A multimodal exercise countermeasure prevents the negative impact of head-down tilt bed rest on muscle volume and mitochondrial health in older adults.

Mitochondrial dysfunctions are thought to contribute to muscle atrophy and weakness that develop during ageing and mechanical unloading caused by immobilization, bed rest and microgravity. Older adults are at greater risk of developing muscle and mitochondrial dysfunctions in response to unloading. Although exercise is well known to promote muscle and mitochondrial health, its protective effect during mechanical unloading in older adults remains largely unexplored. Here, we investigated the impact of 14 days of head-down tilt bed rest (HDBR) with and without a multimodal exercise countermeasure in older men and women (55-65 years). Leg muscle volume was assessed using magnetic resonance imaging. Biopsies of the vastus lateralis were performed to assess markers of mitochondrial content, respiration, reactive oxygen species (ROS) production and calcium retention capacity (mCRC). Indices of mitochondrial quality control (MQC), including markers of fusion (MFN1 and 2), fission (Drp1), mitophagy (Parkin) and autophagy (p62 and LC3I and II) were measured using immunoblots. Muscle cross-sections were stained for neural cell adhesion molecule (NCAM, a marker of denervation). HDBR triggered muscle atrophy, decreased mitochondrial content and respiration and increased mitochondrial ROS production. HDBR had no impact on mCRC or MQC markers but increased markers of autophagy and denervation. Exercise prevented the deleterious effects of HDBR on leg muscle volume, mitochondrial ROS production and markers of autophagy and denervation. Exercise also increased mitochondrial content and respiration without altering mCRC and MQC markers. Collectively, our results indicate that an exercise countermeasure that can be performed in bed is effective in protecting muscle and mitochondrial health during HDBR in older adults. KEY POINTS: Conditions associated with muscle unloading, such as immobilization, bed rest or microgravity, result in muscle atrophy and weakness, particularly in older adults. Mitochondrial dysfunctions are thought to contribute to muscle atrophy caused by unloading and ageing. However, whether exercise can counteract the deleterious effects of unloading in older adults remains largely unexplored. Here, we report that older adults exposed to 14 days of head-down tilt bed rest (HDBR) displayed upper leg muscle atrophy, a decrease in mitochondrial content and respiration, an increase in H2O2 emission, and an increase in autophagy and denervation markers. No impact of HDBR on mitochondrial quality control was observed. A multimodal exercise countermeasure prevented the deleterious effects of HDBR on upper leg muscle volume, mitochondrial reactive oxygen species emission, and markers of autophagy and denervation and increased mitochondrial content and respiration. These findings highlight the effectiveness of exercise in promoting muscle and mitochondrial health in older adults undergoing bed rest.

Outcomes reported in randomised trials of surgical prehabilitation: a scoping review.

BACKGROUND: Heterogeneity of reported outcomes can impact the certainty of evidence for prehabilitation. The objective of this scoping review was to systematically map outcomes and assessment tools used in trials of surgical prehabilitation. METHODS: MEDLINE, EMBASE, PsychInfo, Web of Science, CINAHL, and Cochrane were searched in February 2023. Randomised controlled trials of unimodal or multimodal prehabilitation interventions (nutrition, exercise, psychological support) lasting at least 7 days in adults undergoing elective surgery were included. Reported outcomes were classified according to the International Society for Pharmacoeconomics and Outcomes Research framework. RESULTS: We included 76 trials, mostly focused on abdominal or orthopaedic surgeries. A total of 50 different outcomes were identified, measured using 184 outcome assessment tools. Observer-reported outcomes were collected in 86% of trials (n=65), with hospital length of stay being most common. Performance outcomes were reported in 80% of trials (n=61), most commonly as exercise capacity assessed by cardiopulmonary exercise testing. Clinician-reported outcomes were included in 78% (n=59) of trials and most frequently included postoperative complications with Clavien-Dindo classification. Patient-reported outcomes were reported in 76% (n=58) of trials, with health-related quality of life using the 36- or 12-Item Short Form Survey being most prevalent. Biomarker outcomes were reported in 16% of trials (n=12) most commonly using inflammatory markers assessed with C-reactive protein. CONCLUSIONS: There is substantial heterogeneity in the reporting of outcomes and assessment tools across surgical prehabilitation trials. Identification of meaningful outcomes, and agreement on appropriate assessment tools, could inform the development of a prehabilitation core outcomes set to harmonise outcome reporting and facilitate meta-analyses.

