Sport In Japan Research Articles

Recent trends and challenges for older adults at community sport clubs in Japan: Analysis of FY 2016 Survey Results on Comprehensive Community Sports Clubs

Objectives Comprehensive community sports clubs (CCSCs), of which more than 3,500 exist in Japan, have the potential to contribute to healthy aging in older adults, but their effect on this population has not, thus far, been well explored. This study aimed to investigate the current environment affecting seniors at Japanese CCSCs and to examine issues identified by the analysis.Methods Data were collected from the FY 2016 Survey Results on Comprehensive Community Sports Clubs, conducted by the Japan Sports Agency. A total of 2,444 clubs were divided equally into four groups after calculating the proportion of senior members (ages 60 and over) per total number of members in each club. The groups were then ranked from lowest to highest according to proportion of senior members: Groups A, B, C and D. Additionally, the 2,444 clubs were classified into six regions according to location. Group designation (A to D) and regional classification were used as independent variables. The dependent variables were categorized as follows: basic information (e.g. total number of members), crisis management and accident prevention measures (13 specific items in total), and each club's compliance with legal obligations.Results Study results revealed that Group D, containing the highest proportion of senior members, had fewer total members, lower monthly membership fees, lower annual club income, less annual club budget apportioned to each member, and fewer instructors than other groups. Regarding crisis management and accident prevention measures, Group D had lower completion rates on 6 items (health certificate submissions, liability insurance enrollment, safety workshop implementation, heatstroke prevention, liaison with healthcare professionals, and AED availability). Group D also showed a lower rate of compliance with legal obligations than other groups. In comparisons between the six regions, the median proportion of senior members was found to be highest in Chugoku-Shikoku and lowest in Chubu, although each median ranged from only 20% to 30%. Regarding crisis management and accident prevention measures, clubs in Kanto region had the highest completion rates for 10 items, whereas clubs in Kinki region had the lowest completion rates for 8 items.Conclusion The CCSCs with higher proportions of senior members had smaller budgets, fewer members and staff, and delayed implementation of crisis management and accident prevention measures. Regional disparities were also observed both in club scale and management of medical and safety issues. Although our study identified several shortcomings in this area, medical and safety management implementation is an important consideration for CCSCs with high proportions of senior members, as these members are at higher risk for disease and frailty. Affected CCSCs and relevant authorities should therefore acknowledge and address this issue cooperatively.

Mood/emotion in candidates preparing for the Japan Sports Association-Athletic Trainer certification examination: An investigation utilizing the Japanese-version Short Form POMS and self-reports

Mood/emotion in candidates preparing for the Japan Sports Association-Athletic Trainer certification examination: An investigation utilizing the Japanese-version Short Form POMS and self-reports

A research of analysing the effectiveness of speaking-pen on English learning in consideration of individual differences using a linear mixed-effect model

The Ministry of Education, Culture, Sports, Science and Technology in Japan (2011) started the ‘Foreign Language Activities’ in fifth grade based on the new Courses of Study in April of 2011. The ministry has considered beginning this course in third grade and the ‘English Course’ in 5th grade in order to improve students’ reading, writing, listening, and speaking skills. The ministry also developed supplemental teaching instruments, such as the CALL system. The purpose of this study is to model and analyse the effectiveness of a speaking-pen on English learning among elementary school children in consideration of individual differences using a Liner Mixed-Effect Model. The authors constructed models representing students’ overall abilities in four English skills, and analysed the effectiveness of the tools such as a speaking-pen and an audio CD on English learning in consideration of students’ backgrounds including their English learning experiences and individual differences.

