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Fasting-Mimicking-Diet does not reduce skeletal muscle function in healthy young adults: a randomized control trial.
Nardon, M, Venturelli, M, Ruzzante, F, Longo, VD, Bertucco, M
European journal of applied physiology. 2022;(3):651-661
Abstract
PURPOSE The aim of this study was to evaluate the short- and long-term effects of the Fasting-Mimicking-Diet (FMD) intervention on neuromuscular parameters of force production in healthy young men. METHODS Twenty-four physically active men completed the study. Participants were randomly assigned to Fasting-Mimicking (FMD) or Normal Diet (ND) and asked to follow three cycles of dietary intervention. Neuromuscular parameters of force production during maximal voluntary isometric contractions (MVCs) with the leg extensors muscles and anthropometrics were measured at baseline (T0), at the end of the first cycle (T1), and 7-10 days after the 3rd cycle of the nutritional intervention (T2). The study was registered on Clinicaltrials.gov (No. NCT04476615). RESULTS There was a significant decrease in body mass at T1 for FMD (- 2.6 kg, ∆ from baseline, on average; p < 0.05) but not in ND (- 0.1 kg;). Neuromuscular parameters of force production, muscle volume, and MVC torque did not change or differ between groups across visits. Results were similar even when parameters were normalized by muscle volume. CONCLUSION The consumption of FMD in a group of young healthy male subjects showed to be feasible, and it did not affect neuromuscular parameters of force production. The results suggest that FMD could be safely adopted by strength athletes without detrimental effects on force and muscle volume. Further research in clinical population at risk of muscle mass loss, such as elderly and obese subjects with sarcopenia, is warranted.
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High-intensity leg cycling alters the molecular response to resistance exercise in the arm muscles.
Moberg, M, Apró, W, Cervenka, I, Ekblom, B, van Hall, G, Holmberg, HC, Ruas, JL, Blomstrand, E
Scientific reports. 2021;(1):6453
Abstract
This study examined acute molecular responses to concurrent exercise involving different muscles. Eight men participated in a randomized crossover-trial with two sessions, one where they performed interval cycling followed by upper body resistance exercise (ER-Arm), and one with upper body resistance exercise only (R-Arm). Biopsies were taken from the triceps prior to and immediately, 90- and 180-min following exercise. Immediately after resistance exercise, the elevation in S6K1 activity was smaller and the 4E-BP1:eIF4E interaction greater in ER-Arm, but this acute attenuation disappeared during recovery. The protein synthetic rate in triceps was greater following exercise than at rest, with no difference between trials. The level of PGC-1α1 mRNA increased to greater extent in ER-Arm than R-Arm after 90 min of recovery, as was PGC-1α4 mRNA after both 90 and 180 min. Levels of MuRF-1 mRNA was unchanged in R-Arm, but elevated during recovery in ER-Arm, whereas MAFbx mRNA levels increased slightly in both trials. RNA sequencing in a subgroup of subjects revealed 862 differently expressed genes with ER-Arm versus R-Arm during recovery. These findings suggest that leg cycling prior to arm resistance exercise causes systemic changes that potentiate induction of specific genes in the triceps, without compromising the anabolic response.
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Genicular Artery Embolization for Osteoarthritis Related Knee Pain: A Systematic Review and Qualitative Analysis of Clinical Outcomes.
