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INTRODUCTION: The clinical dose of telmisartan necessary for activation of peroxisome proliferator-activated receptor gamma (PPAR-gamma) has not been established. The authors investigated the effect of high-dose telmisartan on serum levels of the high-molecular-weight (HMW) adiponectin in patients with diabetes and hypertension. METHODS: In this open-label, prospective, randomized study, patients with type 2 diabetes and hypertension with poor control of blood pressure by 40 mg/day telmisartan were randomly assigned into the telmisartan 80 mg/day (Tel80) group (dose increase from 40 to 80 mg/day) or the telmisartan 40 mg + amlodipine 5 mg (Tel40 + Aml5) group. Serum levels of HMW adiponectin and parameters of glucose and lipid metabolism were measured at baseline and end of 3-months of treatment. RESULTS: Although the antihypertensive effects of the two doses of telmisartan were similar, a significant increase in HMW adiponectin levels was noted only in the Tel80 group. The increase was evident particularly in a group of patients whose HMW adiponectin levels were less than 4.0 ?g/dL. A significant improvement in homeostasis model assessment of insulin resistance (HOMA-IR), a measure of insulin resistance, was also observed in the Tel80 group only. CONCLUSIONS: In diabetic patients with hypertension, high-dose telmisartan increased HMW adiponectin levels and improved insulin resistance through activation of PPAR-gamma. [ABSTRACT FROM AUTHOR]

Background: Combination therapy with the oral fluoropyrimidine anticancer drug S1 and interferon is reportedly effective for the treatment of advanced hepatocellular carcinoma (HCC), but selection criteria for this therapy have not been clarified. In this study, we attempted to identify factors predicting the effectiveness of this combination therapy.Methods: Pathological specimens of HCC were collected before treatment from 31 patients with advanced HCC who underwent S1+ pegylated-interferon (PEG-IFN) α-2b therapy between January 2007 and January 2009. In these pathological specimens, the expression levels of CD133, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and interferon-receptor 2 (IFNR2) proteins were determined by Western blot assay. The presence or absence of p53 gene mutations was determined by direct sequencing. The relationships between these protein expression levels and the response rate (RR), progression-free survival (PFS), and overall survival (OS) were evaluated.Results: The CD133 protein expression level was significantly lower in the responder group than in the nonresponder group. Comparing the PFS and OS between high- and low-level CD133 expression groups (n = 13 and 18, respectively) revealed that both parameters were significantly prolonged in the latter group. The expression levels of TS, DPD, and IFNR2 protein and the presence of p53 gene mutations did not correlate with the RR.Conclusions: CD133 was identified as a predictor of the therapeutic effect of S1+ PEG-IFN α-2b therapy against advanced HCC. [ABSTRACT FROM AUTHOR]

Objective: We assessed the effects of a 2-day in-hospital diabetes educational program in preventing or delaying progression of impaired glucose tolerance (IGT) to type 2 diabetes, including analysis of changes in serum lipids, body weight, and blood pressure after the program.Research Design and Methods: A total of 426 subjects (51 +/- 9 years, BMI 24.6 +/- 3.9 kg/m(2)) with newly diagnosed IGT were randomly assigned to three groups, 143 as the short-term hospitalization with diabetes education and support (STH) group, 141 as the nonhospitalization but diabetes education and support (DES) group, and 142 as the neither hospitalization nor education (control) group.Results: The average follow-up was 3.1 years. The incidence of diabetes was 8.0, 10.7, and 13.2 cases per 100 person-years for STH, DES, and control groups, respectively. The incidence of diabetes was 42% lower (95% CI 33-51%) in the STH group and 27% lower (15-37%) in the DES group than in the control group. The incidence of diabetes was 21% lower (10-31%) in the STH group than in the DES group.Conclusions: The 2-day in-hospital program with diabetes education and support every 3 months was more effective in preventing or delaying the progression from IGT to diabetes than only diabetes education and support every 3 months. [ABSTRACT FROM AUTHOR]

