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• Generalization of a clinical diagnosis support tool for lumbar spinal stenosis: Can the ankle brachial pressure index be replaced by palpation of the posterior tibial artery in the lumbar spinal stenosis diagnostic support tool? (DISTO project).

  Nikaido T, Sekiguchi M, Yonemoto K, Kakuma T, Watanabe K, Kato K, Kobayashi H, Tominaga R, Otani K, Yabuki S, Kikuchi SI, Konno SI, DISTO-Project Working Group

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association ( Journal of Orthopaedic Science )  28 ( 3 ) 543 - 546   2023.05 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Association of serum s-adenosylmethionine, s-adenosylhomocysteine, and their ratio with the risk of dementia and death in a community.

  Mihara A, Ohara T, Hata J, Chen S, Honda T, Tamrakar S, Isa A, Wang D, Shimizu K, Katakura Y, Yonemoto K, Nakao T, Kitazono T, Ninomiya T

  Scientific reports ( Scientific Reports )  12 ( 1 ) 12427 - 12427   2022.07 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  We examined the association of serum s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH) (methionine metabolites), and their ratio on the risk of dementia and death in a community-dwelling population of older Japanese individuals. 1371 residents of Hisayama, Japan, aged 65 years or older and without dementia, were followed for a median of 10.2 years (2007-2017). We divided serum SAM, SAH, and SAM/SAH ratio into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of serum SAM, SAH, and SAM/SAH ratio levels on the risk of a composite outcome of all-cause dementia or death, and each outcome. During the follow-up, 635 participants developed all-cause dementia and/or died, of which 379 participants developed dementia and 394 deaths occurred. The multivariable-adjusted HRs of the composite outcome decreased significantly with increasing serum SAM levels (P for trend = 0.01), while they increased significantly with higher serum SAH levels (P for trend = 0.03). Higher serum SAM/SAH ratio levels were significantly associated with a lower risk of the composite outcome (P for trend = 0.002), as well as with lower risk of each outcome. Our findings suggest that the balance of methionine metabolites may closely associate with the risk of dementia and death.

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• Intensive or standard blood pressure control in patients with a history of ischemic stroke: RESPECT post hoc analysis.

  Kitagawa K, Arima H, Yamamoto Y, Ueda S, Rakugi H, Kohro T, Yonemoto K, Matsumoto M, Saruta T, Shimada K, Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study Group

  Hypertension research : official journal of the Japanese Society of Hypertension ( Hypertension research : official journal of the Japanese Society of Hypertension )  45 ( 4 ) 591 - 601   2022.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Diagnostic accuracy of the lumbar spinal stenosis-diagnosis support tool and the lumbar spinal stenosis-self-administered, self-reported history questionnaire.

  Tominaga R, Kurita N, Sekiguchi M, Yonemoto K, Kakuma T, Konno SI

  PloS one ( PLoS ONE )  17 ( 5 ) e0267892 - e0267892   2022 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Despite the applicability of the lumbar spinal stenosis (LSS)-diagnosis support tool (DST) and the LSS-self-administered, self-reported history questionnaire (SSHQ), their diagnostic accuracy has never been compared with that of the well-known North American Spine Society (NASS) clinical description of LSS. This study aimed to compare the diagnostic accuracy of the two diagnostic tools with that of the NASS guidelines’ clinical description of LSS in a Japanese secondary care hospital setting. This multicenter cross-sectional study used data from the lumbar spinal stenosis diagnostic support tool (DISTO) project, which was conducted from December 1, 2011 to December 31, 2012. Japanese adults with low back pain (LBP) aged ≥20 years were consecutively included. The reference standard was LSS diagnosed by orthopedic physicians. The diagnostic accuracy of the two support tools was compared. Of 3,331 patients, 1,416 (42.5%) patients were diagnosed with LSS. The NASS clinical description of LSS had a sensitivity of 63.9% and specificity of 89.5%. The LSS-DST and LSS-SSHQ had sensitivities of 91.3% and 83.8% and specificities of 76.0% and 57.6%, respectively, with substantial improvements in sensitivity (P < 0.0001). Similar results were obtained when we limited included patients to those aged >60 years. These findings indicated that the LSS-DST and LSS-SSHQ were more sensitive in screening patients with LBP for a diagnosis of LSS than the NASS clinical description of LSS. This study strongly supports prioritizing the use of either of these two diagnostic support tools for screening.