Towards a common definition of surgical prehabilitation: a scoping review of randomised trials.

BACKGROUND: There is no universally accepted definition for surgical prehabilitation. The objectives of this scoping review were to (1) identify how surgical prehabilitation is defined across randomised controlled trials and (2) propose a common definition. METHODS: The final search was conducted in February 2023 using MEDLINE, Embase, PsycINFO, Web of Science, CINAHL, and Cochrane. We included randomised controlled trials (RCTs) of unimodal or multimodal prehabilitation interventions (nutrition, exercise, and psychological support) lasting at least 7 days in adults undergoing elective surgery. Qualitative data were analysed using summative content analysis. RESULTS: We identified 76 prehabilitation trials of patients undergoing abdominal (n=26, 34%), orthopaedic (n=20, 26%), thoracic (n=14, 18%), cardiac (n=7, 9%), spinal (n=4, 5%), and other (n=5, 7%) surgeries. Surgical prehabilitation was explicitly defined in more than half of these RCTs (n=42, 55%). Our findings consolidated the following definition: 'Prehabilitation is a process from diagnosis to surgery, consisting of one or more preoperative interventions of exercise, nutrition, psychological strategies and respiratory training, that aims to enhance functional capacity and physiological reserve to allow patients to withstand surgical stressors, improve postoperative outcomes, and facilitate recovery.' CONCLUSIONS: A common definition is the first step towards standardisation, which is needed to guide future high-quality research and advance the field of prehabilitation. The proposed definition should be further evaluated by international stakeholders to ensure that it is comprehensive and globally accepted.

Relationship between Adherence to the 2019 Canada's Food Guide Recommendations on Healthy Food Choices and Nutrient Intakes in Older Adults.

BACKGROUND: Following Canada's food guide (CFG) recommendations should ensure adequate nutrient intakes. Older adults have increased needs for certain nutrients and nutrient density; the extent to which adherence to CFG recommendations can help reduce inadequate nutrient intakes is unknown. OBJECTIVES: We aimed to assess the relationship between adherence to CFG recommendations on healthy food choices and intake of key nutrients in adults 65 y and older from the Canadian Community Health Survey 2015 - Nutrition. METHODS: Secondary analysis of data from 4093 older adults of the Canadian Community Health Survey 2015 - Nutrition (mean age, 73.6 y, 54% females). Dietary intakes were measured using an interviewer-administered 24-h dietary recall, including 1 repeat in a subsample (42%). The National Cancer Institute multivariate method was used to estimate usual (i.e., long-term) dietary intakes. Adherence to CFG recommendations was measured using the Healthy Eating Food Index (HEFI)-2019 score. Simple linear and logistic regression models estimated the effect of increased HEFI-2019 score on usual nutrient intakes and the prevalence of inadequate nutrient intakes (i.e., below the estimated average requirements), respectively. RESULTS: Compared with the prevalence of inadequate intakes at median HEFI-2019 score (46.4/80 points), a higher HEFI-2019 (+11 points) was associated with reductions in the prevalence of inadequate intakes of magnesium, vitamin B6 and protein [-19.8% (95% confidence interval (CI): -30.8, -8.9), -12.7% (95% CI: -22.5, -3.0), and -4.7% (95% CI: -9.4, -0.1), respectively]. In contrast, data for higher HEFI-2019 scores were compatible with increased prevalence of inadequate intakes of folate, vitamin D, and calcium [4.0% (95% CI: -8.4, 16.3), 2.6% (95% CI: 1.1, 4.0), and 2.3% (95% CI: -3.0, 7.5), respectively]. CONCLUSIONS: Based on dietary intakes of Canadian older adults in 2015, increasing the degree of adherence to CFG recommendations on healthy food choices may reduce nutrient intake inadequacy for most key nutrients except folate, vitamin D, and calcium.

Impact of 14 Days of Bed Rest in Older Adults and an Exercise Countermeasure on Body Composition, Muscle Strength, and Cardiovascular Function: Canadian Space Agency Standard Measures.

