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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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Abstract
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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Muscle protein breakdown is impaired during immobilization compared to during a subsequent retraining period in older men: no effect of anti-inflammatory medication.
Dideriksen, K, Reitelseder, S, Agergaard, J, Boesen, AP, Aas, SN, Raastad, T, Holm, L
Pflugers Archiv : European journal of physiology. 2020;(2):281-292
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Abstract
Muscle inactivity reduces muscle protein synthesis (MPS), whereas a subsequent period of rehabilitation resistance training (retraining) increases MPS. However, less is known regarding muscle protein breakdown (MPB) during such conditions. Furthermore, nonsteroidal anti-inflammatory drugs (NSAIDs) may have a dampening effect on MPB during periods of inactivity in older individuals. Thus, we measured the average MPB, by use of the deuterated water methodology, during an immobilization period and a subsequent retraining period in older individuals with and without NSAID treatment. Eighteen men (60-80 years: range) were randomly assigned to ibuprofen (1200 mg/d, Ibu) or placebo (Plc). One lower limb was immobilized in a cast for 2 weeks and retrained for 2 weeks, and 2 × 20 g of whey protein was ingested daily during both periods. Besides MPB, the protein expression of different muscle degradation signaling molecules was investigated. MPB was lower during immobilization compared to retraining (p < 0.01). NSAID treatment did not affect the MPB rate during immobilization or retraining (p > 0.05). The protein expression of muscle degradation signaling molecules changed during the study intervention but were unaffected by NSAID treatment. The finding that MPB was lower during immobilization than during retraining indicates that an increased MPB may play an important role in the muscle protein remodeling processes taking place within the initial retraining period. Moreover, NSAID treatment did not significantly influence the MPB rate during 2 weeks of lower limb immobilization or during 2 weeks of subsequent retraining in older individuals.
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Dairy Protein Supplementation Modulates the Human Skeletal Muscle microRNA Response to Lower Limb Immobilization.
D'Souza, RF, Zeng, N, Figueiredo, VC, Markworth, JF, Durainayagam, BR, Mitchell, SM, Fanning, AC, Poppitt, SD, Cameron-Smith, D, Mitchell, CJ
Molecular nutrition & food research. 2018;(7):e1701028
Abstract
Limb immobilization results in a rapid loss of muscle size and strength. The resultant alterations in signaling pathways governing myogenesis, catabolism, and mitochondrial biogenesis are likely to include posttranscriptional regulation mediated by altered microRNAs (miRNAs). Given that protein ingestion exerts an anabolic action and may act as a countermeasure to mitigate muscle loss with immobilization, it is important to examine miRNA in this context. The objective of the study is therefore to characterize the vastus lateralis miRNA response to 14 days of disuse in males (45-60 years) randomized to receive supplementation with 20 g d-1 of dairy protein (n = 12) or isocaloric carbohydrate placebo (n = 13). Biopsies are collected before and after a 2-week immobilization period. Of the 24 miRNAs previously identified in myogenic regulation, seven (miR-133a, -206, -15a, -451a, -126, -208b, and let-7e) are increased with immobilization irrespective of group; five (miR-16, -494, let-7a, -7c, and 7d) increased only in the carbohydrate group; and eight (miR-1, -486, -23a, -23b, -26a, -148b, let-7b, and -7g) are divergently expressed between groups (suppressed with protein). The ability of protein supplementation to differentially regulate miRNAs involved in key muscle regulatory pathways following short-term limb immobilization reflects potential protective function in mitigating muscle loss during limb immobilization.
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Exercise recovery increases skeletal muscle H2O2 emission and mitochondrial respiratory capacity following two-weeks of limb immobilization.
Pileggi, CA, Hedges, CP, D'Souza, RF, Durainayagam, BR, Markworth, JF, Hickey, AJR, Mitchell, CJ, Cameron-Smith, D
Free radical biology & medicine. 2018;:241-248
Abstract
Extended periods of skeletal muscle disuse result in muscle atrophy. Following limb immobilization, increased mitochondrial reactive oxygen species (ROS) production may contribute to atrophy through increases in skeletal muscle protein degradation. However, the effect of skeletal muscle disuse on mitochondrial ROS production remains unclear. This study investigated the effect of immobilization, followed by two subsequent periods of restored physical activity, on mitochondrial H2O2 emissions in adult male skeletal muscle. Middle-aged men (n = 30, 49.7 ± 3.84 y) completed two weeks of unilateral lower-limb immobilization, followed by two weeks of baseline-matched activity, consisting of 10,000 steps a day, then completed two weeks of three times weekly supervised resistance training. Vastus lateralis biopsies were taken at baseline, post-immobilization, post-ambulatory recovery, and post-resistance-training. High-resolution respirometry was used simultaneously with fluorometry to determine mitochondrial respiration and hydrogen peroxide (H2O2) production in permeabilized muscle fibres. Mitochondrial H2O2 emission with complex I and II substrates, in the absence of ADP, was greater following immobilization, however, there was no effect on mitochondrial respiration. Both ambulatory recovery and resistance training, following the period of immobilization, increased in mitochondrial H2O2 emissions. These data demonstrated that 2 weeks of immobilization increases mitochondrial H2O2 emissions, but subsequent retraining periods of ambulatory recovery and resistance training also led to in robust increases in mitochondrial H2O2 emissions in skeletal muscle.
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An integrative review exploring decision-making factors influencing mental health nurses in the use of restraint.