Introduction: With health promotion initiatives in small companies lagging behind those in larger corporations, strengthening health and productivity management in small companies through innovative strategies is an urgent priority. We hypothesized that an outreach strategy involving a public-private partnership would be beneficial for this purpose. The present study examines the implementation of a public-private partnership strategy in Yokohama City, Japan, assessing its impact on health and productivity management in small enterprises, focusing on implementation outcomes., Methods: As part of the Yokohama Linkworker Project (Y-Link Project), this study describes and examines a public-private partnership program in Yokohama City, Japan, involving the city's government and a private life insurance company. Trained insurance sales representatives served as "Linkworkers" for the program, reaching out to small enterprises in the city. These Linkworkers provided tailored support to these companies, assisting them with obtaining the "Yokohama Health and Productivity Management Certification" issued by the City of Yokohama authorities and collaborating with external entities to offer health promotion programs for employees. Program interventions took place from August to September 2020. The RE-AIM framework was utilized to evaluate the Project. Data were extracted from Linkworkers' activity records, certification records, the Linkworker survey, and follow-up surveys with participating companies at 6- and 18- months post-interventions., Results: Within 2 months, 71 Linkworkers visited 500 companies (50% were small firms, <50 employees). Among them, 224 (45%) enterprises received certifications, contributing to an increased regional certification rate. Linkworker-assisted companies tended to be significantly smaller in size. The odds ratios of implementing workplace health promotion programs in certified firms, compared to non-certified firms, were 4.09 (95% CI: 1.79-9.35) at 6 months and 2.31 (95% CI: 1.04-5.11) at 18 months. For small firms, the odds ratios were 6.87 (95% CI: 1.74-27.06) at 6 months and 3.42 (95% CI: 1.17-10.03) at 18 months. The certification retention rate at 24 months was 60%, irrespective of company size. Linkworkers perceived the outreach strategy as having a positive impact on their primary operations., Conclusion: The Y-Link Project's outreach strategy enhanced health and productivity management in small enterprises in Yokohama City, enabling long-term health promotion programs addressing program availability disparities related to company size., Competing Interests: The Meiji Yasuda Life Foundation of Health and Welfare, where YK, YF, KY, YM-N, TN, and TA work, receives donations from Company M. However, this organization is a public interest incorporated foundation under the jurisdiction of the Cabinet Office of the Japanese government and is obligated to conduct research activities for the public interest. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kai, Fujii, Takashi, Yoshiba, Muramatsu-Noguchi, Noda, Jindo, Kidokoro, Yajima, Kasuga and Arao.)

Background: The novel coronavirus disease 2019 (COVID-19) pandemic may have reduced opportunities for engaging in physical activity (PA) and increased sedentary behavior (SB) among workers. However, most previous studies used self-reported assessments. This study aimed to examine the changes in accelerometer-measured PA and SB from before to after COVID-19 outbreak among Japanese workers., Methods: This 1-year longitudinal study used data from the annual health check-ups of workers who lived in the Tokyo metropolitan area. Baseline and follow-up data were collected from June to November of 2019 and June to November of 2020, respectively. Participants were asked to wear the accelerometer on their hip during awake hours for at least 10 days in both the surveys. Before the analysis, considering the difference in wearing time, time spent in PA and SB were converted to the percentage of wearing time. To investigate the changes in PA or SB from before to during COVID-19 outbreak, paired t-tests were performed., Results: Of the 757 eligible participants, 536 were included in the analysis (70.8%). Participants' mean age was 53.3 years, 69.6% were female, and most were full-time employees. Time spent in PA decreased, regardless of weekdays or weekends, although changes on the weekends were not significant. Conversely, time spent in SB increased on both weekdays and weekends in 2020. These changes corresponded to approximately 10 minutes per day decrease in PA and increase in SB., Conclusion: Objectively measured PA decreased and SB increased by approximately 10 minutes per day after the COVID-19 outbreak among Japanese workers.

Objectives　Japan has a high prevalence of low back pain among older adults requiring long-term care, which results in increasing expenses; therefore, prevention measures are necessary. This study aimed to examine the relationship between low back pain and physical activity and sitting time according to sex and age (65-74 years [young-old adults]; ≥75 years [old-old adults]) who had not received long-term care certification.Methods　A self-administered survey was mailed to 7,080 adults >65 years of age residing in Tsuru City (Yamanashi Prefecture, Japan) from January to February 2018, and had not received long-term care certification. Demographic information, health status (body mass index and medical history), lifestyle (dietary habits, alcohol consumption, and smoking), presence of low back pain, physical activity, sitting time, and social participation were measured. Low back pain was evaluated by asking, "Did you experience pain in parts of the body other than the knees for the past month?" Those who answered, "experienced low back pain" were categorized as "with low back pain". The short form of the International Physical Activity Questionnaire was used to assess physical activity, which was categorized into three groups: <150, 150-299, and ≥300 min/week. Sitting time was divided into two groups: <480 and ≥480 min/day. Multiple logistic regression analysis was used to determine the association between low back pain and physical activity and sitting time, according to sex and age.Results　Of the 7,080 individuals surveyed, 4,877 responded (2,217 male, 2,660 female), corresponding to a response rate of 68.9%. The number of older adults with low back pain was 1,542 (31.6%) including 673 (30.4%) males and 869 (32.7%) females. The rate of low back pain in young-old adults was 29.8% and 33.6% in old-old adults. There was no significant relationship between lower back pain and physical activity among the young-old adults. In the old-old adults, there was a significant relationship in the male ≥300 min group (odds ratio [OR] 0.66 [95%CI 0.48-0.89]), and in both female 150-299 (OR 0.69 [95%CI 0.48-0.99]) and ≥300 (OR 0.59 [95%CI 0.44-0.80]) min/week groups.Conclusion　The complaint rate for low back pain was approximately 30%, regardless of sex or age. These results suggest that interventions to prevent low back pain are necessary. Moreover, physical activity, but not sitting time, was associated with low back pain in both males and females among the old-old adults.