INTRODUCTION: Head-down bed rest (HDBR) has long been used as an analog to microgravity, and it also enables studying the changes occurring with aging. Exercise is the most effective countermeasure for the deleterious effects of inactivity. The aim of this study was to investigate the efficacy of an exercise countermeasure in healthy older participants on attenuating musculoskeletal deconditioning, cardiovascular fitness level, and muscle strength during 14 days of HDBR as part of the standard measures of the Canadian Space Agency. METHODS: Twenty-three participants (12 males and 11 females), aged 55-65 years, were admitted for a 26-day inpatient stay at the McGill University Health Centre. After 5 days of baseline assessment tests, they underwent 14 days of continuous HDBR followed by 7 days of recovery with repeated tests. Participants were randomized to passive physiotherapy or an exercise countermeasure during the HDBR period consisting of 3 sessions per day of either high-intensity interval training (HIIT) or low-intensity cycling or strength exercises for the lower and upper body. Peak aerobic power (V̇O2peak) was determined using indirect calorimetry. Body composition was assessed by dual-energy X-ray absorptiometry, and several muscle group strengths were evaluated using an adjustable chair dynamometer. A vertical jump was used to assess whole-body power output, and a tilt test was used to measure cardiovascular and orthostatic challenges. Additionally, changes in various blood parameters were measured as well as the effects of exercise countermeasure on these measurements. RESULTS: There were no differences at baseline in main characteristics between the control and exercise groups. The exercise group maintained V̇O2peak levels similar to baseline, whereas it decreased in the control group following 14 days of HDBR. Body weight significantly decreased in both groups. Total and leg lean masses decreased in both groups. However, total body fat mass decreased only in the exercise group. Isometric and isokinetic knee extension muscle strength were significantly reduced in both groups. Peak velocity, flight height, and flight time were significantly reduced in both groups with HDBR. CONCLUSION: In this first Canadian HDBR study in older adults, an exercise countermeasure helped maintain aerobic fitness and lean body mass without affecting the reduction of knee extension strength. However, it was ineffective in protecting against orthostatic intolerance. These results support HIIT as a promising approach to preserve astronaut health and functioning during space missions, and to prevent deconditioning as a result of hospitalization in older adults.

Relative Validation of an Artificial Intelligence-Enhanced, Image-Assisted Mobile App for Dietary Assessment in Adults: Randomized Crossover Study.

BACKGROUND: Thorough dietary assessment is essential to obtain accurate food and nutrient intake data yet challenging because of the limitations of current methods. Image-based methods may decrease energy underreporting and increase the validity of self-reported dietary intake. Keenoa is an image-assisted food diary that integrates artificial intelligence food recognition. We hypothesized that Keenoa is as valid for dietary assessment as the automated self-administered 24-hour recall (ASA24)-Canada and better appreciated by users. OBJECTIVE: We aimed to evaluate the relative validity of Keenoa against a 24-hour validated web-based food recall platform (ASA24) in both healthy individuals and those living with diabetes. Secondary objectives were to compare the proportion of under- and overreporters between tools and to assess the user's appreciation of the tools. METHODS: We used a randomized crossover design, and participants completed 4 days of Keenoa food tracking and 4 days of ASA24 food recalls. The System Usability Scale was used to assess perceived ease of use. Differences in reported intakes were analyzed using 2-tailed paired t tests or Wilcoxon signed-rank test and deattenuated correlations by Spearman coefficient. Agreement and bias were determined using the Bland-Altman test. Weighted Cohen κ was used for cross-classification analysis. Energy underreporting was defined as a ratio of reported energy intake to estimated resting energy expenditure <0.9. RESULTS: A total of 136 participants were included (mean 46.1, SD 14.6 years; 49/136, 36% men; 31/136, 22.8% with diabetes). The average reported energy intakes (kcal/d) were 2171 (SD 553) in men with Keenoa and 2118 (SD 566) in men with ASA24 (P=.38) and, in women, 1804 (SD 404) with Keenoa and 1784 (SD 389) with ASA24 (P=.61). The overall mean difference (kcal/d) was -32 (95% CI -97 to 33), with limits of agreement of -789 to 725, indicating acceptable agreement between tools without bias. Mean reported macronutrient, calcium, potassium, and folate intakes did not significantly differ between tools. Reported fiber and iron intakes were higher, and sodium intake lower, with Keenoa than ASA24. Intakes in all macronutrients (r=0.48-0.73) and micronutrients analyzed (r=0.40-0.74) were correlated (all P<.05) between tools. Weighted Cohen κ scores ranged from 0.30 to 0.52 (all P<.001). The underreporting rate was 8.8% (12/136) with both tools. Mean System Usability Scale scores were higher for Keenoa than ASA24 (77/100, 77% vs 53/100, 53%; P<.001); 74.8% (101/135) of participants preferred Keenoa. CONCLUSIONS: The Keenoa app showed moderate to strong relative validity against ASA24 for energy, macronutrient, and most micronutrient intakes analyzed in healthy adults and those with diabetes. Keenoa is a new, alternative tool that may facilitate the work of dietitians and nutrition researchers. The perceived ease of use may improve food-tracking adherence over longer periods.