Sporadic Inclusion Body Myositis Underling Mitochondrial Dysfunction Ameliorated by Mitochondrial Homing Drug, MA-5

Background: Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and mitochondrial abnormalities may be involved. Methods: We recruited 9 sIBM patients and we examined mitochondrial functions with bioenergetic and examinations and dynamics of patient myoblasts with measuring a mitochondrial disease marker growth differential factor 15 (GDF15). We also examined the effect of a new candidate drug, Mitochondria acid-5 (MA-5). Findings: Bioenergetic analysis of sIBM patient myoblasts revealed damaged mitochondrial function with decreased ATP, mitochondrial size and impaired mitochondrial dynamics and cell vulnerability. MA-5 increased the ATP level and reduced mitochondrial ROS, following the protection against cell death. The reduced levels of Opa1 and Drp1 showed the impairment of mitochondrial fusion/fission process and that MA-5 ameliorated. Skin fibroblasts from sIBM patients can be used for diagnosis. Interpretation: GDF15 and MA-5 could provide both a new maker and therapeutic strategy for sIBM patients. Funding Statement: These works were supported in part by National grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18H02822), Translational Research Network Program (C50) from Japan Agency for Medical Research and Development (AMED). MEXT and AMED, JAPAN. Declaration of Interests: The authors state: None. Ethics Approval Statement: Myoblasts and fibroblasts obtained by muscle and skin biopsy of sIBM patients were collected in Tohoku University Hospital under the approval of the Ethical Committee of Tohoku University.

Global integration and local responsiveness in managing international branch campuses: an empirical investigation of McGill MBA Japan Program

ABSTRACT The study investigates the practices of the McGill MBA Japan Program in dealing with the issue of adapting to the host country while providing education comparable to that of the home institution. Based on semi-structured interviews with academic directors, academic staffs, administrators, students and other stakeholders of the McGill MBA Japan Program, we found that the McGill MBA Japan Program maintained a very high degree of global integration with the home institution regarding staffing and curriculum and like many other international branch campuses, it does not emphasise the importance of localising research in operation. These findings, we argue, result from the interaction between the McGill MBA Japan Program and its external stakeholders including McGill University’s Desautels Faculty of Management, students, the Ministry of Education, Culture, Sports, Science and Technology in Japan and local competitors.

P6234The relationship of alcohol consumption with risk factors of coronary heart disease and the intake of macro- and micro-nutrients in Japanese: the INTERLIPID study

Abstract Background Many studies have reported the J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk; therefore, light-drinkers is generally recognized to be associated with the lower risk of CHD. However, the mechanisms of lower risk for CHD in light-drinkers are still unclear. Alcohol drinking status is likely to be associated with not only CHD risk factors but also dietary intake. Nevertheless, few studies report these relationships in detail. Purpose The purpose of this study is to evaluate the relationships of alcohol drinking status with CHD classical risk factors and the intake of macro- and micro- nutrients in Japanese. Methods Study participants were 1,090 Japanese men and women aged 40–59 years from The INTERLIPID study excepted for 55 individuals who had missing data (n=26) and were past-drinkers (n=29). Alcohol consumption was assessed with two 7-day alcohol records, and average ethanol intake (per week) was calculated. Participants were classified into following 4 groups: non-drinkers (0g/week), light-drinkers (<100 g/week), moderate-drinkers (100–299 g/week), and heavy-drinkers (≥300 g/week). Serum LDL and HDL cholesterol, blood pressure (BP), the prevalence of hypertension and dyslipidemia, and smoking status were assessed as CHD risk factors. The intake of energy and macro- and micro-nutrients were evaluated from the four-timed in-depth 24-hr dietary recalls. Nutrient intake densities were calculated per total energy intake without alcohol. The analysis of variance and chi-squared test were used to evaluate the relations of alcohol status with CHD risk factors and nutrient intake. Results Serum HDL cholesterol levels increased and LDL cholesterol levels decreased with increasing alcohol consumption. Systolic and diastolic BP increased with increasing alcohol consumption. J-shaped relationships with alcohol consumption were observed for the proportion of current smoker, number of cigarettes, and the prevalence of hypertension; that is, light-drinkers was lowest among all groups. The prevalence of dyslipidemia was the highest in non-drinkers, and decreased with increasing alcohol consumption. In heavy-drinkers, total energy (kcal/day) was the highest, but energy intake without alcohol (kcal/day) was the lowest. For macronutrients, the intake of carbohydrate (%kcal) decreased, and the intakes of total and animal protein (%kcal) increased with increasing alcohol consumption. The intakes of total cholesterol (mg/1000kcal) and sodium (mg/1000kcal) increased, and total fiber (g/1000kcal) decreased with increasing alcohol consumption. These associations were similar in men and women. Conclusions Alcohol consumption was related with not only CHD classical risk factors but also the intake of macro- and micro-nutrients. Non-drinkers had a higher proportion of some CHD risk factors than light-drinkers. These results might influence on J-shaped relationship between alcohol consumption and CHD risk. Acknowledgement/Funding 1: Ministry of Education, Science, Sports, and Culture of Japan, 2: National Institutes of Health, Bethesda, MD, USA