Background: It has not been determined whether mentally active sedentary behavior (MASB) and passive sedentary behavior (PSB) differentially affect cognitive function and whether these associations differ according to physical activity (PA) level. We examined the comparative impacts of MASB and PSB on dementia onset and aimed to understand whether the associations differed by PA level., Methods: We conducted a 5-year longitudinal study involving all community-dwelling older adults in a rural area in Japan (n = 5,323). Dementia onset was examined using long-term care insurance data. PA was evaluated using the International Physical Activity Questionnaire and categorized as low (<2.5 metabolic equivalent of task [MET]-h/week), moderate (2.5-16.0 MET-h/week), or high (≥16.0 MET-h/week). We also assessed PSB (TV-watching time; <1 h/day, 1-3 h/day, ≥3 h/day) and MASB (Book-reading time; <10 min/day, 10-30 min/day, ≥30 min/day). To examine the associations of MASB and PSB with dementia onset, we performed the Fine-Gray models accounting for competing risk of death., Results: During the follow-up period, 606 (11.4%) participants developed dementia. MASB was independently associated with a lower risk of dementia; the magnitude of the impact was significant at higher PA levels. There was no association between PSB and developing dementia across all PA levels. Furthermore, dementia risk for individuals with high PA levels and moderate or high MASB levels was approximately 60% lower than those with low PA levels and low MASB., Conclusion: Providing interventions to promote MASB, which reduces dementia risk, and PA, which increases MASB's effect on dementia incidence, can be beneficial in delaying or preventing dementia onset.

Objective In this study, we aimed to assess the safety and efficacy of the dose escalation of luseogliflozin (LUSEO) in type 2 diabetes mellitus (T2DM) patients with poor glycemic control. To that end, we compared two groups assigned to two different doses of luseogliflozin (LUSEO) for 12 weeks. Methods Patients with a hemoglobin A1c (HbA1c) level of 7% or higher already on treatment with luseogliflozin 2.5 mg/day for 12 weeks or longer were randomly assigned to either the 2.5-mg/day group (control group) or the 5-mg/day group (dose-escalation group) of luseogliflozin through the envelope method and were treated for 12 weeks. Blood and urine samples were collected at two different time points: at weeks 0 and 12 after randomization. The primary outcome was the change in HbA1c from the baseline to 12 weeks. The secondary outcomes were changes in the body mass index (BMI), body weight (BW), blood pressure (BP), fasting plasma glucose (FPG), lipid parameters, hepatic function, or renal function from the baseline to 12 weeks. Results Based on our findings, HbA1c levels significantly decreased in the dose-escalation group when compared to the control group (p<0.001) at week 12. Conclusion For T2DM patients with poor glycemic control under treatment with LUSEO at a dose of 2.5 mg, dose escalation of LUSEO to 5 mg safely improved glycemic control, and this might prove to be an effective and safe treatment option., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Arao et al.)

Objective: Previous studies have suggested a positive association between physical activity (PA) and executive function in older adults. However, they did not adequately consider the compositional nature of daily time use and accumulated PA patterns. Therefore, this study aimed to examine the association between intensity or accumulated PA patterns and executive functions (inhibitory control, working memory, and cognitive flexibility) in community-dwelling older adults, considering the interaction of daily time spent in PA, sedentary behavior (SB), and sleep., Method: This cross-sectional study used baseline data from a randomized controlled trial on the effect of exercise on cognitive function conducted between 2021 and 2022. Data from 76 community-dwelling older adults were used in the analysis. The time spent in PA and SB was assessed using an accelerometer, and sleep duration was self-reported. The Stroop task (inhibitory control), N-back task (working memory), and task-switching task (cognitive flexibility) were conducted to evaluate the subcomponents of executive function. Considering various potential confounders, compositional multiple linear regression analysis and compositional isotemporal substitution were performed to examine the association of PA with executive function and to estimate predicted changes in executive function in response to the hypothetical time-reallocation of movement behaviors, respectively., Results: A longer time spent in light-intensity PA (LPA), relative to remaining behaviors, was associated with better Stroop task performance. Moreover, this association was stronger in LPA lasting longer than 10 min than in sporadic LPA. Additionally, theoretical 30 min/day time reallocation from SB or sleep to LPA was associated with better Stroop task performance (corresponding to approximately a 5%-10% increase). On the other hand, no significant associations of time spent in moderate- to vigorous-intensity PA with any subcomponents of executive function were observed., Conclusion: LPA was positively associated with inhibitory control, and this association was stronger in bouts of LPA than in sporadic LPA. Moreover, reducing the time spent in SB or sleep and increasing the time spent in LPA, especially long-bout LPA, could be important measures for managing inhibitory control in late life. Future large longitudinal and intervention studies are needed to confirm these associations and reveal the causality and underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hyodo, Kitano, Ueno, Yamaguchi, Watanabe, Noda, Nishida, Kai and Arao.)

