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Reita Kadowaki,1 Fumihiko Ogata,1 Miku Nishida,1 Miri Komatsu,1 Hiroko Otake,1 Yosuke Nakazawa,2 Naoki Yamamoto,3 Naohito Kawasaki,1 Noriaki Nagai1 1Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka, Japan; 2Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, Japan; 3Support Office for Bioresource Research, Research Promotion Headquarters, Fujita Health University, Toyoake, Aichi, JapanCorrespondence: Noriaki Nagai, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka, 577-8502, Japan, Tel +81 6 4307 3638, Fax +81 6 6730 1394, Email nagai_n@phar.kindai.ac.jpPurpose: Medical therapies, such as the use of anti-inflammatory agents, are commonly used for the treatment of oral mucositis (OM). However, these treatments have limited efficacy in treating severe cases of OM. In this study, we aimed to develop a carbopol gel incorporating troxipide (TRO) nanoparticles and methylcellulose (TRO-NP gel) and demonstrate its efficacy in accelerating wound healing in a hamster model of OM (OM model) induced by acetic acid injection.Methods: TRO nanoparticles were prepared using bead milling. The crystalline form was determined by powder X-ray diffraction, and the particle size was measured using a NanoSight LM10 instrument. The drug release was determined using a Franz diffusion cell, and the hamsters injected with acetic acid were selected to evaluate the therapeutic effect of OM.Results: After preparing TRO nanoparticles, we observed a mixture of crystals and amorphous TRO, and the particle size of TRO in the TRO-NP gel ranged from 50 to 280 nm. The TRO-NP gel exhibited a more uniform TRO distribution and viscosity compared to the Carbopol gel containing TRO microparticles (TRO-MP gel). However, the solubility of TRO was comparable in both TRO-MP and TRO-NP gels. The TRO-NP gel released a higher amount of TRO than that from the TRO-MP gel, with detectable release of TRO nanoparticles. TRO levels in the cheek pouches of hamsters treated with TRO-NP gel were higher than those treated with TRO-MP gel. The increased TRO levels in the cheek pouches of hamsters treated with TRO-NP gel were attenuated by treatment with 40 μM dynasore, an inhibitor of clathrin-dependent endocytosis (CME). Moreover, the therapeutic effect of the TRO-NP gel was superior to that of the TRO-MP gel in the hamster model of OM.Conclusion: We have designed a TRO-NP gel, and this gel showed excellent TRO delivery into the cheek pouch tissue through the CME pathway. Moreover, the TRO-NP gel treatment enhanced wound healing after acetic acid injection. Keywords: troxipide, nanoparticle, oral mucositis, hydrogel, endocytosis

Shunsuke Takagi,1 Hikaru Hori,2 Tatsuya Yamaguchi,3,4 Shinichiro Ochi,5 Masaki Nishida,6 Takashi Maruo,1 Hidehiko Takahashi1 1Department of Psychiatry and Behavioral Neurosciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan; 2Department of Psychiatry, School of Medicine, Fukuoka University, Fukuoka, 814-0180, Japan; 3Institute for Integrated Sports Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, 160-8582, Japan; 4Department of Neuropsychiatry, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan; 5Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Ehime, 791-0295, Japan; 6Faculty of Sport Science, Waseda University Tokorozawa, Saitama, 359-1192, JapanCorrespondence: Shunsuke Takagi, Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan, Tel +81-3-5803-5238, Fax +81-3-5803-0135, Email stakagi.psyc@tmd.ac.jpBackground: The development of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs) has various influences on physical abilities. Identification of specific physical abilities of people with ADHD/ASDs as biomarkers for diagnosing these conditions is necessary. Therefore, in the present review, we aimed firstly to extract the difference in physical abilities of people with ADHD or ASDs compared to those of normal individuals. Secondly, we aimed to extract the specific physical ability characteristics for identifying potential diagnostic biomarkers in people with ADHD/ASDs.Methods: A systematic literature review was performed. The databases were searched for relevant articles on motor function deficits and characteristics of ADHD or ASD.Results: Forty-one cross-sectional studies and three randomized controlled trials were identified, comprising 33 studies of ADHD, 10 studies of ASDs, and 1 study of both ADHD and ASDs. The quality of studies varied. Three types of physical activities/exercises were identified, including coordinated movement, resistance-type sports, and aerobic-type sports. People with ADHD/ASDs generally exhibited poorer physical abilities for all types of activities, possibly because of low levels of physical activity. Specifically, we found temporal discoordination of movement in ADHD and integration or synchronization of separate movements in ASDs.Conclusion: Specific deficits in physical ability may be attributed to ADHD/ASDs. However, there is not enough research on the physical abilities of people with ADHD and ASDs to clarify the specific deficits. Investigation of specific motor functions that characterize ADHD/ASDs should be facilitated.Keywords: motor function, neurodevelopmental disorders, sports, coordination, neural deficits

