Search

Tatsuru Sonobe,1 Koji Otani,1 Miho Sekiguchi,1 Kenichi Otoshi,2 Takuya Nikaido,1 Shinichi Konno,1 Yoshihiro Matsumoto1 1Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan; 2Department of Sports Medicine, Fukushima Medical University School of Medicine, Fukushima, 960-1295, JapanCorrespondence: Koji Otani, Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, 1 hikarigaoka, Fukushima-shi, Fukushima, 960-1295, Japan, Tel +81-24-547-1276, Fax +81-24-548-5505, Email kotani@fmu.ac.jpPurpose: Decreased physical function with increasing life expectancy is a public health concern worldwide. Knee osteoarthritis (KOA) is considered one of the primary illnesses causing decreased physical function. Depression affects decreased physical function and is closely related to knee pain in KOA. However, the effect of these interacting factors on physical function is not clear.Patients and Methods: We conducted a cross-sectional analysis of the baseline data of 1106 subjects of the 2009 Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS). We determined the association between their Timed Up and Go test (TUG) scores and radiographic KOA, knee pain, and depression in a multivariate analysis.Results: Severe knee pain was significantly associated with decreased physical function (the odds ratio [OR] was 2.13, 95% confidence interval [CI]: 1.32– 4.89), as was depression (OR 2.64, 95% CI 1.61– 4.33). Only Kellgren-Lawrence (KL) grade 4 was significantly associated with decreased physical function in the radiographic KOA severity (OR 6.58, 95% CI 1.75– 24.68).Conclusion: Severe knee pain and depression were significantly associated with decreased physical function, but not radiographic KOA severity except for KL grade 4. The limitations of using radiographic KOA severity alone as the indicator of assessment for physical function were suggested. When assessing decreased physical function, the clinical focus tends to be on radiographic KOA severity, but it is important to consider the patient’s knee pain and psychological factors.Keywords: knee osteoarthritis, knee pain, physical function, depression, aging, TUG test

Yukihiro Matsumoto,1– 3 Yuichi Azuma,3 Yasue Karasawa,2 Noriyuki Suzuki3 1Eye Care Clinic, Saitama, Japan; 2Eye Care Clinic Tokyo, Tokyo, Japan; 3Eye Care Clinic Fukushima, Fukushima, JapanCorrespondence: Yukihiro Matsumoto, Eye Care Clinic, 829 Hikawa-cho, Souka, Saitama, 340-0034, Japan, Tel +81 30 6262 6100, Email ginzaeyecare@gmail.comPurpose: To evaluate postoperative outcomes after implantation of toric intraocular lenses (IOLs) made of high-water-content hydrophobic acrylic material in Japanese patients using a swept-source optical coherence tomography (SS-OCT) biometer integrated with a surgical guiding system.Patients and Methods: In this prospective observational study, toric IOL models CNW0T3 to CNW0T9 (Alcon) were implanted in 33 eyes of 33 patients and followed-up for one month. Powers and toric models were determined using an SS-OCT biometer ARGOS® Ver 1.5 (Alcon), and the IOLs were aligned using surgical guidance. Differences between planned and actual axis positions at the end of the surgery (misalignment) and rotations from the end of surgery to one month postoperatively were measured. Additionally, postoperative uncorrected visual acuity, refraction, and residual astigmatism were evaluated.Results: Mean and median misalignments were 2.3° (standard deviation [SD]: 1.6, 95% confidence interval [CI]: 1.7– 2.9) and 2°, and those of postoperative rotation were 2.4° (SD: 2.6, 95% CI: 1.5– 3.4) and 2°, respectively. Mean postoperative refraction was 0.06 D (SD: 0.62). Prediction errors within ± 0.5 and ± 1.0 D were 69.7% and 93.9%, respectively. Mean residual astigmatisms were 0.19 D (SD: 0.41), and mean uncorrected visual acuity was 0.00 logMAR (SD: 0.11), and 64% of the eyes scored 20/20 or better.Conclusion: Implantation of high-water-content hydrophobic acrylic toric IOLs using SS-OCT biometry integrated with a surgical guiding system effectively corrected corneal astigmatism with accurate IOL alignment in Japanese patients.Keywords: toric intraocular lens, swept-source optical coherence tomography, biometry, surgical guiding system

