorrespondence: Masato Muraki, Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital, 1248-1 Otoda-cho, Ikoma, Nara, 630-0293, Japan, Tel +81 743 77 0880, Fax +81 743 77 0890, Email muraki-m@med.kindai.ac.jpPatients and Methods: A questionnaire survey was administered to 18, 14, and 3 patients introduced to home self-injection of dupilumab or mepolizumab using a pen-type device for atopic dermatitis, asthma alone, and asthma plus chronic rhinosinusitis with nasal polyps, respectively.Results: All but one participant wished to continue self-injection. Most participants affirmed the reduction in copayment (88.6%) and saving time and labor for hospital visits (88.6%). Six patients who received dupilumab complained of side effects, but all, except for one, continued the treatment. Of the 13 patients who had previously used a syringe-type device, 10 preferred the pen type because of its ease of use, while 3 (23%) preferred the syringe type because of the self-adjustable injection speed for pain control.Conclusion: Administration of biologics using pen-type devices is easier, and the introduction of home self-injection leads to a reduction in outpatient visits and copayment.Keywords: dupilumab, mepolizumab, self-injection, asthma, atopic dermatitis, chronic sinusitis with nasal polyps

Haruka Matsumoto,1 Shigenari Suzuki,1 Mayumi Nagata,1 Tadashi Senoo,1 Meri Watanabe,2 Hidetoshi Kawashima2 1Department of Ophthalmology, Dokkyo Medical University, Mibu, Japan; 2Department of Ophthalmology, Jichi Medical University, Shimotsuke, JapanCorrespondence: Haruka Matsumoto, Department of Ophthalmology, Dokkyo Medical University, 880 Kitakobayashi, Shimotsuga-gun, Mibu, Tochigi, 321-0293, Japan, Tel +81 282 86 1111, Fax +81 282 86 0630, Email wataharu@dokkyomed.ac.jpPurpose: This study aimed to investigate the clinical features of patients with syphilis having ocular symptoms as the initial manifestation.Patients and Methods: Eleven patients diagnosed with ocular syphilis at Dokkyo Medical University Hospital and Jichi Medical University Hospital between November 2018 and April 2022 were studied retrospectively.Results: Six patients were diagnosed with secondary, three were latent, and one was tertiary stage syphilis. Ten out of 11 patients underwent cerebrospinal fluid analysis, and 1 refused. Nine out of 10 patients tested positive, of which 4 presented with neurological symptoms and the others were asymptomatic. Nine out of 11 patients tested negative for human immunodeficiency virus. Antiluetic therapy was administered to 10 out of 11 patients, which improved or maintained visual acuity at − 0.1 logMAR in 9 patients. One patient achieved the best-corrected visual acuity − 0.1 logMAR in one eye, whereas the other showed no improvement due to severe chorioretinal degeneration.Conclusion: Ocular syphilis presents with various clinical findings and has no significant ocular manifestations without acute syphilitic posterior placoid chorioretinitis. Patients diagnosed with syphilis based on ocular symptoms should undergo cerebrospinal fluid analysis.Keywords: syphilis, ocular syphilis, secondary stage syphilis, antiluetic therapy, neurosyphilis, sexually transmitted disease

Tomoko Miyakubo, Ryo Mukai, Hidetaka Matsumoto, Masahiro Morimoto, Maki Takahashi, Kazuki Nagai, Kosuke Nakamura, Junki Hoshino, Hideo Akiyama Department of Ophthalmology, Gunma University, Graduate School of Medicine, Maebashi, Gunma, JapanCorrespondence: Ryo Mukai, Department of Ophthalmology, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan, Tel +81-27-220-8338, Fax +81-27-233-3841, Email rmukai@gunma-u.ac.jpPurpose: To compare the efficacies of photodynamic therapy (PDT) combined with intravitreal aflibercept (IVA) injections and IVA monotherapy using a treat-and-extend regimen (TAE) for treatment-naïve polypoidal choroidal vasculopathy (PCV).Patients and Methods: One hundred and nine eyes treated with PDT combined with IVA (PDT+IVA group: 51 eyes) or IVA monotherapy (IVA group: 58 eyes) were assessed for 2 years. The main outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), number of IVA injections, and macular atrophy (MA). Polypoidal lesions before and after the loading phase were assessed using indocyanine green angiography.Results: In both groups, BCVA significantly improved after the loading phase and was maintained for 2 years. CMT and CCT were significantly reduced in both groups, without significant differences after 2 years between the groups (P=0.2708). The mean number of IVA injections in the IVA and PDT+IVA groups during the 2 years were 13.2± 3.3 and 12.7± 1.8, respectively, without a significant difference (P=0.06). The frequencies of MA expansion in the IVA and PDT+IVA groups during the 2 years were 25.9% and 33.4%, respectively, with no significant difference in the incidence (odds ratio: 1.40, P=0.4253). The ratios of polyp regression after the loading phase in the IVA and PDT+IVA groups were 55.2% and 94.1%, respectively, with a significant difference (P< 0.0001).Conclusion: PDT combined with IVA injections using a TAE regimen is effective for anatomical and visual function improvement, without a significant difference as compared to IVA monotherapy. It can facilitate complete regression of polyps with higher odds.Keywords: polypoidal choroidal vasculopathy, aflibercept, photodynamic therapy, treat-and-extend, macular atrophy

