Association between doubly labelled water-calibrated energy intake and objectively measured physical activity with mortality risk in older adults.

BACKGROUND: Physical activity or biomarker-calibrated energy intake (EI) alone is associated with mortality in older adults; the interaction relationship between the combined use of both factors and mortality has not been examined. We evaluated the relationship between mortality and calibrated EI and step counts in older adults. METHODS: This prospective study included 4,159 adults aged ≥65 years who participated in the Kyoto-Kameoka study in Japan and wore a triaxial accelerometer between 1 April and 15 November 2013. The calibrated EI was calculated based on a previously developed equation using EI biomarkers. The step count was obtained from the accelerometer ≥ 4 days. Participants were classified into the following four groups: low EI (LEI)/low step counts (LSC) group (EI: <2,400 kcal/day in men and <1,900 kcal/day in women; steps: <5,000 /day), n = 1,352; high EI (HEI)/LSC group (EI: ≥2,400 kcal/day in men and ≥1,900 kcal/day in women; steps: <5,000 /day), n = 1,586; LEI/high step counts (HSC) group (EI: <2,400 kcal/day in men and < 1,900 kcal/day in women; steps: ≥5,000 /day), n = 471; and HEI/HSC group (EI: ≥2,400 kcal/day in men and ≥1,900 kcal/day in women; steps: ≥5,000 /day), n = 750. Mortality-related data were collected until 30 November 2016. We performed a multivariable Cox proportional hazard analysis. RESULTS: The median follow-up period was 3.38 years (14,046 person-years), and 111 mortalities were recorded. After adjusting for confounders, the HEI/HSC group had the lowest all-cause mortality rate compared to other groups (LEI/LSC: reference; HEI/LSC: hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.41-1.23; LEI/HSC: HR: 0.59, 95% CI: 0.29-1.19; and HEI/HSC: HR: 0.10, 95% CI: 0.01-0.76). No significant interaction was observed between the calibrated EI and steps with mortality. The spline model showed that 35-42 kcal/100 steps/day of EI/100 steps was associated with the lowest mortality risk. CONCLUSIONS: HR mortality risk was lowest at 35-42 kcal/100 steps/day, suggesting that very high (≥56 kcal) or low (<28 kcal) EI/100 steps are not inversely associated with mortality. Adherence to optimal EI and adequate physical activity may provide sufficient energy balance to explain the inverse association with mortality among older Japanese adults.

Association between physical activity and the prevalence of tumorigenic bacteria in the gut microbiota of Japanese adults: a cross-sectional study.

Escherichia coli harboring polyketide synthase (pks+ E. coli) has been suggested to contribute to colorectal cancer development. Physical activity is strongly associated with lower colorectal cancer risks, but its effects on pks+ E. coli remain unclear. The aim of this study was to investigate the association between pks+ E. coli prevalence and physical activity. A cross-sectional study was conducted on 222 Japanese adults (27-79-years-old, 73.9% female). Triaxial accelerometers were used to measure light-intensity physical activity, moderate-to-vigorous intensity physical activity, the physical activity level, step-count, and time spent inactive. Fecal samples collected from participants were used to determine the prevalence of pks+ E. coli. Multivariate logistic regression analysis and restricted cubic spline curves were used to examine the association between pks+ E. coli prevalence and physical activity. The prevalence of pks+ E. coli was 26.6% (59/222 participants). The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the highest tertile with reference to the lowest tertile of physical activity variables were as follows: light-intensity physical activity (OR 0.63; 95% CI 0.26-1.5), moderate-to-vigorous intensity physical activity (OR 0.85; 95% CI 0.39-1.87), physical activity level (OR 0.69; 95% CI 0.32-1.51), step-count (OR 0.92; 95% CI 0.42-2.00) and time spent inactive (OR 1.30; 95% CI 0.58-2.93). No significant dose-response relationship was found between all physical activity variables and pks+ E. coli prevalence. Our findings did not suggest that physical activity has beneficial effects on the prevalence of pks+ E. coli. Longitudinal studies targeting a large population are needed to clarify this association.

