Skeletal muscle hypertrophy rewires glucose metabolism: An experimental investigation and systematic review.

BACKGROUND: Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy. METHODS: We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-13C6]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level. RESULTS: The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: -36.8%; P = 0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-13C6]glucose is increasingly incorporated by ~13% (P = 0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P < 0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n = 450 243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P < 5.0e-8). CONCLUSIONS: Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis.

Effect of a slump posture on pain, proprioception, and electrical activity of the muscles in office workers with chronic non-specific neck pain. A retrospective study.

BACKGROUND: The impact of computer typing in a slump posture on pain, proprioception and muscle recruitment has not been extensively investigated. Therefore, the purpose of this study was to evaluate the extent of pain, proprioception and muscle activity resulting from computer typing in a slump posture in women who already suffer from chronic neck pain. METHODS: This cross-sectional study was conducted between May 20 to July 10, 2021. A total of 15 female 42-(±4.96)-year-old office workers with chronic non-specific neck pain participated in this study. Before and after 60 min of computer typing in a slump posture, proprioception and pain were measured using an inclinometer and visual analog scale (VAS), respectively. The activity of the cervical erector spine (CES) and upper trapezius (UT) muscle was also measured before and after the slump-posture computer typing, in upright, forward, and slump postures. RESU: lts: Paired-samples t-tests showed that pain was increased and proprioception in all directions (flexion, extension, right and left lateral flexion, and right, and left rotation) was less accurate (P < 0.05) after 60 min computer typing. The CES and UT muscle activity were elevated more in the forward head and slump posture than in the upright posture (P < 0.05). CONCLUSION: Sixty minutes computer typing in a slump posture increased neck pain, resulted in a decreased proprioception in the neck and was accompanied by an increased activity of the neck musculature.

Evaluating the effects of hormone therapy termination on skeletal muscle and physical independence in postmenopausal women.

OBJECTIVE: In women, the age-related decline in skeletal muscle structure and function is accelerated after menopause, which implicates the role of decreased circulating estrogen levels. Indeed, boosting estrogen, by means of postmenopausal hormone therapy (HT), generally proves beneficial to skeletal muscle. The evidence regarding whether these benefits persist even after cessation of HT is limited, nor is it clear how physical behavior (PB) impacts on benefits. Hence, this exploratory study focused on the interplay between HT administration/cessation, PB and in vivo skeletal muscle structure and function. METHODS: Fifty healthy women (≥60 y) were included; 19 had an HT administration history (≥9 mo, with now ~8-y hiatus in treatment) and 31 no such history. On seven continuous days, PB data were collected using triaxial accelerometry and analyzed using compositional data analysis. Gastrocnemius medialis muscle volume, architecture, and function were determined using ultrasonography, electromyography, dual x-ray absorptiometry, and dynamometry. Current serum estradiol levels were measured using ELISA. RESULTS: Only fascicle length and duration of HT administration were positively associated. With respect to PB levels, we found a pattern suggesting greater vitality (higher physical activity and lower sedentarism) in previous HT users, compared with nonusers, despite the two groups currently no longer exhibiting significantly different levels of circulating estradiol. CONCLUSIONS: After an 8-year hiatus in treatment, HT provides limited advantages in gastrocnemius medialis muscle properties. Interestingly, it perhaps enhances vitality despite prolonged cessation, which in the longer term would facilitate greater physical independence, especially considering the association of sedentary behavior with greater frailty.