Riahi, S, Thomson, G, Duxbury, J
Journal of psychiatric and mental health nursing. 2016;(2):116-28
Abstract
UNLABELLED WHAT IS KNOWN ON THE SUBJECT?: There is emerging evidence highlighting the counter therapeutic impact of the use of restraint and promoting the minimization of this practice in mental health care. Mental health nurses are often the professional group using restraint and understanding factors influencing their decision-making becomes critical. To date, there are no other published papers that have undertaken a similar broad search to review this topic. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Eight emerging themes are identified as factors influencing mental health nurses decisions-making in the use of restraint. The themes are: 'safety for all', 'restraint as a necessary intervention', 'restraint as a last resort', 'role conflict', 'maintaining control', 'staff composition', 'knowledge and perception of patient behaviours', and 'psychological impact'. 'Last resort' appears to be the mantra of acceptable restraint use, although, to date, there are no studies that specifically consider what this concept actually is. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: These findings should be considered in the evaluation of the use of restraint in mental health settings and appropriate strategies placed to support shifting towards restraint minimization. As the concept of 'last resort' is mentioned in many policies and guidelines internationally with no published understanding of what this means, research should prioritize this as a critical next step in restraint minimization efforts. INTRODUCTION While mechanical and manual restraint as an institutional method of control within mental health settings may be perceived to seem necessary at times, there is emergent literature highlighting the potential counter-therapeutic impact of this practice for patients as well as staff. Nurses are the professional group who are most likely to use mechanical and manual restraint methods within mental health settings. In-depth insights to understand what factors influence nurses' decision-making related to restraint use are therefore warranted. AIM: To explore what influences mental health nurses' decision-making in the use of restraint. METHOD An integrative review using Cooper's framework was undertaken. RESULTS Eight emerging themes were identified: 'safety for all', 'restraint as a necessary intervention', 'restraint as a last resort', 'role conflict', 'maintaining control', 'staff composition', 'knowledge and perception of patient behaviours', and 'psychological impact'. These themes highlight how mental health nurses' decision-making is influenced by ethical and safety responsibilities, as well as, interpersonal and staff-related factors. CONCLUSION Research to further understand the experience and actualization of 'last resort' in the use of restraint and to provide strategies to prevent restraint use in mental health settings are needed.
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Neuromuscular electrical stimulation prevents muscle disuse atrophy during leg immobilization in humans.
Dirks, ML, Wall, BT, Snijders, T, Ottenbros, CL, Verdijk, LB, van Loon, LJ
Acta physiologica (Oxford, England). 2014;(3):628-41
Abstract
AIM: Short periods of muscle disuse, due to illness or injury, result in substantial skeletal muscle atrophy. Recently, we have shown that a single session of neuromuscular electrical stimulation (NMES) increases muscle protein synthesis rates. The aim was to investigate the capacity for daily NMES to attenuate muscle atrophy during short-term muscle disuse. METHODS Twenty-four healthy, young (23 ± 1 year) males participated in the present study. Volunteers were subjected to 5 days of one-legged knee immobilization with (NMES; n = 12) or without (CON; n = 12) supervised NMES sessions (40-min sessions, twice daily). Two days prior to and immediately after the immobilization period, CT scans and single-leg one-repetition maximum (1RM) strength tests were performed to assess quadriceps muscle cross-sectional area (CSA) and leg muscle strength respectively. Furthermore, muscle biopsies were taken to assess muscle fibre CSA, satellite cell content and mRNA and protein expression of selected genes. RESULTS In CON, immobilization reduced quadriceps CSA by 3.5 ± 0.5% (P < 0.0001) and muscle strength by 9 ± 2% (P < 0.05). In contrast, no significant muscle loss was detected following immobilization in NMES although strength declined by 7 ± 3% (P < 0.05). Muscle MAFbx and MuRF1 mRNA expression increased following immobilization in CON (P < 0.001 and P = 0.07 respectively), whereas levels either declined (P < 0.01) or did not change in NMES, respectively. Immobilization led to an increase in muscle myostatin mRNA expression in CON (P < 0.05), but remained unchanged in NMES. CONCLUSION During short-term disuse, NMES represents an effective interventional strategy to prevent the loss of muscle mass, but it does not allow preservation of muscle strength. NMES during disuse may be of important clinical relevance in both health and disease.
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Effects of traditional swaddling on development: a randomized controlled trial.
Manaseki-Holland, S, Spier, E, Bavuusuren, B, Bayandorj, T, Sprachman, S, Marshall, T
Pediatrics. 2010;(6):e1485-92
Abstract
OBJECTIVE Evidence of the effects of tight, prolonged binding of infants on development is inconclusive and based on small ethnographic studies. The null hypothesis was that Mongolian infants not swaddled or swaddled tightly in a traditional setting (to >7 months of age) do not have significantly different scores for the Bayley Scales of Infant Development, Second Edition (BSID-II). PATIENTS AND METHODS In a randomized controlled trial, 1279 healthy newborns in Ulaanbaatar, Mongolia, were allocated at birth to traditional swaddling or nonswaddling. The families received 7 months of home visits to collect data and monitor compliance. At 11 to 17 months of age, the BSID-II was administered to 1100 children. RESULTS No significant between-group differences were found in mean scaled mental and psychomotor developmental scores. The unadjusted mean difference between the groups was -0.69 (95% confidence interval [CI]: -2.59 to 1.19) for psychomotor and -0.42 (95% CI: -1.68 to 0.84) for mental scores in favor of the swaddling group. A subgroup analysis of the compliant sample produced similar results. BSID-II-scaled psychomotor and mental scores were 99.98 (95% CI: 99.03-100.92) and 105.52 (95% CI: 104.89-106.14), respectively. Background characteristics were balanced across the groups. CONCLUSIONS In the Mongolian context, prolonged swaddling in the first year of life did not have any significant impact on children's early mental or psychomotor development. Additional studies in other settings need to confirm this finding. The Mongolian infants in this trial had scaled BSID-II mental and psychomotor scores comparable to United States norms.