Glutathione depression alters cellular mechanisms of skeletal muscle fatigue in early stage of recovery and prolongs force depression in late stage of recovery.

The effects of reduced glutathione (GSH) on skeletal muscle fatigue were investigated. GSH was depressed by buthionine sulfoximine (BSO) (100 mg/kg body wt/day) treatment for 5 days, which decreased GSH content to ∼10%. Male Wistar rats were assigned to the control (N = 18) and BSO groups (N = 17). Twelve hours after BSO treatment, the plantar flexor muscles were subjected to fatiguing stimulation (FS). Eight control and seven BSO rats were rested for 0.5 h (early stage of recovery), and the remaining were rested for 6 h (late stage of recovery). Forces were measured before FS and after rest, and physiological functions were estimated using mechanically skinned fibers. The force at 40 Hz decreased to a similar extent in both groups in the early stage of recovery and was restored in the control but not in the BSO group in the late stage of recovery. In the early stage of recovery, sarcoplasmic reticulum (SR) Ca2+ release was decreased in the control greater than in the BSO group, whereas myofibrillar Ca2+ sensitivity was increased in the control but not in the BSO group. In the late stage of recovery, SR Ca2+ release decreased and SR Ca2+ leakage increased in the BSO group but not in the control group. These results indicate that GSH depression alters the cellular mechanism of muscle fatigue in the early stage and delays force recovery in the late stage of recovery, due at least in part, to the prolonged Ca2+ leakage from the SR.

Longitudinal trajectory of vascular age indices and cardiovascular risk factors: a repeated-measures analysis.

This study aimed to identify the modifiable cardiovascular risk factors associated with longitudinal changes, which are nine functional and structural biological vascular aging indicators (BVAIs), to propose an effective method to prevent biological vascular aging. We conducted a longitudinal study of 697 adults (a maximum of 3636 BVAI measurements) who were, at baseline, aged between 26 and 85 years and whose BVAIs were measured at least twice between 2007 and 2018. The nine BVAIs were measured using vascular testing and an ultrasound device. Covariates were assessed using validated questionnaires and devices. During the mean follow-up period of 6.7 years, the average number of BVAI measurements ranged from 4.3 to 5.3. The longitudinal analysis showed a moderate positive correlation between the common carotid intima-media thickness (IMT) and chronological age in both men (r = 0.53) and women (r = 0.54). In the multivariate analysis, BVAIs were associated with factors such as age, sex, residential area, smoking status, blood clinical chemistry test levels, number of comorbidities, physical fitness, body mass, physical activity, and dietary intake. The IMT is the most useful BVAI. Our findings suggest that modifiable cardiovascular risk factors are associated with longitudinal changes in BVAI as represented by IMT.

The SGLT2 inhibitor empagliflozin improves cardiac energy status via mitochondrial ATP production in diabetic mice.

Empagliflozin, a sodium-glucose co-transporter 2 inhibitor developed, has been shown to reduce cardiovascular events in patients with type 2 diabetes and established cardiovascular disease. Several studies have suggested that empagliflozin improves the cardiac energy state which is a partial cause of its potency. However, the detailed mechanism remains unclear. To address this issue, we used a mouse model that enabled direct measurement of cytosolic and mitochondrial ATP levels. Empagliflozin treatment significantly increased cytosolic and mitochondrial ATP levels in the hearts of db/db mice. Empagliflozin also enhanced cardiac robustness by maintaining intracellular ATP levels and the recovery capacity in the infarcted area during ischemic-reperfusion. Our findings suggest that empagliflozin enters cardiac mitochondria and directly causes these effects by increasing mitochondrial ATP via inhibition of NHE1 and Nav1.5 or their common downstream sites. These cardioprotective effects may be involved in the beneficial effects on heart failure seen in clinical trials.