Takashi Kato,1 Koichi Nagata,2,3 Junta Yamamichi,4 Soichi Tanaka,5 Tetsuro Honda,6 Norihito Shimizu,7 Kenichi Utano,8 Michiaki Hirayama,9 Hiroshi Matsumoto,10 Shoichi Horita1 1Department of Internal Medicine, Hokkaido Gastroenterological Hospital, Sapporo, Japan; 2Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan; 3Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan; 4Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan; 5Department of Coloproctology, Matsuaikai Matsuda Hospital, Hamamatsu, Japan; 6Department of Gastroenterology, Nagasaki Harbor Medical Center, Nagasaki, Japan; 7Department of Radiology, Medical Corporation Matsuoka Clinic, Nara, Japan; 8Department of Coloproctology, Aizu Medical Center, Fukushima Medical University, Aizuwakamatsu, Fukushima, Japan; 9Department of Gastroenterology, Tonan Hospital, Sapporo, Japan; 10Department of Gastroenterology, Kawasaki Medical University School of Medicine, Kurashiki, JapanCorrespondence: Takashi KatoDepartment of Internal Medicine, Hokkaido Gastroenterological Hospital, Sapporo, Hokkaido 065-0041, JapanTel +8111-784-1811Fax +8111-784-1838Email tkskato45@gmail.comPurpose: Patients who test positive on the fecal immunochemical test (FIT) for colorectal cancer (CRC) are referred for colonoscopy for further diagnostic evaluation. Colonoscopy is not a perfect method and may be a challenge for some FIT-positive patients. Computed tomographic colonography (CTC) is an alternative method that is less invasive and allows examination of the whole colon. The study objective was to evaluate the preference of FIT-positive patients for either colonoscopy or CTC for CRC examination.Patients and Methods: Individuals older than 40 years with a positive FIT test at eight Japanese hospitals between December 2012 and July 2015 were invited to participate. Participants were given detailed information regarding colonoscopy and CTC before deciding on either examination. They completed questionnaires before the procedure regarding their preference and after the procedure regarding their experience.Results: The pre- and post-questionnaires of 846 and 834 participants, respectively, were analyzed. Participants preferred colonoscopy over CTC (colonoscopy, 72%; CTC, 28%). The possibility of obtaining biopsy samples and removing colorectal polyps during the procedure was the main reason for colonoscopy selection. Patients selected CTC to reduce discomfort but reported that CTC bowel preparation was more burdensome than colonoscopy bowel preparation. The overall experience of the examination did not differ between the groups.Conclusion: Colonoscopy is the standard examination for FIT-positive patients. However, when given a choice, almost one-third of participants chose CTC because they thought it would be a more “comfortable” examination. Clinicians should therefore be aware of patients’ potential preference for noninvasive colorectal examinations.Keywords: computed tomographic colonography, colonoscopy, patient preference, fecal immunochemical test

Iwamoto J, Sato Y, Uzawa M, Takeda T, Matsumoto H. Ther Clin Risk Manag. 2010;6:593–600. The Editor and Publisher of Therapeutics and Clinical Risk Management wish to retract the published article. Following publication of the Expression of Concern, this article has been retracted due to acknowledgement of allegations of scientific misconduct regarding data integrity, inappropriate authorship, duplicate reporting, ethical oversight, and data fabrication. In addition, it has been recognised that numerous other publications from this research group have also been retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Ayaka Niina,1 Ryoko Kibe,2 Ryohei Suzuki,1 Yunosuke Yuchi,1 Takahiro Teshima,1 Hirotaka Matsumoto,1 Yasushi Kataoka,2 Hidekazu Koyama1 1Laboratory of Veterinary Internal Medicine, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino, Tokyo, Japan; 2Laboratory of Veterinary Microbiology, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino, Tokyo, JapanCorrespondence: Ayaka NiinaLaboratory of Veterinary Internal Medicine, School of Veterinary Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-Cho, Musashino-Shi, Tokyo 180-8602, JapanTel +81 422 31 4151Fax +81 422 31 4560Email a.niina2173@gmail.comPurpose: Recently, fecal microbiota transplantation (FMT) has been tested in veterinary medicine as a treatment option for multiple gastrointestinal (GI) diseases, such as inflammatory bowel disease (IBD). However, there are no reports of changes in the microbial diversity of fecal microbiome after treatment with FMT in canine IBD cases. Moreover, little is known about the long-term efficacy and safety of FMT treatment for dogs. Herein, we present a case of canine intractable IBD treated with repeated, long-term FMT.Patients and methods: The patient was a 10-year-old, neutered, male, 4-kg Toy Poodle with a prolonged history of vomiting and diarrhea. Fecal examination for pathogens was negative. Despite treatment with multiple antibacterial and antidiarrheal agents, the patient showed no improvement. Endoscopic mucus sampling diagnosed a case of lymphocytic-plasmacytic duodenitis, ie, idiopathic IBD. Eventually, we performed periodic, long-term fecal microbiota transplantation of fresh donor feces collected from a 4-year-old, 32.8-kg, neutered male Golden Retriever by rectal enema. Additionally, we performed 16S rRNA sequence analysis, before and after FMT, to evaluate the microbiome diversity.Results: Fecal microbiome diversity after FMT resembled that of the healthy donor dog’s fecal microbiome, before FMT, which led us to conclude that the fecal microbiome in our patient normalized with FMT. Moreover, the clinical symptoms improved remarkably with regard to the changes in the fecal microbiome. Additionally, we noted no observable side effects during FMT treatment.Conclusion: This report indicates the efficacy and safety of long-term, periodic FMT for a case of canine IBD based on attenuation of clinical symptoms and changes in fecal microbiome diversity. Therefore, FMT could be chosen as a treatment option for IBD in canines in the future.Keywords: fecal microbiota transplantation, inflammatory bowel disease, canine, dysbiosis, microbiome, diversity