Casadaban, LC, Mandell, JC, Epelboym, Y
Cardiovascular and interventional radiology. 2021;(1):1-9
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Objective To systematically review the published literature on genicular artery embolization (GAE) for osteoarthritis (OA) related knee pain. Materials and Methods Using three databases, a systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Outcome measures included the Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results Three single-arm studies were included from an initial search yielding 305 results. One hundred and eighty-six knees in 133 patients with either mild-to-moderate (174/186, 94%) or severe (12/186, 6%) OA underwent embolization with either imipenem/cilastatin sodium (159/186, 85%) or embozene (27/186, 15%). Technical success was 100%. Average VAS improved from baseline at 1 day, 1 week, 1 month, 3 months, 4 months, 6 months, 1 year and 2 years (66.5 at baseline vs 33.5, 32.7, 33.8, 28.9, 29.0, 22.3, 14.8 and 14.0, respectively). Average WOMAC scores improved from baseline at 1, 3, 4, 6, 12 and 24 months (45.7 at baseline vs 24.0, 31.0, 14.8, 14.6, 8.2 and 6.2). Severe OA in 12 cases showed initially improved VAS, but was not sustained. Minor adverse events such as erythema in the region of embolization (21/186, 11%), puncture-site hematoma (18/186, 10%), paresthesia (2/186, 1%) and fever (1/186, 0.5%) were reported. Conclusion Limited single-arm studies report GAE is promising for treating OA-related pain. Most treatments performed for mild-to-moderate OA demonstrated durable clinical responses from 6 months to 4 years. Limited data for severe OA suggest a non-durable response. Future studies should be standardized to facilitate comparison and control for placebo effect.
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Microvascular Function Is Impaired after Short-Term Immobilization in Healthy Men.
Rytter, N, Piil, P, Carter, H, Nyberg, M, Hellsten, Y, Gliemann, L
Medicine and science in sports and exercise. 2020;(10):2107-2116
Abstract
PURPOSE We examined whether 2 wk of one-leg immobilization would impair leg microvascular function and to what extent a subsequent period of intense aerobic cycle training could restore function. METHODS Study participants were healthy young men (n = 12; 20-24 yr of age). Leg microvascular function was determined before the intervention, after the immobilization period, and after a 4-wk exercise training period. Microvascular function was assessed as the vasodilator response to intra-arterial infusion of acetylcholine and sodium nitroprusside and as the vasoconstrictor response to endogenous noradrenaline release induced by tyramine infusion. Vasodilator enzymes as well as prooxidant and antioxidant enzymes were assessed by protein analysis in skeletal muscle samples: endothelial nitric oxide synthase, NADPH oxidase (NOX p67 and NOX gp91), and superoxide dismutase 2 (SOD2). RESULTS The acetylcholine-induced change in vascular conductance was reduced after the 2 wk of immobilization (P = 0.003), tended to increase (P = 0.061), and was back to baseline levels after the subsequent 4 wk of exercise training. Plasma prostacyclin levels in response to acetylcholine infusion were lower after immobilization than before (P = 0.041). The changes in vascular conductance with sodium nitroprusside and tyramine were similar during all conditions. Skeletal muscle protein levels of endothelial nitric oxide synthase in the experimental leg were unchanged with immobilization and subsequent training but increased 47% in the control leg with training (P = 0.002). NOX p67, NOX gp91, and SOD2 in the experimental leg remained unaltered with immobilization, and SOD2 was higher than preimmobilization after 4 wk of training (P < 0.001). CONCLUSIONS The study shows that 2 wk of immobilization impairs leg microvascular endothelial function and prostacyclin formation but that 4 wk of intense aerobic exercise training restores the function. The underlying mechanism may reside in the prostacyclin system.
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One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension.
