Relationship of leisure-time and household physical activity level and type with cardiovascular disease: secondary analysis of the Takashima Study data

滋賀医科大学博士（医学）application/pdfBackground: High levels of participation in leisure-time and household physical activity lower the risk of cardiovascular disease (CVD), although it is unclear whether the number of activity types is related to new-onset CVD. We aimed to evaluate the effect of the amount of leisure-time physical activity and the number of types of leisure-time physical activities on the risk of CVD incidence.Methods: From 2002 to 2003, 3,741 participants without any history of CVD participated in the Takashima Study. Data on the amount of leisure-time and household physical activity and the types of leisure-time and household physical activity were obtained from a self-administered questionnaire. Hazard ratios for CVD (acute myocardial infarction and stroke) incidence (follow-up data from 2002 to 2013), according to the participation level and number of activity types, were calculated using Cox proportional hazards models.Results: The mean age of the subjects was 58.7 ± 13.1 years. During the mean follow-up period of 8.0 ± 1.1 years, 92 participants developed CVD. An inverse dose-response relationship was noted between the amount of leisure-time and household physical activity and CVD events. After adjusting for baseline characteristics, lifestyle-related diseases, and the amount of physical activity other than leisure-time and household, the risk of CVD onset was compared by dividing the participants into two groups by the level of participation; the highest activity group had an adjusted hazard ratio (95% confidence interval) of 0.40 (0.20-0.82) compared to the lowest activity group. Compared to participants who engaged in 0-1 type of activity, participants who engaged in two or more types of activities had a multivariable-adjusted hazard ratio (95% confidence interval) of 0.31 (0.12-0.79).Conclusion: Increasing the amount of leisure-time and household physical activity and promoting engagement in two or more types of such activities may reduce the rate of CVD incidence in the Japanese general population.Thesis or Dissertation令和4年度doctoral thesi

Dynamic Rupture Simulations Based on the Characterized Source Model of the 2011 Tohoku Earthquake

The 2011 Off the Pacific Coast of Tohoku earthquake (Tohoku earthquake, M_w 9.0) occurred on the Japan Trench and caused a devastating tsunami. Studies of this earthquake have revealed complex features of its rupture process. In particular, the shallow parts of the fault (near the trench) hosted large slip and long period seismic wave radiation, whereas the deep parts of the rupture (near the coast) hosted smaller slip and strong radiation of short period seismic waves. Understanding such depth-dependent feature of the rupture process of the Tohoku earthquake is necessary as it may occur during future mega-thrust earthquakes in this and other regions. In this study, we investigate the “characterized source model” of the Tohoku earthquake through dynamic rupture simulations. This source model divides the fault plane into several parts characterized by different size and frictional strength (main asperity, background area, etc.) and is widely used in Japan for the prediction of strong ground motion and tsunami through kinematic rupture simulations. Our characterized source model of the Tohoku earthquake comprises a large shallow asperity with moderate frictional strength, small deep asperities with high frictional strength, a background area with low frictional strength, and an area with dynamic weakening close to the trench (low dynamic friction coefficient as arising from, e.g., thermal pressurization). The results of our dynamic rupture simulation reproduce the main depth-dependent feature of the rupture process of the Tohoku earthquake. We also find that the width of the area close to the trench (equal to the distance from the trench to the shallow asperity, interpreted as the size of the accretionary prism) and the presence of dynamic weakening in this area have a significant influence on the final slip distribution. These results are useful to construct characterized source models for other subduction zones with different scale of the accretionary prism, such as the Chile subduction zone and the Nankai Trough. Dynamic rupture simulations based on the characterized source model might provide useful insights for hazard assessment associated with future mega-thrust earthquakes

Noninvasive prediction of shunt operation outcome in idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by gait disturbance, cognitive deterioration and urinary incontinence in elderly individuals. These symptoms can be improved by shunt operation in some but not all patients. Therefore, discovering predictive factors for the surgical outcome is of great clinical importance. We used normalized power variance (NPV) of electroencephalography (EEG) waves, a sensitive measure of the instability of cortical electrical activity, and found significantly higher NPV in beta frequency band at the right fronto-temporo-occipital electrodes (Fp2, T4 and O2) in shunt responders compared to non-responders. By utilizing these differences, we were able to correctly identify responders and non-responders to shunt operation with a positive predictive value of 80% and a negative predictive value of 88%. Our findings indicate that NPV can be useful in noninvasively predicting the clinical outcome of shunt operation in patients with iNPH

Different Characteristics of Cognitive Impairment in Elderly Schizophrenia and Alzheimer's Disease in the Mild Cognitive Impairment Stage

We compared indices of the revised version of the Wechsler Memory Scale (WMS-R) and scaled scores of the five subtests of the revised version of the Wechsler Adult Intelligence Scale (WAIS-R) in 30 elderly schizophrenia (ES) patients and 25 Alzheimer's disease (AD) patients in the amnestic mild cognitive impairment (aMCI) stage (AD-aMCI). In the WMS-R, attention/concentration was rated lower and delayed recall was rated higher in ES than in AD-aMCI, although general memory was comparable in the two groups. In WAIS-R, digit symbol substitution, similarity, picture completion, and block design scores were significantly lower in ES than in AD-aMCI, but the information scores were comparable between the two groups. Delayed recall and forgetfulness were less impaired, and attention, working memory and executive function were more impaired in ES than in AD-aMCI. These results should help clinicians to distinguish ES combined with AD-aMCI from ES alone

Polymorphisms and Body Mass Index Across Life Course

Background: Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities. Methods: We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20), and change in BMI (BMI change), among 11,586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models. Results: We found a significant association (P < 0.05/282 = 1.77 × 10−4) between BMI and 11 polymorphisms in or near FTO, BDNF, TMEM18, HS6ST3, and BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on FTO were associated with all BMI traits, whereas those on TMEM18 and HS6SR3 were only associated with BMI at 20. The association of FTO loci with BMI remained, even after additional adjustment for dietary energy intake. Conclusions: Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways

The p250GAP Gene Is Associated with Risk for Schizophrenia and Schizotypal Personality Traits

BACKGROUND: Hypofunction of the glutamate N-Methyl-d-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. p250GAP is a brain-enriched NMDA receptor-interacting RhoGAP. p250GAP is involved in spine morphology, and spine morphology has been shown to be altered in the post-mortem brains of patients with schizophrenia. Schizotypal personality disorder has a strong familial relationship with schizophrenia. Several susceptibility genes for schizophrenia have been related to schizotypal traits. METHODS: We first investigated the association of eight linkage disequilibrium-tagging single-nucleotide polymorphisms (SNPs) that cover the p250GAP gene with schizophrenia in a Japanese sample of 431 schizophrenia patients and 572 controls. We then investigated the impact of the risk genetic variant in the p250GAP gene on schizotypal personality traits in 180 healthy subjects using the Schizotypal Personality Questionnaire. RESULTS: We found a significant difference in genotype frequency between the patients and the controls in rs2298599 (χ(2) = 17.6, p = 0.00015). The minor A/A genotype frequency of rs2298599 was higher in the patients (18%) than in the controls (9%) (χ(2) = 15.5, p = 0.000083). Moreover, we found that subjects with the rs2298599 risk A/A genotype, compared with G allele carriers, had higher scores of schizotypal traits (F(1,178) = 4.08, p = 0.045), particularly the interpersonal factor (F(1,178) = 5.85, p = 0.017). DISCUSSION: These results suggest that a genetic variation in the p250GAP gene might increase susceptibility not only for schizophrenia but also for schizotypal personality traits. We concluded that the p250GAP gene might be a new candidate gene for susceptibility to schizophrenia