Factors associated with dynamic changes in the objectively measured physical activity have not been well understood. We aimed to 1) evaluate the longitudinal change in the physical activity trajectory according to sex which is associated with age and to 2) determine the factors associated with the dynamic change in physical activity-related variables across a wide age range among Japanese adults. This longitudinal prospective study included 689 Japanese adults (3914 measurements) aged 26-85 years, whose physical activity data in at least two surveys were available. Physical activity-related variables, such as intensity (inactive, light [LPA; 1.5 to 2.9 metabolic equivalents (METs)], moderate-to-vigorous [MVPA; ≥3.0 METs]), total energy expenditure (TEE), physical activity level (PAL), and step count, were evaluated using a validated triaxial accelerometer. Statistical analysis involved the latent growth curve models and random-effect panel data multivariate regression analysis. During a mean follow-up period of 6.8 years, physical activity was assessed an average of 5.1 times in men and 5.9 times in women. The profiles for the inactive time, LPA (only men), MVPA, step count, PAL, and TEE showed clear curvature, indicating an accelerated rate of change around the age of 70. In contrast, other variables exhibited minimal or no curvature over the age span. The MVPA trajectory was positively associated with alcohol consumption, hand grips, leg power, and trunk flexibility and negatively associated with age, local area, body mass index (BMI), comorbidity score, and heart rate over time. Our results indicated that the physical activity trajectory revealed clear curvature, accelerated rate of change around the age of 70, and determined physical health and fitness and BMI as dynamic factors associated with physical activity changes. These findings may be useful to help support populations to achieve and maintain the recommended level of physical activity.

PURPOSE: Whether the association between objectively assessed physical activity and mortality differs between adults with versus those without frailty is unclear. We investigated this association in community-dwelling older adults. METHODS: This prospective study used the data of 4165 older adults aged 65 years or older from the Kyoto-Kameoka study in Japan who wore a triaxial accelerometer (EW-NK52). The number of steps was classified by quartiles using the average daily value of data obtained from the accelerometer across four or more days. Frailty was evaluated using the validated Kihon Checklist. We evaluated the association between mortality and daily steps using a multivariable Cox proportional hazards analysis and restricted spline model. RESULTS: The average daily steps for the first, second, third, and fourth quartiles were 1786, 3030, 4452, and 7502, respectively. In total, 113 deaths were recorded during a median follow-up of 3.38 years (14061 person-years). After adjusting for confounders, the top quartile was associated with a lower hazard ratio (HR) for mortality than the bottom quartile (HR: 0.39, 95% confidence interval: 0.18-0.85). In a stratified model by frailty status, the daily step count dose-response curve at which the HR for mortality plateaued among non-frail individuals was approximately 5000-7000 steps per day. In contrast, the daily step count showed an inverse relationship with mortality at approximately 5000 steps or more per day in frail individuals. CONCLUSIONS: The relationship between daily steps and mortality is different between those with and those without frailty, and people with frailty may require more daily steps than those with non-frailty to achieve the inverse relationship with mortality. These findings may be useful for informing future physical activity guidelines.

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lacks access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5604 people from the ages of 8 days to 96 years from 23 countries using isotope-tracking (2H) methods. Age, body size, and composition were significantly associated with WT, as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People who lived in countries with a low human development index (HDI) had higher WT than people in high-HDI countries. On the basis of this extensive dataset, we provide equations to predict human WT in relation to anthropometric, economic, and environmental factors.

BACKGROUND: The body mass index (BMI) is closely related to mortality risk, and energy intake (EI) is essential for maintaining energy balance in weight control. However, self-reported EI has been shown to lead to a systematic underestimation. Total energy expenditure measured using the doubly labelled water (DLW) method is considered an objective biomarker of EI and the gold standard for its estimation in individuals with stable body weight. We aimed to examine the association between DLW-calibrated EI and BMI on overall mortality risk in older adults. METHODS: A prospective cohort study was performed using data of 8051 (4267 women and 3784 men) Japanese older adults from the Kyoto-Kameoka Study in Japan. Calibrated EI was calculated from the estimated EI using a food frequency questionnaire and equation developed based on DLW. Participants were classified by quartiles based on their EI stratified by sex. BMI was calculated using self-reported height and body weight. Mortality data were collected between 30 July 2011 and 30 November 2016. Statistical analysis was performed using the multivariable-adjusted Cox proportional hazard model with a restricted cubic spline. RESULTS: The 8051 participants' mean (standard deviation) age and BMI were 73.5 (6.1) years and 22.6 (3.0) kg/m2 , respectively. The mean (standard deviation) EI with and without calibration was 1909 (145) kcal/day and 1569 (358) kcal/day in women and 2383 (160) kcal/day and 1980 (515) kcal/day in men, respectively. During the median 4.75 years of follow-up (36 552 person-years), 661 deaths were recorded. In both women (hazard ratio [HR], 0.63; 95% confidence interval [CI] [0.41, 0.98]) and men (HR, 0.62; 95% CI [0.44, 0.87]), after adjusting for confounders, the top quartile as compared with the bottom calibrated EI quartile showed a negative association with risk of all-cause mortality. The lowest HR for all-cause mortality was 1900-2000 kcal/day in women and 2400-2600 kcal/day in men. However, after adjusting for BMI, no significant association was observed between the calibrated EI and the risk of death. These associations could not be confirmed in the uncalibrated EI. The HR for mortality was minimal at a BMI of 23 kg/m2 in both men and women, with or without adjustment for the calibrated EI. CONCLUSIONS: Calibrated EI was negatively associated with mortality risk but not uncalibrated EI. This may be mediated by an increase in body weight over time. Caution is required when interpreting the association between EI and mortality risk without adjusting for self-reported measurement errors and outcomes.