Athletic Training Services in Japan: A Comparison of the United States and Japan Based on Educational Background

Context Each country has a unique history in the development of its athletic training professionals and education and credentialing systems. In Japan, the majority of athletic trainers hold a domestic credential (JSPO-AT) obtained from the Japan Sport Association (JSPO) or a US-based credential from the Board of Certification (BOC-AT). Objective To determine whether differences in demographic, professional, and educational characteristics exist between Japanese BOC-ATs and JSPO-ATs who currently practice athletic training services in Japan. Design Cross-sectional study. Setting Online survey. Patients or Other Participants Eight hundred twenty-nine Japanese athletic trainers in Japan (BOC-AT, n = 64; JSPO-AT, n = 765). Main Outcome Measure(s) Pearson's χ2 test and Fisher's exact test were used to determine differences in demographic, professional, and educational characteristics between BOC-ATs and JSPO-ATs. Results The proportion of female respondents was greater for BOC-ATs (29.7%) than for JSPO-ATs (18.7%; χ2 [1] = 4.5, P = .03). A greater proportion of BOC-ATs reported having master's degrees or higher (χ2 [3] = 81.6, P < .01). The percentage of respondents with at least 1 therapist or medical practitioner license in Japan was greater for JSPO-ATs (73.1%) than for BOC-ATs (20.3%; P < .01). The percentage of respondents with at least 1 credential in exercise, nutrition, or teaching was greater for BOC-ATs (62.5%) than for JSPO-ATs (45.2%; P < .01). A large difference was observed in the proportion of individuals who identified as therapists (JSPO-ATs = 29.8%, BOC-ATs = 6.3%; χ2 [5] = 18.9, P < .01). The median income for BOC-ATs was 401–600 million yen (US$36 500–$54 500), whereas the median income for JSPO-ATs was 0–200 million yen (US$0–$18 200). Conclusions BOC-ATs in Japan were more established than JSPO-ATs as athletic training professionals with higher educational backgrounds, while more JSPO-ATs tended to be therapists. Findings from the current study may serve as benchmark data for the athletic training profession and service characteristics in Japan.

Development of Stem Cell-Based Therapy for Limbal Stem Cell Deficiency—From Tissue Stem Cell to iPS Cell

Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan. Correspondence: Kohji Nishida, MD, PhD, Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan (e-mail: [email protected]). Supported in part by the Japan Agency for Medical Research and Development (AMED) under Grant Number JP19bm0504005 and JP19bk0104080, the Japan Science and Technology Agency (JST), The Ministry of Health, Labour and Welfare of Japan, and Grants-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology of Japan. The author has no conflicts of interest to disclose.