Hiroshi Kobayashi,1 Miho Sekiguchi,1 Koji Otani,1 Rei Ono,2 Takuya Nikaido,1 Kazuyuki Watanabe,1 Kinshi Kato,1 Yoshihiro Kobayashi,1 Shoji Yabuki,1 Shin-ichi Konno,1 Yoshihiro Matsumoto1 1Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan; 2Department of Physical Activity Research, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Settsu, JapanCorrespondence: Hiroshi Kobayashi, Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Tokyo, 960-1295, Japan, Tel +8124-547-1276, Fax +8124-548-5505, Email hiroshik@fmu.ac.jpPurpose: Insomnia has been reported to coexist with various musculoskeletal disorders. Although lumbar spinal stenosis (LSS) is the most frequently operated on spinal disease, the causal relationship between LSS and development of sleep disorders remains unclear due to lack of longitudinal studies. This study aimed to determine whether LSS was a risk factor for developing new sleep disorders, primarily insomnia, using a prospective cohort of community residents.Patients and Methods: This study was a prospective cohort study. Participants aged ≥ 65 years from the “Locomotive Syndrome and Health Outcomes in Aizu Cohort Study (LOHAS)” conducted in 2008 formed our study population. LSS was diagnosed using the self-administered, self-reported history questionnaire, a validated diagnostic support tool for LSS. Sleep disorder was investigated using a questionnaire during the 2-year follow-up. The impact of LSS on sleep disorder onset was analyzed after adjusting for potential confounders, such as age, sex, obesity, hypertension, diabetes, depression, and smoking habits, using propensity score matching.Results: Of the 489 participants who were followed up for two years, 38 (7.8%) had newly developed a sleep disorder in 2010. After adjusting for confounding factors, a comparison of 133 participants each in the control and LSS groups showed significantly higher frequency of new-onset sleep disorders (19 [14.3%] in the LSS group versus 6 [4.5%] in the control group).Conclusion: LSS was found to be an independent risk factor for sleep disorders.Keywords: lumbar spinal stenosis, sleep disorder, insomnia, cohort study, musculoskeletal disorder, locomotive syndrome

Makito Miyake,1 Nobutaka Nishimura,1,2 Takuto Shimizu,1,3 Mikiko Ohnishi,4 Masaomi Kuwada,4 Yoshitaka Itami,5 Takeshi Inoue,5 Kenta Ohnishi,6 Yoshihiro Matsumoto,6 Takanori Yoshida,7 Yoshihiro Tatsumi,8 Masatake Shinohara,9 Shunta Hori,1 Yosuke Morizawa,1 Daisuke Gotoh,1 Yasushi Nakai,1 Satoshi Anai,1 Kazumasa Torimoto,1 Katsuya Aoki,1 Tomomi Fujii,10 Nobumichi Tanaka,1,11 Kiyohide Fujimoto1 1Department of Urology, Nara Medical University, Kashihara, Nara, 634-8522, Japan; 2Department of Urology, Okanami General Hospital, Iga, Mie, Japan; 3Department of Urology, Saiseikai Chuwa Hospital, Nara, Japan; 4Department of Urology, Matsusaka Chuo General Hospital, Matsusaka, Mie, Japan; 5Department of Urology, Nara Prefecture General Medical Center, Nara, Japan; 6Department of Urology, Hoshigaoka Medical Center, Hirakata, Osaka, Japan; 7Department of Urology, Tane General Hospital, Osaka, Japan; 8Department of Urology, JCHO Yamato Koriyama Hospital, Koriyama, Nara, Japan; 9Department of Urology, Osaka Gyoumeikan Hospital, Osaka, Japan; 10Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara, 634-8522, Japan; 11Department of Prostate Brachytherapy, Nara Medical University, Kashihara, Nara, 634-8522, JapanCorrespondence: Makito Miyake, Department of Urology, Nara Medical University, 840 Shijo-cho, Nara, 634-8522, Japan, Tel +81-744-22-3051 (ext 2338), Fax +81-744-22-9282, Email makitomiyake@yahoo.co.jpPurpose: The treatment landscape for advanced, unresectable, or metastatic urothelial carcinoma (aUC) has shifted substantially since the advent of immune checkpoint inhibitors (ICIs). We investigated the extent to which pembrolizumab therapy is superior to conventional chemotherapy as a second-line treatment.Patients and Methods: A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 94 patients (21%) who received second-line pembrolizumab and 75 (17%) who received second-line chemotherapy but never received third-line or later ICI therapy were included. We compared overall survival (OS) from the initial date of first-line chemotherapy between two groups by adjusting for prognostic factors through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The IPTW-adjusted hazard ratio and 95% confidence interval were estimated using a multivariate Cox regression analysis. To identify patients who were more likely to benefit from second-line pembrolizumab than from chemotherapy, we performed a subgroup analysis for OS with an IPTW-adjusted model.Results: The PSM-adjusted comparison showed a significant improvement in the prognosis with second-line pembrolizumab use (P = 0.01). The OS benefit with the advent of pembrolizumab was 8 months (18 months vs 26 months). Multivariable analyses using IPTW adjustment demonstrated that lymph node metastasis (P = 0.001), lung metastasis (P = 0.013), and bone metastasis (P = 0.003) were poor independent prognostic factors, and pembrolizumab use (P = 0.021) was a favorable independent prognostic factor. Subgroup analyses revealed that pembrolizumab was associated with survival benefits over chemotherapy in all subgroups, including young patients (age < 70 years), those who received radical surgery, and those without visceral metastasis.Conclusion: We demonstrated a significant improvement in prognosis after the advent of pembrolizumab for patients with aUC. ICIs should not be restricted based on patient characteristics.Keywords: urinary bladder neoplasms, immunotherapy, chemotherapy, survival, propensity score