Background: During the COVID-19 epidemic, opportunities for social interaction and physical activity among older people are decreasing, which may have a negative impact on their health. As a solution, a web-based group exercise program provided through a videoconferencing platform would be useful. As a web-based exercise program that older adults can easily, safely, and enjoyably perform at home, we developed a short-duration, light-intensity aerobic dance exercise program. Before studying the effectiveness of this exercise program, its characteristics, such as feasibility, safety, enjoyment, and system usability, should be examined among older adults., Objective: This pilot study aimed to examine the feasibility, safety, and enjoyment of a web-based aerobic dance exercise program and the usability of a web-based exercise delivery system using a videoconferencing platform for older adults., Methods: This study was designed as a prospective single-arm pilot study. A total of 16 older adults participated in an 8-week web-based aerobic dance program held every morning (8:30 AM to 8:50 AM) on weekdays at home. Retention and adherence rates were measured for the program's feasibility. Safety was assessed by the heart rate reserve, an index of exercise intensity calculated from heart rate, and the number of adverse events during exercise sessions. Enjoyment of this exercise program was assessed by an 11-point Likert scale ranging from 0 (not enjoyable at all) to 10 (extremely enjoyable) obtained through telephone interviews after the first-, third-, sixth-, and eighth-week intervention. For usability, the ease of the videoconferencing platform system was assessed through telephone interviews after the intervention., Results: A female participant with hypertension dropped out in the second week because of the continuously reported high blood pressure (≥180 mmHg) before attending the exercise session in the first week. Therefore, the retention rate was 93.8% (15/16). Among the remaining participants, the median (IQR) overall adherence rate was 97.4% (94.7-100). Regarding safety, the mean (SD) heart rate reserve during the aerobic dance exercise was 29.8% (6.8%), showing that the exercise was relatively safe with very light to light intensity. There were no adverse events during the exercise session. The enjoyment score (0-10 points) significantly increased from the first (6.7 [1.7]) to sixth (8.2 [1.3]) and eighth week (8.5 [1.3]). Regarding usability, 11 participants reported difficulties at the beginning, such as basic touch panel operations and the use of unfamiliar applications; however, all got accustomed to it and subsequently reported no difficulty., Conclusions: This study showed high feasibility, enjoyment, and safety of the web-based aerobic dance exercise program in older adults, and the web-based exercise delivery system may have areas for improvement, albeit without serious problems. Our web-based aerobic dance exercise program may contribute to an increase in physical and social activities among older adults., (©Kazuki Hyodo, Tetsuhiro Kidokoro, Daisuke Yamaguchi, Michitaka Iida, Yuya Watanabe, Aiko Ueno, Takayuki Noda, Kenji Kawahara, Sumiyo Nishida, Yuko Kai, Takashi Arao. Originally published in JMIR Aging (https://aging.jmir.org), 16.01.2023.)

Aim: This study examined the relationship between continuity of social participation and progression of frailty among community-dwelling older adults, by baseline frailty level., Methods: This study was part of a 3-year community-based cohort study among adults aged ≥65 years, living independently in a rural municipality in Japan. Mail surveys were carried out in 2016, 2018 and 2019. This study involved 2799 participants who responded to the question about social participation in every survey. Frailty was evaluated by Kihon Checklist total scores. Social participation was categorized into consistent non-participation, interrupted recent non-participation, interrupted recent participation and consistent participation. We assessed the relationship between social participation and change in frailty scores using general linear regression analysis, stratifying the participants into groups by their frailty level at baseline., Results: There was a smaller frailty score increase in the robust (β -0.61, 95% CI -0.99 to -0.22) and prefrail groups (β -0.73, 95% CI -1.18 to -0.27) for consistent participation than consistent non-participation. Interrupted recent participation showed significant suppression in the prefrail group (β -0.96, 95% CI -1.60 to -0.32). Social participation had no clear effect on progression in the frail group., Conclusions: Consistent social participation might reduce the progression of frailty in robust and prefrail people. Inconsistent participation might also help to reduce progression in prefrail older adults. It is important for prefrail older adults to return to their social activities and continue to engage as long as possible, even if their participation was intermittent in the past. Geriatr Gerontol Int 2023; 23: 25-31., (© 2022 Japan Geriatrics Society.)