Effects of preoperative nutrition and multimodal prehabilitation on functional capacity and postoperative complications in surgical lung cancer patients: a systematic review.

OBJECTIVE: To determine the effect of preoperative nutrition and multimodal prehabilitation on clinical and functional outcomes in surgical lung cancer patients. METHODS: We searched MEDLINE, Cochrane Library and CENTRAL, EMBASE, Scopus, and clinical trial registries ( clinicaltrials.gov , International Clinical Trials Registry Platform and Google Scholar) to identify studies involving a preoperative nutrition-based intervention or multimodal prehabilitation (nutrition with exercise) of at least 7 days, in lung cancer patients awaiting surgery. Studies must have reported results on at least one of the following outcomes: functional capacity, pulmonary function, postoperative complications, and length of hospital stay. The quality of included studies was assessed using the Cochrane risk of bias assessment tool for randomized trials and the modified Newcastle-Ottawa scale for non-controlled trials. RESULTS: Five studies were included (1 nutrition-only and 4 multimodal prehabilitation studies). Due to substantial heterogeneity in the interventions across studies, a meta-analysis was not conducted. Findings suggest that multimodal prehabilitation, compared with standard hospital care, is associated with improvements in both functional walking capacity and pulmonary function during the preoperative period; however it does not appear to have an effect on postoperative outcomes. Rather, the finding of significantly lower rates of postoperative complications in the intervention group was unique to the nutrition-only study. CONCLUSION: Multimodal prehabilitation programs that combine nutrition and exercise may have beneficial effects on various physical function outcomes in patients with lung cancer awaiting surgery. Optimizing preoperative nutrition may have postoperative benefits which remain to be confirmed.

Fidelity of muscle fibre reinnervation modulates ageing muscle impact in elderly women.

KEY POINTS: Susceptibility to age-related muscle atrophy relates to the degree of muscle denervation and the capacity of successful reinnervation. However, the specific role of denervation as a determinant of the severity of muscle aging between populations with low versus high physical function has not been addressed. We show that prefrail/frail elderly women exhibited marked features of muscle denervation, whereas world class octogenarian female master athletes showed attenuated indices of denervation and greater reinnervation capacity. These findings suggest that the difference in age-related muscle impact between low- and high-functioning elderly women is the robustness of the response to denervation of myofibers. ABSTRACT: Ageing muscle degeneration is a key contributor to physical frailty; however, the factors responsible for exacerbated vs. muted ageing muscle impact are largely unknown. Based upon evidence that susceptibility to neurogenic impact is an important determinant of the severity of ageing muscle degeneration, we aimed to determine the presence and extent of denervation in pre-frail/frail elderly (FE, 77.9 ± 6.2 years) women compared to young physically inactive (YI, 24.0 ± 3.5 years) females, and contrast these findings to high-functioning world class octogenarian female masters athletes (MA, 80.9 ± 6.6 years). Muscle biopsies from vastus lateralis muscle were obtained from all three groups to assess denervation-related morphological and transcriptional markers. The FE group displayed marked grouping of slow fibres, accumulation of very small myofibres, a severe reduction in type IIa/I size ratio, highly variable inter-subject accumulation of neural cell adhesion molecule (NCAM)-positive myofibres, and an accumulation of pyknotic nuclei, indicative of recurring cycles of denervation/reinnervation and persistent denervation. The MA group exhibited a smaller decline in type IIa/I size ratio and fewer pyknotic nuclei, accompanied by a higher degree of type I fibre grouping and larger fibre group size, suggesting a greater reinnervation of denervated fibres. Consistent with this interpretation, MA had higher mRNA levels of the reinnervation-promoting cytokine fibroblast growth factor binding protein 1 (FGFBP1) than FE. Our results indicate that the muscle of FE women has significant neurogenic atrophy, whereas MA muscle exhibit superior reinnervation capacity, suggesting that the difference in age-related muscle impact between low- and high-functioning elderly women is the robustness of the response to denervation of myofibres.

Leucine Supplementation Does Not Alter Insulin Sensitivity in Prefrail and Frail Older Women following a Resistance Training Protocol.