Previous cross-sectional studies have indicated that low relative appendicular lean mass (ALM) against body weight (divided by body weight, ALM/Wt, or divided by body mass index, ALM/BMI) was negatively associated with metabolic syndrome (MetS). Conversely, previous cross-sectional studies have indicated that the absolute ALM or ALM divided by squared height (ALM/Ht2) were positively associated with MetS. The aim of this longitudinal study was to investigate the association between low absolute or relative skeletal muscle mass, leg muscle power, or percent body fat and the development of MetS in Japanese women in a 7-y prospective study. The study participants included 346 Japanese women aged 26 to 85 years. The participants were divided into low and high groups based on the median values of ALM/Wt, ALM/BMI, ALM/Ht2, absolute ALM, or leg power. The longitudinal relationship between ALM indices or leg power and MetS development was examined using Kaplan-Meier curves and Cox regression models (average follow-up duration 7 years, range 1 to 10 years). During follow-up, 24 participants developed MetS. MetS incidence was higher in the low ALM/Wt group than the high ALM/Wt group even after controlling for age, obesity, waist circumference, family history of diabetes, smoking, and physical activity [adjusted hazard ratio = 5.60 (95% CI; 1.04-30.0)]. In contrast, MetS incidence was lower in the low ALM/Ht2 group than the high ALM/Ht2 group [adjusted hazard ratio = 10.6 (95%CI; 1.27-89.1)]. MetS incidence was not significantly different between the low and high ALM/BMI, absolute ALM, and leg power groups. Both ALM/Ht2 and ALM/Wt were not significant predictive variables for MetS development when fat mass or percent body fat was taken into account in the Cox model. At the very least, the results of this study underscore the importance of body composition measurements in that percent body fat, but not ALM, is associated with MetS development.

BACKGROUND: Whether sleep quality and duration-combination assessed from multiple domains are strongly associated with mortality risk in older adults remains unelucidated. We aimed to clarify these relationships. METHODS: We enrolled 7,668 older (age ≥65) Japanese adults in the Kyoto-Kameoka prospective cohort study who provided valid responses to the Pittsburgh Sleep Quality Index (PSQI) in a mail-in survey. Sleep quality and duration were classified into six groups using previously validated PSQI: short sleep duration (SSD: <360 min/day)/sleep disturbance (SD: ≥5.5 PSQI points), n=701; SSD/non-sleep disturbance (NSD: <5.5 PSQI points), n=100; optimal sleep duration (OSD: 360-480 min/day)/NSD, n=1863; OSD/SD, n=2113; long sleep duration (LSD: >480 min/day)/NSD, n=1972; LSD/SD, n=919. Mortality data were collected from February 15, 2012, to November 30, 2016. We evaluated the relationship between all-cause mortality risk and sleep quality and duration-combination using a multivariable Cox proportional hazards model that included baseline covariates. RESULTS: The median follow-up period was 4.75 years (34,826 person-years), with a total of 616 deaths. After adjusting for confounders, compared with other groups, SSD/SD and LSD/SD had the highest hazard ratio (HR) of mortality [SSD/SD: HR, 1.56 (95% confidence interval [CI]: 1.10-2.19); SSD/NSD: HR, 1.27 (95%CI: 0.47-3.48); OSD/NSD: reference; OSD/SD: HR, 1.20 (95%CI: 0.91-1.59); LSD/NSD: HR, 1.35 (95%CI: 1.03-1.77); LSD/SD: HR, 1.83 (95%CI: 1.37-2.45)]. However, mortality risk was not associated with the interaction between sleep quality and duration. CONCLUSIONS: Older adults with sleep disturbances involving SSD and LSD have a strong positive association with mortality risk, suggesting an additive effect between sleep quality and duration.

PURPOSE: To examine how physical activity (PA) and sitting time (ST) are associated with mortality in older Japanese adults. METHODOLOGY: We used the data of 10 233 older Japanese adults aged ≥65 years who provided valid responses to the International Physical Activity Questionnaire-Short Form (IPAQ-SF) by a mail survey. Both PA and ST were assessed using the IPAQ-SF. The results were classified into high or low categories using ≥3.0 metabolic equivalent PA (150 min/week) and ST (300 min/day) into the following four groups: High PA (HPA)/Low ST (LST), HPA/High ST (HST), Low PA (LPA)/LST, and LPA/HST. Mortality data were collected from July 30, 2011, to November 30, 2016. We assessed the interaction of PA and ST status with the risk of all-cause mortality using the multivariable Cox proportional-hazards model. RESULTS: A total of 1014 people were recorded to have died during a median follow-up period of 5.3 years (51 553 person-years). After adjustment for confounders, the risk of mortality was higher in the LPA/HST group than in all other groups (HPA/LST: reference; HPA/HST group: hazard ratio [HR] 0.86 (95% confidence interval [CI]: 0.66 to 1.12); LPA/LST group: HR 1.09 (95% CI: 0.88 to 1.35); LPA/HST group: HR 1.36 (95% CI: 1.10 to 1.67); and multiplicative interaction: HR 1.44 (95% CI: 1.07 to 1.94)). CONCLUSIONS: The risk of mortality associated with LPA/HST depends on the level of PA, duration of ST, and their interaction with each other. Our results may be useful in ameliorating the adverse effects leading to mortality in individuals with lower PA, by reducing ST.

BACKGROUND: Protein supplementation augments muscle strength gain during resistance training. Although some studies focus on the dose-response relationship of total protein intake to muscle mass or strength, the detailed dose-response relationship between total protein intake and muscle strength increase is yet to be clarified, especially in the absence of resistance training. OBJECTIVE: We aimed to assess the detailed dose-response relationship between protein supplementation and muscle strength, with and without resistance training. DESIGN: Systematic review with meta-analysis. DATA SOURCES: PubMed and Ichushi-Web (last accessed on March 23, 2022). ELIGIBILITY CRITERIA: Randomized controlled trials investigating the effects of protein intake on muscle strength. SYNTHESIS METHODS: A random-effects model and a spline model. RESULTS: A total of 82 articles were obtained for meta-analyses, and data from 69 articles were used to create spline curves. Muscle strength increase was significantly augmented only with resistance training (MD 2.01%, 95% CI 1.09-2.93) and was not augmented if resistance training was absent (MD 0.13%, 95% CI - 1.53 to 1.79). In the dose-response analysis using a spline model, muscle strength increase with resistance training showed a dose-dependent positive association with total protein intake, which is 0.72% (95% CI 0.40-1.04%) increase in muscle strength per 0.1 g/kg body weight [BW]/d increase in total protein intake up to 1.5 g/kg BW/d, but no further gains were observed thereafter. CONCLUSION: Concurrent use of resistance training is essential for protein supplementation to improve muscle strength. This study indicates that 1.5 g/kg BW/d may be the most appropriate amount of total protein intake for maintaining and augmenting muscle strength along with resistance training.