An In Silico Cardiomyocyte Reveals the Impact of Changes in CaMKII Signalling on Cardiomyocyte Contraction Kinetics in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is characterised by asymmetric left ventricular hypertrophy, ventricular arrhythmias, and cardiomyocyte dysfunction that may cause sudden death. HCM is associated with mutations in sarcomeric proteins and is usually transmitted as an autosomal-dominant trait. The aim of this in silico study was to assess the mechanisms that underlie the altered electrophysiological activity, contractility, regulation of energy metabolism, and crossbridge cycling in HCM at the single-cell level. To investigate this, we developed a human ventricular cardiomyocyte model that incorporates electrophysiology, metabolism, and force generation. The model was validated by its ability to reproduce the experimentally observed kinetic properties of human HCM induced by (a) remodelling of several ion channels and Ca2+-handling proteins arising from altered Ca2+/calmodulin kinase II signalling pathways and (b) increased Ca2+ sensitivity of the myofilament proteins. Our simulation showed a decreased phosphocreatine-to-ATP ratio (-9%) suggesting a negative mismatch between energy expenditure and supply. Using a spatial myofilament half-sarcomere model, we also compared the fraction of detached, weakly bound, and strongly bound crossbridges in the control and HCM conditions. Our simulations showed that HCM has more crossbridges in force-producing states than in the control condition. In conclusion, our model reveals that impaired crossbridge kinetics is accompanied by a negative mismatch between the ATP supply and demand ratio. This suggests that improving this ratio may reduce the incidence of sudden death in HCM.

Smoking cessation only partially reverses cardiac metabolic and structural remodeling in mice.

AIMS: Active cigarette smoking is a major risk factor for chronic obstructive pulmonary disease that remains elevated after cessation. Skeletal muscle dysfunction has been well documented after smoking, but little is known about cardiac adaptations to cigarette smoking. The underlying cellular and molecular cardiac adaptations, independent of confounding lifestyle factors, and time course of reversibility by smoking cessation remain unclear. We hypothesized that smoking negatively affects cardiac metabolism and induces local inflammation in mice, which do not readily reverse upon 2-week smoking cessation. METHODS: Mice were exposed to air or cigarette smoke for 14 weeks with or without 1- or 2-week smoke cessation. We measured cardiac mitochondrial respiration by high-resolution respirometry, cardiac mitochondrial density, abundance of mitochondrial supercomplexes by electrophoresis, and capillarization, fibrosis, and macrophage infiltration by immunohistology, and performed cardiac metabolome and lipidome analysis by mass spectrometry. RESULTS: Mitochondrial protein, supercomplex content, and respiration (all p < 0.03) were lower after smoking, which were largely reversed within 2-week smoking cessation. Metabolome and lipidome analyses revealed alterations in mitochondrial metabolism, a shift from fatty acid to glucose metabolism, which did not revert to control upon smoking cessation. Capillary density was not different after smoking but increased after smoking cessation (p = 0.02). Macrophage infiltration and fibrosis (p < 0.04) were higher after smoking but did not revert to control upon smoking cessation. CONCLUSIONS: While cigarette-impaired smoking-induced cardiac mitochondrial function was reversed by smoking cessation, the remaining fibrosis and macrophage infiltration may contribute to the increased risk of cardiovascular events after smoking cessation.

Obesity-related reduced spirometry and altered breathing pattern are associated with mechanical disadvantage of the diaphragm.

The aim of this study was to characterize the breathing patterns of individuals with obesity during routine activities such as sitting and standing, and to identify potential contributors to alterations in these patterns. Measurements performed in 20 male subjects with obesity (BMI, 31.8±1.5 kg/m2) and 20 controls (BMI, 23.5±1.4 kg/m2) included anthropometric parameters, breathing-patterns in sitting and standing positions, spirometry, maximal respiratory pressures, and diaphragm B-mode ultrasonography. Individuals with obesity exhibited lower tidal volume and increased respiratory rate to maintain a similar minute-ventilation (p<0.05). Subjects with obesity demonstrated impaired spirometry and respiratory muscle strength, with inspiratory functions being notably compromised (p<0.05). Individuals with obesity had a greater diaphragm thickness at end inspiration but lower thickening-fraction at end quiet and forced breathings and reduced diaphragmatic displacement and excursion during maximal breaths (p<0.05). BMI was negatively associated with all respiratory function markers (p<0.05). Individuals with obesity exhibit a higher respiratory rate but lower tidal volume, likely to accommodate decreased compliance and excess thoracic and abdominal fat, further hindering inspiratory function. Moreover, increased adiposity is associated with a thicker but weaker diaphragm, primarily due to the diaphragm's mechanical disadvantage rather than its intrinsic inability to generate force.