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• Study design and baseline characteristics of a population-based prospective cohort study of dementia in Japan: the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD).

  Ninomiya T, Nakaji S, Maeda T, Yamada M, Mimura M, Nakashima K, Mori T, Takebayashi M, Ohara T, Hata J, Kokubo Y, Uchida K, Taki Y, Kumagai S, Yonemoto K, Yoshida H, Muto K, Momozawa Y, Akiyama M, Kubo M, Ikeda M, Kanba S, Kiyohara Y, JPSFC-AD Study Group.

  Environmental health and preventive medicine ( Environmental health and preventive medicine )  25 ( 1 ) 64 - 64   2020.10 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  © 2020, The Author(s). Background: The burden of dementia is growing rapidly and has become a medical and social problem in Japan. Prospective cohort studies have been considered an effective methodology to clarify the risk factors and the etiology of dementia. We aimed to perform a large-scale dementia cohort study to elucidate environmental and genetic risk factors for dementia, as well as their interaction. Methods: The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a multisite, population-based prospective cohort study of dementia, which was designed to enroll approximately 10,000 community-dwelling residents aged 65 years or older from 8 sites in Japan and to follow them up prospectively for at least 5 years. Baseline exposure data, including lifestyles, medical information, diets, physical activities, blood pressure, cognitive function, blood test, brain magnetic resonance imaging (MRI), and DNA samples, were collected with a pre-specified protocol and standardized measurement methods. The primary outcome was the development of dementia and its subtypes. The diagnosis of dementia was adjudicated by an endpoint adjudication committee using standard criteria and clinical information according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Revised Edition. For brain MRI, three-dimensional acquisition of T1-weighted images was performed. Individual participant data were pooled for data analyses. Results: The baseline survey was conducted from 2016 to 2018. The follow-up surveys are ongoing. A total of 11,410 individuals aged 65 years or older participated in the study. The mean age was 74.4 years, and 41.9% were male. The prevalence of dementia at baseline was 8.5% in overall participants. However, it was 16.4% among three sites where additional home visit and/or nursing home visit surveys were performed. Approximately two-thirds of dementia cases at baseline were Alzheimer’s disease. Conclusions: The prospective cohort data from the JPSC-AD will provide valuable insights regarding the risk factors and etiology of dementia as well as for the development of predictive models and diagnostic markers for the future onset of dementia. The findings of this study will improve our understanding of dementia and provide helpful information to establish effective preventive strategies for dementia in Japan.

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• tissue distribution and toxic mechanism of indium nano particles

  Grant-in-Aid for Scientific Research(B)

  Project Year: 2016.04  -  2019.03 

  Investigator(s): Tanaka Akiyo 

  Direct: 12,700,000 (YEN)  Overheads: 16,510,000 (YEN)  Total: 3,810,000 (YEN)

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  To clarify health effects of indium nanoparticles, we studied animal experiment using rats. Rats received a dose of 10 mg In/kg of indium nanoparticles (In Metal:In(OH)3;8:2, mean diameter: 6 nm) or indium oxide(In2O3, mean diameter:150 nm) once intratracheally . A subset of rats was euthanized periodically throughout the study from 1 day to 36 weeks after a treatment. The indium concentration each organ in the both groups gradually increased over time until 36 weeks. The levels of indium in the organs in the In nano group was higher than that in the In2O3 group during observation period. The severity of lung lesions in the In nano group was more severe in comparison with the In2O3 group. Furthermore, indium nanoparticles were detected in the bladder urine of rats. It is necessary to consider the effects of exposure to indium nanoparticles in humans, and precautions against such exposure are paramount with regard to health management.

