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Aim: This study aimed to determine whether practicing coordination exercises, compared with other physical exercise types, is associated with better cognitive function in older Japanese adults., Methods: This cross-sectional study used data from a health checkup project carried out from 2015 to 2019 among older adults living in Kasama City, Ibaraki Prefecture, Japan. Data from 569 participants (mean age 74.0 ± 5.4 years, 53.8% women) were analyzed. The types of physical exercise practiced within the seven preceding days were identified. The Five-Cog test and Trail Making Test were used to evaluate general cognitive function and executive function, respectively. The cognitive functions of practitioners and non-practitioners of each type of physical exercise - coordination, endurance, resistance, and stretching - were examined using an analysis of covariance., Results: Although practitioners of any physical exercise did not have significantly better cognitive function than non-practitioners, in an analysis stratified by exercise amount, those who practiced more coordination exercise had better general cognitive function than non-practitioners (P = 0.046), in a fully adjusted model., Conclusion: Those who practiced more coordination exercises had better general cognitive function. Geriatr Gerontol Int 2024; 24: 1173-1180., (© 2024 Japan Geriatrics Society.)

Epidemiological studies have reported that Asian dust (AD), a type of desert dust, has harmful effects on human health. This study aimed to examine the association between AD exposure and hospitalization due to pneumonia. Data on patients in Western Japan admitted for pneumonia were included from a real-world database derived from electronic medical records. We used the meteorological observatory data of the most populous city in each prefecture, in which AD event was defined as a loss of visibility from a distance ≤10 km. A case-crossover design and conditional logistic regression model were used. Overall, 12 938 patients were included, and AD exposure events were observed for 557 days. Exposure to an AD event five days prior to hospitalization was significantly associated with hospitalization for pneumonia after adjusting for weather variables (odds ratio = 1.17). These findings suggest that AD exposure is associated with an increased rate of admission for pneumonia in Western Japan., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The amyloid-β1-42 (Aβ42) level is a biomarker that is widely used to evaluate individual cognitive dysfunction early in neurodegenerative diseases, as well as differentiate between normal cognitive function, mild cognitive impairment, Alzheimer's disease, and vascular cognitive impairment., Objective: Our cross-sectional study evaluated the association between daily exercise and physical and cognitive function and Aβ42 levels among a subsample of 325 older adults from the Kasama Study., Methods: Participants (age: 74.5 [range 65-90] years) were classified into three exercise groups: the dual-task (DEG, n = 128), single-task (SEG, n = 122), and non-exercise (NEG, n = 75) groups. The main outcomes were the plasma Aβ42 levels and the scores of the five cognitive (5-COG) tests and five cognition-related physical function (5-PHYS) tests., Results: The Aβ42 levels and 5-COG and 5-PHYS scores were higher in the SEG and DEG than in the NEG. The Aβ42 levels were higher in the DEG than in the NEG (p = 0.008)., Conclusions: Physical activities such as regular exercise may benefit older adults, improving their cognitive and physical function.

Aim: To investigate the association of the Japan Science and Technology Agency Index of Competence with physical and cognitive functions in community-dwelling older adults., Methods: This study used the data of 565 community-dwelling adults aged ≥65 years (mean age: 74.3 ± 5.2 years) from the Kasama Health Checkup for Longevity survey in Japan. The Japan Science and Technology Agency Index of Competence was used to comprehensively evaluate the higher-level functional capacity and subscale functional capacity: technology usage, information practice, life management and social engagement. Physical functions were assessed using grip strength, the five-repetition sit-to-stand test, 5-m habitual walking test, one-leg standing test and hand working test with a pegboard. Cognitive functions were evaluated using the Five-Cog test consisting of attention, memory ability, visuospatial function, language ability and reasoning ability. Multiple regression analysis was conducted to examine the associations between total Japan Science and Technology Agency Index of Competence score and physical and cognitive functions., Results: After adjusting for potential confounders, the total Japan Science and Technology Agency Index of Competence score was favorably associated with static balance ability (β = 0.09; B = 0.01; 95% confidence interval: 0.00-0.02), lower limb strength (β = -0.19; B = -0.29; 95% confidence interval: -0.41 to -0.16), walking ability (β = -0.15; B = -0.67; 95% confidence interval: -1.05 to -0.30), hand dexterity (β = -0.13; B = -0.08; 95% confidence interval: -0.14 to -0.03) and overall cognitive function (β = 0.28; B = 0.04; 95% confidence interval: 0.03-0.05)., Conclusions: Physical and cognitive functions are important for maintaining higher-level functional capacity. Geriatr Gerontol Int 2022; 22: 753-758., (© 2022 Japan Geriatrics Society.)

Deteriorating sleep quality and physical or mental fatigue in older adults leads to decreased quality of life and increased mortality rates. This study investigated the effects of the time-dependent intake of nicotinamide mononucleotide (NMN) on sleep quality, fatigue, and physical performance in older adults. This randomized, double-blind placebo-controlled study evaluated 108 participants divided into four groups (NMN_AM; antemeridian, NMN_PM; post meridian, Placebo_AM, Placebo_PM). NMN (250 mg) or placebo was administered once a day for 12 weeks. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index. Fatigue was evaluated using the "Jikaku-sho shirabe" questionnaire. Grip strength, 5-times sit-to-stand (5-STS), timed up and go, and 5-m habitual walk were evaluated to assess the physical performance. Significant interactions were observed between 5-STS and drowsiness. 5-STS of all groups on post-intervention and drowsiness of the NMN_PM and Placebo_PM groups on mid- and post-intervention showed significant improvement compared with those in pre-intervention. The NMN_PM group demonstrated the largest effect size for 5-STS (d = 0.72) and drowsiness (d = 0.64). Overall, NMN intake in the afternoon effectively improved lower limb function and reduced drowsiness in older adults. These findings suggest the potential of NMN in preventing loss of physical performance and improving fatigue in older adults.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment is a therapeutic approach for type 2 diabetes mellitus (T2DM). Some reports have shown that SGLT2i treatment improves insulin resistance; however, few studies have evaluated insulin resistance by the glucose clamp method. Hepatic insulin clearance (HIC) is a new pathophysiological mechanism of T2DM. The effect of SGLT2i treatment on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i treatment on insulin resistance, insulin secretion, incretin levels, body composition, and hepatic insulin clearance. We conducted a meal tolerance test (MTT) and a hyperinsulinemic-euglycemic clamp test in 9 T2DM patients. Ipragliflozin (50 mg/day) was administered, and the MTT and clamp test were performed after 4 months. We calculated HIC as the postprandial C-peptide AUC-to-insulin AUC ratio. We also measured GLP-1, GIP, and glucagon levels during the MTT. Body weight and HbA1c were decreased, although not significantly, after 4 months of treatment. Postprandial glucose, fasting insulin and postprandial insulin were significantly decreased. Insulin resistance with the glucose clamp was not changed, but the HOMA-IR and insulin sensitivity indices were significantly improved. Incretin and glucagon levels were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. The FIB-4 index and fatty liver index were significantly reduced. The HOMA-beta and insulinogenic indices were not changed, but the C-peptide index was significantly increased. Although the number of patients was small, these results suggested that SGLT2i treatment improved liver function, decreased hepatic insulin resistance, and increased hepatic insulin clearance, despite the small weight reduction., (© 2022. The Author(s).)