Concurrent Validity of Four Activity Monitors in Older Adults.

Sedentary behaviour (SB) and physical activity (PA) have been shown to be independent modulators of healthy ageing. We thus investigated the impact of activity monitor placement on the accuracy of detecting SB and PA in older adults, as well as a novel random forest algorithm trained on data from older persons. Four monitor types (ActiGraph wGT3X-BT, ActivPAL3c VT, GENEActiv Original, and DynaPort MM+) were simultaneously worn on five anatomical sites during ten different activities by a sample of twenty older adults (70.0 (12.0) years; 10 women). The results indicated that collecting metabolic equivalent (MET) data for 60 s provided the most representative results, minimising variability. In addition, thigh-worn monitors, including ActivPAL, Random Forest, and Sedentary Sphere-Thigh, exhibited superior performance in classifying SB, with balanced accuracies ≥ 94.2%. Other monitors, such as ActiGraph, DynaPort MM+, and GENEActiv Sedentary Sphere-Wrist, demonstrated lower performance. ActivPAL and GENEActiv Random Forest outperformed other monitors in participant-specific balanced accuracies for SB classification. Only thigh-worn monitors achieved acceptable overall balanced accuracies (≥80.0%) for SB, standing, and medium-to-vigorous PA classifications. In conclusion, it is advisable to position accelerometers on the thigh, collect MET data for ≥60 s, and ideally utilise population-specific trained algorithms.

Sedentary behaviour (especially accumulation pattern) has an independent negative impact on skeletal muscle size and architecture in community-dwelling older adults.

Prolonged sedentary behaviour (SB) i.e. longer bouts, is suggested to have a range of negative health effects, independent of habitual light and medium-to-vigorous physical activity (LIPA or MVPA). Any effect on musculoskeletal size, architecture or morphology has seldom been reported in older adults. Moreover, no study has yet determined if any association would persist following adjustment for covariates. Therefore, the aim of the present study was to investigate the associations between SB, and properties of the Gastrocnemius Medialis (GM) muscle, in a cross-sectional sample of older adults using compositional data analysis. 105 healthy older adults (73±6y) wore a thigh mounted tri-axial accelerometer for seven consecutive days, and underwent ultrasound [e.g. muscle length (Lm), anatomical cross-sectional area (ACSA), muscle volume (VM), fascicle length (LF), & physiological cross-sectional area (PCSA)], body composition (e.g. DEXA) and health (e.g. medical history) assessments. In-unadjusted models, SB time was negatively associated with ACSA at 75% of Lm (R2adj = 0.085), VM (R2adj = 0.020), and PCSA (R2adj = 0.039). Standing was positively associated with pennation angle (R2adj = 0.110), which persisted following co-variate adjustment (R2adj = 0.296). In fully adjusted models, both SB & LIPA time were associated with ACSA at 75% of Lm (Both R2adj = 0.393). Standing and light activity time were also associated with LF, VM, & PCSA (R2adj 0.116-0.573). In fully adjusted models, SB pattern parameters (i.e. the manner in which sedentary behaviour is accumulated daily throughout waking hours such as the timing, duration and frequency of sedentary bouts), were associated with GM muscle properties (R2adj 0.156-0.564) including LM, LF, and VM. The pattern, rather than accumulated daily SB time, was associated with the size and architecture of the GM. Our results suggest that regardless of co-existing habitual physical activities, SB bouts should be kept short and frequently interrupted to offset some of the deleterious ageing-related muscle architecture characteristics changes.

Predictors of Running-Related Injury Among Recreational Runners: A Prospective Cohort Study of the Role of Perfectionism, Mental Toughness, and Passion in Running.

