Days Of Immobilization Research Articles

Resistance exercise preconditioning prevents disuse muscle atrophy by inhibiting apoptosis and protein degradation via SESN2 in C57BL/6J mice

AimTo compare the effects of different exercise preconditioning in the context of skeletal muscle atrophy and to investigate the potential involvement of Sestrin2 (SESN2), a stress-inducible protein that can be regulated by exercise, in exercise preconditioning on preventing disuse muscle atrophy. MethodsEight-week-old male C57BL/6J mice were randomly assigned to sedentary groups (SD), aerobic exercise groups (AE), resistance exercise groups (RE), and combined exercise groups (CE) with or without 7 days of immobilization. The duration of the exercise intervention was 10 weeks. The effects of different exercise preconditioning to prevent muscle atrophy were analyzed by evaluating skeletal muscle function and mass. Additionally, to investigate the potential underlying mechanism of exercise-induced protection of skeletal muscle, wild-type and SESN2‐−/‐− mice were randomly divided into sedentary group and resistance exercise preconditioning group. C2C12 cells were treated with SESN2 adenoviruses and MK2206 (an AKT inhibitor) for 48 h to elucidate the underlined mechanism. ResultsRE was more effective in preserving skeletal muscle function, muscle mass and maintaining skeletal muscle protein homeostasis than AE and CE under immobilized condition. Importantly, exercise performance, muscle mass to body weight ratio, and the cross-sectional area of muscle fibers were significantly lower in SESN2−/− mice than wild-type mice after resistance exercise preconditioning. Mechanistically, the absence of SESN2 led to activation of the ubiquitin-proteasome system and induction of apoptosis. In vitro experiments showed that MK2206 treatment mitigated the regulatory effects of overexpression-SESN2 on protein hydrolysis and apoptosis. ConclusionRE was more effective than AE or CE in preventing disuse muscle atrophy. SESN2 mediated the protective effects of resistance exercise preconditioning on skeletal muscle atrophy.

A non-invasive mouse model that recapitulates disuse-induced muscle atrophy in immobilized patients

Disuse muscle atrophy occurs consequent to prolonged limb immobility or bed rest, which represents an unmet medical need. As existing animal models of limb immobilization often cause skin erosion, edema, and other untoward effects, we here report an alternative method via thermoplastic immobilization of hindlimbs in mice. While significant decreases in the weight and fiber size were noted after 7 days of immobilization, no apparent skin erosion or edema was found. To shed light onto the molecular mechanism underlying this muscle wasting, we performed the next-generation sequencing analysis of gastrocnemius muscles from immobilized versus non-mobilized legs. Among a total of 55,487 genes analyzed, 787 genes were differentially expressed (> fourfold; 454 and 333 genes up- and down-regulated, respectively), which included genes associated with muscle tissue development, muscle system process, protein digestion and absorption, and inflammation-related signaling. From a clinical perspective, this model may help understand the molecular/cellular mechanism that drives muscle disuse and identify therapeutic strategies for this debilitating disease.

The muscle proteome reflects changes in mitochondrial function, cellular stress and proteolysis after 14 days of unilateral lower limb immobilization in active young men.

Skeletal muscle unloading due to joint immobilization induces muscle atrophy, which has primarily been attributed to reductions in protein synthesis in humans. However, no study has evaluated the skeletal muscle proteome response to limb immobilization using SWATH proteomic methods. This study characterized the shifts in individual muscle protein abundance and corresponding gene sets after 3 and 14 d of unilateral lower limb immobilization in otherwise healthy young men. Eighteen male participants (25.4 ±5.5 y, 81.2 ±11.6 kg) underwent 14 d of unilateral knee-brace immobilization with dietary provision and following four-weeks of training to standardise acute training history. Participant phenotype was characterized before and after 14 days of immobilization, and muscle biopsies were obtained from the vastus lateralis at baseline (pre-immobilization) and at 3 and 14 d of immobilization for analysis by SWATH-MS and subsequent gene-set enrichment analysis (GSEA). Immobilization reduced vastus group cross sectional area (-9.6 ±4.6%, P <0.0001), immobilized leg lean mass (-3.3 ±3.9%, P = 0.002), unilateral 3-repetition maximum leg press (-15.6 ±9.2%, P <0.0001), and maximal oxygen uptake (-2.9 ±5.2%, P = 0.044). SWATH analyses consistently identified 2281 proteins. Compared to baseline, two and 99 proteins were differentially expressed (FDR <0.05) after 3 and 14 d of immobilization, respectively. After 14 d of immobilization, 322 biological processes were different to baseline (FDR <0.05, P <0.001). Most (77%) biological processes were positively enriched and characterized by cellular stress, targeted proteolysis, and protein-DNA complex modifications. In contrast, mitochondrial organization and energy metabolism were negatively enriched processes. This study is the first to use data independent proteomics and GSEA to show that unilateral lower limb immobilization evokes mitochondrial dysfunction, cellular stress, and proteolysis. Through GSEA and network mapping, we identify 27 hub proteins as potential protein/gene candidates for further exploration.

