Ca2+ storage function is altered in the sarcoplasmic reticulum of skeletal muscle lacking mitsugumin 23.

Mitsugumin 23 (MG23) has been identified as a ball-shaped cation channel in the sarcoplasmic reticulum (SR) but its physiological role remains unclear. This study aimed to examine the contribution of MG23 to Ca2+ storage function in skeletal muscle by using Mg23-knockout (Mg23-/-) mice. There was no difference in the isometric specific force of the extensor digitorum longus (EDL) and soleus (SOL) muscles between Mg23-/- and wild-type (Wt) mice. In Mg23-/- mice, the calsequestrin 2 content in the EDL muscle and SR Ca2+-ATPase 2 content in the SOL were increased. We have examined SR and myofibril functions using mechanically skinned fibers and determined their fiber types based on the response to Sr2+, which showed that Mg23-/- mice, compared with Wt, had: 1) elevated total Ca2+ content in the membranous components including SR, mitochondria, and transverse tubular system referred to as endogenous Ca2+ content, in both type I and II fibers of the EDL and SOL; 2) increased maximal Ca2+ content in both type I and II fibers of the EDL and SOL; 3) decreased SR Ca2+ leakage in type I fibers of the SOL; and 4) enhanced SR Ca2+ uptake in type I fibers of the SOL, although myofibril function was not different in both type I and II fibers of the SOL and EDL muscles. These results suggest that MG23 decreases SR Ca2+ storage in both type I and type II fibers, likely due to increased SR Ca2+ leakage.NEW & NOTEWORTHY The function of calcium storage within sarcoplasmic reticulum (SR) plays a pivotal role in influencing the health and disease states of skeletal muscle. In the present study, we demonstrated that mitsgumin 23, a novel non-selective cation channel, modifies SR Ca2+ storage in skeletal muscle fibers. These findings provide valuable insights into the physiological regulation of Ca2+ in skeletal muscle, offering significant potential for uncovering the mechanisms underlying muscle fatigue, muscle adaptation, and muscle diseases.

Intrinsic contractile dysfunction due to impaired sarcoplasmic reticulum Ca2+ release in compensatory hypertrophied muscle fibers following synergist ablation.

Synergist ablation (SA) is an experimental procedure for the induction of hypertrophy. However, SA causes a decrease in specific force (i.e., force per cross-sectional area), likely due to excessive muscle use. Here, we investigated the mechanisms behind the SA-induced intrinsic contractile dysfunction, especially focusing on the excitation-contraction (EC) coupling. Male Wistar rats had unilateral surgical ablation of gastrocnemius and soleus muscles to induce compensatory hypertrophy in the plantaris muscles. Two weeks after SA, plantaris muscle was dissected from each animal and used for later analyses. SA significantly increased the mean fiber cross-sectional area (+18%). On the other hand, the ratio of depolarization-induced force to the maximum Ca2+-activated specific force, an indicator of sarcoplasmic reticulum (SR) Ca2+ release, was markedly reduced in mechanically skinned fibers from the SA group (-51%). These functional defects were accompanied by an extensive fragmentation of the SR Ca2+ release channel, the ryanodine receptor 1 (RyR1), and a decrease in the amount of other triad proteins (i.e., DHPR, STAC3, and junctophilin1). SA treatment also caused activation of calpain-1 and increased the amount of NADPH oxidase 2, endoplasmic reticulum (ER) stress proteins (i.e., Grp78, Grp94, PDI, and Ero1), and lipid peroxidation [i.e., 4-hydroxynonenal (4-HNE)] in SA-treated muscles. Our findings show that SA causes skeletal muscle weakness due to impaired EC coupling. This is likely to be induced by Ca2+-dependent degradation of triad proteins, which may result from Ca2+ leak from fragmented RyR1 triggered by increased oxidative stress.NEW & NOTEWORTHY Synergist ablation (SA) has widely been used to understand the mechanisms behind skeletal muscle hypertrophy. However, compensatory hypertrophied muscles display intrinsic contractile dysfunction, i.e., a hallmark of overuse. Here, we demonstrate that SA-induced compensatory hypertrophy is accompanied by muscle weakness due to impaired sarcoplasmic reticulum Ca2+ release. This dysfunction may be caused by the degradation of triad proteins due to the reciprocal amplification of reactive oxygen species and Ca2+ signaling at the junctional space microdomain.

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.

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.

Combined Use of Sleep Quality and Duration Is More Closely Associated With Mortality Risk Among Older Adults: A Population-based Kyoto-Kameoka Prospective Cohort Study.

BACKGROUND: Whether sleep quality and duration assessed from multiple domains, either individually or in combination, 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 years) 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 the 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 = 1,863; OSD/SD, n = 2,113; long sleep duration (LSD: >480 min/day)/NSD, n = 1,972; 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 (and their combinations) 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. CONCLUSION: 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.