BACKGROUND: The health benefits associated with recreational running are challenged by the occurrence of running-related injuries (RRIs). Effective preventive measures require knowledge of sport injury etiology. Psychological factors such as perfectionism, mental toughness, and passion are believed to predispose to sports injury by influencing training behaviors, motivation to run, and suppression of feelings of fatigue and pain. Yet their association with RRIs are understudied. HYPOTHESIS: Perfectionism, mental toughness, and passion predict an increased risk of RRIs in recreational runners. STUDY DESIGN: Prospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 143 recreational runners (age 34.9 ± 13.9 years, 37% women) with a response rate of 76.5% answered an online questionnaire about their characteristics, running behaviors, and psychological variables (perfectionism, mental toughness, and running passion) as well as a sports injury survey. Then, as a primary outcome, RRIs were recorded biweekly for 6 months. The incidence of injuries was expressed as RRI per 1000 hours of running. The association between predictive factors and RRIs was estimated using logistic regression. RESULTS: The incidence of RRIs during follow-up was 5.16 per 1000 hours of running. The knee was the location injured most often (26.4%), followed by the foot (18.9%) and lower leg (13.2%). Higher obsessive passion (OP) for running (odds ratio [OR], 1.11; 95% CI, 1.04-1.20) and perfectionistic concerns (OR, 1.22; CI,1.05-1.41) were associated with a greater risk of RRIs, as were previous injury (OR, 2.49; CI,1.10-5.70), weekly running distance (OR,1.10; CI, 1.03-1.16), and both supinated (OR, 4.51; CI, 1.11-18.30) and pronated (OR, 3.55; CI, 1.29-9.80) foot type. Following a running schedule (OR, 0.24; CI, 0.09-0.66) was associated with a lower risk of RRIs. CONCLUSION: History of previous RRI, pronated and supinated foot type, weekly running distance, perfectionistic concerns, and OP increased RRI risk in recreational runners. Following a running schedule was a protective factor. CLINICAL RELEVANCE: Multiple factors, including runners' psychological characteristics, predict RRIs. These findings can inform the development of injury risk management strategies.

No ageing-related increase in fibre type grouping in sprint-trained masters runners: A 10-year follow-up study.

BACKGROUND: Previous research suggests that an ageing-associated remodelling and loss of motor units due to motor neuron death contributes significantly to muscle weakness in old age. In histological sections, motor unit remodelling is reflected by increased fibre type grouping. While regular exercise may not attenuate the loss of motor units during ageing, it has been suggested to facilitate reinnervation resulting in larger motor units, and a higher number and larger fibre type groups in histological sections of muscles from aged individuals. METHODS: In a 10-year follow-up study, we assessed changes in the prevalence and size of fibre type groups in the vastus lateralis muscle from 34 male masters sprinters (40-85 years at start). RESULTS: Over the 10 years, there was an ageing-related reduction in performance in the 60-m sprint (P < 0.001) without significant changes in fibre type composition and fibre cross-sectional area. Neither the number of fibre type groups, defined as a fibre surrounded exclusively by fibres of the same type, nor the group size changed significantly in the 10-year period. CONCLUSIONS: These histological data show that there is limited to no significant fibre type grouping over a 10-year period in masters athletes who continued sprint run training. This observation challenges the paradigm that ageing, at least in systematically trained sprinters, is associated with motor unit remodelling.

Oldies, but goldies-preserved morphology and stability of antigenic determinants in decades-old cryosections of human m. vastus lateralis.

Fibre typing by immunohistochemistry on cryosections from human skeletal muscle biopsies is an essential tool in the diagnosis and research of muscular diseases, ageing, and responses to exercise training and disuse. Preserving a good quality in these frozen specimens can be challenging especially if they are stored for longer periods before histological processing, which is often the case in studies with a large number of test subjects and/or repeated sampling separated by multiple years. We demonstrate in this article that both, the morphology and reactivity of epitopes to myosin heavy chain isoforms and dystrophin are well preserved in up to 18-year-stored unfixed and unstained cryosections of human m. vastus lateralis (n = 241). Any variation in staining intensity between samples was unrelated to the age of the biopsy donor or the storage period of the unstained cryosections, and in all cases, the obtained images were appropriate for image analysis, such as the determination of the fibre type composition and the fibre cross-sectional area, and quantitative analysis of muscle capillarisation.