Tomoko Miyakubo, Ryo Mukai, Kosuke Nakamura, Hidetaka Matsumoto, Hideo Akiyama Department of Ophthalmology, Gunma University Graduate School of Medicine, Maebashi, Gunma, JapanCorrespondence: Ryo MukaiDepartment of Ophthalmology, Gunma University Graduate School of Medicine, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8511, JapanTel +81 27 220 8338Fax +81 27 233 3841Email ryohmukai@gmail.comPurpose: Ipilimumab is an immune checkpoint inhibitor that is now widely used for patients with metastatic malignant melanoma. However, this immune checkpoint inhibitor can induce related adverse events in various organs. Here, we report a case of bilateral drug (ipilimumab)-induced serous retinal detachment (SRD), and the characteristic features found during swept-source optical coherence tomography (SS-OCT).Case: A 78-year-old man with metastatic melanoma received 4 cycles of dacarbazine, nimustine, vincristine, and interferon-beta starting in January 2014, followed by 47 cycles of nivolumab starting in September 2014. Treatment with ipilimumab was started in June 2017. After 2 cycles of ipilimumab, the patient noticed impairment of the visual field in both of his eyes (at day 22) and visited our department in August 2017. Best corrected visual acuity at this initial visit was 16/20 in both eyes, while a fundus examination revealed SRD and retinal pigment epithelial detachments in both eyes. When using the horizontal and vertical 12 mm B-scanned images of SS-OCT, we detected SRD accompanied by a widely distributed high reflection of the photoreceptor outer segment, including the area where the SRD appeared. In addition, the image also showed the interdigitation zone was indistinguishable. Fluorescein angiography showed little leakage in the maculae. During his course of follow-up examinations, there was an increase in the SRD at the beginning, after which it then gradually decreased. However, the obscurity of the interdigitation zone remained.Conclusion: Ipilimumab may cause impairment of the outer retinal layer. We suggest that this is a presumed ipilimumab-induced SRD.Keywords: ipilimumab, metastatic malignant melanoma, serous retinal detachment

Koichiro Azuma,1 Yasushi Sera,1 Takuma Shinjo,1 Michiyo Takayama,2 Eisuke Shiomi,2 Suketaka Momoshima,2 Yasushi Iwao,2 Hiroyuki Ishida,3 Hideo Matsumoto1 1Institute for Integrated Sports Medicine, Keio University School of Medicine, 2Center for Preventive Medicine, Keio University Hospital, Shinjuku-ku, Tokyo, 3Sports Medicine Research Center, Keio University, Kohoku-ku, Yokohama, Kanagawa, Japan Background: Knee osteoarthritis (OA) is an increasing health problem worldwide. So far, only obesity and quadriceps weakness are identified as modifiable risk factors for knee OA. Core muscle strengthening is becoming increasingly popular among older adults because of its ability to enhance the activities of daily living during old age. This study investigated the associations of the size and quality of the abdominal trunk muscles with radiographic knee osteoarthritis (RKOA). Methods: From 2012 to 2016, data were collected from 146 males and 135 females (age 63.9±13.4 years, BMI 23.2±3.8 kg/m2) at annual musculoskeletal examinations, including knee radiographs and body composition analyses, by dual-energy X-ray absorptiometry. Cross-sectional areas of abdominal trunk muscles were measured using a single-slice computed tomography scan image obtained at the level of the umbilicus. Results: The prevalence of RKOA was 21.2% in males and 28.1% in females. Compared to subjects without RKOA, subjects with RKOA were ~6 years older and had smaller paraspinal muscle (38.4±8.7 vs 33.1±10.1 cm2, p