• Development of an innovative method to modify life style using a dietary pattern score

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2016.04  -  2019.03 

  Investigator(s): FUNAKI Makoto 

  Direct: 3,600,000 (YEN)  Overheads: 4,680,000 (YEN)  Total: 1,080,000 (YEN)

  　View Summary

  Appropriate diet is indispensable to prevent an onset of metabolic syndrome. Intensive studies have been made to reveal the type of food favorable/unfavorable to develop metabolic syndrome. However, meals are composed of multiple types of foods and avoiding/choosing certain types of foods will affect the intake of other types of foods, as well. Therefore, to determine if some diets are favorable/unfavorable to an onset of metabolic syndrome, it is crucial to elucidate a dietary pattern associated with an onset of metabolic syndrome and establish a method to evaluate how close/distant a certain meal is to/from such a dietary pattern. In this study, we succeeded in establishing a dietary pattern, which is associated with an onset of metabolic syndrome, and made a formula to score the distance between certain dietary patterns and the one associated with developing metabolic syndrome. This score will enable to assess the risk of developing metabolic syndrome from a dietary pattern.

• Indium exposure in the hair of workers dealing with indium compounds

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2013.04  -  2016.03 

  Investigator(s): Hirata Mikyuki, TANAKA Akiyo, NAKANO Makiko, TANAKA Shigeru, YONEMOTO Koji, MIYAUCHI Hiroyuki, SUGIYAMA Takeharu, KAMITANI Kazuyuki, HANADA Kenji 

  Direct: 3,900,000 (YEN)  Overheads: 5,070,000 (YEN)  Total: 1,170,000 (YEN)

  　View Summary

  To prevent workers from indium exposure in the workplaces of producing or handling of indium compounds including ITO, workers are mandated to effective respiratory protective equipment. The hair of workers is exposed by indium up to ug/g, but there is no attention to hair exposure. In this study, personal breathing zone samplings and hair samplings of workers was examined for indium exposure. Indium concentrations of hair at morning and evening were increased dose-dependently to breathing zone concentrations of total indium dust, respectively. Spectroscopic analysis using synchrotron radiation by SPring-8 revealed indium chemical adsorption in the surface of hair.

• Asymmetric and nonlinear statistical theory and its applications to economics and bioscience

  Grant-in-Aid for Scientific Research(A)

  Project Year: 2011.04  -  2015.03 

  Investigator(s): TANIGUCHI Masanobu, YONEMOTO Kouji, HIRUKAWA Junichi, TAKAGI Yoshiji, HOSHINO Nobuaki, WANG Jin FANG, LIU Qing FENG, NAITO Kanta, SEKIYA Yuri, MATSUDA Shinichi, AKAHIRA Masafumi, TAKEMURA Akimichi, NISHIYAMA Yoshihiko, KANO Yutaka, AMANO Tomoyuki 

  Direct: 36,800,000 (YEN)  Overheads: 47,840,000 (YEN)  Total: 11,040,000 (YEN)

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  We investigated a class of very general stochastic processes with nonlinear dynamics and asymmetric innovation distributions, which can be applied to a varitety of fields e.g., economics, finance, bionics, natural phenomenon etc., as a paradigm model. For them we developed the optimal inference based on LAN, and the empirical likelihood method to a class of stable processes. Shrinked estimation theory has been developed for stochastic processes. The theoretical results have been applied to estimation of portfolios, and the problem of causality. From the applications of the theoretical results, we have got some interesting feedback to mathematical theory. Also, in the process of research, we have raised young researchers.

• Exercise epidemiological study on relationships of several health outcomes with changes of physical activity, exercise and physical fitness

  Grant-in-Aid for Scientific Research(A)

  Project Year: 2010.04  -  2015.03 

  Investigator(s): KUMAGAI SHUZO, KIYOHARA Yutaka, NAGANO Mayumi, HATAYAMA Tomoko, YONEMOTO Koji, NAITO Yoshihiko, YAMATSU Koji, UEZONO Keiko 

  Direct: 38,000,000 (YEN)  Overheads: 49,400,000 (YEN)  Total: 11,400,000 (YEN)

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  Almost exercise epidemiological studies had been evaluated by using single exposure at baseline only. The major limitation of this kind of study design was not able to evaluate the changes of several exposures such as physical activity, exercise, sedentary behavior and physical fitness. Therefore, we try to assess the relationships of several health outcomes with the changes in physical activity, exercise, sedentary time and physical fitness in Japanese several populations. In addition, we investigated the levels and changes of physical activity and sedentary time objectively evaluated by tri-axial accelerometers in Japanese populations. Finally, we discussed about methodological problem in multiple evaluations of several exposures.