Bilet, L, Phielix, E, van de Weijer, T, Gemmink, A, Bosma, M, Moonen-Kornips, E, Jorgensen, JA, Schaart, G, Zhang, D, Meijer, K, et al
Diabetologia. 2020;(6):1211-1222
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AIMS/HYPOTHESIS Physical inactivity, low mitochondrial function, increased intramyocellular lipid (IMCL) deposition and reduced insulin sensitivity are common denominators of chronic metabolic disorders, like obesity and type 2 diabetes. Yet, whether low mitochondrial function predisposes to insulin resistance in humans is still unknown. METHODS Here we investigated, in an intervention study, whether muscle with low mitochondrial oxidative capacity, induced by one-legged physical inactivity, would feature stronger signs of lipid-induced insulin resistance. To this end, ten male participants (age 22.4 ± 4.2 years, BMI 21.3 ± 2.0 kg/m2) underwent a 12 day unilateral lower-limb suspension with the contralateral leg serving as an active internal control. RESULTS In vivo, mitochondrial oxidative capacity, assessed by phosphocreatine (PCr)-recovery half-time, was lower in the inactive vs active leg. Ex vivo, palmitate oxidation to 14CO2 was lower in the suspended leg vs the active leg; however, this did not result in significantly higher [14C]palmitate incorporation into triacylglycerol. The reduced mitochondrial function in the suspended leg was, however, paralleled by augmented IMCL content in both musculus tibialis anterior and musculus vastus lateralis, and by increased membrane bound protein kinase C (PKC) θ. Finally, upon lipid infusion, insulin signalling was lower in the suspended vs active leg. CONCLUSIONS/INTERPRETATION Together, these results demonstrate, in a unique human in vivo model, that a low mitochondrial oxidative capacity due to physical inactivity directly impacts IMCL accumulation and PKCθ translocation, resulting in impaired insulin signalling upon lipid infusion. This demonstrates the importance of mitochondrial oxidative capacity and muscle fat accumulation in the development of insulin resistance in humans. TRIAL REGISTRATION ClinicalTrial.gov NCT01576250. FUNDING PS was supported by a 'VICI' Research Grant for innovative research from the Netherlands Organization for Scientific Research (Grant 918.96.618).
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Treatment of distal deep vein thrombosis.
Kirkilesis, G, Kakkos, SK, Bicknell, C, Salim, S, Kakavia, K
The Cochrane database of systematic reviews. 2020;(4):CD013422
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BACKGROUND The treatment of distal (below the knee) deep vein thrombosis (DVT) is not clearly established. Distal DVT can either be treated with anticoagulation, or monitored with close follow-up to detect progression to the proximal veins (above the knee), which requires anticoagulation. Proponents of this monitoring strategy base their decision to withhold anticoagulation on the fact that progression is rare and most people can be spared from potential bleeding and other adverse effects of anticoagulation. OBJECTIVES To assess the effects of different treatment interventions for people with distal (below the knee) deep vein thrombosis (DVT). SEARCH METHODS The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 12 February 2019. We also undertook reference checking to identify additional studies. SELECTION CRITERIA Randomised controlled trials (RCTs) for the treatment of distal DVT. DATA COLLECTION AND ANALYSIS Two review authors independently selected trials and extracted data. We resolved disagreements by discussion. Primary outcomes of interest were recurrence of venous thromboembolism (VTE), DVT and major bleeding and follow up ranged from three months to two years. We performed fixed-effect model meta-analyses with risk ratio (RRs) and 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE. MAIN RESULTS We identified eight RCTs reporting on 1239 participants. Five trials randomised participants to anticoagulation for up to three months versus no anticoagulation. Three trials compared anticoagulation treatment for different time periods. Anticoagulant compared to no intervention or placebo for distal DVT treatment Anticoagulation with a vitamin K antagonist (VKA) reduced the risk of recurrent VTE during follow-up compared with participants receiving no anticoagulation (RR 0.34, 95% CI 0.15 to 0.77; 5 studies, 496 participants; I2 = 3%; high-certainty evidence), and reduced the risk of recurrence of DVT (RR 0.25, 95% CI 0.10 to 0.67; 5 studies, 496 participants; I2 = 0%; high-certainty evidence). There was no clear effect on risk of pulmonary embolism (PE) (RR 0.81, 95% CI 0.18 to 3.59; 4 studies, 480 participants; I2 = 0%; low-certainty evidence). There was little to no difference in major bleeding with anticoagulation compared to placebo (RR 0.76, 95% CI 0.13 to 4.62; 4 studies, 480 participants; I2 = 26%; low-certainty evidence). There was an increase in clinically relevant non-major bleeding