Ikuko Yataba,1 Noboru Otsuka,1 Isao Matsushita,1 Hideo Matsumoto,2 Yuichi Hoshino3 1Taisho Pharmaceutical Co, Ltd, 2Institute for Integrated Sports Medicine, School of Medicine, Keio University, Tokyo, 3Department of Orthopedics Surgery, School of Medicine, Jichi Medical University, Tochigi, Japan Background: Nonsteroidal anti-inflammatory drug (NSAID) patches are convenient for use and show much less gastrointestinal side effects than oral NSAIDs, whereas its percutaneous absorption is not sufficient for the expression of clinical efficacy at satisfactory level. S-flurbiprofen plaster (SFPP) has shown dramatic improvement in percutaneous absorption results from animal and clinical studies. In this study, the efficacy and safety of SFPP were compared with placebo in patients with knee osteoarthritis (OA) to determine its optimal dose. This was a multicenter, randomized, double-blind, parallel-group comparative study. Patients and methods: Enrolled 509 knee OA patients were treated with placebo or SFPP at 10, 20, or 40 mg applied on the affected site once daily for 2 weeks. The primary endpoint for efficacy was improvement in knee pain on rising from the chair assessed by visual analog scale (VAS). The other endpoints were clinical symptoms, pain on walking, and global assessment by both investigator and patient. Safety was evaluated by observing adverse events (AEs). Results: VAS change in knee pain from baseline to trial end was dose-dependent, least squares mean was 29.5, 31.5, 32.0, and 35.6 mm in placebo and SFPP 10, 20, and 40 mg, respectively. A significant difference was observed between placebo and SFPP 40 mg (P=0.001). In contrast, the effect of SFPP at a dose ≤20 mg was not significantly different from that of placebo. The proportion of the patients who achieved 50% pain relief was 72.4% in 40 mg and 51.2% in placebo (P

Yusuke Doi,1 Amr S Abu Lila,1–3 Haruna Matsumoto,1 Tomoko Okada,1 Taro Shimizu,1 Tatsuhiro Ishida1 1Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; 3Department of Pharmaceutics, Faculty of Pharmacy, Hail University, Hail, Saudi Arabia Abstract: The efficient delivery of nanocarrier-based cancer therapeutics into tumor tissue is problematic. Structural abnormalities, tumor vasculature heterogeneity, and elevated intratumor pressure impose barriers against the preferential accumulation of nanocarrier-based cancer therapeutics within tumor tissues and, consequently, compromise their therapeutic efficacy. Recently, we have reported that metronomic S-1, orally available tegafur formulation, dosing synergistically augmented the therapeutic efficacy of oxaliplatin (l-OHP)-containing PEGylated liposome without increasing the toxicity in animal model. However, the exact mechanism behind such synergistic effect was not fully elucidated. In this study, therefore, we tried to shed the light on the contributions of metronomic S-1 dosing to the enhanced accumulation and/or spatial distribution of PEGylated liposome within tumor tissue. Tumor priming with metronomic S-1 treatment induced a potent apoptotic response against both angiogenic endothelial cells and tumor cells adjacent to tumor blood vessels, resulting in enhanced tumor blood flow via transient normalization of tumor vasculature, along with alleviation of intratumor pressure. Such a change in the tumor microenvironment imparted by S-1 treatment allows efficient delivery of PEGylated liposome to tumor tissue and permits their deep penetration/distribution into the tumor mass. Such a priming effect of S-1 dosing can be exploited as a promising strategy to enhance the therapeutic efficacy of nanocarrier-based cancer therapeutics suffering from inadequate/heterogeneous delivery to tumor tissues. Keywords: tumor microenvironment, metronomic chemotherapy, S-1, liposome, nanocarrier, EPR effect

Yuka Tsukahara, Jun Iwamoto, Kosui Iwashita, Takuma Shinjo, Koichiro Azuma, Hideo MatsumotoInstitute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan Background: Whole-body vibration (WBV) exercise is widely used for training and rehabilitation. However, the optimal posture for training both the upper and lower extremities simultaneously remains to be established. Objectives: The objective of this study was to search for an effective posture to conduct vibration from the lower to the upper extremities while performing WBV exercises without any adverse effects. Methods: Twelve healthy volunteers (age: 22–34 years) were enrolled in the study. To measure the magnitude of vibration, four accelerometers were attached to the upper arm, back, thigh, and calf of each subject. Vibrations were produced using a WBV platform (Galileo 900) with an amplitude of 4 mm at two frequencies, 15 and 30 Hz. The following three postures were examined: posture A, standing posture with the knees flexed at 30°; posture B, crouching position with no direct contact between the knees and elbows; and posture C, crouching position with direct contact between the knees and elbows. The ratio of the magnitude of vibration at the thigh, back, and upper arm relative to that at the calf was used as an index of vibration conduction. Results: Posture B was associated with a greater magnitude of vibration to the calf than posture A at 15 Hz, and postures B and C were associated with greater magnitudes of vibration than posture A at 30 Hz. Posture C was associated with a vibration conduction to the upper arm that was 4.62 times and 8.26 times greater than that for posture A at 15 and 30 Hz, respectively. Conclusion: This study revealed that a crouching position on a WBV platform with direct contact between the knees and elbows was effective for conducting vibration from the lower to the upper extremities. Keywords: whole-body vibration exercise, upper extremities, lower extremities