Immobilization of uranium soil by geopolymer coupled with nHAP

The leaching of uranium in uranium soil will pose great risks to human health and the ecological environment. The immobilization of uranium by coal gangue geopolymers (CGG) and Nano-hydroxyapatite (nHAP)-based composite geopolymers were investigated in this study. The ability of geopolymers to immobilize uranium was evaluated in terms of the static and dynamic leaching concentration. The experimental results confirmed that the lowest static leaching concentration of composite uranium soil solidified body and uranium soil solidified body was 15.94 mg/kg and 21.27 mg/kg after 28 days of immobilization, respectively. During the 28-d dynamic leaching experiment, the highest leaching concentration was 155.38 mg/kg and 166.63 mg/kg, respectively. The composite uranium soil solidified body shows better overall leaching resistance.

In-situ remediation of zinc contaminated soil using phosphorus recovery product: Hydroxyapatite/calcium silicate hydrate (HAP/C–S–H)

This work discussed the feasibility and stability of utilizing C–S–H phosphorus recovered products, HAP/C–S–H, to remove Zn(Ⅱ) from aqueous solution and in-situ immobilize Zn(Ⅱ) in contaminated soil. The removal mechanisms of Zn(Ⅱ) by HAP/C–S–H were relatively complex, combining multiple reactions including electrostatic attraction, ion exchange, surface complexation and (co-)precipitation. The removal rate of Zn(Ⅱ) by HAP/C–S–H raised with the increase of pH value, reaching 99.47% at pH of 8 in aqueous solution. The ion strength of background solution negatively affected the adsorption efficiency. The pseudo-second-order model and Langmuir model were more suitable to fit the Zn(Ⅱ) adsorption experimental data for the adsorbent. The adsorption process was endothermic and spontaneous naturally according to thermodynamic parameter. The maximum adsorption capacity of HAP/C–S–H can reach 114.0 mg/g at 308 K. After 28 days of immobilization, the release of Zn(Ⅱ) in soil with HAP/C–S–H remarkably decreased to 0.6 mg/L, compared with control group (2.9 mg/L). BCR sequential extraction results indicated that HAP/C–S–H could convert acid-soluble Zn(Ⅱ) into reducible and residual Zn(Ⅱ), reducing the bioavailability and ecotoxicity of Zn(Ⅱ) in contaminated soil. pH-dependent leaching tests revealed that the soil with HAP/C–S–H had stronger resistance to acid impact.

Effects of two months of bed rest and antioxidant supplementation on attentional processing

Physical inactivity across the lifespan is a growing public health concern affecting the cardiovascular, musculoskeletal, and central nervous system. Data on the effects of dietary antioxidants as neuroprotective treatments when physical activity levels are impaired are lacking. In this randomized controlled study, twenty young healthy men underwent 60 days of bed rest. Participants were randomly assigned to a treatment group (n = 10) receiving a daily antioxidant supplement comprising polyphenols, omega-3 fatty acids, vitamin E, and selenium or a control group (n = 10). Event-related potentials (ERPs) and behavioral data from a three-stimulus oddball paradigm were collected eight days before bed rest, after 60 days of immobilization, and after eight days of recovery. After two months of bed rest, we found a significant decrease in task efficiency irrespective of the treatment that was corroborated by lower ERPs in fronto-central and parietal brain regions. Neither behavioral nor electrocortical data returned to baseline values after eight days of recovery. Our results provide support for the adverse and persistent neurobehavioral effects of prolonged bed rest, which could not be mitigated by antioxidant supplementation. These findings raise important implications for situations in which physical activity levels become severely restricted such as medical conditions or sedentary lifestyles.