The impact of bed rest on human skeletal muscle metabolism.

Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.

A simple framework to distinguish 'individualistic' from a 'uniform rate' of ageing within or between study populations.

Ageing is accompanied by a progressive decline in physiological functions. It is often argued that the rate of ageing differs between people and is 'highly individualistic'. This view is not unequivocally shared, and others have argued that the rate of ageing is rather 'uniform'. Distinguishing conclusively between these views requires longitudinal data, but these are difficult to obtain as they require decades of data collection from individuals. Here, a simple framework is proposed to assess in cross-sectional data whether in a given population the rate is 'highly individualistic' or rather 'uniform'. It is illustrated that an age-related decrease in the standard deviation (SD) of a certain parameter combined with a non-changing coefficient of variation (COVAR) reflects a 'uniform' rate of ageing, whilst an increase or decrease in COVAR with or without a concomitant increase in SD reflects a 'highly individualistic' rate of ageing. This framework is applied to some published data, focussing on muscle strength, power and physical function for the sake of illustration, and it is suggested that most studies do in fact show a 'highly individualistic' rate of ageing, perhaps apart from a 'uniform' rate of ageing in master athletes.

A modelling approach to disentangle the factors limiting muscle oxygenation in smokers.

Cigarette smoking is associated with a lower exercise capacity and lower muscle fatigue resistance. This is at least partly attributable to carboxyhaemoglobin (HbCO) in the blood that via reduction in the oxygen-carrying capacity, and the left-shift of the Hb-dissociation curve would reduce tissue oxygenation. On the other hand, a reduced oxygen uptake due to mitochondrial dysfunction would result in improved oxygenation. We used previously collected capillarisation, myoglobin and estimated cellular maximal muscle oxygen consumption data derived from succinate dehydrogenase-stained sections from the vastus lateralis muscle from six smokers and five non-smokers. These data were fed into an expanded Krogh tissue oxygenation model to assess whether an impaired muscle fatigue resistance in smokers is primarily due to HbCO or impaired mitochondrial respiration. The model showed that in smokers with 6% and 20% HbCO (causing a left-shift of the Hb-dissociation curve) average muscle oxygenation was reduced by 1.9% and 7.2%, respectively. Muscle oxygenation was increased by 13.3% when maximal mitochondrial respiration was reduced by 29%. A combination of a 29% reduction in maximal mitochondrial respiration and 20% HbCO led to no significant difference in muscle oxygenation from that in non-smokers. This indicates that while HbCO may explain the reduced exercise capacity after just one smoking session, in chronic smokers impaired mitochondrial respiration appears more important in reducing oxygen extraction and exercise capacity with only a small contribution of the left-shift of the Hb-dissociation curve.

Is an Exercise-Based Injury Prevention Programme Effective in Team Handball Players? A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to assess the effectiveness of exercise-based injury prevention programmes in preventing sports injuries in team handball players. DATA SOURCES: Two independent researchers performed a systematic search in the electronic databases Scopus, PubMed, Web of Science (WOS), SPORTDiscus, and CINAHL from inception until Aprile 2023. STUDY SELECTION: Studies were included if they were randomized-controlled or prospective cohort trials, contained a population of competitive team handball players, included an intervention designed specifically to prevent or reduce the risk of team handball injury, and reported injury incidence rates specific to team handball players. Two researchers independently assessed trials for inclusion criteria and methodological quality. DATA EXTRACTION: Study design, intervention details, participant characteristics, and the number of injuries in each group were extracted from each study by two independent researchers. The outcome of interest was the incidence rate of injury. Injury data were classified into 5 groups: lower extremity injuries, shoulder injuries, knee injuries, ankle sprains, or ACL injuries. Extracted data were analyzed by Comprehensive Meta-Analysis software, version 3.0 (CMA.V2) using a random-effects model to compute the overall effect estimates of injury prevention programmes in reducing the risk of injuries. Odds ratios (ORs) with 95% CIs were calculated based on the number of injuries in each group. DATA SYNTHESIS: Meta-analyses were conducted independently for each injury classification. Results indicate that prevention programmes significantly reduced the risk of shoulder injuries (OR, 0.56; 95% CI, 0.36-0.87; P = 0.01), lower extremity (OR, 0.59; 95% CI, 0.37-0.98; P = 0.03), knee (OR, 0.53; 95% CI, 0.35-0.78; P = 0.002) and ankle sprains (OR, 0.57; 95% CI, 0.40-0.81; P = 0.002), and ACL ruptures (OR, 0.67; 95% CI, 0.45-0.97; P = 0.03) in team handball players. CONCLUSION: In team handball players, prevention programmes appear effective in reducing the risk of shoulder, lower extremity, knee, ankle, and ACL injuries.