Distribution of water turnover by sex and age as estimated by prediction equation in Japanese adolescents and adults: the 2016 National Health and Nutrition Survey, Japan.

BACKGROUND: Although water is essential to the maintenance of health and life, standard values for human water requirements are yet to be determined. This study aimed to evaluate the distribution of water turnover (WT) according to sex and age, estimated using a prediction equation, in Japanese adolescents and adults. METHODS: This cross-sectional study used data from the 2016 National Health and Nutrition Survey, Japan. Data were obtained from electronically available aggregated reports in the survey's official website. Participants aged between 15 and 80 years (10,546 men, 12,355 women) were selected using stratified random sampling. WT was calculated considering lifestyle and environmental factors, and using an equation (coefficient of determination = 0.471) previously developed by the international doubly labelled water (DLW) database group. As data on physical activity levels (PAL) were not collected in the survey, we used two evaluation methods: (1) energy intake assessed by dietary records and (2) total energy expenditure measured by the DLW method reported in previous Japanese studies, divided by basal metabolic rate predicted using the equation. We evaluated the relationship between WT and age using a restricted cubic spline model. RESULTS: The average WT for the 15-19, 20-29, 30-39, 40-49, 50-59, 60-69, and ≥ 70 years was 3291, 3151, 3213, 3243, 3205, 3104, and 2790 ml/day, respectively in men, and 2641, 2594, 2741, 2739, 2753, 2707, and 2482 ml/day, respectively in women. In the spline model, WT showed an inverse association with age in men older than 50 years, whereas women showed a reverse U-shaped relationship between WT and age (p for non-linearity < 0.001), although results differed with body weight adjustment. Similar results were found for both PAL evaluation methods, and the range of WT per body weight was 45-56 ml/day for both sexes. CONCLUSIONS: We determined the standard values of WT in Japanese population using a prediction equation and national large-scale survey data. These findings may be useful for setting water requirements for dietary guidelines in future.

Mechanisms of eccentric contraction-induced muscle damage and nutritional supplementations for mitigating it.

Eccentric contraction (ECC) often results in large and long-lasting force deficits accompanied by muscle soreness, primarily due to muscle damage. In this sense, exercises that involve ECC are less desirable. Paradoxically, exercise training that includes a substantial eccentric phase leads to a more powerful activation of the genes responsible for skeletal muscle remodeling (e.g., hypertrophy) than other types of training that emphasize a concentric or isometric phase. Therefore, effective strategies that lessen ECC-induced muscle damage will be of interest and importance to many individuals. The purpose of this brief review is to highlight the published literature on the effects of ECC and/or nutritional supplementations on proteins, lipids, metabolic and ionic changes, and enzyme activities in skeletal muscles subjected to an acute bout of ECC. First, we discuss the potential mechanisms by which ECC causes muscle damage. Previous findings implicate a Ca2+ overload-oxidative modification pathway as one possible mechanism contributing to muscle damage. Thereafter, the efficacy of two nutritional supplementations, i.e., L-arginine and antioxidant, is discussed because L-arginine and antioxidant would be expected to ameliorate the adverse effects of Ca2+ overload and oxidative modification, respectively. Of these, L-arginine ingestion before ECC seems likely to be the effective strategy for mitigating ECC-related proteolysis. More studies are needed to establish the effectiveness of antioxidant ingestion. The application of effective strategies against muscle damage may contribute to improvements in health and fitness, muscle function, and sports performance.

Adherence to the food-based Japanese dietary guidelines and prevalence of poor oral health-related quality of life among older Japanese adults in the Kyoto-Kameoka study.

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.

Diet quality and physical or comprehensive frailty among older adults.

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.

Association of the interaction between physical activity and sitting time with mortality in older Japanese adults.

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.

Validation of the Kihon Checklist and the frailty screening index for frailty defined by the phenotype model in older Japanese adults.

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.

Persistent trigeminal artery variant associated with ipsilateral hypoplasia of the internal carotid artery.

A persistent trigeminal artery is the most common persistent carotid-vertebrobasilar anastomosis, while persistent trigeminal artery variants involve termination at the cerebellar artery without connecting to the basilar artery. Internal carotid artery hyperplasia is also a rare congenital anomaly. To the best of our knowledge, there are no reports of persistent trigeminal artery variant associated with ipsilateral hypoplasia of the internal carotid artery. Herein, we report a case of a 44 year-old woman who visited a neurosurgical clinic because of chronic headaches. Magnetic resonance angiography showed impaired delineation of the left internal carotid artery, and she was referred to our hospital for catheter angiography. Angiogram revealed left internal carotid artery hypoplasia and a left persistent trigeminal artery variant that terminated at the left anterior inferior cerebellar artery. Computed tomography bone images showed a narrow left carotid canal. We diagnosed congenital hypoplasia of the left internal carotid artery concomitant with ipsilateral persistent trigeminal artery variant. Careful imaging assessment is important for identifying persistent trigeminal artery variant when associated with ipsilateral internal carotid artery hypoplasia.

