Search

Methods of preventing and treating knee injuries have changed with the rapid development and refinement of knee braces. Prophylactic knee braces are designed to protect uninjured knees from valgus stresses that could damage the medial collateral ligaments. However, no conclusive evidence supports their effectiveness, and they are not recommended for regular use. Functional knee braces are intended to stabilize knees during rotational and anteroposterior forces. They offer a useful adjunct to the treatment and rehabilitation of ligamentous knee injuries. Patellofemoral knee braces have been used to treat anterior knee disorders and offer moderate subjective improvement without significant disadvantages. Additional well-designed studies are needed to demonstrate objectively the benefits of all knee braces. Knee braces should be used in conjunction with a rehabilitation program that incorporates strength training, flexibility, activity modification and technique refinement. [ABSTRACT FROM AUTHOR]

Background: Protein is most commonly consumed as whole foods as opposed to single nutrients. However, the food matrix regulation of the postprandial muscle protein synthetic response has received little attention., Objectives: The purpose of this study was to assess the effects of eating salmon (SAL) and of ingesting the same nutrients as an isolated mixture of crystalline amino acids and fish oil (ISO) on the stimulation of postexercise myofibrillar protein synthesis (MPS) and whole-body leucine oxidation rates in healthy young adults., Methods: Ten recreationally active adults (24 ± 4 y; 5 men, 5 women) performed an acute bout of resistance exercise, followed by the ingestion of SAL or ISO in a crossover fashion. Blood, breath, and muscle biopsies were collected at rest and after exercise during primed continuous infusions of L-[ring- 2 H 5 ]phenylalanine and L-[1- 13 C]leucine. All data are presented as means ± SD and/or mean differences (95% CIs)., Results: Postprandial essential amino acid (EAA) concentrations peaked earlier (P = 0.024) in the ISO group than those in the SAL group. Postprandial leucine oxidation rates increased over time (P < 0.001) and peaked earlier in the ISO group (1.239 ± 0.321 nmol/kg/min; 63 ± 25 min) than those in the SAL group (1.230 ± 0.561 nmol/kg/min; 105 ± 20 min; P = 0.003). MPS rates for SAL (0.056 ± 0.022 %/h; P = 0.001) and ISO (0.046 ± 0.025 %/h; P = 0.025) were greater than the basal rates (0.020 ± 0.011 %/h) during the 0- to 5-h recovery period, with no differences between conditions (P = 0.308)., Conclusion: We showed that the postexercise ingestion of SAL or ISO stimulate postexercise MPS rates with no differences between the conditions. Thus, our results indicate that ingesting protein from SAL as a whole-food matrix is similarly anabolic to ISO in healthy young adults. This trial was registered at www., Clinicaltrials: gov as NCT03870165., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