We aimed to verify the combined use of two frailty tools in predicting mortality in older adults. We used the data of 10,276 Japanese older adults (aged ≥ 65 years) who provided valid responses to two frailty assessment tools in a mail survey in Japan's Kyoto‒Kameoka Prospective cohort study. Frailty status was categorized into four groups depending on the validated frailty screening index and Kihon Checklist, respectively: Non-frailty (n = 5960), Physical frailty (n = 223), Comprehensive frailty (n = 2211), and Combination (n = 1882) groups. Mortality data were collected between July 30, 2011, and November 30, 2016. We assessed the relationship between frailty status and all-cause mortality risk using multivariate Cox proportional hazards models. During a median follow-up of 5.3 years, we recorded 1257 deaths. After adjusting for confounders, the Combination group had the highest mortality risk compared with the other groups [Non-frailty: reference; Physical frailty: hazards ratio [HR], 0.99 (95% confidence interval [CI] 0.58 to 1.70); Comprehensive frailty: 1.91 (1.63 to 2.23); Combination: 2.85 (2.44 to 3.22)]. People who are positive for frailty in both instruments have a higher risk of death than those who are positive to one model.

Abstract

Background

The term “frailty” might appear simple, but the methods used to assess it differ among studies. Consequently, there is inconsistency in the classification of frailty and predictive capacity depending on the frailty assessment method utilised. We aimed to examine the diagnostic accuracy of several screening tools for frailty defined by the phenotype model in older Japanese adults.

Methods

This cross-sectional study included 1,306 older Japanese adults aged ≥ 65 years who underwent physical check-up by cluster random sampling as part of the Kyoto-Kameoka Study in Japan. We evaluated the diagnostic accuracy of several screening instruments for frailty using the revised Japanese version of the Cardiovascular Health Study criteria as the reference standard. These criteria are based on the Fried phenotype model and include five elements: unintentional weight loss, weakness (grip strength), exhaustion, slowness (normal gait speed), and low physical activity. The Kihon Checklist (KCL), frailty screening index (FSI), and self-reported health were evaluated using mailed surveys. We calculated the non-parametric area under the receiver operating characteristic curve (AUC ROC) for several screening tools against the reference standard.

Results

The participants’ mean (standard deviation) age was 72.8 (5.5) years. The prevalence of frailty based on the Fried phenotype model was 12.2% in women and 10.3% in men. The AUC ROC was 0.861 (95% confidence interval: 0.832–0.889) for KCL, 0.860 (0.831–0.889) for FSI, and 0.668 (0.629–0.707) for self-reported health. The cut-off for identifying frail individuals was ≥ 7 points in the KCL and ≥ 2 points in the FSI.

Conclusions

Our results indicated that the two instruments (KCL and FSI) had sufficient diagnostic accuracy for frailty based on the phenotype model for older Japanese adults. This may be useful for the early detection of frailty in high-risk older adults.

OBJECTIVES: Some epidemiological studies of older American adults have reported a relationship between life-space mobility (LSM) and mortality. However, these studies did not show a dose-response relationship and did not include individuals from other countries. Therefore, we evaluated the dose-response relationship between LSM and mortality in older adults. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: We used the data of 10,014 older Japanese adults (aged ≥65 years) who provided valid responses to the Life-Space Assessment (LSA) in the Kyoto-Kameoka study in Japan. METHODS: LSM was evaluated using the self-administered LSA consisting of 5 items regarding life-space from person's bedroom to outside town. The LSM score was calculated by multiplying life-space level by frequency score by independence score, yielding a possible range of 0 (constricted life-space) to 120 (broad life-space). These scores were categorized into quartiles (Qs). Mortality data were collected from July 30, 2011 to November 30, 2016. A multivariate Cox proportional hazards model that included baseline covariates were used to evaluate the relationship between LSM score and mortality risk. RESULTS: A total of 1030 deaths were recorded during the median follow-up period of 5.3 years. We found a negative association between LSM score and overall mortality even after adjusting for confounders [Q1: reference; Q2: hazard ratio (HR) 0.81, 95% CI 0.69-0.95; Q3: HR 0.70, 95% CI 0.59-0.85; Q4: HR 0.68, 95% CI 0.55-0.84, P for trend < .001]. Similar results were observed for the spline model; up to a score of 60 points, LSM showed a strong dose-dependent negative association with mortality, but no significant differences were observed thereafter (L-shaped relationship). CONCLUSIONS AND IMPLICATIONS: Our findings demonstrate an L-shaped relationship between LSM and mortality. This study will be useful in establishing target values for expanding the range of mobility among withdrawn older adults with a constricted life-space.

BACKGROUND: Weight misperception adversely affects health-related quality of life (HRQol); however, few studies have evaluated the relationship between weight misperception and muscle mass. This study aimed to examine the relationship of weight misperception with low muscle mass using skeletal muscle index (SMI) estimated by multifrequency bioelectrical impedance analysis (MF-BIA) among community-dwelling Japanese. METHODS: Participants were 525 Japanese individuals aged 40-91 years old (male 89, female 436). Misperception was calculated by subtracting measured value from self-reported weight, presented as a percentage and categorized into tertiles based on sex (under-reporters, acceptable reporters, and over-reporters). Appendicular lean mass was estimated using MF-BIA, and low muscle mass was defined using SMI values of 7.0 and 5.7 kg/m2 for males and females, respectively, based on the Asian Working Group for Sarcopenia 2019 consensus. We evaluated the association between prevalence of low muscle mass and weight misperception (under-reporters and over-reporters) using multivariate logistic regression including covariate. RESULTS: In total, 9.3% (49/525) of participants had low muscle mass. After adjusting for covariates, prevalence of low muscle mass was higher among over-reporters than acceptable-reporters (odds ratio [OR]; 2.37, 95% confidence interval [CI]; 1.03-5.44). Additionally, sensitivity analysis was performed on females, which confirmed that the prevalence of low muscle mass was higher in over-reporters than in acceptable-reporters (OR, 3.27; 95% CI, 1.18-9.12). CONCLUSION: Weight misperception was significantly correlated with low muscle mass, especially in over-reporters.