Masafumi Kon,1 Michiko Nakamura,1 Kimihiko Moriya,1,2 Yoko Nishimura,1 Yurie Hirata,1 Mutsumi Nishida,3 Madoka Higuchi,1 Takeya Kitta,1 Nobuo Shinohara1 1Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan; 2Department of Urology, Sapporo City General Hospital, Sapporo, Japan; 3Diagnostic Center for Sonography and Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, JapanCorrespondence: Kimihiko MoriyaDepartment of Urology, Sapporo City General Hospital, 1-1 North 11, West 13, Chuo-ku, Sapporo, 060-8604, JapanTel +81-11-726-2211Fax +81-11-726-7912Email k-moriya@med.hokudai.ac.jpIntroduction: Recent guidelines do not recommend routine screening of vesicoureteral reflux after a first febrile urinary tract infection in children without abnormal findings on ultrasound or atypical/recurrent urinary tract infection. Currently, there are no clear ultrasonographic parameters for detecting abnormalities in renal size, especially in young children. The aim of the present study was to determine an optimal cutoff value for detecting small kidney in children without apparent congenital anomalies except vesicoureteral reflux by retrospective chart review.Patients and Methods: Children aged ≤ 3 years who had undergone nuclear renal scans and ultrasound were enrolled. Small kidney was defined as split renal function of < 40%. Optimal cutoff values of various ultrasonographic parameters for detecting small kidney were calculated.Results: Of the 69 children included in the present study, small kidney was identified in 20. There was a significant difference in renal size between each kidney in patients with small kidney, whereas there was no significant difference in those without small kidney. With a ratio of estimated renal area of 74.26%, maximum area under the curve with the highest sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate were obtained. In addition, simple measurement of renal length with a cutoff of 4.97 cm showed high specificity comparable with estimated renal area.Conclusion: Small kidney may be screened by two-dimensional measurement on ultrasonographic examination, even in young children. With the cutoff described, risk stratification or an individualized approach may be possible.Keywords: small kidney, ultrasound, screening, cutoff value

Tetsumasa Kamei,1 Hiroyuki Kobayashi,2,3 Maika Nishida,2 Kenzo Muramoto,2 Shohei Nishimoto2 1Shonan Fujisawa Tokushukai Hospital, Kanagawa, Japan; 2Eisai Co., Ltd., Medical Headquarters, Tokyo, Japan; 3Department of Neuropsychiatry, School of Medicine, Toho University, Tokyo, JapanCorrespondence: Shohei NishimotoEisai Co., Ltd., 4-6-10 Koishikawa, Bunkyo-ku, Tokyo, 112-8088, JapanTel +81-3-3817-3700Fax +81-3-5229-0705Email s-nishimoto@hhc.eisai.co.jpPurpose: Medication discontinuation for patients with Alzheimer’s dementia (AD) influences treatment efficacy. This study aimed to evaluate the effect of psychoeducational intervention (PI) on donepezil retention rates and identify the factors associated with donepezil continuation in patients with AD.Patients and Methods: One hundred and seventeen patients with AD were randomly allocated to the PI (n = 58) or standard care (SC; n = 59) groups. All patients were prescribed donepezil for 48 weeks. Primary endpoints were the 48-week donepezil retention rate and the reasons for donepezil discontinuation in the PI and SC groups. The secondary endpoint was the predictive factors, among the baseline clinical variables, for donepezil continuation in all patients.Results: The donepezil retention rate was 62.1% (36/58) in the PI group and 66.1% (39/59) in the SC group. The most common reason for discontinuation in both groups was adverse events (PI, 12.1%; SC, 10.2%). Logistic regression analysis revealed that the results of the pentagon copying test in the Mini-Mental State Examination administered at baseline was a significant predictor of donepezil continuation for all patients in both the groups (odds ratio: 0.359; 95% confidence interval: 0.154– 0.839).Conclusion: There was no significant difference between the PI and SC groups concerning donepezil retention rate in patients with AD. Our results demonstrate that the pentagon copying test can significantly predict donepezil continuation in patients with AD, indicating that impaired visuospatial and executive functions may reflect medication discontinuation.Trial Registration: UMIN-CTR:UMIN000012617.Keywords: adherence, cholinesterase inhibitors, medication discontinuation, Mini-Mental State Examination, pentagon copying task