Microstructure dependence on mechanical properties were investigated for Ti-17 forged at temperatures between 700 and 850 ˚C with deformation ratio from 33 to 80 %, and solutiontreated at 800˚C for 4 hours and aged at 620 ˚C for 8 hours. The microstructure was observed after solution and aging treatments. The volume fraction and the size of the primary alpha phase was controlled by solution treatment temperature, not forging temperature and deformation ratio. Forging temperature affected the morphology of grain boundary (GB) alpha phase. Deformation ratio affected the grain size and the aspect ratio of the horizontal and vertical grain size of the prior beta phase. The tensile strength was investigated at room temperature, 450, and 600 ˚C. Forging temperature and deformation ratio did not affect the tensile strength because there is no large difference of the volume fraction of the alphaphase. On the other hand, the elongation and the reduction of area increased with increase of the aspect ratio of the prior beta grains; that means, increase of the deformation ratio. Raising of forging temperature also increased elongation and reduction of area due to the film-like GB alphaphase.

The hot deformation behavior and microstructural evolution of Ti–5Al–2Sn–2Zr–4Mo–4Cr (Ti-17) alloy in the β-phase field were examined. Hot compression tests were conducted at temperatures ranging from 700 and 1100 °C and strain rates ranging from 10-3 to 1 s-1. The obtained true stress–true strain curves exhibited steady-state flow behavior at temperatures above the β-transus temperature (Tβ ~ 890 °C). The microstructural observations suggested that the dynamic recovery process represents a dominant mechanism for the β-phase of the alloy. In contrast, the flow softening was identified at 700 °C at a strain rate of 10–3 s–1. The formation of fine acicular α microstructures was noticed in such a deformation condition, indicating that dynamic phase transformation can occur in the metastable β-phase during hot deformation. Such a dynamic phase transformation also occurred preferentially at the initial β-grain boundaries as well as sub-boundaries that created within the βmatrix via dynamic recovery. The β-processing conditions were also examined by constructing processing maps based on the dynamic materials model (DMM).

Iwamoto J, Sato Y, Uzawa M, Takeda T, Matsumoto H. Therapeutics and Clinical Risk Management. 2010;6:593–600.The Editor-in-Chief and Publisher of Therapeutics and Clinical Risk Management wish to issue an Expression of concern for the above published article. The Journal Editors received notification from an investigator raising concerns about the published paper. These concerns relate to the high similarity in content to the article ‘Experience with alendronate treatment for 7 years among Japanese men with osteoporosis or osteopenia and clinical risk factors for fractures’. Iwamoto J, Uzawa M. Clinical Rheumatology. 2016;35:205–212. There were also concerns raised relating to the timeline for study conduct and manuscript preparation. The article reports the study took place between July 1st and September 30th, 2010 and was submitted for publication on Oct 24, 2010.Dove Medical Press attempted to contact the authors of the article and their affiliated institution regarding these concerns but received no response. As we were unable to make a definitive conclusion, we would like to alert readers to these issues and allow them to draw their own conclusions. This decision follows the recommendations of the Committee on Publication Ethics (COPE).The Editor and Dove Medical Press make every effort to ensure publication ethics are upheld and are committed to supporting the high standards of the Therapeutics and Clinical Risk Management journal. Read the original article

Eri Ito, Jun Iwamoto, Koichiro Azuma, Hideo MatsumotoInstitute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, JapanAbstract: The purpose of the present study was to investigate sex-specific differences in injury types among basketball players. According to our database, during the 20-year period between October 1991 and June 2011, 1,219 basketball players (640 males and 579 females) consulted our sports medicine clinic; in total, 1,414 injuries in basketball players (729 injuries in males and 685 injuries in females) were recorded. The mean age of patients was 19.6 years. The most common injury site was the knee, followed by the foot and ankle, lower back, and upper extremities. There was a higher proportion of female players presenting with a knee injury, compared with male players (50.4% vs 41.7%), and a lower proportion of female players presenting with an upper extremity injury (5.1% vs 9.7%). The proportion of anterior cruciate ligament injury in the 10–19-year-old age group was higher among female players than among male players (45.9% vs 22.1%), while the proportions of Osgood–Schlatter disease in the 10–19-year-old age group and jumper's knee (patellar and femoral tendinopathy) in the 20–29-year-old age group were higher among male players than among female players (12.5% vs 1.8% and 14.6% vs 3.7%, respectively). However, the proportions of other injuries did not differ significantly between male and female players. The present observational study, which was performed using a retrospective case-series design, showed the existence of sex-specific differences in knee injuries sustained while participating in basketball.Keywords: sports injury, sex, anterior cruciate ligament injury, Osgood–Schlatter disease, basketball