PURPOSE: While the association between diet quality and mortality has been previously demonstrated, the association between frailty and diet quality has not been evaluated well. This study aimed to investigate the association between diet quality and prevalence of both physical and comprehensive frailty, using two validated tools, in a community-based cohort of older adults. METHODS: We conducted cross-sectional analyses using baseline data of 7022 participants aged ≥ 65 years in the Kyoto-Kameoka study. Diet quality was assessed by calculating the adherence scores to the Japanese Food Guide Spinning Top using a validated questionnaire; the participants were stratified into quartile groups based on these scores. Physical and comprehensive frailty was assessed using the Fried phenotype model-based Frailty Screening Index and the Kihon Checklist, respectively. Multivariable logistic regression and the restricted cubic spline model were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for associations between adherence scores and frailty prevalence. RESULTS: Higher adherence scores signified a higher intake of vitamin C, vegetables, dairy products, and fruits. Physical and comprehensive frailty prevalence was 14.2 and 35.8%, respectively. In a multivariable adjusted model, compared with the bottom adherence score quartile, the top quartile was associated with lower ORs of physical (OR 0.64; 95% CI 0.52-0.80) and comprehensive frailty (OR 0.60; 95% CI 0.51-0.71). These relationships were similar to results in the spline model. CONCLUSIONS: This study shows an inverse dose-response relationship between diet quality and prevalence of both physical and comprehensive frailty in older adults.

<sec><title>Background</title>Many cross-sectional studies have identified modifiable factors such as dietary intake, physique, and physical activity associated with diet quality but were unable to determine how a specific individual's diet quality changes with these factors. These relationships may vary depending on an individual's dietary intake. We aimed to determine the association between temporal changes in diet quality and concurrent changes in dietary intake, body mass index (BMI), and physical activity according to the diet quality trajectory pattern.

</sec><sec><title>Methods</title>This longitudinal prospective study included 697 Japanese adults aged 26–85 years, at baseline, with available data from at least two dietary intake surveys (4,118 measurements). Dietary intake and physical activity were evaluated using validated dietary questionnaires and a triaxial accelerometer. Diet quality was calculated using the Nutrient-Rich Food Index 9.3 (NRF9.3), while physical activity was calculated based on the duration of activity performed at each level of intensity (sedentary, light, moderate, and vigorous). Body mass index was calculated from the measured height and weight. Statistical analyses involved latent class growth models (LCGM) and random-effect panel data analysis.

</sec><sec><title>Results</title>During a mean follow-up period of 6.8 years, NRF9.3 scores were assessed, on average, 5.4 times in men and 6.1 times in women. Based on the NRF9.3 score, three separate trajectory groups—“low-increasing,” “medium-increasing,” and “high-stable”—among individuals aged 26–90 years were identified using LCGM. In the multivariate analysis, the NRF9.3 score trajectory was positively associated with intake of energy, protein, dietary fiber, vitamins A and C, magnesium, and food items, such as fruits and vegetables, and was negatively associated with BMI and the intake of added sugar, saturated fats, sodium, and food items, such as meat and sugar and confectioneries, even after adjusting for covariates. These relationships displayed heterogeneity across the identified NRF9.3 score trajectory groups. In the low-increasing group, an inverse relationship was observed between sedentary behavior and NRF9.3 score trajectory.

</sec><sec><title>Conclusions</title>We identified modifiable factors associated with temporal changes in diet quality across a wide age range; however, these factors may vary according to the diet quality trajectories. Our findings may help develop effective strategies for improving diet quality, according to the trajectory of diet quality.

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OBJECTIVES: Defining an adequate protein intake in older adults remains unresolved. We examined the association between calibrated protein intake and comprehensive frailty by sex in the Kyoto-Kameoka study. DESIGN: Cross-sectional study of baseline data. SETTING AND PARTICIPANTS: The study included 5679 Japanese participants aged 65 years or older. METHODS: Calibration coefficients were estimated from food frequency questionnaires and 7-day dietary records as a reference. Comprehensive frailty was evaluated using the 25-item Kihon Checklist (KCL) and defined as a total KCL score of ≥7points. Sex-specific calibrated protein intakes were presented as % of energy, per kg of actual body weight (BW), and per kg of ideal BW. RESULTS: Multiple logistic regression analysis showed that calibrated protein intake is inversely associated with comprehensive frailty. The association between protein intake and comprehensive frailty was also evaluated using curve fitting with non-linear regression, a weak U-shaped association was found in males and an L-shaped association in females. Men had a low prevalence of frailty at a calibrated protein intake of 15-17% energy from protein, 1.2 g/kg actual BW/day, or 1.4 g/kg ideal BW/day, and women had a low prevalence of frailty at 17-21% energy from protein or 1.6 g/kg ideal BW/day, with the prevalence of frailty remaining unchanged at higher protein intakes. Meanwhile, the inverse relationship between protein intake per ABW and frailty showed a gradual decrease at 1.4 g/kg ABW/day for protein in women. CONCLUSIONS AND IMPLICATIONS: A non-linear relationship was found between calibrated protein intake and frailty, with a U-shaped association in men and an L-shaped association in women. Adequate protein intake in healthy Japanese older adults was higher than the current recommended daily allowance.

Water and energy are essential for the human body. The doubly labeled water (DLW) method measures water turnover (WT) and total energy expenditure (TEE), which serves as a benchmark for the adequate intake (AI) of water and estimated energy requirements (EER). The objective of the current study was to examine the association of WT and TEE with physical activity and body composition in Japanese preschool children. We included 41 preschool children (22 girls, 19 boys) aged 3-6 in this study. WT, TEE, and fat-free mass (FFM) were obtained using DLW. Physical activity was measured using a triaxial accelerometer and categorized as light (LPA; 1.5-2.9 Metabolic equivalents, METs) and of moderate-to-vigorous intensity (MVPA; ≥3.0 METs). Exercise duration (Ex) was defined as ≥4.0 METs of physical activity. WT and TEE moderately positively correlated with Ex, but not with LPA. WT moderately positively correlated with BW and FFM while TEE strongly. We established predictive equations for WT and TEE using body weight (BW), FFM, step count, and Ex to guide the AI of water and EER in Japanese preschool children. We found that FFM and step count are the determinants of TEE, and that BW and Ex are the determinants of WT in preschool children.