events in the group treated with anticoagulants (RR 3.34, 95% CI 1.07 to 10.46; 2 studies, 322 participants; I2 = 0%; high-certainty evidence). There was one death, not related to PE or major bleeding, in the anticoagulation group. Anticoagulation for three months or more compared to anticoagulation for six weeks for distal DVT treatment Three RCTs of 736 participants compared three or more months of anticoagulation with six weeks of anticoagulation. Anticoagulation with a VKA for three months or more reduced the incidence of recurrent VTE to 5.8% compared with 13.9% in participants treated for six weeks (RR 0.42, 95% CI 0.26 to 0.68; 3 studies, 736 participants; I2 = 50%; high-certainty evidence). The risk for recurrence of DVT was also reduced (RR 0.32, 95% CI 0.16 to 0.64; 2 studies, 389 participants; I2 = 48%; high-certainty evidence), but there was probably little or no difference in PE (RR 1.05, 95% CI 0.19 to 5.88; 2 studies, 389 participants; I2 = 0%; low-certainty evidence). There was no clear difference in major bleeding events (RR 3.42, 95% CI 0.36 to 32.35; 2 studies, 389 participants; I2 = 0%; low-certainty evidence) or clinically relevant non-major bleeding events (RR 1.76, 95% CI 0.90 to 3.42; 2 studies, 389 participants; I2 = 1%; low-certainty evidence) between three months or more of treatment and six weeks of treatment. There were no reports for overall mortality or PE and major bleeding-related deaths. AUTHORS' CONCLUSIONS Our review found a benefit for people with distal DVT treated with anticoagulation therapy using VKA with little or no difference in major bleeding events although there was an increase in clinically relevant non-major bleeding when compared to no intervention or placebo. The small number of participants in this meta-analysis and strength of evidence prompts a call for more research regarding the treatment of distal DVT. RCTs comparing different treatments and different treatment periods with placebo or compression therapy, are required.
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Variable resistance training versus traditional weight training on the reflex pathway following four weeks of leg press training.
Smith, CM, Housh, TJ, Hill, EC, Keller, JL, Anders, JPV, Johnson, GO, Schmidt, RJ
Somatosensory & motor research. 2019;(3):223-229
Abstract
Purpose: The purpose of this study was to examine the changes in reflex-electromechanical delay (EMD) as a result of 2- and 4-wks of variable resistance training (VRT) or dynamic constant external resistance (DCER) leg press training. Material and Methods: Thirty-six men were randomised into either the Control, DCER, or VRT groups. The DCER and VRT groups performed 3 sets of 10 leg press repetitions 3-d·wk-1 for 4-wks. Reflex-EMD was measured at Baseline, Week-2, and Week-4. Results: The reflex-EMD durations decreased from Baseline at Week-2 and Week-4 for the VRT group, but not the DCER or Control groups. The reflex response < electrochemical process < mechanical process < total reflex-EMD for all groups. Conclusions: VRT elicited greater reflex adaptations compared to DCER training which indicated that VRT may be beneficial to incorporate into training or physical therapy programmes for pilots, soldiers, elderly, athletes, or professions that require quick reflexes and response times.
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Factors associated with upper leg muscle strength in knee osteoarthritis: A scoping review.
de Zwart, AH, Dekker, J, Lems, W, Roorda, LD, van der Esch, M, van der Leeden, M
Journal of rehabilitation medicine. 2018;(2):140-150
Abstract
OBJECTIVE Muscle weakness is common and strongly related to clinical outcome in patients with knee or hip osteoarthritis. To date, there is no clear overview of the information on factors associated with muscle strength in knee and hip osteoarthritis. The aim of this paper is to provide an overview of current knowledge on factors associated with upper leg muscle strength in this population. DESIGN The framework of a scoping review was chosen. MEDLINE database was searched systematically up to 22 April 2017. Studies that described a relationship between a factor and muscle strength in knee or hip osteoarthritis were included. RESULTS A total of 65 studies met the inclusion criteria. In studies of knee osteoarthritis, 4 factors were consistently found to be associated with lower muscle strength. Due to the low number of studies on hip osteoarthritis no conclusions could be drawn on associations. CONCLUSION Lower muscle quality, physical inactivity, more severe joint degeneration, and higher pain are reported to be associated with lower strength in the upper leg muscles in knee osteoarthritis. Future research into knee osteoarthritis should focus on other potential determinants of muscle strength, such as muscle quantity, muscle activation, nutrition and vitamins, and inflammation. In hip osteoarthritis, more research is needed into all potential determinants.