Background: Moderate- to vigorous-intensity physical activity (PA) may reduce the risk of dementia; however, few studies have examined the effects of PA intensity on dementia risk., Objective: To prospectively examine the dose-response relationship of PA intensity with the incidence of suspected dementia in community-dwelling older adults., Methods: We conducted a baseline mail survey with an 8-year follow-up of 3,722 older adults in Japan. We assessed PA levels using the International Physical Activity Questionnaire short form and calculated the amount of time per week spent performing moderate- and vigorous-intensity PA (VPA). Information regarding suspected dementia was obtained from the city database during the follow-up period. Cox proportional-hazard models with age as time scale, and delayed entry and restricted cubic spline regression as variables were used to estimate risk of developing suspected dementia, excluding cases occurring < 1 year after baseline evaluation., Results: The cumulative incidence of suspected dementia during the follow-up period was 12.7%. Compared with those who did not practice moderate-intensity PA (MPA), those who practiced≥300 min (hazard ratio, 0.73; 95% confidence interval 0.56-0.95) of MPA showed a lower risk of developing suspected dementia. Furthermore, when the dose-response relationship was examined, the hazard of developing suspected dementia decreased almost linearly with MPA. A significantly lower hazard was observed from 815 minutes/week. There was no significant association between VPA and suspected dementia., Conclusion: This study suggested that MPA is often practiced in older adults and this PA intensity has a sufficiently favorable effect on dementia prevention.

Objectives: Frailty might be useful to identify older drivers who are at risk for traffic crashes. We aim to examine the association between pre-frailty/frailty defined by the Kihon Checklist (KCL) and the involvement of traffic crashes and clarify whether some domains of the KCL are associated with traffic crashes. Methods: This cross-sectional study analyzed data from 2,208 Japanese community-dwelling older drivers aged ≥ 65 years in Kasama City, who participated in our postal survey in November 2019. A self-reported history of traffic crashes was used to divide participants into non-crash-involved and crash-involved groups. Results: A total of 192 (8.7%) participants had been involved in traffic crashes in the past year. The crash-involved group was found to have gained more body mass index, driven more frequently, and scored higher on the total KCL score than the non-crash-involved group (all P < .05). Binary logistic regression analyses showed that after adjusting for age, sex, education, driving frequency, and driving distance, pre-frailty (OR = 1.52, 95% CI: 1.10-2.10) was more significantly associated with traffic crashes as compared to robustness. Those who had impairment in the oral domain (OR = 1.57, 95% CI: 1.09-2.27) and memory domain (OR = 1.38, 95% CI: 1.01-1.90) were also more likely to be involved in traffic crashes. Conclusion: The results suggest that identifying pre-frailty may play an important pole in crash prevention. Additionally, more attention should be given to older drivers with oral dysfunction and cognitive impairment.

This study aimed to examine the factors related to participation in volunteer-managed preventive care exercises by focusing on the distance to exercise facilities and interpersonal social networks. A postal mail survey was conducted in 2013 in Kasama City in a rural region of Japan. Older adults (aged ≥ 65 years) who were living independently ( n = 16,870) were targeted. Potential participants who were aware of silver-rehabili taisou exercise (SRTE) and/or square-stepping exercise (SSE) were included in the analysis ( n = 4005). A multiple logistic regression analysis revealed that social and environmental factors were associated with participation in SRTE and SSE. After adjusting for confounding variables, exercise participation was negatively associated with an extensive distance from an exercise facility in both sexes for SRTE and SSE. Among women, participation in SRTE was negatively associated with weak interpersonal social networks (odds ratio (OR) = 0.57), and participation in SRTE and SSE was negatively associated with being a car passenger (SRTE, OR = 0.76; SSE, OR = 0.60). However, there were no significant interactions between sex and social and environmental factors. Our findings suggest the importance of considering location and transportation to promote participation in preventive care exercise.