OBJECTIVE: Self-reported energy intake (EI) estimation may incur systematic errors that could be attenuated through biomarker calibration. We aimed to confirm whether calibrated EI was comparable to total energy expenditure (TEE) measured using the doubly labelled water (DLW) technique. DESIGN: Cross-sectional study. SETTING: General older population from the Kyoto-Kameoka Study, Japan. PARTICIPANTS: This study included sub- and main cohorts of 72 and 8058 participants aged≥ 65 years, respectively. EI was evaluated using a validated FFQ, and calibrated EI was obtained using a previously developed equation based on the DLW method. TEE was considered representative of true EI and also measured using the DLW method. We used a Wilcoxon signed-rank test and correlation analysis to compare the uncalibrated and calibrated EI with TEE. RESULTS: In the sub-cohort, the median TEE, uncalibrated EI and calibrated EI were 8559 kJ, 7088 kJ and 9269 kJ, respectively. The uncalibrated EI was significantly lower than the TEE (median difference = -1847 kJ; interquartile range (IQR): -2785 to -1096), although the calibrated EI was not (median difference = 463 kJ; IQR: -330 to 1541). The uncalibrated (r = 0·275) and calibrated EI (r = 0·517) significantly correlated with TEE. The reproducibility was higher for calibrated EI (interclass correlation coefficient (ICC) = 0·982) than for uncalibrated EI (ICC = 0·637). Similar findings were observed when stratifying the sample by sex. For medians, uncalibrated EI was lower (about 17 %) than calibrated EI in the main cohort. CONCLUSIONS: Biomarker calibration may improve the accuracy of self-reported dietary intake estimation.

Although better diet quality is inversely related to the risk of geriatric disorders, the association of adherence to dietary guidelines with oral health-related quality of life (OHRQoL) is unclear. We aimed to investigate this association in older Japanese adults. This cross-sectional study included 7984 Japanese participants aged ≥ 65 years from the population-based Kyoto-Kameoka study. Dietary intake was estimated using a validated self-administered FFQ. The scores for adherence to the Japanese Food Guide Spinning Top (range: 0 (worst) to 80 (best)) were calculated. These scores were stratified into quartiles (Qs). Poor OHRQoL was defined as a score ≤ 50 using a 12-item Geriatric Oral Health Assessment Index. The OR and 95 % CI were calculated using multivariable logistic regression and the spline model. Higher adherence score was associated with a lower prevalence of poor OHRQoL (Q1-Q4:36·0 %, 32·1 %, 27·9 % and 25·1 %, respectively). An inverse association was found between the score for adherence to the food-based Japanese dietary guidelines and the OR of poor OHRQoL among all the participants (Q1: reference; Q2: OR, 0·87 (95 % CI: 0·75, 1·00); Q3: OR, 0·77 (95 % CI: 0·66, 0·90); Q4: OR, 0·72 (95 % CI: 0·62, 0·85); Pfor trend < 0·001). These relationships were similar to the results in the spline model. Higher adherence to the food-based Japanese dietary guidelines is inversely associated with the prevalence of poor OHRQoL in older adults. Our results may provide useful insights to improve and maintain oral health.

<title>Abstract</title><sec>
<title>Background</title>
Colibactin-producing <italic>Escherichia coli</italic> containing polyketide synthase (<italic>pks</italic>⁺<italic>E. coli</italic>) has been shown to be involved in colorectal cancer (CRC) development through gut microbiota analysis in animal models. Stool status has been associated with potentially adverse gut microbiome profiles from fecal analysis in adults. We examined the association between stool patterns and the prevalence of <italic>pks</italic>⁺<italic>E. coli</italic> isolated from microbiota in fecal samples of 224 healthy Japanese individuals.


</sec><sec>
<title>Results</title>
Stool patterns were determined through factorial analysis using a previously validated questionnaire that included stool frequency, volume, color, shape, and odor. Factor scores were classified into tertiles. The prevalence of <italic>pks</italic>⁺<italic>E. coli</italic> was determined by using specific primers for <italic>pks</italic>⁺<italic>E. coli</italic> in fecal samples. Plasma and fecal fatty acids were measured via gas chromatography-mass spectrometry. The prevalence of <italic>pks</italic>⁺<italic>E. coli</italic> was 26.8%. Three stool patterns identified by factorial analysis accounted for 70.1% of all patterns seen (factor 1: lower frequency, darker color, and harder shape; factor 2: higher volume and softer shape; and factor 3: darker color and stronger odor). Multivariable-adjusted odds ratios (95% confidence intervals) of the prevalence of <italic>pks</italic>⁺<italic>E. coli</italic> for the highest versus the lowest third of the factor 1 score was 3.16 (1.38 to 7.24; <italic>P</italic> for trend = 0.006). This stool pattern exhibited a significant positive correlation with fecal isobutyrate, isovalerate, valerate, and hexanoate but showed a significant negative correlation with plasma eicosenoic acid and α-linoleic acid, as well as fecal propionate and succinate. No other stool patterns were significant.


</sec><sec>
<title>Conclusions</title>
These results suggest that stool patterns may be useful in the evaluation of the presence of tumorigenic bacteria and fecal fatty acids through self-monitoring of stool status without the requirement for specialist technology or skill. Furthermore, it may provide valuable insight about effective strategies for the early discovery of CRC.