Keisuke Noto,1 Akihito Suzuki,1 Toshinori Shirata,1 Yoshihiko Matsumoto,1 Nana Takahashi,1 Kaoru Goto,2 Koichi Otani1 1Department of Psychiatry, Yamagata University School of Medicine, Yamagata 990-9585, Japan; 2Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, JapanCorrespondence: Toshinori Shirata Email white_gregory000@yahoo.co.jpPurpose: Attachment research shows that attachment experiences with parents in childhood influence the characterization of personality traits. Meanwhile, it is known that mu-opioid receptor function is involved in human attachment. Furthermore, a few studies suggest that the A118G polymorphism of the mu-opioid receptor gene (OPRM1) is associated with altered mu-opioid receptor function. Thus, we examined if the OPRM1 polymorphism moderates the sensitivity to parental behaviors and thereby contributes to the characterization of personality traits.Materials and Methods: Participants were 725 healthy Japanese. Parenting practices of their parents were evaluated by the Parental Bonding Instrument (PBI) with the care and protection subscales. Personality was evaluated using the Temperament and Character Inventory (TCI). The OPRM1 A118G polymorphism was detected by a PCR method.Results: Multiple regression analyses revealed significant effects of the interaction between the OPRM1 genotype and maternal protection on scores of the self-directedness and cooperativeness dimensions, while significant main effects of the OPRM1 genotype on scores of the TCI were not found. Further analyses showed that there were significant negative correlations between maternal protection scores and the two dimensional scores in the A/A and A/G genotypes with higher correlation coefficients in the former, but not in the G/G genotype.Conclusion: The present study suggests that the OPRM1 polymorphism contributes to the characterization of personality traits by moderating the sensitivity to parental behaviors, especially maternal protection.Keywords: OPRM1, attachment, personality, PBI, TCI, gene–environment interaction

Toshinori Shirata,1 Akihito Suzuki,1 Yoshihiko Matsumoto,1 Keisuke Noto,1 Kaoru Goto,2 Koichi Otani1 1Department of Psychiatry, Yamagata University School of Medicine, Yamagata 990-9585, Japan; 2Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, JapanCorrespondence: Toshinori Shirata Email white_gregory000@yahoo.co.jpPurpose: It is suggested that increased methylation of the brain-derived neurotrophic factor (BDNF) gene is involved in the pathogenesis of depression, while sociotropy and autonomy are proposed as personality vulnerability factors in cognitive model of depression. We examined the interrelation between BDNF gene methylation and sociotropy or autonomy, with taking into account the previously reported deleterious effect of parental overprotection on sociotropy. Materials and Methods: The participants consisted of 90 healthy Japanese volunteers. Methylation levels of the BDNF gene in peripheral blood were quantified by bisulfite pyrosequencing. Sociotropy and autonomy were assessed by the Sociotropy-Autonomy Scale, and perceived parental protection was evaluated by the Parental Bonding Instrument.Results: In Pearson’s correlation analysis, there was a positive correlation between methylation levels of the BDNF gene and sociotropy scores (p< 0.05) but not autonomy scores, and a positive correlation between maternal protection scores and sociotropy scores (p< 0.05). In structural equation modeling, two models were proposed; the first one is that hypermethylation of the BDNF gene and maternal overprotection independently contribute to high sociotropy, and the second one is that maternal overprotection contributes to high sociotropy which then leads to hypermethylation of the BDNF gene.Conclusion: The present study suggests an interrelation between increased BDNF gene methylation and high sociotropy.Keywords: autonomy, BDNF gene, methylation, parental protection, sociotropy