Objective: Previous studies have reported opposite effects of occupational or non-occupational physical activity (PA) and sedentary behavior (SB) on health outcomes. However, no study has investigated the relationship between domain-specific movement behaviors and cardiometabolic health (CMH) among office workers, considering the compositional nature of time-use data. We investigated the associations of accelerometer-measured PA and SB for each domain (working time, non-working time on workday, and non-workday) with CMH indicators among office workers, using compositional data analysis., Methods: This cross-sectional study included 1258 Japanese office workers. The time spent on SB, light-intensity PA (LPA), and moderate- to vigorous-intensity PA (MVPA) were assessed using an accelerometer. CMH indicators were retrieved from the annual health check-up data., Results: Compositional multiple linear regression indicated that PA and SB during non-working time on workdays, but not working time or non-workdays, were significantly associated with CMH. In particular, during non-working time, time reallocations from SB to LPA and from SB to MVPA were associated with favorable changes in cardiometabolic risk score and lipid metabolism, respectively. Paradoxically, a greater proportion of LPA during non-working time was associated with favorable diastolic blood pressure (β = 1.61; 95% confidence interval [CI] = 0.02, 3.19), whereas occupational LPA was detrimental (β = -2.48; 95% CI = -4.87, -0.09)., Conclusion: Our results suggested that reducing SB and increasing PA during non-working time on workdays may be effective for managing CMH among office workers. Future longitudinal studies using compositional data analysis are required to confirm our results., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To clarify the association between moderate-to-vigorous physical activity (MVPA) and/or sedentary behaviour (SB) and the incidence of functional disability (FD) in older adults., Design: Prospective cohort study., Setting: Local municipality of Tsuru, Yamanashi, Japan. We conducted a baseline survey in January 2016. Follow-up was commenced on 1 February 2016 and completed on 31 October 2018., Participants: All individuals (6661 people) aged >65 years who were independently living in the community were eligible., Methods and Outcome Measures: MVPA (min/week) and SB (min/day) were measured using self-administered questionnaires in 5311 independently living older adults who participated in this study. The follow-up period was 33 months, and the incidence of FD was objectively determined by experts. The participants were divided into three groups based on MVPA distribution (non-MVPA, 0 min; short-MVPA, 1-299 min and long-MVPA, ≥300 min/week) and into two groups based on the median value of SB (short-SB,<190 min; and long-SB, ≥190 min/day). The participants were also classified into six categories based on different combinations of MVPA and SB. Cox proportional hazards model was used to calculate the HR and 95% CI for FD development with MVPA, SB and a combination of these behaviours., Results: Among the included participants, 2415 were male and 2896 were female. The mean ages (SD) of the male and female participants were 74.5 (6.8) and 74.9 (6.9) years, respectively. The total number of participants with chronic conditions was 3489 (65.7%). Using the non-MVPA group as the reference, the multivariable-adjusted HR (95% CI) was 0.68 (0.54 to 0.84) in the short-MVPA group and 0.53 (0.41 to 0.69) in the long-MVPA group. Regarding SB, the short-SB group had an HR of 0.86 (0.71 to 1.03) compared with the long-SB group. The combined behaviour showed the lowest HR in the long-MVPA and short-SB group 0.49 (0.34 to 0.72) and the long-MVPA and long-SB group 0.49 (0.34 to 0.68), respectively., Conclusions: Long-MVPA had a robust association with FD development, whereas short-SB had a modest association. Moreover, a combination of these behaviours had a stronger association than individual behaviours. If the identified associations are assumed to be causal in nature, these findings suggest that encouraging older adults to engage in MVPA and reduce SB in their daily lives could be effective to prevent or delay FD development., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To clarify the relationship between ambulatory glucose profile (AGP) indexes and standardized continuous glucose monitoring (CGM) metrics in patients with type 2 diabetes (T2D)., Methods: This is an exploratory, cross-sectional analysis of baseline data collected from a prospective, multicentre, 5-year follow-up observational study conducted and published previously by our group. The study participants were 999 outpatients with T2D who used CGM at baseline, and had no apparent history of cardiovascular disease. We investigated the relationship between average interquartile range (IQR) and time in range (TIR). We also calculated, for the first time, the cutoff values to achieve the TIR target values., Results: In both the TIR more than 70% and TIR more than 90% achievement groups, the average IQR was notably small compared with the non-achievement groups. Particularly in comparison of the TIR quartiles, the average IQR became significantly smaller as the TIR became larger. The average IQR correlated negatively with TIR, and the cutoff values for TIR of more than 70% achievement and TIR of more than 90% achievement were an average IQR (>70%/>90%) of 2.13/1.85 mmol/L., Conclusion: Our results showed a negative correlation between TIR and the range of blood glucose variations visually represented in AGP. The results also showed that the range of blood glucose variations in AGP is associated with indices of intraday and interday blood glucose variations and also with hypoglycaemia. Our results may provide new perspectives in the assessment and application of AGP in the clinical setting., (© 2021 John Wiley & Sons Ltd.)