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BACKGROUND: Previous epidemiological studies have demonstrated the prevalence and relationship of various factors associated with sarcopenia in older adults; however, few have examined the status of sarcopenia in middle-aged adults. In this study, we aimed to, 1) evaluate the validity of the finger-circle test, which is potentially a useful screening tool for sarcopenia, and 2) determine the prevalence and factors associated with sarcopenia in middle-aged and older adults. METHODS: We conducted face-to-face surveys of 525 adults, who were aged 40-91 years and resided in Settsu City, Osaka Prefecture, Japan to evaluate the validity of finger-circle test. The finger-circle test evaluated calf circumference by referring to an illustration printed on the survey form. The area under the receiver operating characteristic curves (AUROC) was plotted to evaluate the validity of the finger-circle test for screening sarcopenia and compared to that evaluated by skeletal muscle mass index (SMI) measured using bioimpedance. We also conducted multisite population-based cross-sectional anonymous mail surveys of 9337 adults, who were aged 40-97 years and resided in Settsu and Hannan Cities, Osaka Prefecture, Japan. Participants were selected through stratified random sampling by sex and age in the elementary school zones of their respective cities. We performed multiple logistic regression analysis to explore associations between characteristics and prevalence of sarcopenia. RESULTS: Sarcopenia, defined by SMI, was moderately predicted by a finger-circle test response showing that the subject's calf was smaller than their finger-circle (AUROC: 0.729, < 65 years; 0.653, ≥65 years); such subjects were considered to have sarcopenia. In mail surveys, prevalence of sarcopenia screened by finger-circle test was higher in older subjects (approximately 16%) than in middle-aged subjects (approximately 8-9%). In a multiple regression model, the factors associated with sarcopenia were age, body mass index, smoking status, self-reported health, and number of meals in all the participants. CONCLUSIONS: Sarcopenia, screened by the finger-circle test, was present not only among older adults but also among middle-aged adults. These results may provide useful indications for developing public health programs, not only for the prevention, but especially for the management of sarcopenia. TRIAL REGISTRATION: UMIN000036880, registered prospectively May 29, 2019,  https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042027.

CONTEXT: Lean body mass is essential for health, yet consensus regarding the effectiveness of protein interventions in increasing lean body mass is lacking. OBJECTIVE: The aim of this systematic review was to evaluate the dose-response relationship of the effects of protein intake on lean body mass. DATA SOURCES: The PubMed and Ichushi-Web databases were searched electronically, and reference lists of the literature included here and in other meta-analyses were searched manually. STUDY SELECTION: Randomized controlled trials evaluating the effects of protein intake on lean body mass were included. DATA EXTRACTION: Two authors independently screened the abstracts; 5 reviewed the full texts. RESULTS: A total of 5402 study participants from 105 articles were included. In the multivariate spline model, the mean increase in lean body mass associated with an increase in protein intake of 0.1 g/kg of body weight per day was 0.39 kg (95%CI, 0.36-0.41) and 0.12 kg (95%CI, 0.11-0.14) below and above the total protein intake of 1.3 g/kg/d, respectively. CONCLUSIONS: These findings suggest that slightly increasing current protein intake for several months by 0.1 g/kg/d in a dose-dependent manner over a range of doses from 0.5 to 3.5 g/kg/d may increase or maintain lean body mass. SYSTEMATIC REVIEW REGISTRATION: UMIN registration number UMIN000039285.

OBJECTIVES: Although previous studies have reported lower mortality and morbidity in people with higher daily step counts, the association between frailty and objectively measured step counts has not been evaluated well. We investigated the association between step counts and prevalence of frailty in community-dwelling older adults. DESIGN: A cross-sectional study. SETTING: The Kyoto-Kameoka study in Japan. PARTICIPANTS: We used data of 3,616 Japanese older adults, aged 65 years or older, with valid daily step count data, obtained by an accelerometer-based pedometer. MEASUREMENTS: The step count during 4 or more days was objectively obtained by a validated triaxial accelerometer. Participants were classified by quartiles (Qs) based on their step counts. Frailty was defined using the Fried phenotype (FP) model and the Kihon Checklist (KCL). We evaluated the association between prevalence of frailty and step counts using multivariate logistic regression and the restricted cubic spline model. RESULTS: Mean step counts across low-to-high Qs of distribution were 1,759, 2,988, 4,377, and 7,200 steps/day, respectively. The prevalence of frailty, as defined by the FP model and KCL, was 11.3% and 26.8%, respectively. After adjusting for confounders, there was a negative association between the odds ratio (OR) and prevalence of frailty, as defined by the FP model among people with higher step counts (Q1: reference; Q2: OR = 0.73; 95% confidence interval (CI) = 0.56-0.96; Q3: OR = 0.56; 95% CI = 0.42-0.76; and Q4: OR = 0.41; 95% CI = 0.30-0.57; P for trend <.001). The mean step count of the population was 4,081. The OR of frailty for a 1,000-steps/day increment was 0.74 (95% CI = 0.58-0.91) and 0.85 (95% CI = 0.72-0.97) below 4,000 steps and above 4,000 steps, respectively. In the spline model, this relationship was similar between the FP model and KCL. CONCLUSION: These findings suggest that slightly increasing the current step count, as by 1,000 steps/day (about 10 minutes of activity), may potentially prevent frailty. J Am Geriatr Soc 68:2310-2318, 2020.

The relative contribution of diet to colorectal cancer (CRC) incidence is higher than that for other cancers. Animal models have revealed that Escherichia coli containing polyketide synthase (pks+ E. coli) in the gut participates in CRC development. The purpose of this cross-sectional study was to examine the relationship between dietary intake and the prevalence of pks+ E. coli isolated from the microbiota in faecal samples of 223 healthy Japanese individuals. Dietary intake was assessed using a previously validated brief-type self-administered diet history questionnaire. The prevalence of pks+ E. coli was evaluated using faecal samples collected from participants and specific primers that detected pks+ E. coli. The prevalence of pks+ E. coli was 26.9%. After adjusting for baseline confounders, the prevalence of pks+ E. coli was negatively associated with the intake of green tea (odds ratio [OR], 0.59 [95% confidence interval (CI) 0.30-0.88] per 100 g/1,000 kcal increment) and manganese (OR, 0.43 [95% CI 0.22-0.85] per 1 mg/1,000 kcal increment) and was positively associated with male sex (OR, 2.27 [95% CI 1.05-4.91]). While futher studies are needed to validate these findings, these results provide insight into potential dietary interventions for the prevention of CRC.