Lien Le,1,* Linh Khanh Tran,1,* Tam-Duong Le-Ha,1 Bich-Phuong Tran,1 Hong-Ngoc Le-Vo,1 Yen-Nhi Nguyen,1 Hanh-Lan Nguyen,1 Khanh-Quynh Hoang-Ngoc,1 Yuki Matsumoto,2 Daisuke Motooka,2 Shota Nakamura,2 James W Jones,3 Tetsuya Iida,2,4 Van Cao1 1Department of Immunology and Microbiology, Pasteur Institute in Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; 3Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; 4Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan*These authors contributed equally to this workCorrespondence: Van CaoDepartment of Immunology and Microbiology, Pasteur Institute in Ho Chi Minh City, 167 Pasteur Street, District 3, Ho Chi Minh City, VietnamTel +8428 38 205131Fax +8428 38 231419Email vancao.pasteur@gmail.comAbstract: In this study, we characterized the first clinical Klebsiella pneumoniae strain co- harboring mcr-1 and blaNDM-4 genes in Vietnam, which was recovered from a patient admitted to hospital in 2015. This strain demonstrated nonsusceptible to all tested antibiotics, including last-line antibiotics such as carbapenems (MICs ≥128 μg/mL) and colistin (MIC =32 μg/mL), except tigecycline (MIC =1 μg/mL). Whole-genome analysis using both MinION and MiSeq data revealed that the strain carried 29 resistance genes. Particularly, mcr-1 and blaNDM-4 genes were carried by different self-conjugative plasmids and able to be transferred to a recipient by conjugation. The colistin resistance of this strain was conferred by mcr-1 and additional chromosomal resistance determinants. Eight amino acid substitutions found in PmrA, PmrB, PmrC, PmrI, and PmrJ, all proteins that are involved in lipopolysaccharide modifications, may be associated with chromosomal colistin resistance. The accumulation of multiple antibiotic resistance mechanisms in this clinical isolate raises alarm on potential spread of extensively drug-resistant K. pneumoniae in healthcare settings.Keywords: coexistence, mcr-1, blaNDM-4, Klebsiella pneumoniae, Vietnam

A new hyperon-proton scattering experiment, dubbed J-PARC E40, was performed to measure differential cross sections of the Σ+p, Σ−p elastic scatterings and the Σ−p → Λn scattering by identifying a lot of Σ particles in the momentum ranging from 0.4 to 0.8 GeV/c produced by the π±p → K+Σ± reactions. We successfully measured the differential cross sections of these three channels with a drastically improved accuracy with a fine angular step. These new data will become important experimental constraints to improve the theories of the two-body baryon-baryon interactions. Following this success, we proposed a new experiment to measure the differential cross sections and spin observables by using a highly polarized Λ beam for providing quantitative information on the ΛN interaction. The results of three Σp channels and future prospects of the Λp scattering experiment are described.

Toshinori Shirata,1 Akihito Suzuki,1 Yoshihiko Matsumoto,1 Nana Takahashi,1 Keisuke Noto,1 Kaoru Goto,2 Koichi Otani1 1Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan; 2Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata, Japan Background: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has an important function in neuroplasticity and neuronal development. It is suggested that increased methylation of the BDNF gene resulting in decreased BDNF activity is associated with depression. Meanwhile, neuroticism is a well-known risk factor for developing depression. In the present study, the relationship between methylation of the BDNF gene and personality traits including neuroticism was examined. Subjects and methods: The subjects were 98 healthy Japanese. Methylation levels of the BDNF gene were determined by the bisulfite-pyrosequencing method. Personality traits including neuroticism were assessed by the NEO Personality Inventory-Revised. Results: There was a positive correlation between neuroticism scores and methylation levels of the BDNF gene. The subjects with higher neuroticism scores had higher levels of BDNF gene methylation compared with those with lower neuroticism scores. Meanwhile, other personality traits were not associated with BDNF gene methylation. Conclusion: The present study suggests that high neuroticism is related to increased methylation of the BDNF gene. Keywords: BDNF, depression, epigenetics, methylation, neuroticism

Koichi Otani, Akihito Suzuki, Yoshihiko Matsumoto, Toshinori Shirata Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan Objective: The cognitive model of depression posits two distinctive personality vulnerabilities termed sociotropy and autonomy, each of which is composed of a cluster of maladaptive self-schemas. It is postulated that negative core beliefs about self underlie maladaptive self-schemas as a whole, whereas those about others may be implicated in the autonomous self-schemas. Therefore, the present study examined the relations of sociotropy and autonomy with core beliefs about self and others.Methods: The sample of this study consisted of 321 healthy Japanese volunteers. Sociotropy and autonomy were evaluated by the corresponding subscales of the Sociotropy–Autonomy Scale. Core beliefs about self and others were assessed by the negative-self, positive-self, negative-other and positive-other subscales of the Brief Core Schema Scales.Results: In the forced multiple regression analysis, sociotropy scores were correlated with negative-self scores (β = 0.389, P < 0.001). Meanwhile, autonomy scores were correlated with positive-self scores (β = 0.199, P < 0.01) and negative-other scores (β = 0.191, P < 0.01).Conclusion: The present study suggests marked differences in core beliefs about self and others between sociotropy and autonomy, further contrasting the two personality vulnerabilities to depression. Keywords: sociotropy, autonomy, core belief, self, other, personality, cognitive vulnerability