Yusuke Osawa,1,2,* Koichiro Azuma,3,* Shogo Tabata,3 Fuminori Katsukawa,2 Hiroyuki Ishida,2 Yuko Oguma,2 Toshihide Kawai,4 Hiroshi Itoh,4 Shigeo Okuda,5 Hideo Matsumoto3 1Japan Society for the Promotion of Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan; 2Sports Medicine Research Center, Keio University, Kanagawa, Japan; 3Institute for Integrated Sports Medicine, School of Medicine, Keio University, Tokyo, Japan; 4Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan; 5Department of Radiology, School of Medicine, Keio University, Tokyo, Japan *Yusuke Osawa and Koichiro Azuma are co-first authors of this article Abstract: It is unclear whether combined leg and arm high-intensity interval training (HIIT) improves fitness and morphological characteristics equal to those of leg-based HIIT programs. The aim of this study was to compare the effects of HIIT using leg-cycling (LC) and arm-cranking (AC) ergometers with an HIIT program using only LC. Effects on aerobic capacity and skeletal muscle were analyzed. Twelve healthy male subjects were assigned into two groups. One performed LC-HIIT (n=7) and the other LC- and AC-HIIT (n=5) twice weekly for 16 weeks. The training programs consisted of eight to 12 sets of >90% VO2 (the oxygen uptake that can be utilized in one minute) peak for 60 seconds with a 60-second active rest period. VO2 peak, watt peak, and heart rate were measured during an LC incremental exercise test. The cross-sectional area (CSA) of trunk and thigh muscles as well as bone-free lean body mass were measured using magnetic resonance imaging and dual-energy X-ray absorptiometry. The watt peak increased from baseline in both the LC (23%±38%; P

In the solar flare observed on June 3, 2012, high energy gamma-rays and neutrons were observed. The event includes a remarkable feature of a high neutron/gamma-ratio in the secondary particles. We have examined whether this high n/γ-ratio can be explained by simulation. As a result of simulations using the GEANT4 program, the high n/γ-ratio may be reproduced for the case that helium and other heavy ions were dominantly accelerated in the flare.

Jun Iwamoto,1 Yoshihiro Sato,2 Mitsuyoshi Uzawa,3 Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, 2Department of Neurology, Mitate Hospital, Fukuoka, 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanAbstract: We report the 11-year follow-up of a man with osteogenesis imperfecta type I who was treated with bisphosphonates and alfacalcidol. A 36-year-old Japanese man with osteogenesis imperfecta type I who had frequently experienced painful fragility fractures consulted our clinic because of chronic back pain. The patient had multiple morphometric vertebral fractures and a low bone mineral density (BMD) at the lumbar spine. The patient was treated with cyclical etidronate 200 mg, for 2 weeks every 3 months, plus alfacalcidol 1 µg daily, for 2 years; and alendronate 5 mg daily or 35 mg weekly, plus alfacalcidol 1 µg daily for 9 years. After 11 years of treatment, BMD at the lumbar spine increased by 6.4%, following a 20.3% reduction in serum alkaline phosphatase. Serum calcium, phosphorus, and intact parathyroid hormone levels remained within the normal ranges. Three clinical fractures occurred at two ribs and the metacarpus, and two morphometric vertebral fractures occurred at the thoracic spine during the 11-year treatment period, but the patient experienced no adverse effects. Thus, the present case report shows the long-term outcome and safety of bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I.Keywords: etidronate, alendronate, fragility fracture, bone mineral density, osteogenesis imperfecta

Jun Iwamoto,1 Tetsuya Takada,2 Yoshihiro Sato,3 Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, 2Department of Internal Medicine, Hiyoshi Medical Clinic, Kanagawa, 3Department of Neurology, Mitate Hospital, Fukuoka, JapanPurpose: The influence of alendronate (ALN) treatment on the quantitative ultrasound parameters of the calcaneus remains to be established in Japanese patients. The aim of the present clinical practice-based observational study was to examine the influence of ALN treatment for 1 year on the speed of sound (SOS) of the calcaneus and bone turnover markers in postmenopausal Japanese women with osteoporosis.Patients and methods: Forty-five postmenopausal Japanese women with osteoporosis who had received treatment with ALN for more than 1 year were enrolled in the study. The SOS and bone turnover markers were monitored over 1 year of ALN treatment.Results: The urinary levels of cross-linked N-terminal telopeptides of type I collagen and serum levels of alkaline phosphatase decreased significantly from the baseline values (–44.9% at 3 months and –22.2% at 12 months, respectively). The SOS increased modestly, but significantly, from the baseline value (0.6% at both 6 and 12 months). The percentage decrease in the urinary levels of cross-linked N-terminal telopeptides of type I collagen at 3 months was significantly correlated with the percentage increase in the SOS only at 6 months (correlation coefficient, 0.299).Conclusion: The present study confirmed that ALN treatment suppressed bone turnover, producing a clinically significant increase in the SOS of the calcaneus in postmenopausal Japanese women with osteoporosis.Keywords: postmenopausal osteoporosis, quantitative ultrasound (QUS), SOS, bone turnover, biochemical markers