Lipid Dynamics due to Muscle Atrophy Induced by Immobilization.

Muscle atrophy refers to skeletal muscle loss and dysfunction that affects glucose and lipid metabolism. Moreover, muscle atrophy is manifested in cancer, diabetes, and obesity. In this study, we focused on lipid metabolism during muscle atrophy. We observed that the gastrocnemius muscle was associated with significant atrophy with 8 days of immobilization of hind limb joints and that muscle atrophy occurred regardless of the muscle fiber type. Further, we performed lipid analyses using thin layer chromatography, liquid chromatography-mass spectrometry, and mass spectrometry imaging. Total amounts of triacylglycerol, phosphatidylserine, and sphingomyelin were found to be increased in the immobilized muscle. Additionally, we found that specific molecular species of phosphatidylserine, phosphatidylcholine, and sphingomyelin were increased by immobilization. Furthermore, the expression of adipose triglyceride lipase and the activity of cyclooxygenase-2 were significantly reduced by atrophy. From these results, it was revealed that lipid accumulation and metabolic changes in specific fatty acids occur during disuse muscle atrophy. The present study holds implications in validating preventive treatment strategies for muscle atrophy.

Females and males exhibit similar functional, mechanical, and morphological outcomes in a rat model of posttraumatic elbow contracture.

Posttraumatic joint contracture (PTJC) is a debilitating condition characterized by loss of joint motion following injury. Previous work in a rat model of elbow PTJC investigated disease etiology, progression, and recovery in only male animals; this study explored sex-based differences. Rat elbows were subjected to a unilateral anterior capsulotomy and lateral collateral ligament transection followed by 42 days of immobilization and 42 days of free mobilization. Grip strength and gait were collected throughout the free mobilization period while joint mechanical testing, microcomputed tomography and histological analysis were performed postmortem. Overall, few differences were seen between sexes in functional, mechanical, and morphological outcomes with PTJC being similarly debilitating in male and female animals. Functional measures of grip strength and gait showed that, while some baseline differences existed between sexes, traumatic injury produced similar deficits that remained significantly different long-term when compared to control animals. Similarly, male and female animals both had significant reductions in joint range of motion due to injury. Ectopic calcification (EC), which had not been previously evaluated in this injury model, was present in all limbs on the lateral side. Injury caused increased EC volume but did not alter mineral density regardless of sex. Furthermore, histological analysis of the anterior capsule showed minor differences between sexes for inflammation and thickness but not for other histological parameters. A quantitative understanding of sex-based differences associated with this injury model will help inform future therapeutics aimed at reducing or preventing elbow PTJC.

Skeletal Muscle Anti-Atrophic Effects of Leucine Involve Myostatin Inhibition.

Lack of mechanical load leads to skeletal muscle atrophy, and one major underlying mechanism involves the myostatin pathway that negatively regulates protein synthesis and also activates Atrogin-1/MAFbx and MuRF1 genes. In hindlimb immobilization, leucine was observed to attenuate the upregulation of the referred atrogenes, thereby shortening the impact on fiber cross-sectional area, nonetheless, the possible connection with myostatin is still elusive. This study sought to verify the impact of leucine supplementation on myostatin expression. Male Wistar rats were supplemented with leucine and hindlimb immobilized for 3 and 7 days, after which soleus muscles were removed for morphometric measurements and analyzed for gene and protein expression by real-time PCR and Western blotting, respectively. Muscle wasting was prominent 7 days after immobilization, as expected, leucine feeding mitigated this effect. Atrogin-1/MAFbx gene expression was upregulated only after 3 days of immobilization, and this effect was attenuated by leucine supplementation. Atrogin-1/MAFbx protein levels were elevated after 7 days of immobilization, which leucine supplementation was not able to lessen. On the other hand, myostatin gene expression was upregulated in immobilization for 3 and 7 days, which returned to normal levels after leucine supplementation. Myostatin protein levels followed gene expression at a 3-day time point only. Follistatin gene expression was upregulated during immobilization and accentuated by leucine after 3 days of supplementation. Concerning protein expression, follistatin was not altered neither by immobilization nor in immobilized animals treated with leucine. In conclusion, leucine protects against skeletal muscle mass loss during disuse, and the underlying molecular mechanisms appear to involve myostatin inhibition and Atrogin-1 normalization independently of follistatin signaling.