Abstract: The aim of this study was to clarify the effect of living alone on the cognitive function of older people and the mediating effect of instrumental activities of daily living (IADL) ability.The data for a final sample of 3276 participants aged 65 years and above who did not require long-term care at the baseline were used from a 4-year prospective cohort study conducted in Kasama City, Japan. Demographic data including age, sex, and depression at baseline were used as covariates. The Kihon checklist evaluated the IADL ability at baseline and cognitive function at follow-up. The characteristics of those living alone and with others were compared using the student t test and χ2 test. The effect of living alone on cognitive function was analyzed using logistic regression analysis. Mediation analyses determined the mediating effects of IADL.A total of 325 participants were living alone; they were significantly older than those living with others, more likely to be female, not provide emotional support, and have low physical function, more severe depression, and lower IADL disability. Living alone had a significantly lower risk of cognitive decline at follow-up than living with others. The mediation analysis revealed that IADL disability at follow-up was significantly associated with cognitive decline. Thus, greater IADL ability decreased cognitive decline risk.Older people living alone had a significantly lower risk of cognitive decline, and cognitive function significantly mediated IADL ability. Health support for enhancing IADL abilities may help older people living alone maintain good cognitive function., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The quality of care for dementia in acute-care settings has been criticised. In 2016, the Japanese universal health insurance system introduced a financial incentive scheme for dementia care by dementia specialist teams in acute-care hospitals. This study aimed to investigate the effectiveness of this financial incentive scheme on short-term outcomes (in-hospital mortality and 30-day readmission)., Design and Methods: Using a Japanese nationwide inpatient database, we identified older adult patients with moderate-to-severe dementia admitted for pneumonia, heart failure, cerebral infarction, urinary tract infection, intracranial injury or hip fracture from April 2014 to March 2018. We selected 180 propensity score-matched pairs of hospitals that adopted (n = 180 of 185) and that did not adopt (n = 180 of 744) the financial incentive scheme. We then conducted a patient-level difference-in-differences analysis. In a sensitivity analysis, we restricted the postintervention group to patients who actually received dementia care., Results: There was no association between a hospital's adoption of the incentive scheme and in-hospital mortality (adjusted odds ratio [aOR]: 0.97; 95% confidence interval [CI]: 0.88-1.06; p = 0.48) or 30-day readmission (aOR: 1.04; 95% CI: 0.95-1.14; p = 0.37). Only 29% of patients in hospitals adopting the scheme actually received dementia care. The sensitivity analysis showed that receiving dementia care was associated with decreased in-hospital mortality., Conclusions: The financial incentive scheme to enhance dementia care by dementia specialist teams in Japan may not be working effectively, but the results do suggest that individual dementia care was associated with decreased in-hospital mortality., (© 2021 John Wiley & Sons Ltd.)

Background Arterial stiffness is an important predictor of cardiovascular events; however, indexes for measuring arterial stiffness have not been widely incorporated into routine clinical practice. This study aimed to determine whether the cardio-ankle vascular index (CAVI), based on the blood pressure-independent stiffness parameter β and reflecting arterial stiffness from the origin of the ascending aorta, is a good predictor of cardiovascular events in patients with cardiovascular disease risk factors in a large prospective cohort. Methods and Results This multicenter prospective cohort study, commencing in May 2013, with a 5-year follow-up period, included patients (aged 40‒74 years) with cardiovascular disease risks. The primary outcome was the composite of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. Among 2932 included patients, 2001 (68.3%) were men; the mean (SD) age at diagnosis was 63 (8) years. During the median follow-up of 4.9 years, 82 participants experienced primary outcomes. The CAVI predicted the primary outcome (hazard ratio, 1.38; 95% CI, 1.16‒1.65; P <0.001). In terms of event subtypes, the CAVI was associated with cardiovascular death and stroke but not with myocardial infarction. When the CAVI was incorporated into a model with known cardiovascular disease risks for predicting cardiovascular events, the global χ 2 value increased from 33.8 to 45.2 ( P <0.001), and the net reclassification index was 0.254 ( P =0.024). Conclusions This large cohort study demonstrated that the CAVI predicted cardiovascular events. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01859897.

We clarified the relationship between occupational dysfunction and social isolation among community-dwelling adults. We used a self-administered questionnaire with a cross-sectional study for 2879 independently living older adults in Kasama City, Japan. Participants responded to a self-reported questionnaire in November 2019. Occupational dysfunction and social isolation were assessed. The participants were classified into two groups: healthy occupational function group, and occupational dysfunction group. To examine the relationship between occupational dysfunction and social isolation, we performed a logistic regression analysis with social isolation as a dependent variable and occupational dysfunction as an independent variable. In the crude model, the occupational dysfunction group had a higher risk of social isolation than the healthy occupational function group (odds ratio (OR) = 2.04; 95% confidence interval (CI), 1.63-2.55; p < 0.001). In the adjusted model, the occupational dysfunction group had a higher risk of social isolation than the healthy occupational function group (OR = 1.51; 95% CI, 1.17-1.94; p = 0.001). The results showed that occupational dysfunction was significantly associated with social isolation. These results can be used in constructing a support method for social isolation from a new perspective.

Aims: We compared the clinical outcomes of curved intertrochanteric varus osteotomy (CVO) with bone impaction grafting (BIG) with CVO alone for the treatment of osteonecrosis of the femoral head (ONFH)., Methods: This retrospective comparative study included 81 patients with ONFH; 37 patients (40 hips) underwent CVO with BIG (BIG group) and 44 patients (47 hips) underwent CVO alone (CVO group). Patients in the BIG group were followed-up for a mean of 12.2 years (10.0 to 16.5). Patients in the CVO group were followed-up for a mean of 14.5 years (10.0 to 21.0). Assessment parameters included the Harris Hip Score (HHS), Oxford Hip Score (OHS), Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ), complication rates, and survival rates, with conversion to total hip arthroplasty (THA) and radiological failure as the endpoints., Results: There were no significant differences in preoperative and postoperative HHS or postoperative OHS and JHEQ between the BIG group and the CVO group. Complication rates were comparable between groups. Ten-year survival rates with conversion to THA and radiological failure as the endpoints were not significantly different between groups. Successful CVO (postoperative coverage ratio of more than one-third) exhibited better ten-year survival rates with radiological failure as the endpoint in the BIG group (91.4%) than in the CVO group (77.7%), but this difference was not significant (p = 0.079)., Conclusion: Long-term outcomes of CVO with BIG were favourable when proper patient selection and accurate surgery are performed. However, this study did not show improvements in treatment results with the concomitant use of BIG. Cite this article: Bone Joint J  2021;103-B(4):665-671.

We clarified the effect of exercising with others on the risks of incident functional disability and all-cause mortality among community-dwelling adults. We used an inventory mail survey with a five-year follow-up for 1520 independently living older adults (mean age: 73.4 ± 6.3 years) in Kasama City, Japan. Subjects responded to a self-reported questionnaire in June 2014. Exercise habits and the presence of exercise partners were assessed. Subjects were classified into three groups: Non-exercise, exercising alone, and exercising with others. Follow-up information and date of incident functional disability and death during the five-year follow-up were collected from the database. To compare the association between exercise habits and functional disability and mortality, Cox regression analysis was conducted. Compared with the non-exercise group, exercising with others had significantly lower hazard ratios (HRs) for functional disability (0.59, 95% confidence interval (CI) 0.40-0.88) and mortality (0.40, 95% CI 0.24-0.66) in the covariate models. Compared with exercising alone, exercising with others decreased the HRs for incident functional disability (0.53, 95% CI: 0.36-0.80) and mortality (0.50, 95% CI 0.29-0.85) rates in the unadjusted model; these associations were not significant in the covariate models. Exercising with others can contribute to functional disability prevention and longevity.