BACKGROUND: Frailty is a clinical condition associated with loss of muscle mass and strength (sarcopenia). Although sarcopenia has multifactorial causes, it might be partly attributed to a blunted response to anabolic stimuli. Leucine acutely increases muscle protein synthesis, and resistance training (RT) is the strongest stimuli to counteract sarcopenia and was recently shown to improve insulin sensitivity (IS) in frail older women. Discrepancies exist regarding whether chronic supplementation of leucine in conjunction with RT can improve muscle mass and IS. OBJECTIVE: The aim of this double-blinded placebo-controlled study was to determine the effects of leucine supplementation and RT on IS in prefrail and frail older women. METHODS: Using the Fried criteria, 19 nondiabetic prefrail (1-2 criteria) and frail (≥3 criteria) older women (77.5 ± 1.3 y; body mass index (kg/m2): 25.1 ± 0.9) underwent a 3-mo intervention of RT 3 times/wk with protein-optimized diet of 1.2 g·kg-1·d-1 and 7.5 g·d-1 of l-leucine supplementation compared with placebo l-alanine. Pre-/postintervention primary outcomes were fasting plasma glucose, serum insulin, and 4-h responses to a standard meal of complete liquid formula. Secondary outcomes of resting energy expenditure using indirect calorimetry and body composition using dual-energy X-ray absorptiometry were obtained. Paired t tests analyzed pooled data, and 2-factor repeated-measures ANOVA determined supplementation, training, and interaction effects. RESULTS: No significant time, group, or interaction effects were observed for postprandial areas under the curve of serum insulin or plasma glucose or for resting energy expenditure in l-leucine compared with l-alanine. Total lean body mass increased and percentage body fat decreased significantly for both groups postintervention (0.76 ± 0.13 and -0.92 ± 0.33 kg, respectively; time effect: P < 0.01). CONCLUSIONS: IS was not affected by RT and leucine supplementation in nondiabetic prefrail and frail older women. Therefore, leucine supplementation does not appear to influence IS under these conditions. This trial was registered at clinicaltrials.gov as NCT01922167.

Effect of a 12-week mixed power training on physical function in dynapenic-obese older men: does severity of dynapenia matter?

INTRODUCTION: Mobility disability affects nearly 15% of people aged 65 or over worldwide. Excess weight or obesity (OB), along with an accentuated loss of muscle strength (dynapenia), is recognized to be one of the most common risk factors for mobility impairment among the elderly. OBJECTIVE: To investigate the effect of a 12-week mixed power training (MPT high-velocity resistance training mixed with functional exercises) on physical function in obese older men exhibiting different severities of dynapenia. METHODS: Community-dwelling older men (69 ± 6 years) were assigned to the study if they were considered obese (OB, fat mass ≥ 25% body weight, BW) and to one of the two groups according to severity of dynapenia [(handgrip strength-HS)/BW]: type 1(OB-DY1) or type 2(OB-DY2), < 1 or 2SD from a young reference group. Participants followed a 12-week MPT, three times/week, 75 min/session. Main outcomes included the performance on the 4-m and 6-min walking tests, Timed Up and Go, stair and balance tests. RESULTS AND DISCUSSION: At baseline, OB-DY1 performed better than OB-DY2 in all functional tests (p < 0.05). Following the intervention, medium-to-large training effect size (ES) were observed for fat (ES = 0.21) and lean (ES = 0.32, p < 0.001) masses, functional performance (ES 0.11-0.54, p < 0.05), HS (ES = 0.10, p < 0.05) and lower limb muscle strength (ES = 0.67, p < 0.001) and power (ES = 0.60, p < 0.05). Training-by-group interaction showed that OB-DY1 lost more FM (ES = 0.11, p = 0.03) and OB-DY2 improved more HS (ES = 0.19, p = 0.006) than their counterparts. CONCLUSIONS: Seniors with obesity and severe dynapenia have poorer physical function than those in the early stage of dynapenia. Both seem to benefit from a high-velocity resistance training mixed with functional exercises, although by slightly different pathways.

High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure.

BACKGROUND: Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia. METHODS: We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28. RESULTS: A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006). CONCLUSIONS: In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384.).

Inactivation of the ubiquitin-specific protease 19 deubiquitinating enzyme protects against muscle wasting.