Doubly labelled water-calibrated energy intake associations with mortality risk among older adults.

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.

Association between skeletal muscle mass or percent body fat and metabolic syndrome development in Japanese women: A 7-year prospective study.

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.

[Restructuring Torso CT Protocol for Radiation Dose Management].

PURPOSE: There are problems with dose management in X-ray computed tomography (CT) because the protocol used for any examination is not always in the same scan range. The purpose of this study was to investigate the usefulness of setting the CT protocol based on the scan range. METHODS: We evaluated the examination data of patients who underwent plain CT based on a scan range of chest to pelvis and abdomen to pelvis. The previous protocol [Chest-Abdomen Routine] was changed to the current protocols [Chest_Abdomen] and [Chest_Pelvis], and the previous protocol of [Abdomen Routine] was changed to the current protocols [Abdomen] and [Abdomen_Pelvis]. Examination data of height, scan length, volume CT dose index (CTDIvol), and dose length product (DLP) were obtained from digital imaging and communications in medicine, and radiation dose structured report using Radimetrics. The relationship between patient height and scan range, and CTDIvol and DLP was indicated in a scatter plot. Standard deviation (SD) of scan length and DLP were compared between current and previous protocols. Outliers were defined as the data exceeding average ±2SD. RESULTS: The SD of scan length decreased by 77.1% on abdomen to pelvis, and the SD of DLP decreased by 65.2% on abdomen to pelvis. The causes of the outliers were CT scan range, scan parameter, arm position, metal implants, and body thickness of patients. CONCLUSION: Setting CT protocols based on the scan range reduced SD of scan length and DLP. It was helpful for reducing the number of scan range outliers and analyzing the cause of outliers.

Association Between Temporal Changes in Diet Quality and Concurrent Changes in Dietary Intake, Body Mass Index, and Physical Activity Among Japanese Adults: A Longitudinal Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Ultrasonographic prevalence of ulnar nerve displacement at the elbow in young baseball players.

BACKGROUND: Overhead-throwing athletes are at risk of elbow injury because of valgus stress, leading to unstable ulnar nerves and neuropathy. Studies regarding ulnar nerve damage/displacement have been performed primarily in adults. OBJECTIVE: To determine the prevalence and related factors associated with ulnar nerve displacement at the elbow in young baseball players. DESIGN: Cross-sectional study. PARTICIPANTS: Youth baseball players ages 10-12 years were eligible to participate. Exclusion criteria were history of neuropathic pain, trauma, or prior surgery of the upper limb. Fifty-seven participants were eligible for inclusion in the study. MAIN OUTCOME MEASUREMENTS: Demographic data and ultrasonography findings of ulnar nerve dynamics at the cubital tunnel were analyzed in a total of 114 elbows. Elbows were grouped into nondislocation and displacement (subluxation or dislocation) groups according to ultrasound findings. Logistic generalized estimating equations were used to identify factors associated with ulnar nerve displacement. RESULTS: Thirty-six (31.6%) elbows demonstrated sonographic findings of ulnar nerve displacement, with 13 (11.4%) subluxations and 23 (20.2%) dislocations. Fourteen (24.6%) participants experienced nerve displacement in the dominant elbow only, whereas nerve displacement in both elbows occurred in 11 (19.3%) participants. Nerve displacement in the nondominant elbow only was not observed. Hand dominance and tenderness of the arcade of Struthers' were factors associated with ulnar nerve displacement (odds ratio, 2.81, and 9.73; 95% confidence interval, 1.34-5.91 and 2.45-38.68; p = .006 and .001, respectively). CONCLUSION: One-third of the young baseball players evaluated had ultrasonographic findings compatible with ulnar nerve displacement at the elbow. Hand dominance and tenderness of Struthers arcade were the only factors associated with ulnar nerve displacement. Ultrasound may help identify patients with ulnar nerve displacement and contribute to the understanding of its pathophysiology in young baseball players.