The activation of the mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of protein synthesis, by anabolic stimuli (such as muscle contraction or essential amino acids) involves its translocation to the cell periphery. Leucine is generally considered the most anabolic of amino acids for its ability to independently modulate muscle protein synthesis. However, it is currently unknown if free leucine impacts region-specific mTORC1-mediated phosphorylation events and protein-protein interactions. In this clinical trial (NCT03952884; registered May 16, 2019), we used immunofluorescence methods to investigate the role of dietary leucine on the postprandial regulation of mTORC1 and ribosomal protein S6 (RPS6), an important downstream readout of mTORC1 activity. Eight young, healthy, recreationally active males (n = 8; 23 ± 3 yrs) ingested 2 g of leucine with vastus lateralis biopsies collected at baseline, 30, 60, and 180 min postprandial. Leucine promoted mTOR translocation to the periphery (~ 18-29%; p ≤ 0.012) and enhanced mTOR localization with the lysosome (~ 16%; both p = 0.049) at 30 and 60 min post-feeding. p-RPS6 Ser240/244 staining intensity, a readout of mTORC1 activity, was significantly elevated at all postprandial timepoints in both the total fiber (~ 14-30%; p ≤ 0.032) and peripheral regions (~ 16-33%; p ≤ 0.014). Additionally, total and peripheral p-RPS6 Ser240/244 staining intensity at 60 min was positively correlated (r = 0.74, p = 0.036; r = 0.80, p = 0.016, respectively) with rates of myofibrillar protein synthesis over 180 min. The ability of leucine to activate mTORC1 in peripheral regions favors an enhanced rate of MPS, as this is the intracellular space thought to be replete with the cellular machinery that facilitates this anabolic process., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Resistance training combined with adequate protein intake supports skeletal muscle strength and hypertrophy. These adaptations are supported by the action of muscle stem cells (MuSCs), which are regulated, in part, by fibro-adipogenic progenitors (FAPs) and circulating factors delivered through capillaries. It is unclear if middle-aged males and females have similar adaptations to resistance training at the cellular level. To address this gap, 27 (13 males, 14 females) middle-aged (40-64 yr) adults participated in 10 wk of whole body resistance training with dietary counseling. Muscle biopsies were collected from the vastus lateralis pre- and posttraining. Type II fiber cross-sectional area increased similarly with training in both sexes ( P = 0.014). MuSC content was not altered with training; however, training increased PDGFRα + /CD90 + FAP content ( P < 0.0001) and reduced PDGFRα + /CD90 - FAP content ( P = 0.044), independent of sex. The number of CD31 + capillaries per fiber also increased similarly in both sexes ( P < 0.05). These results suggest that muscle fiber hypertrophy, stem/progenitor cell, and capillary adaptations are similar between middle-aged males and females in response to whole body resistance training. NEW & NOTEWORTHY We demonstrate that resistance training-induced increases in fiber hypertrophy, FAP content, and capillarization are similar between middle-aged males and females.

β-Hydroxy-β-methylbutyrate (HMB), a leucine metabolite, can increase skeletal muscle size and function. However, HMB may be less effective at improving muscle function in people with insufficient Vitamin D3 (25-OH-D < 30 ng/mL) which is common in middle-aged and older adults. Therefore, we tested the hypothesis that combining HMB plus Vitamin D3 (HMB + D) supplementation would improve skeletal muscle size, composition, and function in middle-aged women. In a double-blinded fashion, women (53 ± 1 yrs, 26 ± 1 kg/m2, n = 43) were randomized to take placebo or HMB + D (3 g Calcium HMB + 2000 IU D per day) during 12 weeks of sedentary behavior (SED) or resistance exercise training (RET). On average, participants entered the study Vitamin D3 insufficient while HMB + D increased 25-OH-D to sufficient levels after 8 and 12 weeks. In SED, HMB + D prevented the loss of arm lean mass observed with placebo. HMB + D increased muscle volume and decreased intermuscular adipose tissue (IMAT) volume in the thigh compared to placebo but did not change muscle function. In RET, 12-weeks of HMB + D decreased IMAT compared to placebo but did not influence the increase in skeletal muscle volume or function. In summary, HMB + D decreased IMAT independent of exercise status and may prevent the loss or increase muscle size in a small cohort of sedentary middle-aged women. These results lend support to conduct a longer duration study with greater sample size to determine the validity of the observed positive effects of HMB + D on IMAT and skeletal muscle in a small cohort of middle-aged women.

Although muscular strength has been linked to greater cognitive function across different cognitive domains, the mechanism(s) through which this occurs remain(s) poorly understood. Indeed, while an emerging body of literature suggests peripheral myokines released from muscular contractions may play a role in this relationship, additional research is needed to understand this link. Accordingly, this study sought to compare the influences of a particular myokine, Cathepsin B (CTSB), and muscular strength on hippocampal-dependent relational memory and cognitive control in 40 adults (age = 50.0±7.3 yrs). Overnight fasted venous blood draws were taken to assess plasma CTSB and muscular strength was assessed as maximal isokinetic strength testing using a Biodex dynamometer. Cognitive performance was assessed using a Spatial Reconstruction Task to assess relational memory and a modified Flanker task to assess cognitive control. Neuroelectric function for cognitive control was assessed using event-related potentials (ERPs) recorded during the Flanker task. Initial bivariate correlational analyses revealed that neither sex, age, lean body mass, or muscular strength was associated with CTSB. However, CTSB was inversely associated with reaction time and fractional peak latency of the P3 component of the Flanker task. Muscular strength was also inversely associated with reaction time and positively associated with relational memory performance. However, the influence of muscular strength on relational memory did not persist following adjustment for covariates. Greater circulating CTSB was selectively associated with greater cognitive control as well as faster information processing speed. These findings are the first to link circulating CTSB to both cognitive control and neuroelectric function. Future intervention studies are needed to examine the effects of changes in muscular strength, circulating myokines, and different domains of cognitive function., Competing Interests: None of the authors have a conflict of interest to report., (© 2022 – The authors. Published by IOS Press.)