Jun Iwamoto1, Yoshihiro Sato2, Mitsuyoshi Uzawa3, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, 2Department of Neurology, Mitate Hospital, Fukuoka, 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanAbstract: We report the 5-year follow-up of a young woman who developed vertebral fractures after pregnancy and lactation and was treated with active vitamin D hormone. A 32-year-old Japanese woman consulted us because of acute lower back pain caused by L2 and L5 vertebral fractures after pregnancy and lactation. Following cessation of breast-feeding, analgesia, bed rest, and wearing of a hard brace, her lower back pain disappeared within 2 months. After 5 years of treatment with alfacalcidol 1 µg daily, the lumbar spine (L1, L3, L4) bone mineral density increased by 21.4% following vigorous reductions in bone turnover markers. No osteoporotic fractures occurred, and the vertebral fractures healed. The patient experienced no side effects, including hypercalcemia. Thus, the present case report shows long-term changes in bone turnover markers and lumbar spine bone mineral density, as well as long-term safety of alfacalcidol treatment in a young woman with pregnancy and lactation-associated osteoporosis and vertebral fractures.Keywords: young woman, pregnancy, alfacalcidol, bone mineral density, osteoporosis, vertebral fracture

Jun Iwamoto1, Azusa Seki2, Yoshihiro Sato3, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Hamri Co, Ltd, Tokyo, Japan; 3Department of Neurology, Mitate Hospital, Fukuoka, JapanBackground and objective: The objective of the present study was to determine whether celecoxib, a cyclo-oxygenase-2 inhibitor, would delay bone healing in a rat femoral osteotomy model by examining bone histomorphometry parameters.Methods: Twenty-one 6-week-old female Sprague-Dawley rats underwent a unilateral osteotomy of the femoral diaphysis followed by intramedullary wire fixation; the rats were then divided into three groups: the vehicle administration group (control, n = 8), the vitamin K2 administration (menatetrenone 30 mg/kg orally, five times a week) group (positive control, n = 5), and the celecoxib administration (4 mg/kg orally, five times a week) group (n = 8). After 6 weeks of treatment, the wires were removed, and a bone histomorphometric analysis was performed on the bone tissue inside the callus. The lamellar area relative to the bone area was significantly higher and the total area and woven area relative to the bone area were significantly lower in the vitamin K2 group than in the vehicle group. However, none of the structural parameters, such as the callus and bone area relative to the total area, lamellar and woven areas relative to the bone area, or the formative and resorptive parameters such as osteoclast surface, number of osteoclasts, osteoblast surface, osteoid surface, eroded surface, and bone formation rate per bone surface differed significantly between the vehicle and celecoxib groups.Conclusion: The present study implies that celecoxib may not significantly delay bone healing in a rat femoral osteotomy model based on the results of a bone histomorphometric analysis.Keywords: femoral osteotomy, bone healing, callus, rat, celecoxib

Jun Iwamoto1, Yoshihiro Sato2, Mitsuyoshi Uzawa3, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, Japan; 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanAbstract: We report the case of a 30-year-old Japanese woman with anorexia nervosa and vertebral fractures who was treated with etidronate. She had a history of anorexia nervosa, chronic back pain, osteoporosis, and multiple vertebral fractures (morphometric fractures) that responded poorly to treatment with alfacalcidol (1 µg daily) for 1 year and was treated with cyclical etidronate (200 mg for 2 weeks every 3 months) for 7 years. The lumbar spine bone mineral density (BMD) increased, and the serum alkaline phosphatase and urinary cross-linked N-terminal telopeptides of type I collagen levels and back pain decreased. During the 7-year period of treatment with etidronate, no osteoporotic fractures occurred. The patient experienced neither renal dysfunction nor hyperparathyroidism caused by osteomalacia. No gastrointestinal tract symptoms were observed. Thus, etidronate was effective for increasing the lumbar spine BMD and reducing back pain over a 7-year period without causing either osteoporotic fractures or adverse events.Keywords: anorexia nervosa, bulimia, etidronate, bone mineral density, osteoporosis, vertebral fracture

Jun Iwamoto1, Yoshihiro Sato2, Mitsuyoshi Uzawa3, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, Japan; 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanPurpose: Combined treatment with alendronate and alfacalcidol is more useful to increase bone mineral density (BMD) than alendronate or alfacalcidol alone. A retrospective study was conducted to investigate the 3-year outcome of combined treatment with alendronate and alfacalcidol in patients with severe bone loss (BMD ≤ 50% of the young adult mean) and osteoporotic fracture.Methods: Thirty-four patients (six men and 28 postmenopausal women) with primary or secondary osteoporosis who had been treated with alendronate and alfacalcidol for more than 3 years were analyzed. The lumbar spine or total hip BMD and bone turnover markers were monitored, and the incidence of osteoporotic fractures was assessed.Results: The urinary level of cross-linked N-terminal telopeptides of type I collagen and serum level of alkaline phosphatase significantly decreased (-42.5% at 3 months and -18.9% at 3 years), and the lumbar spine BMD, but not the total hip BMD, significantly increased (14.8% at 3 years), compared with the baseline values. However, the incidence of vertebral and nonvertebral fractures was 26.5% and 2.9%, respectively, suggesting a high incidence of vertebral fractures.Conclusion: The results of the present study suggest that combined treatment with alendronate and alfacalcidol may be useful to reduce bone turnover and increase the lumbar spine BMD in patients with severe bone loss and osteoporotic fracture. However, its efficacy against vertebral fractures appears not to be sufficient. Thus, anabolic agents such as teriparatide should be taken into consideration as first-line drugs in patients with severe osteoporosis.Keywords: osteoporosis, fragility fracture, bone mineral density, bone turnover

We show via a numerical simulation that the temporal coherence function (TCF) can be shaped by the destructive interference of pulses characterized by different amounts of self-phase modulation (SPM) in the spectral domain. We find that pulse spectra destructively interfering with one another can yield a TCF with distinct peaks. Numerical investigation demonstrates that the shape of the TCF is changeable not only by broadening the spectrum but also by overlapping spectra of the pulses that have experienced different amounts of SPM.