Association between Water and Energy Requirements with Physical Activity and Fat-Free Mass in Preschool Children in Japan.

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.

Predominant cause of faster force recovery in females than males after intense eccentric contractions in mouse fast-twitch muscle.

KEY POINTS: We investigated the mechanisms underlying faster force recovery from eccentric contractions (ECCs) in female than in male mice, focusing on mitochondrial responses. At 3 days after repeated ECCs (REC3), female mice showed faster recovery from ECC-induced force depression than male mice. At REC3, the mitochondria in females displayed superior responses to those in males: (i) mitochondrial Ca2+ uniporter content of muscles at REC3 was higher than that of rested muscles in females, and (ii) mitochondrial volume density in females was higher than that in males at REC3. Ovariectomized (OVX) female mice showed lower mitochondrial responses at REC3, similar to those observed in male mice, but oestrogen replacement nullified such lower responses in OVX. We concluded that: (i) superior mitochondrial responses after ECCs, at least in part, cause faster force recovery from ECCs in females than in males, and (ii) oestrogen contributes to such superior responses in the mitochondria in females. ABSTRACT: The purpose of this study was to investigate the mechanisms underlying sex differences in force recovery after eccentric contractions (ECCs). The left limbs of female and male mice were exposed to repeated ECCs (five sets of 50 contractions) elicited in vivo in the plantar flexor muscles. Isometric torques were measured before, immediately and at 3 days after ECCs (REC3), and gastrocnemius muscles obtained at REC3 were used for biochemical and morphological analyses. At REC3, a greater torque depression at 40 Hz was observed in males than females. Additionally, the following differences were observed at REC3: (i) in males but not females, triad structure was distorted, (ii) mitochondrial Ca2+ uniporter (MCU) content was increased in females but not in males, and (iii) mitochondrial volume density at REC3 was lower in males than in females. To examine the contribution of oestrogen to torque recovery, female mice were assigned to sham-operated (Sham), ovariectomized (OVX) and OVX treated with 17ß-oestradiol (OVX + E2) groups. At REC3, (i) greater torque depression at 40 Hz was observed in the OVX group than in the Sham and OVX + E2 groups, (ii) MCU content was increased in the Sham and OVX + E2 groups but not the OVX group, and (iii) mitochondrial volume density at REC3 was lower in the OVX group than the Sham and OVX + E2 groups. These results suggest that faster force recovery in females than in males is, at least partly, ascribable to superior mitochondrial responses, and oestrogen supplementation, in part, enhances such responses.

Stool pattern is associated with not only the prevalence of tumorigenic bacteria isolated from fecal matter but also plasma and fecal fatty acids in healthy Japanese adults.

BACKGROUND: Colibactin-producing Escherichia coli containing polyketide synthase (pks+ E. coli) 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 pks+ E. coli isolated from microbiota in fecal samples of 224 healthy Japanese individuals. RESULTS: 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 pks+ E. coli was determined by using specific primers for pks+ E. coli in fecal samples. Plasma and fecal fatty acids were measured via gas chromatography-mass spectrometry. The prevalence of pks+ E. coli 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 pks+ E. coli for the highest versus the lowest third of the factor 1 score was 3.16 (1.38 to 7.24; P 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. CONCLUSIONS: 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.

[Prevalence of frailty and its related factors in community-dwelling middle-aged and elderly adults in Settsu and Hannan cities in Osaka prefecture].