Skeletal muscle aging is a multidimensional pathology of atrophy, reduced strength, and oxidative damage. Although some molecular targets may mediate both hypertrophic and oxidative adaptations in muscle, their responsiveness in humans and relationship with functional outcomes like strength remain unclear. Promising therapeutic targets to combat muscle aging like apelin, vitamin D receptor (VDR), and spermine oxidase (SMOX) have been investigated in preclinical models but the adaptive response in humans is not well defined. In an exploratory investigation, we examined how strength gains with resistance training relate to regulators of both muscle mass and oxidative function in middle-aged adults. Forty-one middle-aged adults [18 male (M), 23 female (F); 50 ± 7 yr; 27.8 ± 3.7 kg/m 2 ; means ± SD] participated in a 10-wk resistance training intervention. Muscle biopsies and plasma were sampled at baseline and postintervention. High-resolution fluo-respirometry was performed on a subset of muscle tissue. Apelin signaling (plasma apelin, P = 0.002; Apln mRNA , P < 0.001; apelin receptor mRNA Aplnr, P = 0.001) increased with resistance training. Muscle Vdr mRNA ( P = 0.007) and Smox mRNA ( P = 0.027) were also upregulated after the intervention. Mitochondrial respiratory capacity increased ( V max , oxidative phosphorylation, and uncoupled electron transport system, P < 0.050), yet there were no changes in ADP sensitivity ( K m P = 0.579), hydrogen peroxide emission ( P = 0.469), nor transcriptional signals for mitochondrial biogenesis (nuclear respiratory factor 2, Gapba P = 0.766) and mitofusion (mitochondrial dynamin-like GTPase, Opa1 P = 0.072). Muscular strength with resistance training positively correlated to Apln , Aplnr , Vdr , and Smox transcriptional adaptations, as well as mitochondrial respiratory capacity (unadjusted P < 0.050, r = 0.400-0.781). Further research is required to understand the interrelationships of these targets with aged muscle phenotype. NEW & NOTEWORTHY Although some therapeutic targets may ameliorate hypertrophic and oxidative dysfunction with muscle aging in preclinical models, their responsiveness in human muscle remains unclear. We demonstrated that resistance training concurrently upregulated therapeutic targets of muscle aging and mitochondrial respiratory capacity, which positively correlated to strength gains. Specifically, we are the first to demonstrate that apelin and spermine oxidase are upregulated with resistance training in humans. Our work corroborates preclinical observations, with future work required for clinical efficacy.

Satellite cells are required for muscle regeneration, remodeling, and repair through their activation, proliferation, and differentiation; however, how dietary factors regulate this process remains poorly understood. The L-type amino acid transporter 1 (LAT1) transports amino acids, such as leucine, into mature myofibers, which then stimulate protein synthesis and anabolic signaling. However, whether LAT1 is expressed on myoblasts and is involved in regulating myogenesis is unknown. The aim of this study was to characterize the expressional and functional relevance of LAT1 during different stages of myogenesis and in response to growth and atrophic conditions in vitro. We determined that LAT1 is expressed by C2C12 and human primary myoblasts, and its gene expression is lower during differentiation ( P < 0.05). Pharmacological inhibition and genetic knockdown of LAT1 impaired myoblast viability, differentiation, and fusion (all P < 0.05). LAT1 protein content in C2C12 myoblasts was not significantly altered in response to different leucine concentrations in cell culture media or in two in vitro atrophy models. However, LAT1 content was decreased in myotubes under atrophic conditions in vitro ( P < 0.05). These findings indicate that LAT1 is stable throughout myogenesis and in response to several in vitro conditions that induce muscle remodeling. Further, amino acid transport through LAT1 is required for normal myogenesis in vitro.