High-dose leucine supplementation does not prevent muscle atrophy or strength loss over 7 days of immobilization in healthy young males

Unavoidable periods of disuse lead to muscle atrophy and functional decline. Preventing such declines can reduce the risk of re-injury and improve recovery of normal physiological functioning. We aimed to determine the effectiveness of high-dose leucine supplementation on muscle morphology and strength during 7 d of unilateral lower-limb immobilization, and the role of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis in disuse atrophy. Sixteen healthy males (mean±SEM age: 23±1 y) underwent 7 d of unilateral lower-limb immobilization, with thrice-daily leucine (LEU; n=8) or placebo (PLA; n=8) supplementation (15 g/d). Before and after immobilization, muscle strength and compartmental tissue composition were assessed. A primed continuous infusion of l-[ring-13C6]-phenylalanine with serial muscle biopsies was used to determine postabsorptive and postprandial (20 g milk protein) MyoPS and MitoPS, fiber morphology, markers of protein turnover, and mitochondrial function between the control leg (CTL) and the immobilized leg (IMB). Leg fat-free mass was reduced in IMB (mean±SEM: -3.6%±0.5%; P=0.030) but not CTL with no difference between supplementation groups. Isometric knee extensor strength declined to a greater extent in IMB (-27.9%±4.4%) than in CTL (-14.3%±4.4%; P=0.043) with no difference between groups. In response to 20 g milk protein, postprandial MyoPS rates were significantly lower in IMB than in CTL (-22%±4%; P<0.01) in both LEU and PLA. Postabsorptive MyoPS rates did not differ between legs or groups. Postabsorptive MitoPS rates were significantly lower in IMB than in CTL (-14%±5%; P<0.01) and postprandial MitoPS rates significantly declined in response to 20 g milk protein ingestion (CTL: -10%±8%; IMB: -15%±10%; P=0.039), with no differences between legs or groups. There were no significant differences in measures of mitochondrial respiration between legs, but peroxisome proliferator-activated receptor γ coactivator 1-α and oxidative phosphorylation complex II and III were significantly lower in IMB than in CTL (P<0.05), with no differences between groups. High-dose leucine supplementation (15 g/d) does not appear to attenuate any functional declines associated with 7 d of limb immobilization in young, healthy males.This trial was registered at clinicaltrials.gov as NCT03762278.

Locomotion replacement exercise cannot counteract cartilage biomarker response to 5 days of immobilization in healthy adults.

Biomarkers of cartilage metabolism are sensitive to changes in the biological and mechanical environment and can indicate early changes in cartilage homeostasis. The purpose of this study was to determine if a daily locomotion replacement program can serve as a countermeasure for changes in cartilage biomarker serum concentration caused by immobilization. Ten healthy male subjects (mean ± 1 standard deviation; age: 29.4 ± 5.9 years; body mass: 77.7 ± 4.1 kg) participated in the crossover 5-day bed rest study with three interventions: control (CON), standing (STA), and locomotion replacement training (LRT). Serum samples were taken before, during, and after bed rest. Biomarker concentrations were measured using commercial enzyme-linked immunosorbent assays. Cartilage oligomeric matrix protein (COMP) levels after 24 hours of bed rest decreased independently of the intervention (-16.8% to -9.8%) and continued to decrease until 72 hours of bed rest (minimum, -23.2% to -20.6%). LRT and STA did not affect COMP during bed rests (P = .056) but there was a strong tendency for a slower decrease with LRT (-9.4%) and STA (-11.7%) compared with CON (-16.8%). MMP-3 levels decreased within the first 24 hours of bed rest (CON: -22.3%; STA: -14.7%; LRT: -17%) without intervention effect. Both COMP and MMP-3 levels recovered to baseline levels during the 6-day recovery period. MMP-1, MMP-9, and TNF-α levels were not affected by immobilization or intervention. COMP and MMP-3 are mechano-sensitive cartilage biomarkers affected by immobilization, and simple interventions such as standing upright or LRT during bed rest cannot prevent these changes. Clinical significance: simple locomotion interventions cannot prevent cartilage biomarker change during bed rest.