Koichi Otani, Akihito Suzuki, Yoshihiko Matsumoto, Toshinori Shirata Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan Objective: Cognitive theory assumes a pivotal role of negative core beliefs about the self in dysfunctional attitudes predisposing to depression. Meanwhile, the role of positive core beliefs about the self in cognitive vulnerability to depression is unknown. Therefore, we examined the relationship of negative and positive core beliefs about the self with dysfunctional attitudes in three aspects of life.Methods: The subjects were 311 Japanese volunteers. Core beliefs of negative-self and positive-self were evaluated by the corresponding subscales of the Brief Core Schema Scales. Dysfunctional attitudes in the areas of achievement, dependency and self-control were measured by the corresponding subscales of the 24-item Dysfunctional Attitude Scale.Results: The negative-self subscale was correlated with the achievement, dependency and self-control subscales. The positive-self subscale was correlated with the achievement and self-control subscales.Conclusion: The present study suggests that negative core beliefs about the self underlie all types of dysfunctional attitudes, while positive core beliefs about the self have some connections with dysfunctional attitudes related to achievement and self-control. Keywords: negative-self, achievement, dependency, self-control, depression

Nana Takahashi, Akihito Suzuki, Yoshihiko Matsumoto, Toshinori Shirata, Koichi Otani Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan Objective: Depressed patients are prone to perceive that they were exposed to affectionless control by parents. Meanwhile, high neuroticism is a well-established risk factor for developing depression. Therefore, this study examined whether perceived parental affectionless control is associated with high neuroticism.Methods: The subjects were 664 healthy Japanese volunteers. Perceived parental care and protection were assessed by the Parental Bonding Instrument. Parental rearing was categorized into either optimal parenting (high care/low protection) or three dysfunctional parenting styles including affectionless control (low care/high protection). Neuroticism was evaluated by the NEO Personality Inventory-Revised.Results: The subjects with paternal affectionless control had higher neuroticism scores than those with paternal optimal parenting. Similar tendency was observed in maternal rearing. Neuroticism scores increased in a stepwise manner with respect to the increase in the number of parents with affectionless control.Conclusion: The present study shows that perceived parental affectionless control is associated with high neuroticism, suggesting that this parental style increases neuroticism in recipients. Keywords: parenting, attachment, personality, vulnerability, depression, PBI, NEO PI-R

Kotaro Ono,1 Yoshikazu Takaesu,1 Yukiei Nakai,2 Akiyoshi Shimura,1 Yasuyuki Ono,1 Akiko Murakoshi,1 Yasunori Matsumoto,1 Hajime Tanabe,3 Ichiro Kusumi,2 Takeshi Inoue1 1Department of Psychiatry, Tokyo Medical University, Tokyo, 2Department of Psychiatry, Hokkaido University Graduate School of Medicine, Hokkaido, 3Department of Clinical Human Sciences, Graduate school of Humanities and Social Sciences, Shizuoka University, Shizuoka, Japan Background: Recent studies have suggested that the interactions among several factors affect the onset, progression, and prognosis of major depressive disorder. This study investigated how childhood abuse, neuroticism, and adult stressful life events interact with one another and affect depressive symptoms in the general adult population. Subjects and methods: A total of 413 participants from the nonclinical general adult population completed the Patient Health Questionnaire-9, the Child Abuse and Trauma Scale, the neuroticism subscale of the shortened Eysenck Personality Questionnaire – Revised, and the Life Experiences Survey, which are self-report scales. Structural equation modeling (Mplus version 7.3) and single and multiple regressions were used to analyze the data. Results: Childhood abuse, neuroticism, and negative evaluation of life events increased the severity of the depressive symptoms directly. Childhood abuse also indirectly increased the negative appraisal of life events and the severity of the depressive symptoms through enhanced neuroticism in the structural equation modeling. Limitations: There was recall bias in this study. The causal relationship was not clear because this study was conducted using a cross-sectional design. Conclusion: This study suggested that neuroticism is the mediating factor for the two effects of childhood abuse on adulthood depressive symptoms and negative evaluation of life events. Childhood abuse directly and indirectly predicted the severity of depressive symptoms. Keywords: childhood abuse, depression, neuroticism, stressful life events, structural equation modeling