The ubiquitin system plays a critical role in muscle wasting. Previous work has focused on the roles of ubiquitination. However, a role for deubiquitination in this process has not been established. Because ubiquitin-specific protease (USP)19 deubiquitinating enzyme is induced in skeletal muscle in many catabolic conditions, we generated USP19 knockout (KO) mice. These mice lost less muscle mass than wild-type (WT) animals in response to glucocorticoids, a common systemic cause of muscle atrophy as well as in response to denervation, a model of disuse atrophy. KO mice retained more strength and had less myofiber atrophy with both type I and type IIb fibers being protected. Rates of muscle protein synthesis were similar in WT and KO mice, suggesting that the sparing of atrophy was attributed to suppressed protein degradation. Consistent with this, expression of the ubiquitin ligases MuRF1 and MAFbx/atrogin-1 as well as several autophagy genes was decreased in the muscles of catabolic KO mice. Expression of USP19 correlates with that of MuRF1 and MAFbx/atrogin-1 in skeletal muscles from patients with lung cancer or gastrointestinal cancer, suggesting that USP19 is involved in human muscle wasting. Inhibition of USP19 may be a useful approach to the treatment of many muscle-wasting conditions.

Do patients with advanced cancer have any potential for protein anabolism in response to amino acid therapy?

PURPOSE OF REVIEW: There is evidence that protein anabolism is achievable before cancer evolves into refractory cachexia with attenuation of muscle loss and even muscle gain. This review summarizes recent observations on the role of total and specific amino acids in promoting protein anabolism in human cancer and revisits prior studies in this context. RECENT FINDINGS: Analysis of muscle changes in advanced cancer patients indicated opportunities for inducing anabolism. Maintenance and gain in muscle was reported in a majority of patients, from initiation of oncologic treatment and before the final refractory stage. In addition to being substrates, some amino acids, for example leucine, act as intracellular signals to promote protein synthesis. Recent acute studies demonstrated that provision of amino acids, sufficient to considerably elevate circulating leucine concentrations concurrent with other amino acid and nutrient availability, resulted in significant protein anabolism in cancer patients. This occurred even during weight loss and inflammation. SUMMARY: Patients with cancer have an anabolic potential to be exploited early on in cachexia development. High-leucine and protein supplements are worth testing as part of a multimodal anabolic approach in long-term trials to confirm their efficacy to sustain anabolism, and attenuate or even reverse muscle wasting.

Navigating the Landscape of Translational Geroscience in Canada: A Comprehensive Evaluation of Current Progress and Future Directions.

The inaugural Canadian Conferences on Translational Geroscience were held as 2 complementary sessions in October and November 2023. The conferences explored the profound interplay between the biology of aging, social determinants of health, the potential societal impact of geroscience, and the maintenance of health in aging individuals. Although topics such as cellular senescence, molecular and genetic determinants of aging, and prevention of chronic disease were addressed, the conferences went on to emphasize practical applications for enhancing older people's quality of life. This article summarizes the proceeding and underscores the synergy between clinical and fundamental studies. Future directions highlight national and global collaborations and the crucial integration of early-career investigators. This work charts a course for a national framework for continued innovation and advancement in translational geroscience in Canada.

Epidermal growth factor-induced vacuolar (H+)-atpase assembly: a role in signaling via mTORC1 activation.

Using proteomics and immunofluorescence, we demonstrated epidermal growth factor (EGF) induced recruitment of extrinsic V(1) subunits of the vacuolar (H(+))-ATPase (V-ATPase) to rat liver endosomes. This was accompanied by reduced vacuolar pH. Bafilomycin, an inhibitor of V-ATPase, inhibited EGF-stimulated DNA synthesis and mammalian target of rapamycin complex 1 (mTORC1) activation as indicated by a decrease in eukaryotic initiation factor 4E-binding 1 (4E-BP1) phosphorylation and p70 ribosomal S6 protein kinase (p70S6K) phosphorylation and kinase activity. There was no corresponding inhibition of EGF-induced Akt and extracellular signal-regulated kinase (Erk) activation. Chloroquine, a neutralizer of vacuolar pH, mimicked bafilomycin effects. Bafilomycin did not inhibit the association of mTORC1 with Raptor nor did it affect AMP-activated protein kinase activity. Rather, the intracellular concentrations of essential but not non-essential amino acids were decreased by bafilomycin in EGF-treated primary rat hepatocytes. Cycloheximide, a translation elongation inhibitor known to augment intracellular amino acid levels, prevented the effect of bafilomycin on amino acids levels and completely reversed its inhibition of EGF-induced mTORC1 activation. In vivo administration of EGF stimulated the recruitment of Ras homologue enriched in brain (Rheb) but not mammalian target of rapamycin (mTOR) to endosomes and lysosomes. This was inhibited by chloroquine treatment. Our results suggest a role for vacuolar acidification in EGF signaling to mTORC1.