Increased volume and collagen crosslinks drive soft tissue contribution to post-traumatic elbow contracture in an animal model.

Post-traumatic joint contracture (PTJC) in the elbow is a biological problem with functional consequences. Restoring elbow motion after injury is a complex challenge because contracture is a multi-tissue pathology. We previously developed an animal model of elbow PTJC using Long-Evans rats and showed that the capsule and ligaments/cartilage were the primary soft tissues that caused persistent joint motion loss. The objective of this study was to evaluate tissue-specific changes within the anterior capsule and lateral collateral ligament (LCL) that led to their contribution to elbow contracture. In our rat model of elbow PTJC, a unilateral surgery replicated damage that commonly occurs due to elbow dislocation. Following surgery, the injured limb was immobilized for 42 days. The capsule and LCL were evaluated after 42 days of immobilization or 42 days of immobilization followed by 42 days of free mobilization. We evaluated extracellular matrix protein biochemistry, non-enzymatic collagen crosslink content, tissue volume with contrast-enhanced micro-computed tomography, and tissue mechanical properties. Increased collagen content, but not collagen density, was observed in both injured limb capsules and LCLs, which was consistent with the increased tissue volume. Injured limb LCLs exhibited decreased normalized maximum force, and both tissues had increased immature collagen cross-links compared to control. Overall, increased tissue volume and immature collagen crosslinks in the capsule and LCL drive their contribution to elbow contracture in our rat model.

Production of Bioactive Lichen Compounds by Alginate-Immobilized Bionts Isolated from Cladonia verticillaris: An in Vitro Study

Bionts isolated from thalli of Cladonia verticillaris, immobilized in calcium alginate, produce two depsidones, fumarprotocetraric and protocetraric acids, and the depside atranorin, that exhibit antimicrobial activity against Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. Organic lichen extract (acetone/ether/chloroform) shows the highest antimicrobial activity due to a possible synergism between these substances. Antioxidant capacity of soluble metabolites secreted from the immobilisates to the bath medium of incubation during the first 12 days of immobilization has been found (˃80% oxidation inhibition). The concentration of soluble phenolic substances depends on the immobilization time (during 32 days), exogenous supply of acetate (1.0m mM sodium or calcium acetate) and on the type of isolated biont (phycobionts, mycobionts, whole thallus or immobilized phycobionts co-incubated with the mycobionts ones).&#x0D; &#x0D; The role of phycobionts in phenol production has been interpreted as a possible modification of the polymalonyl pathway; for example, atranorin is actively produced and secreted during immobilization while it is not detected in thallus in natura. Co-incubated bionts secrete higher amounts of atranorin to the media during the first 12 days of immobilization. Immobilization of isolated bionts could be used as a biotechnological technique to obtain a potential source of biological active compounds.&#x0D; &#x0D; On the other hand, the physiological state detected of C. verticillaris in the Cerrado is much better for experimentation than that of the specimens collected in Caatinga since, in this case, the thalli showed the fragility that the extreme environmental conditions of the semi-arid region of NE Brazil impose on this lichen species. To date, no priority has been defined for lichen conservation in Brazilian ecosystems. It is therefore suggested that it imust important to include lichen ecophysiology studies in public conservation policies.