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Twelve weeks' progressive resistance training combined with protein supplementation beyond habitual intakes increases upper leg lean tissue mass, muscle strength and extended gait speed in healthy older women.
Francis, P, Mc Cormack, W, Toomey, C, Norton, C, Saunders, J, Kerin, E, Lyons, M, Jakeman, P
Biogerontology. 2017;(6):881-891
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The age-related decline in functional capability is preceded by a reduction in muscle quality. The purpose of this study was to assess the combined effects of progressive resistance training (PRT) and protein supplementation beyond habitual intakes on upper leg lean tissue mass (LTM), muscle quality and functional capability in healthy 50-70 years women. In a single-blinded, randomized, controlled design, 57 healthy older women (age 61.1 ± 5.1 years, 1.61 ± 0.65 m, 65.3 ± 15.3 kg) consumed 0.33 g/kg body mass of a milk-based protein matrix (PRO) for 12 weeks. Of the 57 women, 29 also engaged in a PRT intervention (PRO + PRT). In comparison to the PRO group (n = 28), those in the PRO + PRT group had an increase in upper leg LTM [0.04 (95% CI -0.07 to 0.01) kg vs. 0.13 (95% CI 0.08-0.18) kg, P = 0.027], as measured by Dual-energy X-ray absorptiometry; an increase in knee extensor (KE) torque [-1.6 (95% CI -7.3 to 4.4 N m) vs. 10.2 (95% CI 4.3-15.8 N m), P = 0.007], as measured from a maximal voluntary isometric contraction (Con-Trex MJ; CMV AG); and an increase in extended gait speed [-0.01 (95% CI -0.52-0.04) m s-1 vs. 0.10 (95% CI 0.05-0.22) m s-1, P = 0.001] as measured from a maximal 900 m effort. There was no difference between groups in the time taken to complete 5 chair rises or the number of chair rises performed in 30 s (P > 0.05). PRT in healthy older women ingesting a dietary protein supplement is an effective strategy to improve upper leg LTM, KE torque and extended gait speed in healthy older women.
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Prior exercise and standing as strategies to circumvent sitting-induced leg endothelial dysfunction.
Morishima, T, Restaino, RM, Walsh, LK, Kanaley, JA, Padilla, J
Clinical science (London, England : 1979). 2017;(11):1045-1053
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We have previously shown that local heating or leg fidgeting can prevent prolonged sitting-induced leg endothelial dysfunction. However, whether physical activity prevents subsequent sitting-induced leg endothelial dysfunction remains unknown. Herein, we tested the hypothesis that sitting-induced leg endothelial dysfunction would be prevented by prior exercise. We also examined if, in the absence of exercise, standing is an effective alternative strategy to sitting for conserving leg endothelial function. Fifteen young healthy subjects completed three randomized experimental trials: (1) sitting without prior exercise; (2) sitting with prior exercise; and (3) standing without prior exercise. Following baseline popliteal artery flow-mediated dilation (FMD) measurements, subjects maintained a supine position for 45 min in the sitting and standing trials, without prior exercise, or performed 45 min of leg cycling before sitting (i.e. sitting with prior exercise trial). Thereafter, subjects were positioned into a seated or standing position, according to the trial, for 3 h. Popliteal artery FMD measures were then repeated. Three hours of sitting without prior exercise caused a significant impairment in popliteal artery FMD (baseline: 3.8±0.5%, post-sitting: 1.5±0.5%, P<0.05), which was prevented when sitting was preceded by a bout of cycling exercise (baseline: 3.8±0.5%, post-sitting: 3.6±0.7%, P>0.05). Three hours of standing did not significantly alter popliteal artery FMD (baseline: 4.1±0.4%, post-standing: 4.3±0.4%, P>0.05). In conclusion, prolonged sitting-induced leg endothelial dysfunction can be prevented by prior aerobic exercise. In addition, in the absence of exercise, standing represents an effective substitute to sitting for preserving leg conduit artery endothelial function.