Objective The decision to perform medical or mechanical therapy in patients with aborted sudden cardiac death (ASCD) due to coronary spasm is controversial. The Japanese Circulation Society guidelines for the diagnosis and treatment of patients with coronary spastic angina mentioned that implantable cardioverter-defibrillator (ICD) is one option in patients with ASCD due to coronary spasm. We investigated the usefulness of spasm provocation tests under medications in five patients with ASCD due to coronary spasm. Methods We performed the spasm provocation tests under medications in five ASCD patients due to coronary spasm. Pharmacological spasm provocation tests, including five acetylcholine (ACh) tests, two ergonovine (ER) tests, and two ACh added after ER tests, were performed to estimate the effect of medications to suppressing the next fatal spasms. Results ACh tests under medications did not provoke spasm in one patient but did provoke in two patients. In the remaining two patients, neither the ACh test nor the ER test provoked spasm, but the ACh added after ER test induced a focal spasm in one coronary artery. We increased the medication dosage in four patients. An ICD was implanted in two patients, including one with refractory spasm and one with left main trunk spasm. One patient died due to pulseless electrical activity without ventricular fibrillation, while the remaining four patients survived. Conclusion Spasm provocation tests under medication in patients with ASCD due to coronary spasm may be an option when deciding on medical or mechanical therapy.

Background: We have previously reported on the prevalence of dietary supplements among college students; it was deduced that their intake of supplements increased according to their grade (i.e., 13.1% in the first grade to 20.5% in the sixth grade). We also reported that some students had experienced adverse events in Japan due to their intake of these supplements. However, awareness of dietary supplements among college students remains limited, even among pharmaceutical students. Being appropriately educated about them is important for pharmaceutical students, both for themselves as well as for their future careers as pharmacists., Methods: We conducted a lecture-based educational intervention about dietary supplements on 328 college students in Japan-184 from pharmaceutical science and 144 from environmental science or food and life science disciplines. The purpose of this study was to evaluate the effects of an educational intervention on college students' understanding of dietary supplements. The intervention involved a lecture that covered the quality of dietary supplements, how they differed from drugs, and a summary of their adverse events. The lecture was evaluated using a 14-question questionnaire. We then compared the pre- and post-intervention responses to the same questionnaire using a Wilcoxon signed-rank test. The questions were assessed using a Likert scale that ranged from "strongly agree" to "strongly disagree"; the latter being the preferred answer., Results: Before the intervention had taken place, the students' understanding of dietary supplements was shown to be deficient. Conversely, post-intervention, their knowledge levels had significantly improved, especially concerning agreement on whether "Dietary supplements are safe because they are just food items". Pre-intervention, 2.7% strongly agreed and 37.5% agreed; post-intervention, 1.2% strongly agreed and 15.6% agreed. On whether "Dietary supplements made from natural ingredients or herbs are safe", at the pre-intervention stage 2.8% strongly agreed and 44.0% agreed and post-intervention, 2.2% strongly agreed and 16.9% agreed. On whether "Dietary supplements made from food items are safe", 4.0% strongly agreed and 43.6% agreed pre-intervention and 0.9% strongly agreed and 16.6% agreed post-intervention. Despite there being a greater number of pharmaceutical students who had a correct understanding of dietary supplements before the intervention, these students still showed improvement after the lecture., Conclusion: An intervention in the form of a single educational lecture has the capacity to improve college students' understanding of dietary supplements. It is important for pharmacists to be appropriately educated about dietary supplements when they consult with patients. We will evaluate the long-term effects of the intervention on the alumni (pharmacists) in a subsequent study.

The aim of this cross-sectional study was to investigate the influence of replacing sedentary time with time engaged in one of two levels of physical activity on sleep quality using an isotemporal substitution model. The participants were 70 community-dwelling older Japanese adults (approximately 70% female). Physical activity types were measured using a triaxial accelerometer and categorized based on intensity as sedentary, light-intensity, and vigorous-intensity. The Pittsburgh Sleep Quality Index assessed subjective sleep quality. Objective sleep parameters were assessed using an actigraph. A series of multi-linear regression models analyzed the statistical relationships. Our findings showed that replacing 30 min of sedentary activity per day with an equal period of light-intensity physical activity significantly influenced sleep quality parameters. However, there was no significant difference in sleep quality when light-intensity activity was replaced with vigorous-intensity activity. Engaging in one activity type means less available time for other types of activity; habitual replacement of sedentary activity with light-intensity physical activity might have long-term benefits on the sleep quality of older people., (© 2019 John Wiley & Sons Australia, Ltd.)

Background: SYMPLICITY HTN-Japan is a prospective, randomized, controlled trial comparing renal denervation (RDN) with standard pharmacologic therapy for treatment of uncontrolled hypertension (HTN). Methods and Results: Patients enrolled had uncontrolled HTN, defined as office systolic blood pressure (SBP) ≥160 mmHg and 24-h ambulatory SBP ≥135 mmHg, on ≥3 antihypertensive drugs of maximally tolerated dose for at least 6 weeks prior to enrollment. Randomization was 1:1 to RDN or maintenance of current medical therapy (control). Patients were followed every 6 months post-randomization for up to 36 months. There were 22 patients randomized to RDN and 19 to control, and 11 patients were crossed over and received RDN at 6 months post-randomization. For the RDN group (n=22), office SBP reduction was -32.8±20.1 mmHg and office DBP reduction was -15.8±12.6 mmHg at 36 months post-procedure, both P<0.001. For the combined RDN and crossover group (n=33), office SBP reduction was -26.7±18.9 mmHg and office DBP reduction was -12.7±11.8 mmHg at 30 months post-procedure, both P<0.001. There were no procedural-, device- or treatment-related safety events through 36 months., Conclusions: SYMPLICITY HTN-Japan is the first randomized controlled trial to evaluate RDN in an Asian population. Despite the small number of enrollments, results show patients who received RDN therapy maintained SBP reduction out to 36 months.