This paper describes a novel approach for realizing femtosecond optical frequency comb (FOFC)-based length measurement. This approach is based on the analogy between the phase unwrapping problem and the integer ambiguity problem. Because the conventional synthetic wavelength method can solve the former, we investigated the possibility of using a synthetic adjacent pulse repetition interval length method to solve the latter. The results of theoretical analyses and numerical investigations show the feasibility of the proposed method. Our results should contribute toward the further development of FOFC-based length measurement methods.

We describe a novel approach for a theoretical analysis of the measurement accuracy of the pulse repetition interval-based excess fraction (PRIEF) method, which is expected to be useful for high-precision length measurement. The proposed approach is introduced by focusing on an analogy between the PRIEF method and the conventional length-measurement method. The theoretical analysis results show that the absolute accuracy achievable by the PRIEF method is nanometer-order, and the relative accuracy achievable by the PRIEF method is 10−8-order, which is affected mainly by the measuring accuracy of the refractive index of air. We conclude that our analysis is useful for further development of the PRIEF method.

Heterointerfaces introduce unique localized defects into ionic conductors. This study explores the nanoionic characteristics exhibited by the proton-conducting oxides SrZr 0.9 Y 0.1 O 3-δ and SrCe 0.95 Yb 0.05 O 3-δ including finely dispersed precipitated platinum nanoparticles. The electrical conductivity of both the platinum-doped oxides revealed reversible nanoionic phenomena caused by the exsolution of the platinum in the form of platinum nanoparticles, at 0.5 vol% relative to the metal oxides, and dissolution in response to a change in gas atmosphere. In comparison with the original conductivity of SrZr 0.9 Y 0.1 O 3-δ and SrCe 0.95 Yb 0.05 O 3-δ , the conductivity of platinum-doped SrZr 0.9 Y 0.1 O 3-δ decreased significantly in a wet hydrogen atmosphere, whereas platinum-doped SrCe 0.95 Yb 0.05 O 3-δ showed almost no decrease in conductivity in the same atmosphere. The different responses of the two materials to the change in gas atmosphere are discussed in relation to the precipitation of platinum nanoparticles.

Upper layer thickness (mixing depth) is an essential parameter for estimating the dissolved inorganic carbon and carbon flux at the water surface based on their association with the vertical flux of dissolved inorganic carbon. Previous studies quantified the mixing depth without SAV meadow or penetration depth in the SAV meadow without stratification and wind stress. However, mixing depth related to interaction with submerged aquatic vegetations (SAVs), stratification, and wind stress has yet to be quantified in the previous studies. Our study is the first to quantify the theoretical mixing depth with SAVs according to wind stress, SAV height, and drag coefficient. Theoretical mixing depth was quantified from modeled vertical temperature profile, vertical profile of horizontal velocity, and gradient Richardson number (Rig,veg). We found that mixing depth at a Rig,veg of 100 demonstrated good agreement with numerical results on average, with the mixing depth estimated in this study (hU,this study) showing high applicability to observations at Komuke Lagoon. Moreover, hU,this study increased with the increasing wind stress and decreasing drag coefficient and SAV height. Further, we found that SAV meadows with stratification and wind stress could be divided into four hydrodynamic regimes: non‐vegetated layers, upper vegetated layers, thermoclines, and benthic boundary layers. Our findings help us estimate mixing depth or vertical flux without complicated numerical simulation and understand flow interaction with SAV, wind stress, and stratification. Plain Language Summary: Upper layer thickness (mixing depth) and flow fields are important to estimate the carbon flux (e.g., "blue carbon") and the transportation of dissolved materials (e.g., dissolved oxygen, dissolved inorganic carbon, dissolved inorganic nitrogen, etc) in submerged aquatic vegetation (SAV) meadows. However, it may not be easy to estimate mixing depth without complex numerical simulations. Additionally, we have not understood the interaction of SAV meadows with stratification, currents, or waves. Our study is the first to quantify the mixing depth analytically and to show the hydrodynamic regimes in SAV meadows with stratification. Our finding helps us to estimate carbon flux and the transportation rate of dissolved materials easily without complicated numerical simulation. Key Points: Mixing depth with submerged aquatic vegetation (SAV) meadows was estimated using an average gradient Richardson number 100SAV meadows with stratification and wind stress were divided into four hydrodynamic regimesWind stress, SAV, and stratification effects were used to accurately estimate the mixing depth [ABSTRACT FROM AUTHOR]