831 Optimal Timing for Range of Motion to Upper Extremities Following Split Thickness Skin Autographing: A Five Year Retrospective Review

Abstract Introduction The hand and upper extremity is one of the most common sites for burn injury. The total body surface area (TBSA) of the hand is small but the resultant impairment can limit a patient’s ability to return to functional independence. Split thickness skin grafting (STSG) has long been supported in the literature as the main means of treatment following full thickness burn injury. Surgical placement of STSG is often followed by a period of immobilization to the grafted area for graft adherence. The length of time which the grafted area is immobilized has evolved over time as surgical methods have improved. There is no set standard to balance the length of time necessary to prevent complications while maintaining functional mobility. A literature review revealed several studies and a meta-analysis examining the optimal timing for immobilization and bedrest following STSG to the lower extremities. Additional studies have examined guidelines for range of motion protocols and splinting as well as reconstructive procedures for improved function following burn injury. There are currently no studies examining the optimal timing for immobility following the placement of STSG and the implications this can have on functional independence. The proposed study details the results of one burn center’s standard of treatment following STSG to the upper extremity. Methods Following obtaining approval from the IRB, deidentified data was retrospectively collected from the electronic medical record from January 1, 2014-January 1, 2019 for all inpatients ages 18 and up who underwent split thickness skin grafting to the upper extremity. Results Data collected from 2014–2018 revealed a decreasing trend in the days of immobilization following STSG from an average of 4 days to 2 days to the resumption of range of motion (ROM). Additional trends include a decrease in the utilization of splinting as a prophylactic treatment for contractures with a shift towards interventional splinting. Access to home health care services upon hospital discharge also showed a decline from 2014–2018. Conclusions The decrease in days of immobilization following STSG combined with the shift from prophylactic to interventional splinting put more emphasis on increasing patient autonomy for functional independence. This trend coincides with a significant decrease in the utilization of home health services upon hospital discharge in the same time period. Applicability of Research to Practice The findings of this retrospective study provide evidence supporting that decreasing the length of immobilization following STSG to 2 days did not result in an increase in post-operative complications. There was also not a significant decrease in functional independence found with a change in splinting practices from prophylactic to interventional.

Clenbuterol accelerates recovery after immobilization-induced atrophy of rat hindlimb muscle

Using immunohistochemistry, we investigated whether daily administration of clenbuterol (CLE; 1 mg/kg body weight per day) accelerates recovery after casted immobilization(IMM)-induced atrophy of fast-twitch plantaris and slow-twitch soleus muscles. Adult male Sprague-Dawley rats were assigned to the control (CON), casted immobilization (IMM), casted immobilization following recovery control (RCON), and casted immobilization following recovery with CLE administration (RCLE) groups. Casted immobilization and recovery periods were 9 and 14days, respectively. Rats of the CON group were subjected to the experiment simultaneously with the IMM group.Nine days of immobilization induced muscle fiber atrophy, which was greater in the soleus muscle than in the plantaris muscle. After the 2-week recovery period, the cross-sectional areas of each fiber type in both muscles were higher in the RCON group than in the IMM group. The cross-sectional areas of each fiber type in both muscles in the RCLE group were larger than those in the RCON group. The myonuclear number of each fiber type of the plantaris muscle in the RCON and RCLE groups was higher than that in the CON group. In contrast, the myonuclear number per fiber of the soleus muscle was not affected by hindlimb immobilization, reloading, and clenbuterol administration regardless of muscle fiber type.These results suggest that CLE accelerates the recovery of atrophied plantaris and soleus muscles fibers and that their mechanisms of responses to CLE in both muscles may be different during recovery period after muscle atrophy.

Short-term muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates.

Short-term muscle disuse has been reported to lower both postabsorptive and postprandial myofibrillar protein synthesis rates. This study assessed the impact of disuse on daily myofibrillar protein synthesis rates following short-term (2 and 7 days) muscle disuse under free living conditions. Thirteen healthy young men (age: 20 ± 1 yr; BMI: 23 ± 1 kg/m-2) underwent 7 days of unilateral leg immobilization via a knee brace, with the nonimmobilized leg acting as a control. Four days before immobilization participants ingested 400 mL of 70% deuterated water, with 50-mL doses consumed daily thereafter. Upper leg bilateral MRI scans and muscle biopsies were collected before and after 2 and 7 days of immobilization to determine quadriceps volume and daily myofibrillar protein synthesis rates. Immobilization reduced quadriceps volume in the immobilized leg by 1.7 ± 0.3 and 6.7 ± 0.6% after 2 and 7 days, respectively, with no changes in the control leg. Over the 1-wk immobilization period, myofibrillar protein synthesis rates were 36 ± 4% lower in the immobilized (0.81 ± 0.04%/day) compared with the control (1.26 ± 0.04%/day) leg (P < 0.001). Myofibrillar protein synthesis rates in the control leg did not change over time (P = 0.775), but in the immobilized leg they were numerically lower during the 0- to 2-day period (16 ± 6%, 1.11 ± 0.09%/day, P = 0.153) and were significantly lower during the 2- to 7-day period (44 ± 5%, 0.70 ± 0.06%/day, P < 0.001) when compared with the control leg. We conclude that 1 wk of muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates in healthy young men.