Background: Screening for undiagnosed type 2 diabetes mellitus is recommended for Asian Americans with a body mass index ≥23. However, the optimal body mass index cut-off score for predicting the risk of diabetes mellitus in Japanese people is not well known. The aim of this study was to determine the best body mass index cut-off score for predicting insulin resistance and diabetes mellitus in the Japanese population., Methods: This study had two parts, a clinical investigation and a retrospective observational investigation. In the clinical part of the study, 58 participants (26 with type 2 diabetes mellitus and 32 non-diabetics) underwent a hyperinsulinemic-euglycemic clamp from which their glucose disposal rate was measured. For the retrospective part of the study, medical check-up data from 88,305 people in the Tottori Prefecture were analyzed for clinical evidence of diabetes mellitus. The optimal BMI cut-off scores for prediction of insulin resistance and diabetes mellitus were determined., Results: In the clamp study, the optimal body mass index cut-off score to predict insulin resistance in non-diabetic patients was 22.7. All participants with type 2 diabetes mellitus were insulin resistant, and the optimal body mass index cut-off score for prediction of severe insulin resistance was 26.2. When the data from the type 2 diabetic and the non-diabetic participants were combined, the optimal body mass index cut-off score for prediction of insulin resistance was 23.5. Analysis of 88,305 medical check-up records yielded an optimal body mass index cut-off score for prediction of diabetes mellitus of 23.6., Conclusions: These results suggest that having a body mass index ≥23 is a risk factor for insulin resistance and diabetes mellitus in the Japanese population., Competing Interests: The authors have declared that no competing interests exist.

Arrhythmias are associated with reduced quality of life and poor prognosis in patients with hypertrophic cardiomyopathy (HCM). Recent genome-wide association studies revealed that a nonsynonymous single nucleotide polymorphism, rs6795970, in the SCN10A gene was associated with the PR interval. We examined whether the PR prolonging allele (A allele) in the SCN10A gene may be associated with cardiac conduction abnormalities in HCM patients.We genotyped the polymorphism in 149 HCM patients. Conduction abnormalities were defined as first-degree heart block, bundle-branch block, and bifascicular heart block. Patients were divided into two groups: group A consisted of 122 patients (82%) without a conduction abnormality; and group B consisted of 27 patients (18%) with one or more cardiac conduction abnormalities. The frequency distribution of the SCN10A genotypes (G/G, G/A, and A/A) among the patients with HCM was 71%, 26%, and 3%, respectively. A cardiac conduction abnormality was documented in 9% with G/G and 40% with G/A or A/A. There was a significant difference in the genotype distribution between the two groups (P = 0.0002). In the dominant A allele model, there was a significant difference in genotypes between the two groups (P < 0.0001). In addition, the A allele remained significant after adjusting for other covariates in a multivariate model (odds ratio = 6.30 [95% confidence interval: 2.24 to 19.09], P = 0.0005).The rs6795970 in the SCN10A gene, which is reported to carry a high risk of heart block, might be associated with cardiac conduction abnormalities in HCM patients.

Background: SYMPLICITY HTN-Japan is a prospective, randomized, controlled trial comparing renal artery denervation (RDN) with standard pharmacotherapy for treatment of resistant hypertension (systolic blood pressure [SBP] ≥160 mmHg on ≥3 anti-hypertensive drugs including a diuretic for ≥6 weeks). When SYMPLICITY HTN-3 failed to meet the primary efficacy endpoint, the HTN-Japan enrollment was discontinued before completion. METHODS AND RESULTS: The 6-month change in office and 24-h ambulatory SBP were compared between RDN (n=22) and control (n=19) subjects. Mean baseline office SBP was 181.0±18.0 mmHg and 178.7±17.8 mmHg for the RDN and control groups, respectively. The 6-month office SBP change was -16.6±18.5 mmHg for RDN subjects (P<0.001) and -7.9±21.0 mmHg for control subjects (P=0.117); the difference between the 6-month change in RDN and control subjects was -8.64 (95% CI: -21.12 to 3.84, P=0.169). Mean 24-h SBP was 164.7±18.3 (RDN group) and 163.3±17.2 mmHg (control group). The 24-h 6-month SBP change for the RDN group was -7.52±11.98 mmHg (P=0.008) and -1.38±10.2 mmHg (P=0.563) for control subjects; the between-group difference in SBP change was -6.15 (95% CI: -13.23 to 0.94, P=0.087). No major adverse events were reported., Conclusions: SYMPLICITY HTN-Japan, the first randomized controlled trial of RDN in an Asian population, was underpowered for the primary endpoint analysis and did not demonstrate a significant difference in 6-month BP change between RDN and control subjects.