The relationship between mixing ability of masticatory functions and frailty has not been well evaluated. This study investigated the prevalence of physical and comprehensive frailty and its association with mixing ability in 1106 older adults aged ≥65 years who underwent physical examination as part of the Japanese Kyoto-Kameoka Study. Mixing ability was assessed using color-changing chewing gum (1-5 points, 5 representing the best mixing ability). Participants were divided into four groups (5 points, 4 points, 3 points, and 1 or 2 points). The modified Japanese versions of the Cardiovascular Health Study (mJ-CHS) criteria and the validated Kihon Checklist (KCL) were used to assess physical and comprehensive frailty, respectively. Multivariate logistic regression was used to evaluate the association between frailty and mixing ability. The prevalence of physical and comprehensive frailty was 11.8% and 27.9%, respectively. After adjusting for confounders, the odds ratios of physical and comprehensive frailty comparing the highest to the lowest chewing gum score groups were 3.64 (95% confidence interval (CI): 1.62 to 8.18; p for trend = 0.001) and 2.09 (95% CI: 1.09 to 4.03; p for trend = 0.009), respectively. Mixing-ability tests involving chewing gum may be an indicator associated with both physical and comprehensive frailty.

BACKGROUND: Appropriate energy intake (EI) is essential to prevent frailty. Because self-reported EI is inaccurate and has systematic errors, adequate biomarker calibration is required. This study examined the association between doubly labeled water (DLW)-calibrated EI and the prevalence of frailty among community-dwelling older adults. METHODS: A cross-sectional study was performed using baseline data of 7022 older adults aged ≥65 years in the Kyoto-Kameoka Study. EI was evaluated using a validated food frequency questionnaire (FFQ), and calibrated EI was obtained from a previously established equation using the DLW method. Physical and comprehensive frailty were defined by the Fried phenotype (FP) model and the Kihon Checklist (KCL), respectively. We used multivariable-adjusted restricted cubic spline logistic regression analysis. RESULTS: The prevalence of physical frailty was 14.8% and 13.6% in women and men, respectively. The spline models showed significant reverse J-shaped or U-shaped relationships between the prevalence of physical or comprehensive frailty against the DLW-calibrated EI, respectively. The lowest prevalence of both types of frailty was found at 1900-2000 kcal·d-1 in women and 2400-2500 kcal·d-1 in men, which corresponded to approximately 40 kcal·d-1·kg IBW-1 (ideal body weight = 22 × height2) with DLW-calibrated EI. Uncalibrated EI underestimated approximately 20% compared with calibrated EI; underestimated EI were attenuated by calibration approach. CONCLUSIONS: This study suggests that low EI has a greater detrimental effect compared with excessive EI, particularly on physical frailty. Using biomarkers to calibrate EI holds promise for providing accurate energy requirements to establish guidelines used in public health and clinical nutrition.

The relationship between body mass index (BMI) and frailty remains unclear. Using two validated frailty assessment tools, this study aimed to investigate the relationship between the prevalence of frailty and BMI in Japanese older adults. This cross-sectional study used baseline data of 7191 individuals aged ≥65 years, living in Kameoka City, Kyoto, Japan. The BMI was calculated based on self-reported height and body weight, and classified into six categories. Frailty was defined using two validated assessment tools, the Fried phenotype (FP) model and Kihon Checklist (KCL). We evaluated the relationship between frailty and BMI using a multivariate restricted cubic spline logistic regression. The prevalence of frailty defined using the FP model was 25.3%, 19.6%, 14.3%, 12.4%, 12.6%, and 19.4% for each BMI category of <18.5, 18.5-19.9, 20.0-22.4, 22.5-24.9, 25.0-27.4, and ≥27.5 kg/m2, respectively. The spline model showed a significant U-shaped relationship between BMI and the prevalence of frailty defined using both, KCL and FP models. This study found that the BMI range corresponding to lowest prevalence of frailty defined using both tools was 21.4-25.7 kg/m2. Thus, a healthy BMI may reduce the prevalence of frailty, and the risk of frailty needs to be evaluated in individuals who are underweight or overweight.

Accurate assessments of a target population's energy intake (EI) are essential to prevent poor nutritional status. However, self-reported dietary records (DRs) or food frequency questionnaires (FFQs) are not always accurate, thereby requiring validation and calibration studies. This study aimed to validate the EI estimated by a FFQ using the doubly labeled water (DLW) method. Participants were 109 Japanese older adults (50 women and 59 men) aged 65-88 years. The EI was obtained by a DR and 47-item FFQ over 1 year. The total energy expenditure (TEE) was measured by DLW for ~2 weeks. EI was significantly lower than TEE (p < 0.01); ratios of EI assessed by DR and FFQ against TEE were 0.91 ± 0.17 and 0.82 ± 0.22, respectively. TEE was significantly and moderately correlated with the EI estimated by the DR (r = 0.45, p < 0.01) and FFQ (r = 0.37, p < 0.01). Furthermore, the EI correlation coefficients estimated by DR and the FFQ in this study were not significantly different (p = 0.46). The EI/TEE ratio was significantly and negatively correlated with the body mass index (BMI). In conclusion, EI estimated with a DR or FFQ modestly correlated with TEE, and calibrating EI with a developed equation in this study can attenuate the underestimation of EI.

To determine the association between geriatric disorders and dietary intake, validation of a food frequency questionnaire (FFQ) for elderly individuals is needed. We compared energy and nutrient intakes derived from dietary records (DR) and FFQ in an elderly population and compared the data against results from middle-aged individuals (30⁻68 years) from a previous study. Current participants included 65 women and 78 men (65⁻88 years) who completed FFQ and 7-day DR in a subpopulation of the Kyoto-Kameoka study. Our FFQ was created for middle-aged individuals. To validate the FFQ, we investigated equivalent precision by comparing the correlation coefficients between the present and previous study. Median correlations for energy and nutrient intake between the DR and FFQ in the current and previous studies were 0.24 and 0.30 (p = 0.329) in women and 0.24 and 0.28 (p = 0.399) in men, respectively. The median ratio of FFQ to DR for these intakes were also similar. The accuracy and precision of the FFQ for energy and nutrient intake in elderly individuals did not differ compared with previous findings in a middle-aged population. A validation study evaluating energy and nutrient intake using recovery biomarkers is further needed.