Sarcopenia is associated with poor clinical outcomes in elderly patients with diffuse large B-cell lymphoma (DLBCL). However, the clinical significance and optimal assessment of sarcopenia remain unclear. We retrospectively evaluated the prognostic value of low skeletal muscle mass based on the psoas muscle index (PMI) in patients with DLBCL aged 70 years and older treated with R-CHOP therapy. We included 71 patients, including 27 classified under low PMI. There were no differences in baseline characteristics (body mass index, lactate dehydrogenase, performance status [PS], stage, revised-IPI, relative dose intensity) and overall response rate between the low and high PMI groups. The low PMI group had a significantly worse overall survival (OS, p=0.015), but not progression-free survival (PFS, p=0.252), compared with the high PMI group. On multivariate analysis, low PMI and PS were independent negative prognostic factors for OS. Subgroup analysis revealed that the low PS groups had significantly worse PFS regardless of the PMI status. The low PMI and low PS group had markedly poorer OS than all the other groups. However, the poor prognosis associated with low PS was overcome by a high PMI.

Aim: To clarify changes in location before hospital admission and discharge destination over the 10-year period of 2010 to 2020 and to identify prognostic factors associated with the survival in hospitals with chronic-phase inpatients., Methods: The subjects were patients newly admitted to 12 hospitals in 2010 and 2020. The age, sex, location before hospital admission, outcomes at 90 days after admission, discharge destination, and results of 6 biochemical tests at admission were evaluated. A survival analysis was performed for the age, sex, and biochemical tests at admission., Results: We analyzed 8007 newly hospitalized patients. Compared with 2010, there were more hospital admissions from acute-care hospitals and fewer admissions from long-term-care facilities in 2020. In addition, relative to 2010, regarding the outcomes at 90 days after admission, there were more discharges to home and residential facilities in 2020, fewer discharges to long-term-care facilities, and lower mortality rates. In the survival analysis, a multivariate analysis revealed that an elderly age, male sex, low albumin, high total cholesterol, high urea nitrogen, and low serum sodium were poor prognostic factors. These five variables were consistently poor prognostic factors in both 2010 and 2020, and Kaplan-Meier curves showed that the scores were dose-dependent prognostic factors for a poor survival., Conclusions: The present analysis of pre-admission location and discharge destination in hospitals with chronic-phase patients revealed an elderly age, male sex, high urea nitrogen, low serum sodium, and low albumin at the time of admission to be strong predictors of poor outcomes in these patients.

Background: Although a few studies have confirmed the association of accelerometer-measured sedentary behaviour (SB) and physical activity (PA) with non-alcoholic fatty liver disease (NAFLD), PA intensity and co-dependent daily time-use of movement behaviours are yet to be studied., Aims: To cross-sectionally examine the dose-response relationship between accelerometer-measured SB or PA and NAFLD using cubic spline analysis and the interdependence of movement behaviours over 24 hours with compositional data analysis., Methods: Data were obtained between May 2017 and February 2020 from 1914 people who were not heavy alcohol drinkers using health check-ups at the Meiji Yasuda Shinjuku Medical Center, Tokyo. SB, light-intensity PA (LPA) and moderate- to vigorous-intensity PA (MVPA) were evaluated using a triaxial accelerometer. Fatty liver was diagnosed by ultrasonography., Results: A multivariable-adjusted logistic model showed an inverse association between MVPA and NAFLD (odds ratio [OR] per 600 metabolic equivalents [MET]-min/week = 0.85, 95% confidence interval [CI] = 0.76-0.96). MVPA showed rapidly decreasing odds of NAFLD to approximately 1800 MET-min/week in cubic spline analysis and then a moderate decline. Although SB was significantly associated with NAFLD in a body mass index (BMI)-unadjusted model, it was not significant in a BMI-adjusted model. In the compositional isotemporal substitution, reallocating 60 min/day of SB to MVPA decreased the odds of NAFLD by 22% (OR = 0.78, 95% CI: 0.65-0.93), whereas reallocating 60 min/day of MVPA to SB increased it by 69% (OR = 1.69, 95% CI: 1.12-2.38)., Conclusions: The inverse dose-response association between MVPA and NAFLD confirms increased MVPA as a target for the prevention of NAFLD., (© 2021 John Wiley & Sons Ltd.)