Masafumi Yamamoto,1 Satoshi Konno,2 Hironi Makita,2,3 Katsuaki Nitta,4 Kaoruko Shimizu,2 Masaru Suzuki,2 Mutsumi Nishida,1 Junichi Sugita,1 Takanori Teshima,1 Masaharu Nishimura2,3 1Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Hokkaido, Japan; 2Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; 3Hokkaido Institute of Respiratory Diseases, Sapporo, Hokkaido, Japan; 4Makita Hospital, Sapporo, Hokkaido, JapanCorrespondence: Masaharu NishimuraDepartment of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15 W-7, Kita-Ku, Sapporo, 060-8638, JapanTel +81-11-706-5911Fax +81-11-706-7899Email ma-nishi@med.hokudai.ac.jpBackground: Generally, the maximal expiratory flow–volume (MEFV) curve must be measured for the diagnosis and staging of chronic obstructive pulmonary disease (COPD). As this test is effort dependent, international guidelines recommend that three acceptable trials are required for each test. However, no study has examined the magnitude and factors for the variability in parameters among three acceptable trials.Methods: We evaluated the intra-individual variations in several parameters among three acceptable MEFV curves obtained at one-time point in patients with COPD (n = 28, stage 1; n = 36, stage 2; n = 21, stages 3– 4). Next, the factors for such variations were examined using forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).Results: The averages of coefficient of variation (CV) for FEV1 and FVC were 2.0% (range: 1.0– 3.0%) and 1.6% (0.9– 2.2%), respectively. Both parameters were significantly better than peak expiratory flow rate, forced expiratory flow at 50% of expired FVC, and forced expiratory flow at 75% of expired FVC (CVs: 5.0– 6.9%). A higher spirometric stage was significantly associated with higher CVs for FVC and FEV1, and older age was significantly correlated with a higher variation in FEV1 alone. Furthermore, a significantly inverse association was observed between emphysema severity, and the CVs for FEV1, but not that for FVC, regardless of spirometric stage.Conclusion: Both FVC and FEV1 are highly reproducible; nevertheless, older age, lower FEV1 at baseline, and non-emphysema phenotype are factors for a higher variability in FEV1 in patients with COPD.Keywords: chronic obstructive pulmonary disease, coefficient of variation, flow–volume curve, forced expiratory volume in 1 second, variability