Key Points: The ingestion of protein potentiates the stimulation of myofibrillar protein synthesis rates after an acute bout of resistance exercise. Protein supplementation (eating above the protein Recommended Dietary Allowance) during resistance training has been shown to maximize lean mass and strength gains in healthy young and older adults. Here, contractile, oxidative, and structural protein synthesis were assessed in skeletal muscle in response to a moderate or higher protein diet during the early adaptive phase of resistance training in middle-aged adults. The stimulation of myofibrillar, mitochondrial or collagen protein synthesis rates during 0-3 weeks of resistance training is not further enhanced by a higher protein diet. These results show that moderate protein diets are sufficient to support the skeletal muscle adaptive response during the early phase of a resistance training programme., Abstract: Protein ingestion augments muscle protein synthesis (MPS) rates acutely after resistance exercise and can offset age-related loss in muscle mass. Skeletal muscle contains a variety of protein pools, such as myofibrillar (contractile), mitochondrial (substrate oxidation), and collagen (structural support) proteins, and the sensitivity to nutrition and exercise seems to be dependent on the major protein fraction studied. However, it is unknown how free-living conditions with high dietary protein density and habitual resistance exercise mediates muscle protein subfraction synthesis. Therefore, we investigated the effect of moderate (MOD: 1.06 ± 0.22 g kg -1  day -1 ) or high (HIGH: 1.55 ± 0.25 g kg -1  day -1 ) protein intake on daily MPS rates within the myofibrillar (MyoPS), mitochondrial (MitoPS) and collagen (CPS) protein fractions in middle-aged men and women (n = 20, 47 ± 1 years, BMI 28 ± 1 kg m -2 ) during the early phase (0-3 weeks) of a dietary counselling-controlled resistance training programme. Participants were loaded with deuterated water, followed by daily maintenance doses throughout the intervention. Muscle biopsies were collected at baseline and after weeks 1, 2 and 3. MyoPS in the HIGH condition remained constant (P = 1.000), but MOD decreased over time (P = 0.023). MitoPS decreased after 0-3 weeks when compared to 0-1 week (P = 0.010) with no effects of protein intake (P = 0.827). A similar decline with no difference between groups (P = 0.323) was also observed for CPS (P = 0.007). Our results demonstrated that additional protein intake above moderate amounts does not potentiate the stimulation of longer-term MPS responses during the early stage of resistance training adaptations in middle-aged adults., (© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.)

Leucine is regarded as an anabolic trigger for the mTORC1 pathway and the stimulation muscle protein synthesis rates. More recently, there has been an interest in underpinning the relevance of branched-chain amino acid (BCAA)-containing dipeptides and their intact absorption into circulation to regulate muscle anabolic responses. We investigated the effects of dileucine and leucine ingestion on postprandial muscle protein turnover. Ten healthy young men (age: 23 ± 3 yr) consumed either 2 g of leucine (LEU) or 2 g of dileucine (DILEU) in a randomized crossover design. The participants underwent repeated blood and muscle biopsy sampling during primed continuous infusions of l-[ ring - 13 C 6 ]phenylalanine and l-[ 15 N]phenylalanine to determine myofibrillar protein synthesis (MPS) and mixed muscle protein breakdown rates (MPB), respectively. LEU and DILEU similarly increased plasma leucine net area under the curve (AUC; P = 0.396). DILEU increased plasma dileucine AUC to a greater extent than LEU ( P = 0.013). Phosphorylation of Akt ( P = 0.002), rpS6 ( P < 0.001), and p70S6K ( P < 0.001) increased over time under both LEU and DILEU conditions. Phosphorylation of 4E-BP1 ( P = 0.229) and eEF2 ( P = 0.999) did not change over time irrespective of condition. Cumulative (0-180 min) MPS increased in DILEU (0.075 ± 0.032%·h -1 ), but not in LEU (0.047 ± 0.029%·h -1 ; P = 0.023). MPB did not differ between LEU (0.043 ± 0.030%·h -1 ) and DILEU conditions (0.051 ± 0.027%·h -1 ; P = 0.659). Our results showed that dileucine ingestion elevated plasma dileucine concentrations and muscle protein turnover by stimulating MPS in young men. NEW & NOTEWORTHY The role of dipeptides as anabolic agents remains unresolved in humans. We show that the ingestion of 2 g dileucine increased plasma dileucine concentrations and resulted in an enhancement of muscle protein turnover by stimulating an increase in muscle protein synthesis rates in healthy young males. The ingestion of 2 g leucine, however, did not stimulate an increase in muscle protein turnover. Our work provides the first insights into the effects of dipeptides on human protein metabolism.