Solvate Ionic Liquid Electrolytes for Mg Batteries

We report here the structures and physicochemical properties of Mg[N(SO2CF3)2]2 (MgTFSA2)/glyme solvate ionic liquid electrolytes for Mg batteries. MgTFSA2 and certain glymes, such as triglyme (G3), tetraglyme (G4), and pentaglyme (G5), form equimolar complexes.1 The melting points of [Mg(G3)]TFSA2, [Mg(G4)]TFSA2, and [Mg(G5)]TFSA2 complexes are 70, 138, and 141 °C, respectively. X-ray crystallography revealed that each glyme wraparound a Mg2+ ion and forms a [Mg(glyme)]2+ complex cation in the crystalline solvate. To decrease the melting points of (MgTFSA2)/glyme complexes, asymmetric structure was introduced to the ligand (glyme). One of the terminal methyl groups of G3 molecule was substituted with other alkyl groups having various chain lengths. In this study, we used triethylene glycol ethyl methyl ether (G3Et) triethylene glycol butyl methyl ether (G3Bu) as ligands. As we expected, the melting point of [Mg(G3Et)]TFSA2 is 57.3 °C, which is lower than that of [Mg(G3)]TFSA2.2 The entropic term of melting increased with increasing asymmetric alkyl chain length, indicating that conformational flexibility successfully decreased the melting point. [Mg(G3Bu)]TFSA2 became a glass forming liquid and maintained liquid state at room temperature. Raman spectra for the [Mg(G3Bu)]TFSA2 indicated that the 1:1 complex structure of [Mg(G3Bu)]2+ is kept even in the liquid state. [Mg(G3Bu)]TFSA2 is thermally stable and does not decompose up to 251 °C. The oxidative stability of [Mg(G3Bu)]TFSA2 was analyzed by linear sweep voltammetry. [Mg(G3Bu)]TFSA2 possesses a higher oxidative stability compared with uncoordinated glymes. This is because the HOMO energy level of glyme is lowered by the complexation with Mg2+ ion.1,3 Mg metal deposition and dissolution are also possible in this electrolyte. Physicochemical properties of [Mg(glyme)]TFSA2 complexes will be compared with those of other glyme-based solvate ionic liquids such as [Li(glyme)]TFSA and [Na(glyme)]TFSA. Acknowledgements This study was supported in part by JSPS KAKENHI (Grant Nos. 18H03926) from the Japan Society for the Promotion of Science (JSPS), the MEXT program “Elements Strategy Initiative to Form Core Research Center” of the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan and the Advanced Low Carbon Technology Research and Development Program (ALCA) of the Japan Science and Technology Agency (JST). References S. Tsuzuki, T. Mandai, S. Suzuki, W. Shinoda, T. Nakamura, K. Ueno, S. Seki, Y. Umebaysashi, K. Dokko, M. Watanabe, Phys. Chem. Chem. Phys., 2017, 19, 18262-18272.K. Hashimoto, S. Suzuki, Morgan L. Thomas, T. Mandai, S. Tsuzuki, K. Dokko, Phys. Chem. Chem. Phys., 2018, 20, 7998-8007.T. Mandai, K. Dokko, M. Watanabe, Chem. Rec. 2019, 19, 708-722.

Short-Term Physical Inactivity Induces Diacylglycerol Accumulation and Insulin Resistance in Muscle via Lipin1 Activation

Background: Physical inactivity impairs muscle insulin sensitivity. However, its mechanism is unclear. Methods: To model physical inactivity, we applied 24-h hind-limb cast immobilization (HCI) to mice with normal or high fat diet (HFD), and evaluated intramyocellular lipids and the insulin signaling pathway in the soleus muscle. Findings: While 2-wk HFD alone did not alter intramyocellular diacylglycerol (IMDG) accumulation, HCI alone increased it by 1.9-fold and HCI after HFD further increased it by 3.3-fold. Parallel to this, we found increased PKCe activity, reduced insulin-induced 2-deoxy-glucose (2-DOG) uptake, and reduced phosphorylation of IRβ and Akt, key molecules for insulin signaling pathway. Lipin1, which converts phosphatidic acid to diacylglycerol, showed enhanced by HCI, and dominant-negative lipin1 expression in muscle prevented HCI-induced IMDG accumulation and impaired insulin-induced 2-DOG uptake. Further, 24-h leg cast immobilization in human increased lipin1 expression. Interpretation: Even short-term immobilization increases IMDG and impairs insulin sensitivity in muscle via enhanced lipin1 activity. Funding Statement: This work was supported by High Technology Research Center Grant, Strategic Research Foundation at Private Universities and KAKENHI (Grant-in-Aid for Scientific Research (C)) (15K01729) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. Declaration of Interests: All authors declare no conflict of interest. Ethics Approval Statement: All subjects gave written informed consent to participate in the study, which was approved by the ethics committee of Juntendo University. This study was carried out in accordance with the principles outlined in the Declaration of Helsinki. The present study complied with the principles and guidelines of the Japanese Council on Animal Care, and it was also approved by the Committee for Animal Research of Juntendo University.