Objective: We investigated associations of walking and other leisure-time physical activity (LTPA) with environmental characteristics and transportation modes in older Japanese adults., Methods: This cross-sectional study in 2010-2011 used data from 421 community-dwelling older adults aged 65-85 years living in Kasama City, rural Japan. We used the Physical Activity Scale for the Elderly to assess walking and other LTPAs, and the International Physical Activity Questionnaire Environment Module for neighborhood environments., Results: After adjusting for confounders, we found that good traffic safety and aesthetics were positively associated with high levels of walking (ORs=1.64-2.12); whereas, good access to public transportation was negatively associated with walking (OR=0.64, 95% CI=0.42-0.98). Good access to recreational facilities, presence of sidewalks, absence of hills, seeing people exercise, and aesthetically pleasing surroundings were positively associated with high levels of LTPA except walking (ORs=1.61-2.13). Individuals who rode bicycles more than once per week were more likely to engage in a LTPA except walking (1-3 days: OR=1.72, 95% CI=1.03-2.87; ≥4 days: OR=2.90, 95% CI=1.71-4.93)., Conclusion: This study adds information on correlates of physical activity among older Japanese adults; the positive association between LTPA except walking and the frequency of bicycle travel is an especially new and intriguing finding., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to examine intervention effects of a community-based prevention program for pre-frail elderly individuals by comparing an intervention group (exercise with nutritional care) with a control group (exercise without nutritional care)., Methods: The study was conducted in Y town and S city in Ibaraki Prefecture in Japan. The subjects comprised 161 pre-frail elderly individuals in the community-based prevention program, who were divided into two groups, the intervention group (N = 81, Y town, mean age : 76.2 +/- 5.7 years), and the control group (N = 81, S city, mean age 76.2 +/- 4.7 years). The items surveyed included age, gender, activities of daily living, functional capacity, and dietary variety score (DVS). Functional fitness measurement items (grip strength, alternate step, 5-repetition sit-to-stand, one-leg balance with eyes open, tandem stance, functional reach (FR), sit and reach, 5-m habitual walk, and timed up and go (TUG)) and blood data were assessed at the beginning and end of the intervention., Results: The DVS of the intervention group was significantly improved compared to that of the control group (P < 0.01). In particular, the food frequencies of fish and shellfish, meat, eggs, milk, fruits, and fat and oil (P < 0.01) were significantly increased in the intervention group, as were those of soybean products, seaweed, and potatoes (P < 0.05). On the other hand, significant increases were seen only in the frequencies of fish and shellfish, meat, and milk in the control group. The intervention group showed significant improvement in five-repetition sit-to-stand, tandem stance, FR, sit and reach, and TUG by the end of the intervention. In addition, the intervention group's performance on one-leg balance with eyes open (P < 0.05) was significantly improved even after adjusting for age, gender, and the functional fitness measurement items which were different at the beginning of the study., Conclusion: This study suggests that a combined exercise and nutrition program for pre-frail elderly individuals improves their food intake and functional fitness.

Aim: The purpose of this study was to cross-sectionally examine the relationships among leisure, household and occupational physical activity with the frequency of going out by various transportation modes, depression and social networks in older adults., Methods: We randomly selected a total of 2,100 community-dwelling adults aged 65 to 85 years of age from the Basic Resident Register. Of these, 340 people were the subjects of this study. The scales of measurement used were the Physical Activity Scale for the Elderly, the Lubben Social Network Scale (LSNS) and the Geriatric Depression Scale (GDS)., Results: In a regression model, leisure-time physical activity significantly correlated with frequency of going out by bicycle (β=0.17) and LSNS score (β=0.17). Household physical activity and occupational physical activity were significantly correlated with LSNS score (β=0.21) and frequency of going out by motor vehicle (β=0.25), respectively. For total physical activity, in the 3 above-mentioned activities a significant correlation was observed among frequency of going out by bicycle (β=0.10), by motor vehicle (β=0.23), GDS score (β=-0.16) and LSNS score (β=0.23)., Conclusion: These results indicate that the frequency of going out by bicycle and by motor vehicle were significant factors to predict leisure and occupational physical activity. Furthermore, social networks appear to be important determiners in leisure and household physical activity in community-dwelling older adults.

Background: The association of elevated serum uric acid (UA) with cardiovascular events in patients with severe coronary artery stenosis was examined., Methods and Results: Patients with stenosis > or = 75% (n=8,832) were followed for "all events" (cardiovascular events and all-cause mortality) for 3 years. The group was divided into quartiles based on baseline UA level. The incidence rate of all events was significantly different among quartiles (58.3, 56.5, 61.2, 76.3/1,000 patients-year, P<0.001). Cox's proportional hazard regression analysis showed that the hazard ratio (HR) for all events was 1.25 [95% confidence interval (CI): 1.07-1.45, P<0.01] in the highest quartile (UA > or = 6.8 mg/dl). The group in which UA increased > or = 1.0 mg/dl after 6 months had significantly higher cardiovascular events rate than the group in which UA did not change (70.6 vs 58.8/1,000 patients-year, P=0.042). Propensity score matching was performed and 4,206 patients were divided into the highest quartile and the rest. High UA remained an independent predictor of all events (HR 1.25, 95%CI 1.06-1.43). However, no significant difference was observed between the group with increased UA > or = 1.0 mg/dl and the group with unchanged UA level., Conclusions: Elevated UA is an independent predictor of cardiovascular events and all-cause mortality combined in patients with coronary artery stenosis.

Objective: Although a 5%-10% loss in the baseline weight has been associated with improvement in obesity-related disorders, only a few studies have explored the factors to alleviate metabolic syndrome (MS). This study aimed to determine the factors that alter MS components in overweight Japanese women., Methods: Between 1999 and 2006, 323 Japanese women aged 24-67 with body mass indices of 25-40 kg/m(2) and the presence of at least 1 component of MS were recruited from Ibaraki and Chiba. The participants were enrolled in a 3-month weight-loss program with a low-calorie diet with or without exercise. The factors to alleviate MS components were explored using classification and regression tree (CART) analyses., Results: Of the 323 participants, 309 completed the weight-loss program and were included in the analyses. The CART analyses revealed that a weight reduction of 8.1% in baseline body weight was sufficient to improve at least 1 component of MS. Similarly, classification trees were generated for improvement in abdominal obesity (essential factor: > or =13.0% weight loss), hypertension (essential factor: baseline age, < or =41.5 years), and hyperglycemia (essential factor: > or =13.2% weight loss)., Conclusion: These results suggest that moderate weight loss of 8%-13% contributes to improving the MS components in overweight Japanese women.