Vasoactive intestinal peptide (VIP) is a modulator of inflammatory responses. VIP receptors are expressed in several tumor types, such as colorectal carcinoma. The study described herein was conducted to confirm the presence of VIP and its receptors (VPAC1 and VPAC2) in surgically resected hepatocellular carcinoma (HCC) tissues and in the HCC cell line Huh7. The mechanism responsible for apoptosis of HCC cells was then examined because VIP treatment (10-10  M) significantly suppressed proliferation of Huh7 cells. In examining apoptosis-related proteins, we found caspase-3 to be significantly increased and Bcl-xL and cyclic AMP (cAMP) response element-binding protein (CREB) to be significantly decreased in Huh7 cells cultured with VIP. Furthermore, the CREB level and phosphorylation were reduced. These effects were reversed by the addition of VIP receptor antagonist or cAMP antagonist Rp-cAMPS. Pretreatment with cAMP analogue blocked the increased apoptosis, suggesting that VIP induces apoptosis via a PKA-independent signaling mechanism. Our data indicate that VIP prevents the progression of HCC by apoptosis through the cAMP/Bcl-xL pathway.

This study investigated whether the association between postprandial plasma glucose (PPG) is affected by five type 2 diabetes mellitus (T2DM) susceptibility genes, and whether four weeks of yogurt consumption would affect these responses. We performed a single-arm intervention study in young nondiabetic Japanese participants, who consumed 150 g yogurt daily for four weeks, after which a rice test meal containing 50 g carbohydrate was administered. PPG and postprandial serum insulin (PSI) were measured between 0 and 120 mins at baseline and after the intervention. Genetic risk was evaluated by weighted genetic risk score (GRS) according to published methodology, and participants were assigned to one of two groups (n = 17: L-GRS group and n = 15: H-GRS group) according to the median of weighted GRS. At baseline, the H-GRS group had higher glucose area under the curve0⁻120 min after intake of the test meal than the L-GRS group (2175 ± 248 mg/dL.min vs. 1348 ± 199 mg/dL.min, p < 0.001), but there were no significant differences after the yogurt intervention. However, there was an improvement in PSI in the H-GRS group compared with baseline. These results suggest that habitual yogurt consumption may improve glucose and insulin responses in nondiabetic subjects who have genetically higher PPG.

Whether the effect of a low-protein diet on progression to end-stage renal disease (ESRD) and mortality risk differs between young and elderly adults with chronic kidney disease (CKD) is unclear. We conducted a retrospective CKD cohort study to investigate the association between protein intake and mortality or renal outcomes and whether age affects this association. The cohort comprised 352 patients with stage G3-5 CKD who had been followed up for a median 4.2 years, had undergone educational hospitalization, and for whom baseline protein intake was estimated from 24-h urine samples. We classified the patients into a very low protein intake (VLPI) group (<0.6 g/kg ideal body weight/day), a low protein intake (LPI) group (0.6⁻0.8 g), and a moderate protein intake (MPI) group (>0.8 g). Compared with the LPI group, the MPI group had a significantly lower risk of all-cause mortality (hazard ratio: 0.29; 95% confidence interval: 0.07 to 0.94) but a similar risk of ESRD, although relatively high protein intake was related to a faster decline in the estimated glomerular filtration rate. When examined per age group, these results were observed only among the elderly patients, suggesting that the association between baseline dietary protein intake and all-cause mortality in patients with CKD is age-dependent.

早産児の肝臓はビリルビンの代謝能が十分でないため黄疸が出現しやすく、重症化することもある。臨床において早産での出生が予想される場合、妊娠母体にグルココルチコイド(GC)投与を施行する。我々は、出生前GC投与が早産児の心臓や肺の発達に寄与することを明らかにしたが、肝臓への作用はまだ不明である。本研究では出生前GC投与によるラット胎仔の肝臓機能への作用について、ビリルビンの代謝に関与する因子に着目し検討した。妊娠ラットの17日および18日目に、デキサメタゾン(DEX)を2日間連続で皮下投与し、19日目に帝王切開で出産させた早産胎仔の肝臓を実験に供した。また自然分娩で出生させた日齢1日目の肝臓を比較対象とした。肝臓組織のアルブミン、ビリルビン代謝に関与するトランスポーターであるmultidrug resistance-associated protein(MRP)2およびorganic anion-transporting plypeptide(OATP)1の蛋白発現を免疫組織染色で検討した。19日胎仔の肝臓組織像は、日齢1ラットと比較し肝実質細胞の構築が未熟で細胞の大きさも不均一であった。しかしDEX投与した肝臓組織では、非投与群と比較しアルブミン、MRP2の発現が増強した。OATP1の発現に影響がなかった。DEXは胎仔肝臓の発達を促進し、ビリルビンの排泄能を増強させることが示唆された。(著者抄録)

シトクロムP450(CYP)は小腸にも存在して、経口投与された薬物の初回通過代謝の原因となるので、白人では小腸のCYPアイソザイムの分布が調べられているが、日本人では調べられていない。聖マリアンナ医大で膵頭十二指腸切除を受けた34名の患者の小腸組織について、CYP(1A2、2C9、2C19、2D6、3A4、3A5)のmRNA発現をリアルタイムRT-PCRで分析した。CYP3A4(63.2%)が主要なCYPで、続いてCYP2C19(21.3%)が多く発現していた。Paine等(2006)の報告によれば、白人ではCYP3A4(82%)が主で、続いてCYP2C9(14%)であり、日本人と白人では小腸でのCYP発現には差が認められた。日本人と白人では経口薬の初回通過代謝や併用薬の相互作用に差がある可能性が示された。

乳癌に対する新規Kinesin spindle protein(KSP)阻害薬KPYB10602の制癌作用を、乳癌細胞および乳癌細胞の皮下異種移植モデルマウスを用いて検討した。本剤の抗増殖活性、制癌作用、阻害機序をcell viability assay、免疫蛍光顕微鏡法、フローサイトメトリー、ELISA、ウエスタンブロット法により調査した。本剤は、MCF-7、MDA-MB-231、HCC1937細胞株において制癌作用を示した。本剤を処置することで有糸分裂停止とmonopolar spindle formationが誘導された後、アポトーシス細胞死が誘導されることが示された。さらに本剤は、皮下異種移植モデルマウスの腫瘍増殖を効果的に抑制した。KPYB10602は乳癌の新規抗癌剤になりうると考えられた。