Orthograde signal of dihydropyridine receptor increases Ca2+ leakage after repeated contractions in rat fast-twitch muscles in vivo.

The purpose of this study was to investigate the mechanism underlying sarcoplasmic reticulum (SR) Ca2+ leakage after in vivo contractions. Rat gastrocnemius muscles were electrically stimulated in vivo, and then mechanically skinned fibers and SR microsomes were prepared from the muscles excised 30 min after repeated high-intensity contractions. The mechanically skinned fibers maintained the interaction between dihydropyridine receptors (DHPRs) and ryanodine receptors (RyRs), whereas the SR microsomes did not. Interestingly, skinned fibers from the stimulated muscles showed increased SR Ca2+ leakage, whereas Ca2+ leakage decreased in SR microsomes from the stimulated muscles. To enhance the orthograde signal of DHPRs, SR Ca2+ leakage in the skinned fiber was measured 1) under a continuously depolarized condition and 2) in the presence of nifedipine. As a result, in either of the two conditions, SR Ca2+ leakage in the rested fibers reached a level similar to that in the stimulated fibers. Furthermore, the increased SR Ca2+ leakage from the stimulated fibers was alleviated by treatment with 1 mM tetracaine (Tet) but not by treatment with 3 mM free Mg2+ (3 Mg). Tet exerted a greater inhibitory effect on the DHPR signal to RyR than 3 Mg, although their inhibitory effects on RyR were almost similar. These results suggest that the increased Ca2+ leakage after muscle contractions is mainly caused by the orthograde signal of DHPRs to RyRs.

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.

Effects of vigorous isometric muscle contraction on titin stiffness-related contractile properties in rat fast-twitch muscles.

This study was conducted to examine the effects of an acute bout of vigorous isometric contractions on titin stiffness-related contractile properties in rat fast-twitch skeletal muscles. Intact gastrocnemius muscles were electrically stimulated in situ until the force was reduced to ∼50% of the initial force. Immediately after cessation of the stimulation, the superficial regions of the muscles were dissected and subjected to biochemical and skinned fiber analyses. The stimulation resulted in a decrease in the titin-based passive force. The amounts of fragmented titin were unchanged by the stimulation. Protein kinase Cα-treatment increased the passive force in stimulated fibers to resting levels. The stimulation had no effect on the maximum Ca2+-activated force (max Ca2+ force) at a sarcomere length (SL) of 2.4 µm and decreased myofibrillar (my)-Ca2+ sensitivity at 2.6-µm SL. Stretching the SL to 3.0 µm led to the augmentation of the max Ca2+ force and my-Ca2+ sensitivity in both rested and stimulated fibers. For the max Ca2+ force, the extent of the increase was smaller in stimulated than in rested fibers, whereas for my-Ca2+ sensitivity, it was higher in stimulated than in rested fibers. These results suggest that vigorous isometric contractions decrease the titin-based passive force, possibly because of a reduction in phosphorylation by protein kinase Cα, and that the decreased titin stiffness may contribute, at least in part, to muscle fatigue.

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.

Doubly labelled water-calibration approach attenuates the underestimation of energy intake calculated from self-reported dietary assessment data in Japanese older adults.

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.

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.

Optimal slice thickness of brain computed tomography using a hybrid iterative reconstruction algorithm for identifying hyperdense middle cerebral artery sign of acute ischemic stroke.

PURPOSE: To determine the optimal slice thickness of brain non-contrast computed tomography using a hybrid iterative reconstruction algorithm to identify hyperdense middle cerebral artery sign in patients with acute ischemic stroke. METHODS: We retrospectively enrolled 30 patients who had presented hyperdense middle cerebral artery sign and 30 patients who showed no acute ischemic change in acute magnetic resonance imaging. Reformatted axial images at an angle of the orbitomeatal line in slice thicknesses of 0.5, 1, 3, 5, and 7 mm were generated. Optimal slice thickness for identifying hyperdense middle cerebral artery sign was evaluated by a receiver operating characteristics curve analysis and area under the curve (AUC). RESULTS: The mean AUC value of 0.5-mm slice (0.921; 95% confidence interval (95% CI), 0.868 to 0.975) was significantly higher than those of 3-mm (0.791; 95% CI, 0.686 to 0.895; p = 0.041), 5-mm (0.691; 95% CI, 0.583 to 0.799, p < 0.001), and 7-mm (0.695; 95% CI, 0.593 to 0.797, p < 0.001) slices, whereas it was equivalent to that of 1-mm slice (0.901; 95% CI, 0.837 to 0.965, p = 0.751). CONCLUSION: Thin slice thickness of ≤ 1 mm has a better diagnostic performance for identifying hyperdense artery sign on brain non-contrast computed tomography with a hybrid iterative reconstruction algorithm in patients with acute ischemic stroke.

[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.