Objective: The objective was to test effects of aerobic exercise training on metabolic syndrome (MetSyn) improvement in response to weight reduction., Research Methods and Procedures: A total of 459 overweight and obese women (age, 49 +/- 9 years; BMI, 28 +/- 3 kg/m(2)) were recruited for a baseline examination to test the relationship between cardiorespiratory fitness and metabolic syndrome prevalence; among these, 67 subjects with MetSyn were treated with 14-week weight-loss programs, which included low-calorie diet and aerobic exercise. The MetSyn was defined according to the Examination Committee of Criteria for "Metabolic Syndrome" in Japan. Maximal oxygen uptake (Vo(2max)) during a maximal cycling test was measured as an index of cardiorespiratory fitness at baseline and after the intervention., Results: In the baseline examination, age- and BMI-adjusted odds ratios for MetSyn prevalence in the low, middle, and upper thirds of Vo(2max) were 1.0 (referent), 0.50 (95% confidence interval, 0.26 to 0.95), and 0.39 (95% confidence interval, 0.14 to 0.96), respectively (linear trend, p = 0.02). The adjusted odds ratios for MetSyn improvement in the two interventions with diet alone and diet plus exercise were 1.0 and 3.68 (95% confidence interval, 1.02 to 17.6; p = 0.04), respectively., Discussion: These results suggest that adding aerobic exercise training to a dietary weight-reduction program further improves MetSyn (adjusted odds ratio, 3.68) in obese women, compared with diet alone. Further studies on an association between Vo(2max) change and MetSyn improvement are needed.

Background: The pulsatility index (PI) and resistive index (RI) are used as markers of peripheral vascular resistance. Recently intrarenal PI and RI were introduced for the evaluation of the severity of acute and chronic renal failure, as well as for the diagnosis of renal artery stenosis and kidney graft rejection. In the present study, we evaluated intrarenal PI and RI in patients with essential hypertension., Methods: Fifty-one patients with essential hypertension participated. The intima-media thickness (IMT) and mean diastolic (Vd) and systolic velocity (Vs) in the common carotid artery (CCA) were measured using ultrasound and Doppler flow methods. Relative diastolic flow velocity (Vd/Vs) was calculated as an assessment of CCA hemodynamics. Renal Doppler flow was obtained from the interlobar arteries in each of two kidneys. The mean PI ([peak systolic velocity--end-diastolic velocity]/mean velocity) and mean RI ([peak systolic velocity--end-diastolic velocity]/peak systolic velocity) were calculated., Results: Intrarenal PI and RI were positively correlated with IMT and negatively correlated with Vd/Vs in CCA, indicating that renal vascular resistance is related to carotid stiffness. A stepwise regression analysis revealed that age and pulse pressure were independently associated with intrarenal PI and RI., Conclusions: These results suggest that the measurement of PI and RI is useful for the evaluation of arterial stiffness in patients with essential hypertension.

Background and Aims: The purpose of this study was to compare the effects of exercise habituation (3-32 years, mean 13.2 years) on physical vitality among five different groups., Methods: One hundred and two independent, community-dwelling elderly Japanese men, aged 64.6 +/- 6.6 years, were recruited as subjects. The vital age test battery consisted of various coronary heart disease risk factors and physical fitness elements., Results: The results of analysis of variance revealed that vital age as an index of physical vitality was youngest in joggers (47.9 yr, N=18), intermediate in trekkers (55.8 yr, N=20) and walkers (59.1 yr, N=18), and oldest (69.6 yr, N=20) in patients with ischemic heart disease (IHD). The difference between chronological age and vital age was approximately 15 years (p<0.05) in joggers, and 8 years (p<0.05) in trekkers and walkers. The vital age of sedentary persons (N=26) was only 1.9 years (NS) younger than their chronological age, which was similar to the difference (vital age of 64.1 +/- 8.5 yr vs chronological age of 65.7 +/- 5.4 yr) previously observed in similarly aged exercising IHD patients., Conclusions: These results indicate that exercise habituation significantly affects the overall health status of most individuals, irrespective of mode of exercise. Among the three modes of exercise, jogging may be most beneficial. Furthermore, regularly exercising coronary patients may have physical vitality similar to that of sedentary men.

Although polymorphism of the mitochondrial DNA 15497guanine/adenine (Mt15497G-->A) leads to the Gly251Ser amino acid replacement on human cytochrome b, it is unknown whether functional alteration of the mitochondrion is induced by the Gly251Ser replacement. To see if an association exists between the Mt15497G-->A polymorphism and obesity, we examined differences in body size, body composition, and regional body fat distribution between the two genotypes in middle-aged and elderly Japanese individuals (825 women and 906 men). The Mt15497 genotype was determined with an automated colorimetric allele-specific DNA probe assay system using the polymerase chain reaction (PCR) method. The Mt15497G-->A polymorphism was detected in 3.5% ( n=60) of all subjects: 2.8% ( n=23) among women and 4.1% ( n=37) among men. After adjusting for age and smoking, we found that body weight, body mass index, waist and hip circumferences, fat mass, fat-free mass, intra-abdominal fat and triglycerides were significantly greater in women with the A allele compared with the G allele ( p=0.001-0.025). For men, waist to hip ratio was significantly greater ( p=0.032), and waist circumference, intra-abdominal fat and triglycerides had a trend to be significantly greater ( p=0.062-0.087) in subjects with the A allele compared with the G allele. These data suggest that the Mt15497 polymorphism may be associated with obesity-related variables and lipid metabolism.

In 1986, the Niigata Registration Committee of Head and Neck Malignant Tumors was established by otolaryngologists in Niigata Prefecture to register cases of head and neck malignancies. Between 1986 and 1999, 4,053 cases were registered and we epidemiologically analyzed them. Men accounted for 2,866 (70.7%) and women for 1,187 (29.3%). The mean age and standard deviation of the age at diagnosis were 63.4 and 12.4 in men and 59.5 and 16.0 in women. The larynx was the most common site (1,154 cases) in men, followed by the oral cavity (360 cases), hypopharynx (273 cases), mesopharynx (239 cases), and maxillary sinus (154 cases). The thyroid gland was the most common site (416 cases) in women, followed by the oral cavity (214 cases), nasal cavity and paranasal sinuses (excluding the maxillary sinus) (76 cases), salivary glands (72 cases), and mesopharynx (71 cases). The site with the highest mean age was the lip (71.3 years old) in men and the larynx (68.7 years old) in women. The thyroid gland showed the lowest mean age for both genders (men: 56.7, women: 53.6), and that markedly lowered the female mean age because the thyroid gland accounted for one third of all cases in women. Comparing our data to national statistics, the incidence of oral malignancy was almost half in our data. We concluded that, in Niigata Prefecture, the dental professions treated as many cases of oral malignancy as we did. A high gender ratio (male/female) was seen for the larynx (22.2), hypopharynx (4.3), and mesopharynx (3.4). It was more than 1 and less than 2 for the oral cavity, salivary gland, neck lymphoma, ear, and nasal cavity and paranasal sinuses (excluding the maxillary sinus). The thyroid gland showed the lowest gender ratio (0.3), which was the only female-dominant site. We concluded that many sites of malignant head and neck tumors have a lower gender ratio than previously anticipated.