High-fat Overfeeding Does Not Exacerbate Rapid Changes in Forearm Glucose and Fatty Acid Balance During Immobilization.

Physical inactivity and high-fat overfeeding have been shown to independently induce insulin resistance. Establish the contribution of muscle disuse and lipid availability to the development of inactivity-induced insulin resistance. 20 healthy males underwent 7 days of forearm cast immobilization combined with a fully controlled eucaloric diet (n = 10, age 23 ± 2 yr, body mass index [BMI] 23.8 ± 1.0 kg·m-2) or a high-fat diet (HFD) providing 50% excess energy from fat (high-fat diet, n = 10, age 23 ± 2 yr, BMI 22.4 ± 0.8 kg·m-2). Prior to casting and following 2 and 7 days of immobilization, forearm glucose uptake (FGU) and nonesterified fatty acid (NEFA) balance were assessed using the arterialized venous-deep venous (AV-V) forearm balance method following ingestion of a mixed macronutrient drink. 7 days of HFD increased body weight by 0.9 ± 0.2 kg (P = 0.002), but did not alter fasting, arterialized whole-blood glucose and serum insulin concentrations or the associated homeostatic model assessment of insulin resistance or Matsuda indices. Two and 7 days of forearm immobilization led to a 40 ± 7% and 52 ± 7% decrease in FGU, respectively (P < 0.001), with no difference between day 2 and 7 and no effect of HFD. Forearm NEFA balance tended to increase following 2 and 7 days of immobilization (P = 0.095). Forearm immobilization leads to a rapid and substantial decrease in FGU, which is accompanied by an increase in forearm NEFA balance but is not exacerbated by excess dietary fat intake. Altogether, our data suggest that disuse-induced insulin resistance of glucose metabolism occurs as a physiological adaptation in response to the removal of muscle contraction.

Daily heat treatment maintains mitochondrial function and attenuates atrophy in human skeletal muscle subjected to immobilization

Skeletal muscle immobilization leads to atrophy, decreased metabolic health, and substantial losses in function. Animal models suggest that heat stress can provide protection against atrophy in skeletal muscle. This study investigated the effects of daily heat therapy on human skeletal muscle subjected to 10 days of immobilization. Muscle biopsies were collected, and MRIs were analyzed from the vastus lateralis of 23 healthy volunteers (11 women, 12 men) before and after either 10 days of immobilization with a daily sham treatment (Imm) or with a targeted, daily 2-h heat treatment using pulsed shortwave diathermy (Imm + H). Diathermy increased intramuscular temperature 4.2 ± 0.29°C (P < 0.0001), with no change during sham treatment. As a result, heat shock protein (HSP)70 and HSP90 increased (P < 0.05) following Imm + H (25 ± 6.6 and 20 ± 7.4%, respectively) but were unaltered with Imm only. Heat treatment prevented the immobilization-induced loss of coupled (-27 ± 5.2% vs. -8 ± 6.0%, P = 0.0041) and uncoupled (-25 ± 7.0% vs. -10 ± 3.9%, P = 0.0302) myofiber respiratory capacity. Likewise, heat treatment prevented the immobilization-induced loss of proteins associated with all five mitochondrial respiratory complexes (P < 0.05). Furthermore, decreases in muscle cross-sectional area following Imm were greater than Imm + H at both the level of the whole muscle (-7.6 ± 0.96% vs. -4.5 ± 1.09%, P = 0.0374) and myofiber (-10.8 ± 1.52% vs. -5.8 ± 1.49%, P = 0.0322). Our findings demonstrate that daily heat treatments, applied during 10 days of immobilization, prevent the loss of mitochondrial function and attenuate atrophy in human skeletal muscle. NEW & NOTEWORTHY Limb immobilization results in substantial decreases in skeletal muscle size, function, and metabolic capacity. To date, there are few, if any, interventions to prevent the deleterious effects of limb immobilization on skeletal muscle health. Heat stress has been shown to elicit a stress response, resulting in increased heat shock protein expression and improved mitochondrial function. We show that during 10 days of lower-limb immobilization in humans, daily exposure to heat stress maintains mitochondrial respiratory capacity and attenuates atrophy in skeletal muscle. Our findings suggest that heat stress may serve as an effective therapeutic strategy to attenuate the decreases of muscle mass and metabolic function that accompany periods of disuse.