Decrements of mobility and power in recreationally active septuagenarians is related to loss of force, but not slowing of the muscle: a 5-year longitudinal study.

A lesser 6-min walk distance (6MWD) and timed up-and-go (TUG) in old compared with young adults was previously linked to slowing of muscle contractile properties. The purpose of the present study was to determine whether any further reductions in 6MWD and TUG over a 5-year period in septuagenarians are associated with further slowing of muscle contractile properties. We measured muscle function by a countermovement jump, isometric maximal knee extensor strength (MVC) on a dynamometer and quadriceps muscle size by magnetic resonance imaging (MRI) in 17 older women (71.1 ± 2.8 y) and 17 older men (71.3 ± 4.1y). Performance in TUG and 6MWD were reduced over the 5-year period, irrespective of sex (P < 0.001), and both were correlated with power at both baseline and follow-up (R ≥ 0.53; P ≤ 0.001). Jump take-off velocity (VCMJ) was slower at follow-up (P < 0.01) and correlated with 6MWD and TUG at both baseline and follow-up in both sexes (R ≥ 0.54; P ≤ 0.001). However, the relationship between 'body mass: maximal muscle force ratio' with VCMJ was not significantly changed, indicating that the lower VCMJ was attributable to muscles working at a higher relative load, hence a lower part of the force-velocity relationship, due to a reduction in MVC (body mass had not changed significantly), rather than slowing of the muscle. The lower VCMJ in women than men (P < 0.001) was likewise attributable to a lower MVC rather than slower contractile properties in women. In conclusion, the decrement in 6MWD and TUG in septuagenarians is due to a loss of muscle mass, rather than further loss of muscle quality.

Efficacy of supervised exercise prehabilitation programs to improve major abdominal surgery outcomes: A systematic review and meta-analysis.

The optimal package of components for a prehabilitation intervention remains unclear. The aim was to determine the efficacy of supervised exercise prehabilitation programs to enhance patient fitness and improve surgical outcomes. The protocol was preregistered (PROSPERO: CRD42020180693). PubMed, MEDLINE, CINAHL, AMED, CENTRAL, PeDro, ClinicalTrials.gov and the WHO International Clinical Trials Registry were searched. Randomized controlled trials (RCTs) of supervised prehabilitation programs before major abdominal surgery were included. Physical function, cardiorespiratory capacity and surgical outcomes were the primary outcomes measures. Risk of bias was assessed according to the Cochrane Risk of Bias 1.0 tool for RCTs. Data are summarized narratively, and where possible, quantitavely. Meta-analyses results are reported as risk ratios (RR), mean difference of changes between baseline and follow-up time points or mean difference between groups and 95% confidence interval (CI). Twenty RCTs were included in the analysis with a total of 1258 patients. The average 6-min walking distance change was +33 m in the prehabilitation group compared to the usual care (UC) group after prehabilitation (95% CI: [13, 53], P < 0.01). Only in studies with more than one supervised session per week changes in 6-min-walk distance were significantly higher in the prehabilitation group compared to the UC group after prehabiliatation (Mean difference: 47 m, 95% [CI]: [20-75], P < 0.01). The change in peak volume of oxygen uptake during a maximum cardiopulmonary test was +1.47 mL·kg-1·min-1 in the prehabilitation group compared to the UC group (95% CI: [0.68, 2.25], P < 0.01). There was no significant difference in the change in oxygen uptake at anaerobic threshold between groups (Mean differences: 0.47, 95% CI: [-0.16, 1.10], P:0.14). Post-operative complications incidence was similar between groups (RR: 0.80, 95% CI: [0.61, 1.05], P:0.11), irrespective of the frequency of supervised session per week (RR: 0.67, 95% CI: [0.43, 1.03], P:0.07). In conclusion, prehabilitation programmes with more than one supervised session per week improved physical function but did not enhance surgical outcomes.