Body fat distribution and abdominal fatness are indicators of risks for coronary heart disease. However, the relationships between resting energy expenditure (REE) and the body fat distribution or the abdominal fatness are unclear. We examined the relationships of REE with whole-body fat distribution (waist, hip and waist-to-hip ratio: WHR) and abdominal fatness (intra-abdominal fat: IF and subcutaneous fat: SF) after adjustment for body composition. 451 men and 471 women were subdivided into two groups, 40-59 years: middle-aged group and 60-79 years: elderly group. REE was measured by an indirect calorimetry system. Percentage of fat mass (%FM), fat mass (FM) and fat-free mass (FFM) were assessed by a dual-energy x-ray absorptiometry method. The IF area (IFA) and SF area (SFA) at the level of the umbilicus were measured using computed tomography. Circumference of waist and hip were measured in a standing position. The WHR, waist circumference and SFA did not significantly (p>0.05) associate with the REE after adjusting for FM, FFM and age in any of the groups. The adjusted REE was significantly and inversely correlated with hip (r=-0.159, p<0.05) and IFA (r=-0.131, p<0.05) in the elderly men. These results suggest that lower REE may contribute to greater hip and IFA rather than WHR and waist in elderly men.

The purpose of this study was to develop a simple and convenient indirect method for estimating maximal oxygen uptake (VO2max) and oxygen uptake at the anaerobic threshold (VO2AT) by using workrate and a rating of perceived exertion (RPE) during a submaximal graded cycling test (GCTsubmax). One hundred and fifty-four healthy Japanese men, aged 20 to 64 years, volunteered to participate in the study. The subjects were randomly divided into two groups, a validation (V) group (n = 100) and a cross-validation (CV) group (n = 54). The V and CV groups performed a maximal cycling test and the GCTsubmax. The GCTsubmax was conducted with documentation of three categories (overall, chest, legs) of RPE, up to a rating of 15. Prediction equations of VO2max and VO2AT were developed by multiple regression analysis using data of the V group. The mean VO2max and VO2AT of the V group were 2462 +/- 484 ml.min-1 and 1349 +/- 334 ml.min-1, respectively. Correlational analyses indicated that the workrate (W) at which the legs RPE (RPElegs) reached 15 or higher was evaluated first (WRPE legs 15) together with WRPE legs 14 both yielded the highest correlation coefficients (r) with VO2max (r = 0.781) and V O2AT (r = 0.790), respectively. The developed prediction equations of VO2max and VO2AT were VO2max (ml.min-1) = 1.19 WRPE legs 15 (kgm.min-1) - 15.84 age (yr) + 13.06 weight (kg) + 1365 (R = 0.849, SEE = 261 ml.min-1) VO2AT (ml.min-1) = 1.34 WRPE legs 14 (kgm.min-1) - 5.49 age (yr) + 665 (R = 0.816, SEE = 195 ml.min-1) Results of a cross-validation analysis indicated a similar estimation (r = 0.793 and 0.853, and SEE = 240 ml.min-1 and 183 ml.min-1) compared with the above equations developed from data of the V group. Reliability coefficients of V O2max (r = 0.891) and VO2AT (r = 0.870) respectively were significant and there was no difference in the mean value between trials 1 and 2. The "RPE method" developed for estimating cardiorespiratory fitness is not only a unique indirect method but also a valid and useful tool in various settings of exercise prescription.

Despite its beneficial role in host defense mechanisms, excessive nitric oxide (NO) production by activated macrophages has been implicated in several inflammatory diseases. To clarify the mechanisms of anti-inflammatory activities of Polygonum tinctorium, we evaluated whether extracts of P. tinctorium could modulate the production of NO by activated macrophages. An AcOEt extract of P. tinctorium markedly inhibited NO synthesis by interferon-gamma (IFN-gamma)/lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages and the macrophage-like cell line RAW 264.7 in a dose-dependent manner. Inhibition of NO synthesis was achieved by reducing inducible NO synthase (iNOS) expression at protein and mRNA levels. However, the AcOEt extract of P. tinctorium failed to inhibit NO synthesis when iNOS was already expressed following stimulation with IFN-gamma and LPS. The AcOEt extract also exhibited inhibitory activity on iNOS expression in human lung epithelial A549 cells stimulated with a combination of IFN-gamma, TNF-alpha and IL-1 beta without affecting the expression of constitutive isoforms of NOS. Furthermore, in vivo injection of the AcOEt extract of P. tinctorium into LPS-treated mice significantly reduced NO synthesis by peritoneal exudate cells under ex vivo conditions. These results suggest that P. tinctorium extract may be a potential therapeutic modulator of NO synthesis in various pathological conditions.

Association between angiotensin-converting enzyme (ACE) gene polymorphism and essential hypertension in a Japanese population with the same socioeconomic background was investigated. Insertion-deletion (I/D) polymorphism of the ACE gene located on intron 16 was detected by polymerase chain reaction. Association between ACE gene polymorphism and family history of essential hypertension as well as the development of vascular damage in eye fundi were also investigated. Variation at ACE loci did not contribute to essential hypertension and the vascular damages in eye fundi. These results suggest that the ACE gene was not directly responsible for essential hypertension in this particular Japanese population with the same socioeconomic background.

1. Human renin gene restriction fragment length polymorphisms (RFLP) were compared in a Japanese family which has a high incidence of essential hypertension. 2. RFLP of human renin gene were observed in three restriction enzymes, Mbo I, Bgl I and Hind III; 1.4 kb and 1.0 kb [Mbo I], 5.0 kb and 9.0 kb [Bgl I] and 9.0 and 6.2 kb [Hind III]. 3. Plasma renin activity was not associated with blood pressure. 4. Renin gene RFLP were not cosegregated with essential hypertension in this Japanese family.