Objectives　The purpose of this study was to examine the prevalence of frailty and its associated factors in community-dwelling middle-aged and elderly adults in Settsu and Hannan cities, which are located in the north and south of Osaka prefecture, respectively.Methods　We conducted a mailed, self-administered, questionnaire survey of individuals aged 40 years and older in Settsu city in 2019 and Hannan city in 2020. There are 10 primary school districts in Settsu city and 8 districts in Hannan city, from each of which 1,000 people were selected according to the age and sex structures of the districts. We included 5,134 individuals from Settsu city and 3,939 individuals from Hannan city. We defined frailty using self-reported questionnaires, the Kihon Checklist (KCL), and Simple Frailty Index (SFI). Multivariate logistic regression analysis was performed for each city to examine the association of frailty with age, sex, body mass index (BMI), family structure, subjective health, economic status, subjective physical fitness, sleeping status, smoking history, alcohol use, meal frequency and awareness of the word "frailty."Results　The average age (standard deviation) of participants was 62.7 (12.5) years in Settsu city and 63.4 (12.2) years in Hannan city. The prevalence of frailty by KCL was 18.7% and 17.9% for participants in their 40s, 18.2% and 14.6% for those in their 50s, 17.0% and 15.7% for those in their 60s, 25.4% and 20.8% for those in their 70s, 39.7% and 36.1% for those 80 years and older from Settsu and Hannan cities, respectively. Using SFI, the prevalence of frailty was 16.2% and 13.5% for participants in their 40s, 15.0% and 11.9% for those in their 50s, 12.5% and 10.0% for those in their 60s, 14.6% and 12.3% for those in their 70s, and 24.7% and 22.3% for those aged 80 years and older in Settsu and Hannan cities, respectively. Significant common independent variables associated with frailty as defined using the KCL and SFI in Settsu and Hannan cities were age, subjective health, economic status, subjective physical fitness, sleeping status, and awareness of the word "frailty."Conclusion　This study found some participants to be frail as early as their 40s or 50s. Thus, efforts must be made to prevent frailty in working-age populations, including those aged 40 years and older. Six factors were associated with frailty. Longitudinal or interventional studies are required to examine their causal relationships and public health significance.

Factors associated with sarcopenia screened by finger-circle test among middle-aged and older adults: a population-based multisite cross-sectional survey in Japan.

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.

Association between dietary intake and the prevalence of tumourigenic bacteria in the gut microbiota of middle-aged Japanese adults.

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.

Vasoactive intestinal peptide increases apoptosis of hepatocellular carcinoma by inhibiting the cAMP/Bcl-xL pathway.

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.

Contribution of impaired myofibril and ryanodine receptor function to prolonged low-frequency force depression after in situ stimulation in rat skeletal muscle.

The aim of this study was to examine whether prolonged low-frequency force depression (PLFFD) that occurs in situ is the result of decreased myofibrillar Ca(2+) sensitivity and/or reduced sarcoplasmic reticulum (SR) Ca(2+) release. Intact rat gastrocnemius muscles were electrically stimulated via the sciatic nerve until force was reduced to ~50% of the initial and dissected 30 min following the cessation of stimulation. Skinned fibre and whole muscle analyses were performed in the superficial region composed exclusively of type IIB fibres. Fatiguing stimulation significantly reduced the ratio of force at low frequency to that at high frequency to 65% in skinned fibres (1 vs. 50 Hz) and 73% in whole muscles (20 vs. 100 Hz). In order to evaluate changes in myofibrillar Ca(2+) sensitivity and ryanodine receptor caffeine sensitivity, skinned fibres were activated in Ca(2+)- and caffeine-containing solutions, respectively. Skinned fibres from fatigued muscles displayed decreased caffeine sensitivity together with increased myofibrillar Ca(2+) sensitivity. Treatment with 2,2'-dithiodipyridine and reduced glutathione induced a smaller increase in myofibrillar Ca(2+)sensitivity in fatigued than in rested fibres. In fatigued muscles, S-glutathionylation of troponin I was increased and submaximal SR Ca(2+) release, induced by 4-chloro-m-cresol, was decreased. These findings suggest that in the early stage of PLFFD that occurs in fast-twitch muscles of exercising animals and humans, S-glutathionylation of troponin I may attenuate PLFFD by increasing myofibrillar Ca(2+) sensitivity and that under such a circumstance, PLFFD may be ascribable to failure of SR Ca(2+) release.