Ravindra M Samarth,1,2 Meenakshi Samarth,3 Yoshihisa Matsumoto4 1Department of Research, Bhopal Memorial Hospital and Research Centre (ICMR), Bhopal, India; 2National Institute for Research in Environmental Health (NIREH), Indian Council of Medical Research, Bhopal, India; 3Department of Zoology, Centre for Advanced Studies, University of Rajasthan, Jaipur, India; 4Research Laboratory for Nuclear Reactors, Tokyo Institute of Technology, Tokyo, Japan Abstract: Systematic biological measurement of “cytogenetic endpoints” has helped phenomenally in assessment of risks associated with radiation exposure. There has been a surge in recent times for the usage of radioactive materials in health care, agriculture, industrial, and nuclear power sectors. The likelihood of radiation exposure from accidental or occupational means is always higher in an overburdened ecosystem that is continuously challenged to meet the population demands. Risks associated with radiation exposure in this era of modern industrial growth are minimal as international regulations for maintaining the safety standards are stringent and strictly adhered to, however, a recent disaster like “Fukushima” impels us to think beyond. The major objective of radiobiology is the development of an orally effective radio-modifier that provides protection from radiation exposure. Once available for mass usage, these compounds will not only be useful for providing selective protection against accidental and occupational radiation exposure but also help to permit use of higher doses of radiation during treatment of various malignancies curtailing unwarranted adverse effects imposed on normal tissues. Bio-active compounds isolated from natural sources enriched with antioxidants possess unique immune-modulating properties, thus providing a double edged benefit over synthetic radioprotectors. We aim to provide here a comprehensive overview of the various agents originating from plant sources that portrayed promising radioprotection in various experimental models with special emphasis on studies that used cytogenetic biomarkers. The agents will include crude extracts of various medicinal plants, purified fractions, and herbal preparations. Keywords: cytogenetic biomarkers, medicinal plants, radioprotectors, radiation exposure

Kuniko Kohyama,1 Yoh Matsumoto2–4 1Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; 2Department of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; 3Immunotherapy Development Inc., Saitama, Japan; 4Geriatric Health Services Facility “Asahigaoka”, Saitama, Japan Abstract: Alzheimer’s disease (AD) is characterized by progressive neurodegeneration and is the most common cause of dementia. Immunotherapy has recently been regarded as a potential treatment for AD. This stems from the fact that the clinical and pathological findings from the active AD vaccine trial suggests that such vaccine therapy may be effective for AD. However, this trial was halted because of the occurrence of meningoencephalitis in some patients. Avoiding excessive immune reaction is necessary for the success of vaccine therapy. For this purpose, adjuvant-free vaccine therapies (eg, passive immunization or DNA vaccines) are currently under investigation. However, the results of clinical trials employing both active and passive anti-amyloid-beta immunotherapy have been unsatisfactory. In this article, we will analyze the reasons for the limited efficacy of currently available immunotherapies and discuss the effectiveness of new vaccine therapies. Finally, we will speculate on the possibility of its clinical application. Keywords: Aβ peptide vaccine, amyloid-beta, amyloid cascade theory, immunotherapy, monoclonal antibody, tau

Eiji Kose,1 Taesong An,2 Akihiko Kikkawa,2 Yoshiaki Matsumoto,3 Hiroyuki Hayashi1 1Department of Pharmacotherapy, School of Pharmacy, Nihon University, Funabashi, 2Yokosuka Kyousai Hospital, Yokosuka, 3Department of Clinical Pharmacokinetics, School of Pharmacy, Nihon University, Funabashi, Japan Background: Chronic kidney disease (CKD) is associated with a high risk of cardiovascular disease complications. Therefore, medical institutions conduct educational hospitalization for early treatment and education of CKD patients. However, patients who have been discharged after achieving educational targets can end up showing poor symptoms at home. There also have been several cases of rehospitalization or disease aggravation. In this study, we analyzed rehospitalized patients who were discharged from the hospital after CKD educational hospitalization and investigated the purpose of analyzing rehospitalization factors. Materials and methods: This was an observational case-control study conducted at Yokosuka Kyousai Hospital. We performed univariate analysis using patient background features and laboratory data between a rehospitalization group and a no-rehospitalization group. Next, we performed multiple logistic regression analysis using the results of the univariate analysis. Results: From the results of this study, we identified independent risk factors, such as serum albumin level, heart-failure complications, and estimated glomerular filtration rate (eGFR). Moreover, the serum Alb level was identified as the most important risk factor for rehospitalization. Therefore, we considered that it is important to live a life that makes it possible to maintain CKD stage G3b for a long time after discharge, because the cutoff level of eGFR is 31 mL/minute/1.73 m2. Conclusion: We believe that it is important to educate patients, their families, and medical staff on the importance of early detection and treatment, and we consider that this approach is important to inclusively protect the kidney. Keywords: albumin, glomerular filtration rate, cardiovascular disease, stages of chronic kidney disease