Protein intake above the recommended dietary allowance (RDA) and resistance training are known anabolic stimuli to support healthy aging. Specifically, protein supplementation after resistance exercise and nightly are strategies to maximize utilization of protein intake above the RDA in healthy adults. As such, the primary objective was to examine the efficacy of protein supplementation and nutritional counseling resulting in either moderate (MOD: ∼1.0 g·kg -1 ·day -1 ) or higher (HIGH: ∼1.6 g·kg -1 ·day -1 ) protein intake during resistance training on strength (one-repetition maximum, 1-RM; isokinetic and isometric peak torque) in healthy middle-aged adults. Exploratory analyses include diet-exercise effects on lean body mass (LBM), clinical biomarkers, gut microbiota, and diet composition. In all, 50 middle-aged adults (age: 50 ± 8 yr, BMI: 27.2 ± 4.1 kg/m 2 ) were randomized to either MOD or HIGH protein intake during a 10-wk resistance training program (3 × wk). Participants received dietary counseling and consumed either 15 g (MOD) or 30 g (HIGH) of protein from lean beef in the immediate postexercise period and each evening. Maximal strength (1-RM) for all upper and lower body exercises significantly increased with no effect of protein intake ( P < 0.050). There was a main effect of time for LBM ( P < 0.005). Cardiovascular, renal, or glycemic biomarkers were not affected by the intervention. Gut microbiota were associated with several health outcomes ( P < 0.050). In conclusion, higher protein intake above moderate amounts does not potentiate resistance training adaptations in previously untrained middle-aged adults. This trial was registered at clinicaltrials.gov as NCT03029975. NEW & NOTEWORTHY Our research evaluates the efficacy of higher in comparison with moderate animal-based protein intake on resistance exercise training-induced muscle strength, clinical biomarkers, and gut microbiota in middle-aged adults through a dietary counseling-controlled intervention. Higher protein intake did not potentiate training adaptations, nor did the intervention effect disease biomarkers. Both diet and exercise modified gut microbiota composition. Collectively, moderate amounts of high-quality, animal-based protein is sufficient to promote resistance exercise adaptations at the onset of aging.

Key Points: Patients with renal failure undergoing maintenance haemodialysis are associated with insulin resistance and protein metabolism dysfunction. Novel research suggests that disruption to the transmembrane protein linkage between the cytoskeleton and the extracellular matrix in skeletal muscle may contribute to reduced amino acid metabolism and insulin resistance in haemodialysis. ILK, PINCH1 and pFAK Tyr397 were significantly decreased in haemodialysis compared to controls, whereas Rac1 and Akt2 showed no different between groups. Rac1 deletion in the Rac1 knockout model did not alter the expression of integrin-associated proteins. Phenylalanine kinetics were reduced in the haemodialysis group at 30 and 60 min post meal ingestion compared to controls; both groups showed similar levels of insulin sensitivity and β-cell function. Key proteins in the integrin-cytoskeleton linkage are reduced in haemodialysis patients, suggesting for the first time that integrin-associated proteins dysfunction may contribute to reduced phenylalanine flux without affecting insulin resistance in haemodialysis patients., Abstract: Muscle atrophy, insulin resistance and reduced muscle phosphoinositide 3-kinase-Akt signalling are common characteristics of patients undergoing maintenance haemodialysis (MHD). Disruption to the transmembrane protein linkage between the cytoskeleton and the extracellular matrix in skeletal muscle may contribute to reduced amino acid metabolism and insulin resistance in MHD patients. Eight MHD patients (age: 56 ± 5 years: body mass index: 32 ± 2 kg m -2 ) and non-diseased controls (age: 50 ± 2 years: body mass index: 31 ± 1 kg m -2 ) received primed continuous l-[ring- 2 H 5 ]phenylalanine before consuming a mixed meal. Phenylalanine metabolism was determined using two-compartment modelling. Muscle biopsies were collected prior to the meal and at 300 min postprandially. In a separate experiment, skeletal muscle tissue from muscle-specific Rac1 knockout (Rac1 mKO) was harvested to investigate whether Rac1 depletion disrupted the cytoskeleton-integrin linkage, allowing for cross-model examination of proteins of interest. ILK, PINCH1 and pFAK Tyr397 were significantly lower in MHD (P < 0.01). Rac1 and Akt showed no difference between groups for the human trial. Rac1 deletion in the Rac1 mKO model did not alter the expression of integrin-associated proteins. Phenylalanine rates of appearance and disappearance, as well as metabolic clearance rates, were lower in the MHD group at 30 and 60 min post meal ingestion compared to controls (P < 0.05). Both groups showed similar levels of insulin sensitivity and β-cell function. Key proteins in the integrin-cytoskeleton linkage are reduced in MHD patients, suggesting for the first time that integrin-associated proteins dysfunction may contribute to reduced phenylalanine flux without affecting insulin resistance in haemodialysis patients., (© 2020 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