A 23 gene–based molecular prognostic score precisely predicts overall survival of breast cancer patients

BackgroundAlthough many prognosis-predicting molecular scores for breast cancer have been developed, they are applicable to only limited disease subtypes. We aimed to develop a novel prognostic score that is applicable to a wider range of breast cancer patients. MethodsWe initially examined The Cancer Genome Atlas breast cancer cohort to identify potential prognosis-related genes. We then performed a meta-analysis of 36 international breast cancer cohorts to validate such genes. We trained artificial intelligence models (random forest and neural network) to predict prognosis precisely, and we finally validated our prediction with the log-rank test. FindingsWe identified a comprehensive list of 184 prognosis-related genes, most of which have been not extensively studied to date. We then established a universal molecular prognostic score (mPS) that relies on the expression status of only 23 of these genes. The mPS system is almost universally applicable to breast cancer patients (log-rank P < 0.05) in a manner independent of platform (microarray or RNA sequencing). InterpretationThe mPS system is simple and cost-effective to apply and yet is able to reveal previously unrecognized heterogeneity among patient subpopulations in a platform-independent manner. The combination of mPS and clinical stage stratifies prognosis even more precisely and should prove of value for avoidance of overtreatment. In addition, the prognosis-related genes uncovered in this study are potential drug targets. FundThis work was supported by KAKENHI grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan to H.S. (19K20403) and to K.I·N (18H05215).

The Caspase-3 Knockout Inhibits Intervertebral Disc Degeneration Related to Injury But Accelerates Degeneration Related to Aging

Background: Approximately 40% of people under 30 and over 90% of people 55 or older suffer from moderate-to-severe levels of degenerative intervertebral disc (IVD) disease in their lumbar spines. Surgical treatments, including discectomy or fusion, are effective; however, several complications have been reported, so new treatments are necessary. Apoptosis may be important in IVD degeneration because suppressing cell apoptosis inside the IVD inhibits degeneration. Caspase-3, the primary effector of apoptosis, may be a key treatment target. Methods: To investigate whether the different pathological mechanisms in injury- (IRD) and age-related IVD degeneration (ARD) affect the response to caspase-3 deletion and whether long term inhibition of caspase-3 results in tumorigenesis, we analyzed the role of the caspase-3 in IRD and ARD models using caspase-3 knockout (Casp-3 KO) mice. Findings: Casp-3 KO delayed IVD degeneration in the injury-induced model but accelerated it in the age-induced model. Our results suggest that this is due to different pathological mechanisms of these two types of IVD degeneration. Specifically, we found that apoptosis is the primary driving factor in injury-related IVD degeneration, but cellular senescence, but not apoptosis, seems to be the primary driving factor in age-related IVD degeneration. Interpretation: The present results suggest that short-term caspase-3 inhibition could be used in the treatment of IRD and provide further evidence that anti-apoptotic treatment of IVD degeneration represents a new avenue of investigation for treating spinal trauma. Funding Statement: Grant-in-Aid for the Ministry of Education, Culture, Sports, Science, and Technology of Japan (26670651 and 17K16669). Declaration of Interests: The authors state: There are no competing interests. Ethics Approval Statement: All animal procedures in this study were approved by the Institutional Animal Care and Use Committee of Hokkaido University. All procedures were carried out in accordance with the approved guidelines.