Background: Most previous studies that examined the association of insomnia with frailty used cross-sectional designs. The temporal relationship between these factors is therefore largely unknown. This study aimed to examine the bidirectional relationship between insomnia and frailty by sex., Methods: A 2-year longitudinal study involving all community-dwelling older adults living in a rural area in Japan (n = 3844). Validated measures of insomnia and frailty were employed. Insomnia was assessed using the Athens insomnia scale, and frailty using the Kihon checklist. We performed a cross-lagged panel model, adjusted for age, sex, years of education, employment status, self-rated health, complications (hypertension, diabetes, stroke, or osteoarthritis), BMI, physical activity, alcohol consumption, and smoking status, and assessed differences by sex., Results: Poor sleep predicted the onset and worsening of frailty during follow up (standardized coefficient [95% confidence interval]: 0.076 [0.045, 0.107]). Frailty also predicted severe insomnia symptoms (0.074 [0.044, 0.104]). However, the temporal association between these conditions varied by sex. In older men, the effect of frailty on insomnia was stronger than that of insomnia on frailty. However, in women, the impact of insomnia on frailty was stronger than that of frailty on insomnia., Conclusions: The primary potential cause of the association between insomnia and frailty may vary by sex, being frailty in men and insomnia in women. Sex-specific interventions to improve sleep quality and duration, and maintain functional abilities in daily life may contribute to the prevention and management of both frailty and insomnia in older adults., (Copyright © 2021 Elsevier B.V. All rights reserved.)

There is a growing body of evidence suggesting that one bout of moderate-intensity exercise enhances executive functions in older adults. However, in terms of safety, feasibility, and continuity, older individuals prefer light, easy, and fun exercises to moderate and stressful exercises for improving executive functions. Therefore, light-intensity aerobic dance exercise (LADE) could be suitable if it produces potential benefits related to executive functions. As for continuous vs. intermittent exercise, intermittent exercise has received a lot of attention, as it results in greater effects on mood and executive functions than continuous exercise; however, its effects in older adults remain uncertain. Thus, in this study, we aimed to examine the acute effects of intermittent LADE (I-LADE) in comparison with those of continuous LADE (C-LADE) on mood and executive functions. Fifteen healthy older adults participated in 10-min I-LADE and C-LADE conditions on separate days. Perceived enjoyment following exercise was assessed using the Physical Activity Enjoyment Scale (PACES). The pleasantness of the mood during exercise and pleasure and arousal levels after exercise were assessed using the Feeling Scale and Two-Dimensional Mood Scale, respectively. Executive function was assessed using the Stroop task before and after exercise. As a result, pleasantness of the mood during exercise and exercise enjoyment levels were greater in I-LADE than in C-LADE. Arousal and pleasure levels and Stroop task performance increased after both LADEs and did not differ between the two exercise conditions. These findings suggest that although enhancement of mood and executive functions after exercise did not differ between C-LADE and I-LADE, I-LADE could be more enjoyable and fun than C-LADE. This study will help in the development of exercise conditions that can enable the elderly to enhance their executive functions in a fun way., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hyodo, Suwabe, Yamaguchi, Soya and Arao.)

Objectives　The aim of this study was to examine the effect of an exercise program targeting knee pain on longitudinal medical costs (MC) of elderly community-dwelling adults.Methods　A community-based health program using specific exercises for improving knee pain was held from January to February, 2015. Twenty-eight individuals participated in the program (intervention group) and seventy individuals were selected from the respondents of a health and lifestyle survey by matching age, sex, and baseline value of severity of knee pain as a control group. Twenty individuals from the intervention group and twenty-nine from the control group were included in the final analysis. The changes in MC from 2014 to 2018 were compared between the two groups using a linear mixed-effects model.Results　The effect of the program on MC, estimated as a change from the baseline in 2014, showed a reduction of -5.6×10 3 yen/person (95% CI: -39.2-28.0) for the entire four-year period after the intervention. However, this difference was not significant. The changes in MC each year after the intervention were 9.3×10 3 yen/person (95% CI: -39.6-58.3) in 2015, -2.0×10 3 yen/person (95% CI: -44.4-40.5) in 2016, -10.3×10 3 yen/person (95% CI: -42.5-21.9) in 2017, and 8.2×10 3 yen/person (95% CI: -39.1-55.4) in 2018.Conclusion　The exercise program did not show a clear benefit in reducing the MC of elderly community-dwellers during the four years after the intervention. Further research with longer study durations and larger sample populations would be necessary to determine the effect of such intervention programs on MC.