Altered serum bile acid profile in fibromyalgia is associated with specific gut microbiome changes and symptom severity.

ABSTRACT: Alterations in the composition and function of the gut microbiome in women with fibromyalgia have recently been demonstrated, including changes in the relative abundance of certain bile acid-metabolizing bacteria. Bile acids can affect multiple physiological processes, including visceral pain, but have yet to be explored for association to the fibromyalgia gut microbiome. In this study, 16S rRNA sequencing and targeted metabolomic approaches were used to characterize the gut microbiome and circulating bile acids in a cohort of 42 women with fibromyalgia and 42 healthy controls. Alterations in the relative abundance of several bacterial species known to metabolize bile acids were observed in women with fibromyalgia, accompanied by significant alterations in the serum concentration of secondary bile acids, including a marked depletion of α-muricholic acid. Statistical learning algorithms could accurately detect individuals with fibromyalgia using the concentration of these serum bile acids. Serum α-muricholic acid was highly correlated with symptom severity, including pain intensity and fatigue. Taken together, these findings suggest serum bile acid alterations are implicated in nociplastic pain. The changes observed in the composition of the gut microbiota and the concentration of circulating secondary bile acids seem congruent with the phenotype of increased nociception and are quantitatively correlated with symptom severity. This is a first demonstration of circulating bile acid alteration in individuals with fibromyalgia, potentially secondary to upstream gut microbiome alterations. If corroborated in independent studies, these observations may allow for the development of molecular diagnostic aids for fibromyalgia as well as mechanistic insights into the syndrome.

Lifestyle Behavior Changes and Associated Risk Factors During the COVID-19 Pandemic: Results from the Canadian COVIDiet Online Cohort Study.

BACKGROUND: The COVID-19 pandemic and related lockdowns have impacted lifestyle behaviors, including eating habits and physical activity; yet, few studies have identified the emerging patterns of such changes and associated risk factors. OBJECTIVE: This study aims to identify the patterns of weight and lifestyle behavior changes, and the potential risk factors, resulting from the pandemic in Canadian adults. METHODS: Analyses were conducted on 1609 adults (18-89 years old; n=1450, 90.1%, women; n=1316, 81.8%, White) of the Canadian COVIDiet study baseline data (May-December 2020). Self-reported current and prepandemic weight, physical activity, smoking status, perceived eating habits, alcohol intake, and sleep quality were collected through online questionnaires. Based on these 6 indicator variables, latent class analysis (LCA) was used to identify lifestyle behavior change patterns. Associations with potential risk factors, including age, gender, ethnicity, education, income, chronic diseases, body image perception, and changes in the stress level, living situation, and work arrangement, were examined with logistic regressions. RESULTS: Participants' mean BMI was 26.1 (SD 6.3) kg/m2. Of the 1609 participants, 980 (60.9%) had a bachelor's degree or above. Since the pandemic, 563 (35%) had decreased income and 788 (49%) changed their work arrangement. Most participants reported unchanged weight, sleep quality, physical activity level, and smoking and alcohol consumption, yet 708 (44%) reported a perceived decrease in eating habit quality. From LCA, 2 classes of lifestyle behavior change emerged: healthy and less healthy (probability: 0.605 and 0.395, respectively; Bayesian information criterion [BIC]=15574, entropy=4.8). The healthy lifestyle behavior change group more frequently reported unchanged weight, sleep quality, smoking and alcohol intake, unchanged/improved eating habits, and increased physical activity. The less healthy lifestyle behavior change group reported significant weight gain, deteriorated eating habits and sleep quality, unchanged/increased alcohol intake and smoking, and decreased physical activity. Among risk factors, body image dissatisfaction (odds ratio [OR] 8.8, 95% CI 5.3-14.7), depression (OR 1.8, 95% CI 1.3-2.5), increased stress level (OR 3.4, 95% CI 2.0-5.8), and gender minority identity (OR 5.5, 95% CI 1.3-22.3) were associated with adopting less healthy behaviors in adjusted models. CONCLUSIONS: The COVID-19 pandemic has appeared to have influenced lifestyle behaviors unfavorably in some but favorably in others. Body image perception, change in stress level, and gender identity are factors associated with behavior change patterns; whether these will sustain over time remains to be studied. Findings provide insights into developing strategies for supporting adults with poorer mental well-being in the postpandemic context and promoting healthful behaviors during future disease outbreaks. TRIAL REGISTRATION: ClinicalTrials.gov NCT04407533; https://clinicaltrials.gov/ct2/show/NCT04407533.