わが国における近代スポーツの展開過程に関する実証的研究 : 「明治神宮競技大会」の戦時体制化をめぐって

わが国における近代スポーツの展開過程に関する実証的研究 : 「明治神宮競技大会」の戦時体制化をめぐって

スポーツ庁「FUN+WALK PROJECT」を支持する声明

スポーツ庁「FUN+WALK PROJECT」を支持する声明

Effects Of Nutritional Status On Arterial Stiffness In The Subjects With Pre-sarcopenia

Sarcopenia associated with arterial stiffness and poor nutrition intake. However, it is unclear whether the effects of nutritional status on arterial stiffness in the subjects with pre-sarcopenia. PURPOSE: The purpose of this study was to investigate whether the effects of nutritional status on arterial stiffness in the subjects with pre-sarcopenia in Japanese men and women. METHODS: The participants included 56 Japanese adults (44-77 years). Men (n=15) and women (n=41) in whom skeletal muscle index (SMI; appendicular muscle mass/height2) was measured by dual-energy X-ray absorptiometry. Pre-sarcopenia was defined as the cut-off value of SMI based on Asian Working Group for Sarcopenia. We assessed nutritional status by Brief-type self-administered Diet History Questionnaire, and the subjects divided into high- and low- nutritional status based on the mean values of this study independent of gender. RESULTS: Two-way ANCOVA with adjustment for age, gender and physical activity as a covariate indicated that total energy intake and sarcopenia interacted to produce a significant effect on the brachial-ankle pulse wave velocity (baPWV) in Japanese adults (P<0.05). The baPWV was significantly higher in the subject with coexisting sarcopenia and low-energy intake than that with non-sarcopenia regardless of total energy intake. CONCLUSION: Low-energy intake effects on arterial stiffness in the subjects with pre-sarcopenia even adjustment of age and physical activity involved. Future prospective studies are needed to assess the effects of nutritional status on arterial stiffness in sarcopenia. Supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (#24300239).

Sex Disparities in Receipt of Bystander Interventions for Students Who Experienced Cardiac Arrest in Japan

Bystander interventions are a factor for improving survival of out-of-hospital cardiac arrest (OHCA), but it is hypothesized that girls and women experiencing OHCA may be less likely to receive bystander interventions than boys and men. To investigate sex disparities in receiving public-access automated external defibrillator (AED) pad application and bystander-initiated cardiopulmonary resuscitation (CPR) among students who experienced OHCA in school settings. This nationwide cohort study used the Stop and Prevent Cardiac Arrest, Injury, and Trauma in Schools (SPIRITS) database to link databases from 2 nationally representative registries-the Injury and Accident Mutual Aid Benefit System of the Japan Sport Council and the All-Japan Utstein Registry of the Fire and Disaster Management Agency. Students from elementary schools (ages 6-12 years), junior high schools (ages 12-15 years), high schools (ages 15-21 years), and technical colleges (ages 15-21 years) who experienced nontraumatic OHCA involving attempted resuscitation by emergency medical service personnel or bystanders in school settings from April 1, 2008, to December 31, 2015, were included. Data analysis was performed from January 5, 2019, to April 11, 2019. Sex and school level. Application of public-access AED pads or initiation of CPR by a bystander. A total of 232 students who experienced OHCA with nontraumatic causes in school settings (mean [SD] age, 14.5 [2.9] years; 175 [75.4%] male) were included. In multivariable analysis of the full cohort of students who experienced OHCA, female sex was associated with significantly lower odds of receiving public-access AED pad application compared with male sex (36 of 57 female students [63.2%] received AED pad application vs 141 of 175 male students [80.6%]; adjusted odds ratio [OR], 0.44; 95% CI, 0.20-0.97; P = .04). In the subgroup analysis of students who experienced OHCA in high schools or technical schools, female sex was associated with significantly lower odds of receiving public-access AED pad application compared with male sex (10 of 18 female students [55.6%] vs 84 of 101 male students [83.2%]; adjusted OR, 0.26; 95% CI, 0.08-0.87; P = .03). Among the full cohort, 48 of 57 female students (84.2%) and 151 of 175 male students (86.3%) received CPR from bystanders (adjusted OR, 0.81; 95% CI, 0.30-2.22), and there were no significant differences in receiving bystander-initiated CPR between sexes, irrespective of school level. Among students who experienced OHCA in schools in Japan, female sex was associated with lower odds of receiving public-access AED pad application compared with male sex.