Kaori Nakanishi, Makoto Nishida, Manabu Taneike, Ryohei Yamamoto, Toshiki Moriyama, Keiko Yamauchi-Takihara Health Care Division, Health and Counseling Center, Osaka University, Osaka, JapanCorrespondence: Keiko Yamauchi-TakiharaHealth Care Division, Health and Counseling Center, Osaka University, 1-17 Machikaneyama, Toyonaka, Osaka 560-0043, JapanTel +81-6-6850-6012Fax +81-6-6850-6040Email takihara@wellness.hss.osaka-u.ac.jpBackground: Assessing the progression of a disorder from its pre-clinical state is important in the prevention of various diseases. In the present study, we evaluated the role of serum levels of αKlotho (αKl) in the progression of several pre-clinical disorders.Methods: This cohort study included 80 males who underwent their annual health checkup during the entry period between April 2005 and March 2008. Physical and biochemical parameters were obtained from all subjects. The associations of baseline serum levels of soluble αKl (sαKl) with the progression of the disorders were assessed in the study.Results: Baseline serum levels of sαKl were significantly lower in subjects developing a high fasting plasma glucose (FPG) level than in subjects not developing a high FPG level. Logistic multivariable analysis showed that baseline serum levels of sαKl and FPG levels significantly associated with a high FPG level progression. It is suggested that low sαKl levels are associated with the progression of hyperglycemia. Evaluation of serum levels of sαKl in subjects with multiple disorders revealed that those with more pre-clinical disorders progression tended to show lower sαKl levels.Conclusion: A decrease in serum levels of sαKl could be associated with the progression of pre-clinical disorders.Keywords: αKlotho, metabolic disorder, hyperglycemia, hypertriglyceridemia, hypertension

Masaki Nishida,1 Yusaku Nakashima,2 Toru Nishikawa11Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo, 2Medical Technology Research Laboratory, Research and Development Division, Medical Business Unit, Sony Corporation, Tokyo, JapanIntroduction: Evidence has accumulated, which indicates that, in healthy individuals, sleep enhances procedural memory consolidation, and that sleep spindle activity modulates this process. However, whether sleep-dependent procedural memory consolidation occurs in patients medicated for major depressive disorder remains unclear, as are the pharmacological and physiological mechanisms that underlie this process.Methods: Healthy control participants (n=17) and patients medicated for major depressive disorder (n=11) were recruited and subjected to a finger-tapping motor sequence test (MST; nondominant hand) paradigm to compare the averaged scores of different learning phases (presleep, postsleep, and overnight improvement). Participants' brain activity was recorded during sleep with 16 electroencephalography channels (between MSTs). Sleep scoring and frequency analyses were performed on the electroencephalography data. Additionally, we evaluated sleep spindle activity, which divided the spindles into fast-frequency spindle activity (12.5–16 Hz) and slow-frequency spindle activity (10.5–12.5 Hz).Result: Sleep-dependent motor memory consolidation in patients with depression was impaired in comparison with that in control participants. In patients with depression, age correlated negatively with overnight improvement. The duration of slow-wave sleep correlated with the magnitude of motor memory consolidation in patients with depression, but not in healthy controls. Slow-frequency spindle activity was associated with reduction in the magnitude of motor memory consolidation in both groups.Conclusion: Because the changes in slow-frequency spindle activity affected the thalamocortical network dysfunction in patients medicated for depression, dysregulated spindle generation may impair sleep-dependent memory consolidation. Our findings may help to elucidate the cognitive deficits that occur in patients with major depression both in the waking state and during sleep.Keywords: depression, memory consolidation, motor skill, polysomnography, sleep spindle, thalamocortical network

The effect of the impact angle of projectiles on the crater shape and ejecta in thick aluminum alloy targets was investigated in hypervelocity impacts. When polycarbonate projectiles and aluminum alloy 6061-T6 target were used, the impact angle of the projectiles clearly affected the crater shape, as expected. The impact angle also affected the ejecta mass, ejecta size and scatter angle. However, the effect at 15∘ and 22.5∘ was not great. When the impact angles were 30∘ and 45∘, the effect was clearly confirmed. The impact angle clearly affected the axial ratio of ejecta fragments, c/a.

Coefficients of Cowper-Symonds constitutive equation for PLLA/PCL = 80/20 were determined using the results of compressive tests at high and low strain rates. The simulation of split Hopkinson pressure bar using the coefficients was carried out under the same condition as the experiments. The diameter and thickness of specimens were measured by a high-speed video camera. The stress and strain histories of specimens, the thickness and the diameter in the simulations at high strain rate were compared with those in the experiments.