Tetsuya Mutoh,1,2 Kevin F Barrette,2 Yukihiro Matsumoto,1 Makoto Chikuda11Department of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Koshigaya City, Saitama, Japan; 2Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USAAbstract: We report our recent experience of four eyes with spontaneous lens dislocation in four patients with no history of trauma or any systemic disease associated with zonular dialysis. Lens dislocation developed with 0.5 to 6 months following laser iridotomy. All patients were male and two eyes were complicated with acute primary angle closure glaucoma preoperatively. Case 1 showed bilateral lens dislocation, while cases 2 and 3 involved unilateral lens dislocation. Cases 2 and 3 showed lenses completely dislocated into the vitreous cavity. All cases needed lens removal and scleral fixation of intraocular lenses. Final visual acuity was 1.2 in all cases. We suspect that laser iridotomy may induce localized zonular dialysis that results in progressive zonular weakness, leading to lens dislocation.Keywords: lens dislocation, laser iridotomy, primary angle closure glaucoma

Yasuhide Nagoshi,1 Akira Watanabe,1 Saiko Inoue,1 Tomoki Kuroda,2 Mitsuo Nakamura,3 Yoshitake Matsumoto,4 Kenji Fukui31Department of Psychiatry (Psychosomatic Medicine), Kyoto First Red Cross Hospital, Kyoto, Japan; 2Gojouyama Hospital, Nara, Japan; 3Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 4Matsumoto Clinic, Kyoto, JapanBackground: Amputation of an extremity often results in the sensation of a “phantom limb” where the patient feels that the limb that has been amputated is still present. This is frequently accompanied by “phantom limb pain”. We report here the use of milnacipran, a serotonin and norepinephrine reuptake inhibitor, to treat phantom limb pain after amputation of injured or diseased limbs in three patients.Methods and results: The severity of phantom pain before and during treatment was quantified using a visual analog scale. In one case, phantom limb pain responded partially to treatment with high doses of paroxetine, and then replacement with milnacipran further improved the pain relief and long-term full pain relief was achieved. In the two other cases, milnacipran was used as first-line treatment and phantom limb pain responded rapidly.Conclusion: These results suggest that milnacipran administration may be useful in phantom limb pain, possibly as a first-line treatment.Keywords: milnacipran, paroxetine, phantom limb pain, selective serotonin reuptake inhibitor (SSRI), serotonin and norepinephrine reuptake inhibitor (SNRI)

Tetsuya Mutoh, Yukihiro Matsumoto, Makoto ChikudaDepartment of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Saitama, JapanAbstract: A case of non-Acanthamoeba keratitis with radial keratoneuritis, which is thought to be pathognomonic for Acanthamoeba keratitis, is reported. A healthy 32-year-old woman with a history of frequent replacement of her contact lenses due to wear was examined at Dokkyo Medical University Koshigaya Hospital (Saitama, Japan) and found to have a slight corneal opacity that was accompanied by radial keratoneuritis. Based on both the patient’s clinical findings and past history, the presence of Acanthamoeba keratitis was highly suspected. However, direct light microscopy of corneal scrapings stained by the Parker ink–potassium hydroxide method only found Acanthamoeba-type material in the specimen collected at her initial visit. In all other specimens collected from the patient, no Acanthamoeba was found either when using the same method or when performing cultures of the surgical debridement of the corneal lesion. In addition, topical antifungal eye drops, systemic antifungal drugs, and surgical debridement were also not effective in this case. Since a precise diagnosis could not be made, the patient was treated with topical 0.1% betamethasone sodium, which ultimately resulted in a dramatic improvement of her corneal inflammation. At 23 days after initiation of topical administration of 0.1% betamethasone sodium, visual acuity was 20/250, with a slight corneal opacity noted at the original site of infection. The outcome of the current case suggests that radial keratoneuritis is not always pathognomonic for Acanthamoeba keratitis.Keywords: radial keratoneuritis, non-Acanthamoeba keratitis, topical corticosteroid