During a traditional set configuration of resistance exercise (TRD), characterized by a continuous completion of repetitions, a decrease in power output tends to occur throughout a set of repetitions. Inclusion of intraset rest, otherwise known as a cluster set configuration (CLU), counteracts this power decline. However, the effect of a CLU configuration on postexercise myofibrillar protein synthesis rates (MPS) and anabolic signaling has not been investigated., Purpose: We aimed to determine if any mechanistic differences exist between TRD and CLU signaling events associated with muscle anabolism., Methods: In randomized crossover trials, eight resistance-trained participants (23 ± 1 yr, 81 ± 4.7 kg, body fat: 18% ± 1.9%; 1 repetition maximum [1RM], 150 ± 9.1 kg) performed an acute bout of CLU (4 sets × (2 × 5) repetitions, 30-s intraset rest, 90-s interset rest) and TRD (4 sets × 10 repetitions, 120-s interset rest) barbell back squats at approximately 70% 1RM with total volume load equated during primed continuous L-[ring-C6]phenylalanine infusions. Blood and muscle biopsy samples were collected at rest and after exercise at 0, 2, and 5 h., Results: There was no difference in postexercise MPS between the CLU and TRD condition (P > 0.05) and no changes in phosphorylation of mTORC1 downstream targets (p70S6K and 4EBP1). Total and phosphorylated yes-associated protein on Ser127 transiently increased (P < 0.01) immediately after exercise (t = 0) in CLU (~2.1-fold) and TRD condition (~2.2-fold)., Conclusions: Our results show that CLU is a viable anabolic option by preserving power output with similar MPS stimulation when compared with the TRD condition in trained young adults.

The anabolic action of "fast" whey protein on the regulation of postprandial muscle protein synthesis has been established to be short-lived in healthy young adults. We assessed the time course of anabolic signaling activation and stimulation of myofibrillar protein synthesis rates (MPS) after ingestion of a food source that represents a more typical meal-induced pattern of aminoacidemia. Seven young men (age: 22 ± 1 y) underwent repeated blood and biopsy sampling during primed, continuous l-[ ring - 2 H 5 ]phenylalanine and l-[1- 13 C]leucine tracer infusions and ingested 38 g of l-[1- 13 C]phenylalanine- and l-[1- 13 C]leucine-labeled milk protein concentrate. A total of ∼27 ± 4 (∼10 g) and ∼31 ± 1% (∼12 g) of dietary protein-derived amino acids were released in circulation between 0 and 120 min and 120-300 min, respectively, of the postprandial period. l-[ ring - 2 H 5 ]phenylalanine-based MPS increased above basal (0.025 ± 0.008%/h) by ∼75% (0.043 ± 0.009%/h; P = 0.05) between 0 and 120 min and by ∼86% (0.046 ± 0.004%/h; P = 0.02) between 120 and 300 min, respectively. l-[1- 13 C]leucine-based MPS increased above basal (0.027 ± 0.002%/h) by ∼72% (0.051 ± 0.016%/h; P = 0.10) between 0 and 120 min and by ∼62% (0.047 ± 0.004%/h; P = 0.001) between 120 and 300 min, respectively. Myofibrillar protein-bound l-[1- 13 C]phenylalanine increased over time ( P < 0.001) and equaled 0.004 ± 0.001, 0.008 ± 0.002, 0.017 ± 0.004, and 0.020 ± 0.003 mole percent excess at 60, 120, 180, and 300 min, respectively, of the postprandial period. Milk protein ingestion increased mTORC1 phosphorylation at 120, 180, and 300 min of the postprandial period (all P < 0.05). Our results show that ingestion of 38 g of milk protein results in sustained increases in MPS throughout a 5-h postprandial period in healthy young men. NEW & NOTEWORTHY The stimulation of muscle protein synthesis after whey protein ingestion is short-lived due to its transient systemic appearance of amino acids. Our study characterized the muscle anabolic response to a protein source that results in a more gradual release of amino acids into circulation. Our work demonstrates that a sustained increase in postprandial plasma amino acid availability after milk protein ingestion results in a prolonged stimulation of muscle protein synthesis rates in healthy young men.