Reporting quality of randomized controlled trials in prehabilitation: a scoping review.

BACKGROUND: Inadequate study reporting precludes interpretation of findings, pooling of results in meta-analyses, and delays knowledge translation. While prehabilitation interventions aim to enhance candidacy for surgery, to our knowledge, a review of the quality of reporting in prehabilitation has yet to be conducted. Our objective was to determine the extent to which randomized controlled trials (RCTs) of prehabilitation are reported according to methodological and intervention reporting checklists. METHODS: Eligibility criteria: RCTs of unimodal or multimodal prehabilitation interventions. SOURCES OF EVIDENCE: search was conducted in March 2022 using MEDLINE, Embase, PsychINFO, Web of Science, CINAHL, and Cochrane. CHARTING METHODS: identified studies were compared to CONSORT, CERT & Modified CERT, TIDieR, PRESENT, and CONSORT-SPI. An agreement ratio (AR) was defined to evaluate if applicable guideline items were correctly reported. Data were analyzed as frequency (n, %) and mean with standard deviation (SD). RESULTS: We identified 935 unique articles and included 70 trials published from 1994 to 2022. Most prehabilitation programs comprised exercise-only interventions (n = 40, 57%) and were applied before oncologic surgery (n = 32, 46%). The overall mean AR was 57% (SD: 20.9%). The specific mean ARs were as follows: CONSORT: 71% (SD: 16.3%); TIDieR: 62% (SD:17.7%); CERT: 54% (SD: 16.6%); Modified-CERT: 40% (SD:17.8%); PRESENT: 78% (SD: 8.9); and CONSORT-SPI: 47% (SD: 22.1). CONCLUSION: Altogether, existing prehabilitation trials report approximately half of the checklist items recommended by methodological and intervention reporting guidelines. Reporting practices may improve with the development of a reporting checklist specific to prehabilitation interventions.

Association of Low Muscle Mass With Cognitive Function During a 3-Year Follow-up Among Adults Aged 65 to 86 Years in the Canadian Longitudinal Study on Aging.

Importance: Cross-sectional studies have shown that combined low muscle mass and strength are associated with cognitive impairment. Whether low muscle mass, reflective of physiologic reserve, is independently associated with faster cognitive decline remains unknown. Objective: To investigate the associations between low muscle mass and cognitive decline in 3 distinct domains among adults aged at least 65 years. Design, Setting, and Participants: The Canadian Longitudinal Study on Aging is a prospective population-based cohort study of community-dwelling adults. Enrollment occurred from 2011 to 2015 with a 3-year follow-up. Analyses for this study were conducted on those aged at least 65 years from April 24 to August 12, 2020. Exposure: Appendicular lean soft tissue mass (ALM) was assessed by dual energy x-ray absorptiometry. Low ALM was identified using the sex-specific Canadian cut points. Main Outcomes and Measures: Memory was assessed using the Rey auditory verbal learning test. Executive function was assessed using the mental alternation test, Stroop high interference (words/dot) test, the animal fluency test, and the controlled oral word association test. Psychomotor speed was assessed using computer-administered choice reaction time. Composite scores by domain were created. Results: Of 8279 participants, 4003 (48%) were female, 8005 (97%) were White, and the mean (SD) age was 72.9 (5.6) years. A total of 1605 participants (19.4%) had low ALM at baseline. Participants with low ALM were older, had lower body mass index and physical activity level. The presence of low ALM at baseline was associated with faster 3-year cognitive decline in executive functions and psychomotor speed from multiple linear regressions. After adjusting for covariates including age, level of education, percentage body fat, and handgrip strength, low ALM remained independently associated with executive function decline (standardized ß: -0.032; P = .03) only. Low ALM was not associated with memory. Conclusions and Relevance: This cohort study found longitudinal associations between low ALM and cognition in aging. Identification of older adults with low muscle mass, a targetable modifiable factor, may help estimate those at risk for accelerated executive function decline. Further longer-term investigation of associations is warranted.