A Nrf2-OSGIN1&2-HSP70 axis mediates cigarette smoke-induced endothelial detachment: implications for plaque erosion.

AIMS: Endothelial erosion of plaques is responsible for ∼30% of acute coronary syndromes (ACS). Smoking is a risk factor for plaque erosion, which most frequently occurs on the upstream surface of plaques where the endothelium experiences elevated shear stress. We sought to recreate these conditions in vitro to identify potential pathological mechanisms that might be of relevance to plaque erosion. METHODS AND RESULTS: Culturing human coronary artery endothelial cells (HCAECs) under elevated flow (shear stress of 7.5 Pa) and chronically exposing them to cigarette smoke extract (CSE) and tumour necrosis factor-alpha (TNFα) recapitulated a defect in HCAEC adhesion, which corresponded with augmented Nrf2-regulated gene expression. Pharmacological activation or adenoviral overexpression of Nrf2 triggered endothelial detachment, identifying Nrf2 as a mediator of endothelial detachment. Growth/Differentiation Factor-15 (GDF15) expression was elevated in this model, with protein expression elevated in the plasma of patients experiencing plaque erosion compared with plaque rupture. The expression of two Nrf2-regulated genes, OSGIN1 and OSGIN2, was increased by CSE and TNFα under elevated flow and was also elevated in the aortas of mice exposed to cigarette smoke in vivo. Knockdown of OSGIN1&2 inhibited Nrf2-induced cell detachment. Overexpression of OSGIN1&2 induced endothelial detachment and resulted in cell cycle arrest, induction of senescence, loss of focal adhesions and actin stress fibres, and disturbed proteostasis mediated in part by HSP70, restoration of which reduced HCAEC detachment. In ACS patients who smoked, blood concentrations of HSP70 were elevated in plaque erosion compared with plaque rupture. CONCLUSION: We identified a novel Nrf2-OSGIN1&2-HSP70 axis that regulates endothelial adhesion, elevated GDF15 and HSP70 as biomarkers for plaque erosion in patients who smoke, and two therapeutic targets that offer the potential for reducing the risk of plaque erosion.

Does Aerobic Exercise Facilitate Vaping and Smoking Cessation: A Systematic Review of Randomized Controlled Trials with Meta-Analysis.

Cigarette smokers try to quit using several strategies including electronic cigarette use (vaping). An alternative, easy and cheap method is exercise. However, little is known about the efficacy of aerobic exercise (AE) to augment smoking and vaping cessation. This study aimed to systematically review and discuss the reported effects of AE on long-term vaping and smoking cessation in randomized control trials (RCTs). RCTs were searched on different databases. The outcome measures included long-term vaping or smoking cessation and maximal or peak oxygen uptake (VO2max/peak) after vaping- or smoking cessation. Meta-analysis was conducted to examine the effects of AE on long-term vaping and smoking cessation, and the effects of AE on VO2max/peak. Cochrane Risk of Bias tool 2 was used to assess trials quality. Thirteen trials were included (5 high, 2 moderate and 6 low quality). Although two high quality trials revealed that 3 vigorous supervised AE sessions a week for 12 to 15 weeks increased the number of long-term successful quitters, the meta-analysis including the other trials showed that AE did not significantly increase success rate of long-term quitters. However, VO2max/peak was improved at the end of treatment. There were no trials on AE and vaping cessation. No evidence was found that AE promotes long-term smoking cessation. Nevertheless, AE improved VO2max and/or VO2peak in quitters.