Objective: Ergonomic office redesigning possibly improves physical activity (PA) and sedentary behavior (SB); however, its impact on cardiometabolic risk has not yet been determined. This study aimed to examine the effect of office relocation on cardiometabolic risk factors., Methods: Annual health check-up data of 95 office workers from four offices in Tokyo, Japan, who relocated to an office with activity-based working (ABW) and height-adjustable desk (HAD) and a propensity-score matched control-cohort were analyzed. PA and SB on weekdays were measured only in the relocation group before and 10 months after relocation., Results: Significant interactions were observed for waist circumference, high-density lipoprotein cholesterol, and glycosylated hemoglobin (HbA1c). HbA1c changes showed a significant negative association with moderate-to-vigorous-intensity PA., Conclusion: An ABW office with HAD improves cardiometabolic risk factors in office workers, possibly through changes in PA and SB., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Background: Although social group engagement (SGE) has been suggested to affect physical activity (PA) in older age, the longitudinal relationship between these variables is unclear. This study used 2-year panel data to investigate the link between changes in SGE and changes in PA among community-dwelling older adults., Methods: This study was a 2-year community-based longitudinal study enrolling older adults living in a rural municipality in Japan. The subjects were all residents in the study area aged ≥ 65 at the baseline. Mail surveys were administered in 2016 and 2018. The 3688 subjects responding to both surveys were included in the analyses. PA was evaluated with the International Physical Activity Questionnaire, and weekly time and metabolic equivalent were computed. SGE was assessed in each wave and classified as consistent engagement (engagement reported in both surveys), new engagement (non-engagement at baseline and engagement at follow-up), leaving the group (engagement at baseline and non-engagement at follow-up), and consistent non-engagement (non-engagement in both surveys). Analysis of covariance was performed to examine the associations of changes in SGE with changes in PA., Results: Compared with those with consistent non-engagement, who showed declines in every PA category, subjects with consistent engagement or new engagement showed significantly smaller changes in total PA, moderate-intensity PA, and brisk walking. Leaving the group (vs. consistent non-engagement) was associated with maintaining moderate-intensity PA., Conclusions: SGE helps to suppress the age-associated decline in PA in older age, with new engagement and continuous engagement, especially, mitigating decreasing PA., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aquatic heavy metal pollution is a growing concern. To facilitate heavy metal monitoring in water, we developed transgenic Daphnia that are highly sensitive to heavy metals and respond to them rapidly. Metallothionein A, which was a metal response gene, and its promoter region was obtained from Daphnia magna. A chimeric gene fusing the promoter region with a green fluorescent protein (GFP) gene was integrated into D. magna using the TALEN technique and transgenic Daphnia named D. magna MetalloG were produced. When D. magna MetalloG was exposed to heavy metal solutions for 1 h, GFP expression was induced only in their midgut and hepatopancreas. The lowest concentrations of heavy metals that activated GFP expression were 1.2 µM Zn 2+ , 130 nM Cu 2+ , and 70 nM Cd 2+ . Heavy metal exposure for 24 h could lower the thresholds even further. D. magna MetalloG facilitates aqueous heavy metal detection and might enhance water quality monitoring.

This cross-sectional study investigated the relationship between 24-hour movement behaviors and mental health among Japanese workers, accounting for the co-dependence of time spent in different behaviors during a single day. This research is part of a prospective cohort study called the Meiji Yasuda LifeStyle study. Participants were 1095 workers in Tokyo, Japan, who underwent annual health check-ups between 2017 and 2018. Time use during workdays and non-workdays was separately evaluated. Behaviors included sleep (self-reported duration), sedentary behavior (SB), light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (assessed with a tri-axial accelerometer). We used the six-item Kessler Psychological Distress scale to evaluate psychological distress and the Utrecht Work Engagement Scale to assess work engagement as indicators for negative and positive mental health, respectively. We performed compositional logistic regression and compositional isotemporal substitution to examine associations between 24-hour movement behaviors and mental health. After controlling for potential confounders, time spent in workdays was significantly associated with higher psychological distress and lower work engagement ( p  < 0.05), respectively. Time spent sleeping was positively correlated with both mental health indicators, whereas time spent in SB or LPA was negatively correlated ( p  < 0.05). During workdays, higher psychological distress and lower work engagement were predicted to be 11.4-26.6% lower when 60 min/day of time spent sleeping were reallocated to SB or LPA. Reallocating time spent on SB or LPA to sleep during workdays may minimize psychological distress and optimize work engagement. Thus, proper time management focused on encouraging sleep may help improve workers' mental health., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Objective: This study evaluated the effect of a community-wide walking intervention (involving walking maps and events) on older residents' walking and environmental perceptions. Method: In this nonrandomized quasi-panel study, older adults living in an intervention and control site were recruited at baseline and follow-up. All households in the intervention site received maps and were invited to participate in a walking event monthly. The intervention lasted for 21 months. The outcomes were walking frequency, duration, and perceptions of local environments. Results: We did not find a significant improvement in walking frequency or duration in the intervention site relative to the control site. However, there was a significant increase in the awareness of others being active and a marginal increase in the perception of aesthetics in the intervention site. Discussion: The increased awareness of others being active may be a positive step in the stages of change toward engagement in physical activity.