The Role of Periarticular Soft Tissues in Persistent Motion Loss in a Rat Model of Posttraumatic Elbow Contracture.

Elbow injuries disrupt the surrounding periarticular soft tissues, which include the muscles, tendons, capsule, ligaments, and cartilage. Damage to these tissues as a result of elbow trauma causes clinically significant contracture in 50% of patients. However, it is unclear which of these tissues is primarily responsible for the decreased range of motion. We hypothesized that all tissues would substantially contribute to elbow contracture after immobilization, but only the capsule, ligaments, and cartilage would contribute after free mobilization, with the capsule as the primary contributor at all time points. Utilizing a rat model of posttraumatic elbow contracture, a unilateral soft-tissue injury was surgically induced to replicate the damage that commonly occurs during elbow joint dislocation. After surgery, the injured limb was immobilized for 42 days. Animals were evaluated after either 42 days of immobilization (42 IM) or 42 days of immobilization with an additional 21 or 42 days of free mobilization (42/21 or 42/42 IM-FM). For each group of animals, elbow mechanical testing in flexion-extension was completed post-mortem with (1) all soft tissues intact, (2) muscles/tendons removed, and (3) muscle/tendons and anterior capsule removed. Total extension was assessed to determine the relative contributions of muscles/tendons, capsule, and the remaining intact tissues (i.e., ligaments and cartilage). After immobilization, the muscles/tendons and anterior capsule contributed 10% and 90% to elbow contracture, respectively. After each free mobilization period, the muscles/tendons did not significantly contribute to contracture. The capsule and ligaments/cartilage were responsible for 47% and 52% of the motion lost at 42/21 IM-FM, respectively, and 26% and 74% at 42/42 IM-FM, respectively. Overall, data demonstrated a time-dependent response of periarticular tissue contribution to elbow contracture, with the capsule, ligaments, and cartilage as the primary long-term contributors. The capsule, ligaments, and cartilage were primarily responsible for persistent motion loss and should be considered during development of tissue-targeted treatment strategies to inhibit elbow contracture following injury.

Nitrogen Removal in Oligotrophic Reservoir Water by a Mixed Aerobic Denitrifying Consortium: Influencing Factors and Immobilization Effects.

Nitrogen pollution in reservoirs has received increasing attention in recent years. Although a number of aerobic denitrifying strains have been isolated to remove nitrogen from eutrophic waters, the situation in oligotrophic water environments has not received significant attention. In this study, a mixed aerobic denitrifying consortium screened from reservoir samples was used to remove nitrogen in an oligotrophic denitrification medium and actual oligotrophic source water. The results showed that the consortium removed 75.32% of nitrate (NO3−-N) and 63.11% of the total nitrogen (TN) in oligotrophic reservoir water during a 24-h aerobic cultivation. More initial carbon source was helpful for simultaneous removal of carbon and nitrogen in the reservoir source water. NO3−-N and TN were still reduced by 60.93% and 46.56% at a lower temperature (10 °C), respectively, though the rates were reduced. Moreover, adding phosphorus promoted bacterial growth and increased TN removal efficiency by around 20%. The performance of the immobilized consortium in source water was also explored. After 6 days of immobilization, approximately 25% of TN in the source water could be removed by the carriers, and the effects could last for at least 9 cycles of reuse. These results provide a good reference for the use of aerobic denitrifiers in oligotrophic reservoirs.