Xanthine Oxidase Inhibition Attenuates Insulin Resistance and Diet-Induced Steatohepatitis in Mice

Background: Hyperuricemia drives the development of nonalcoholic fatty liver disease (NAFLD). Pharmacological inhibition of xanthine oxidase (XO), a rate-limiting enzyme for uric acid (UA) production, has been demonstrated to improve hepatic steatosis in diet-induced obese mice. However, it remains unclear whether inhibition of XO could improve nonalcoholic steatohepatitis (NASH), a more advanced form of NAFLD, in terms of both liver inflammation and fibrosis. Methods: To investigate the effects of febuxostat and allopurinol, XO inhibitors clinically used for gout, on diet-induced NASH, C57BL/6J mice were fed a high-fat, high-cholesterol, and cholate diet (CL diet) with or without either 0.001% febuxostat or 0.003% allopurinol for 18 weeks. Systemic glucose tolerance and insulin sensitivity, liver histology, inflammation, and oxidative stress were tested. Furthermore, we conducted a single-arm, open-label intervention study with febuxostat for NAFLD patients with hyperuricemia. Findings: Despite a similar hypouricemic effect of the XO inhibitors on blood UA level, febuxostat, but not allopurinol, significantly decreased hepatic UA levels in CL diet-fed mice. This reduction in hepatic UA levels was accompanied by alleviated insulin resistance, lipid peroxidation, and classically activated M1-like macrophage accumulation in the liver. Furthermore, in NAFLD patients with hyperuricemia, treatment with febuxostat for 24 weeks decreased the serum UA level, accompanied by a reduction in serum levels of liver enzymes, alanine aminotransferase and aspartate aminotransferase. Interpretation: XO may represent a promising therapeutic target in NAFLD/NASH, especially in patients with hyperuricemia. Trial Registration: The study has been registered with UMIN-CTR (#UMI08686). Funding Statement: This work was supported by Grants-in-aid for Scientific Research (B) (25282017) and Challenging Exploratory Research (15K12698) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Japan Diabetes Foundation (to T.O.). This study was also supported by Teijin Pharma Limited. Declaration of Interests: The authors declare no conflict of interest associated with this manuscript. Ethics Approval Statement: The study was approved by the Ethics Committee of Kanazawa University Hospital. All animal procedures were performed in accordance with the Guidelines for the Care and Use of Laboratory Animals of Kanazawa University, Japan.

Practical Study of the Sports Garbage Pickup Tournament in Japan—Sports Events to Solve Social Problems

Practical Study of the Sports Garbage Pickup Tournament in Japan—Sports Events to Solve Social Problems

Claudin‐5 as a target for drug delivery to the brain by modulation blood‐brain barrier

The regulatory success rate for central nervous system (CNS) drugs is less than half that of non‐CNS drugs. A current bottleneck in the development of CNS drugs is the lack of drug delivery systems to the brain. The blood‐brain barrier (BBB) is a membrane barrier formed by brain capillary endothelial cells and protects the brain from harmful materials circulating in the blood. Most small and all large drugs do not readily cross the BBB. The intercellular space between endothelial cells of the BBB is sealed by complex protein‐based structures called tight junctions (TJs). Claudin‐5 (CLDN‐5), a tetra‐transmembrane protein, is a key component of the TJ seal that prevents the paracellular diffusion of drugs into the CNS. Here, to investigate whether CLDN‐5 can be a target for CNS delivery of drugs, we generated monoclonal antibodies (mAbs) specific to the extracellular domain of CLDN‐5 using DNA immunization. Treatment of MDCKII/CLDN‐5 cells with anti‐CLDN‐5 mAbs time‐ and dose‐dependently decreased the integrity of TJs. The integrity was restored by removal of the anti‐CLDN‐5 mAbs. In an in vitro model of the BBB, anti‐CLDN‐5 mAbs also attenuated the integrity of TJs and enhanced permeability of small (Mw 376 Da) and large (4 kDa) solutes. The anti‐CLDN‐5 mAbs did not decrease TJ integrity in human intestinal epithelium models. In conclusion, CLDN‐5 is a potential target for the development of drug delivery systems to the brain. The anti‐CLDN‐5 mAb is a potential lead compound for development of novel drug delivery systems targeting the CNS.Support or Funding InformationThis study was partly supported by Grant‐in‐Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18K19400, 18H03190, 16K13044).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