Tetsuya Mutoh, Yukihiro Matsumoto, Makoto ChikudaDepartment of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Saitama, JapanBackground: The purpose of this study was to evaluate pars plana vitrectomy (PPV) with phacoemulsification in the vitreous cavity for treatment of complete posterior dislocation of the lens without any damage to the lens capsule.Methods: We evaluated factors such as cause of dislocation, scleral fixation of an intraocular lens (IOL), preoperative and postoperative visual acuity, corneal endothelial cell density, and intraoperative and postoperative complications.Results: Displacement in the eleven eyes studied was mostly caused by ocular trauma and was idiopathic (four eyes each). Scleral fixation of the IOL was performed in seven of the eyes during first-time PPV. Visual acuity was improved in two eyes, unchanged in eight eyes, and worse in one eye. Mean corneal endothelial cell density was 2485 cells/mm2 preoperatively and 2301 cells/mm2 postoperatively. No significant differences were seen before and after the surgeries (P = 0.15, paired t-test). Intraoperative complications included retinal detachment and suprachoroidal hemorrhage in one eye each. The most common postoperative complication was transient ocular hypertension, which occurred in three eyes. IOL dislocation and vitreous incarceration of the anterior chamber in one eye required a second operation, while retinal detachment in one eye required a third operation.Conclusion: When treating a completely dislocated lens, prevention of retinal detachment which subsequently can affect the visual prognosis is the most important factor to be addressed after PPV with intravitreal phacoemulsification.Keywords: lens dislocation, pars plana vitrectomy, phacoemulsification in the vitreous cavity, retinal detachment

Tetsuya Mutoh1,2, Thomas Tien2, Megumi Horie1, Yukihiro Matsumoto1, Makoto Chikuda11Department of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Saitama, Japan; 2Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USAAbstract: We report a case of bilateral complete dislocation of lenses into the vitreous cavities due to elder abuse in a patient with senile dementia. According to the patient’s son, bilateral complete lens dislocation occurred after he hit his father in the head with socks in order to control his violent behavior. Although the patient was taken to our ophthalmological ward for a planned vitrectomy, restlessness and inability to remain in his room during the night led to his leaving the hospital. The patient has not returned but did receive a vitrectomy at another clinic. While the number of patients with senile dementia has dramatically increased, no specific remedy is currently available. When treating medical concerns of seniors with unknown backgrounds, elder abuse needs to be considered as a potential cause of such injuries.Keywords: bilateral dislocation of lenses, elder abuse, senile dementia, vitrectomy

We carried out an experiment to produce the neutron-rich hypernucleus Λ6H via the (π−, K+) reaction on 6Li target at the pion beam momentum of 1.2 GeV/c (J-PARC E10). In order to calibrate the scale of the missing-mass or of the Λ binding energy of the hypernucleus, we also measured the 12C(π+, K+) Λ12C, p(π−, K+)Σ− and p(π+, K+)Σ+reactions. The experiment was performed at the J-PARC Hadron Hall K1.8 beam line in December 2012 and January 2013. The overall collected data sample corresponds to an integrated beam intensity of 1.65 × 1012 pions.

In order to test theoretical frameworks of the baryon-baryon interactions and to confirm the ”Pauli effect between quarks” for the first time, we propose an experiment to measure low-energy hyperon proton scattering cross sections in the following channels with high statistics, 1. Σ− p elastic scattering, 2. Σ− p → Λn inelastic scattering, 3. Σ+ p elastic scattering. According to theoretical models based on quark-gluon picture for the short range part of the baryon-baryon interactions, the Σ+ p channel is expected to have an extremely repulsive core due to the Pauli effect between quarks, which leads a Σ+ p cross section twice as large as that predicted by conventional meson exchange models with a phenomenologically treated short range repulsive core. In addition, measurement of the Σ− p channel where the quark Pauli effect is not effective is also necessary to test the present theoretical models based on meson exchange picture with the flavor SU(3) symmetry. Thus this experiment will provide essential data to test the frameworks of the theoretical models of the baryon-baryon interactions and to investigate the nature of the repulsive core which has not been understood yet. In order to overcome the experimental difficulties in measuring low-energy hyperon proton scattering, we will use a new experimental technique in which a liquid H2 target is used as hyperon production and hyperon scattering targets with a detector system surrounding the LH2 target for detection of a scattered proton and a decay product from a hyperon. The hyperon scattering event is kinematically identified. Because imaging detectors used in past experiments are not employed, high intensity π beam can be used, allowing us to take high statistics data of 100 times more than the previous experiments. We have proposed an experiment of Σp scattering at the K1.8 beam line by utilizing the K1.8 beam line spectrometer and the SKS spectrometer. A high intensity π beams of 2×107/spill at 1.32 GeV/c and 1.42 GeV/c for the Σ− and Σ+ productions, respectively, are used to produce as many hyperon beam as possible.With 16×106 Σ− beam and 55×106 Σ+ beam around 500 MeV/c which are tagged by the spectrometers, we will detect ~10,000 Σ− p and Σ+ p scattering events and ~6,000 Σ− p → Λn inelastic reaction events in 60 days beam time in total. In this proceedings, we will present the experimental plan of the scattering experiment and results of the detailed simulation studies.