&lt;i&gt;CYP2D6&lt;/i&gt; Genotype-Guided Tamoxifen Dosing in Hormone Receptor-Positive Metastatic Breast Cancer (TARGET-1): A Randomized, Open-Label, Phase 2 Study

Background: In patients taking tamoxifen, the CYP2D6 genotype causes different exposure of active metabolite endoxifen. There is a high frequency of CYP2D6 decreased-function variant in Asian populations. Therefore, we prospectively evaluated whetherCYP2D6 genotype-guided tamoxifen dosing in patients with hormone receptor-positive metastatic breast cancer could have an impact in the clinical outcome. Methods: In this randomized, open-label, multicenter, phase 2 study, patients who needed first-line tamoxifen therapy were enrolled in Japan. Based on individual CYP2D6 genotype, patients heterozygous (wt/V) or homozygous (V/V) for variant alleles of decreased or no-function were randomly assigned (1:1) to tamoxifen at increased dose (40 mg daily, ID arm) or regular dose (20 mg daily, RD arm), and patients homozygous for wild-type alleles (wt/wt) received tamoxifen at 20 mg daily. The primary endpoint was progression-free survival (PFS) rate at 6-month. The secondary endpoints included PFS and correlation of (Z)-endoxifen concentration with clinical outcomes. Findings: Between December 2012 and July 2016, 186 patients were enrolled. Of 184 evaluable patients, 136 carried wt/V or V/V (ID arm, 70; RD arm, 66), and 48 carried wt/wt. PFS rates at 6-month were not significantly different between ID and RD arms (67·6% vs. 66·7%). The serum trough concentrations of (Z)-endoxifen in the ID arm were significantly higher than those in the RD arm (median, 89·2 nM vs. 51·1 nM; P < 0.0001) and were also higher compared with wt/wt patients (72·0 nM; P = 0·0452). No significant difference in (Z)-endoxifen concentrations was observed between patients with and without progression at 6-month (p = 0·43). Interpretation: In patients with CYP2D6 variant alleles, increasing tamoxifen dosing did not achieve higher PFS rate at 6-month. The CYP2D6 genotype solely cannot explain individual variability in the efficacy of tamoxifen. Clinical Trial Number: This study is registered with UMIN Clinical Trials Registry, number UMI09155. Funding Statement: This study was supported by grants from the Project for Development of Innovative Research on Cancer Therapeutics and from the Tailor-made Medical Treatment Program (BioBank Japan Project) funded by the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and the AMED under Grant Number 17ck0106191h0003). Declaration of Interests: YF reports grants from the Japan Agency for Medical Research and Development (AMED). MK reports grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT). KT reports grants from AstraZeneca and Daiichi-Sankyo outside the submitted work. CKI, MT, and YT report personal fees from AstraZeneca outside the submitted work. TT and JT report grants and personal fees from Daiichi-Sankyo outside the submitted work. SS reports grants and personal fees from AstraZeneca, and personal fees from Daiichi-Sankyo outside the submitted work. TY and YF report personal fees from AstraZeneca and Daiichi-Sankyo outside the submitted work. NTU reports grants from Daiichi-Sankyo outside the submitted work. YT reports personal fees from Meiji Seika Pharma outside the submitted work. All other authors declare no competing interests. Ethics Approval Statement: We obtained written informed consent from each patient before participation. The trial followed the ethical principles of the Declaration of Helsinki and Japanese Ethical Guidelines and Clinical Research. This study protocol and any amendments thereof were approved by an independent Ethics Committee or Institutional Review Board at each institution.