Key Points: Lifestyle modifications that include the regular performance of exercise are probably important for counteracting the negative consequences of obesity on postprandial myofibrillar protein synthetic responses to protein dense food ingestion. We show that the interactive effect of resistance exercise and feeding on the stimulation of myofibrillar protein synthesis rates is diminished with obesity compared to normal weight adults. The blunted myofibrillar protein synthetic response with resistance exercise in people with obesity may be underpinned by alterations in muscle anabolic signalling phosphorylation (p70S6K and 4E-BP1). The results obtained in the present study suggest that further exercise prescription manipulation may be necessary to optimize post-exercise myofibrillar protein synthesis rates in adults with obesity., Abstract: We aimed to determine whether obesity alters muscle anabolic and inflammatory signalling phosphorylation and also muscle protein synthesis within the myofibrillar (MYO) and sarcoplasmic (SARC) protein fractions after resistance exercise. Nine normal weight (NW) (21 ± 1 years, body mass index 22 ± 1 kg m -2 ) and nine obese (OB) (22 ± 1 years, body mass index 36 ± 2 kg m -2 ) adults received l-[ring- 13 C 6 ]phenylalanine infusions with blood and muscle sampling at basal and fed-state of the exercise (EX) and non-exercise (CON) legs. Participants performed unilateral leg extensions and consumed pork (36 g of protein) immediately after exercise. Basal muscle Toll-like receptor 4 (TLR4) protein was similar between OB and NW groups (P > 0.05) but increased at 300 min after pork ingestion only in the OB group (P = 0.03). Resistance exercise reduced TLR4 protein in the OB group at 300 min (EX vs. CON leg in OB: P = 0.04). Pork ingestion increased p70S6K phosphorylation at 300 min in CON and EX of the OB and NW groups (P > 0.05), although the response was lower in the EX leg of OB vs. NW at 300 min (P = 0.05). Basal MYO was similar between the NW and OB groups (P > 0.05) and was stimulated by pork ingestion in the EX and CON legs in both groups (Δ from basal NW: CON 0.04 ± 0.01% h -1 ; EX 0.10 ± 0.02% h -1 ; OB: CON 0.06 ± 0.01% h -1 ; EX 0.06 ± 0.01% h -1 ; P < 0.05). MYO was more strongly stimulated in the EX vs. CON legs in NW (P = 0.02) but not OB (P = 0.26). SARC was feeding sensitive but not further potentiated by resistance exercise in both groups. Our results suggest that obesity may attenuate the effectiveness of resistance exercise to augment fed-state MYO., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

We have recently demonstrated that whole egg ingestion induces a greater muscle protein synthetic (MPS) response when compared with isonitrogenous egg white ingestion after resistance exercise in young men. Our aim was to determine whether whole egg or egg white ingestion differentially influenced colocalization of key regulators of mechanistic target of rapamycin complex 1 (mTORC1) as means to explain our previously observed divergent postexercise MPS response. In crossover trials, 10 healthy resistance-trained men (21 ± 1 yr; 88 ± 3 kg; body fat: 16 ± 1%; means ± SE) completed lower body resistance exercise before ingesting whole eggs (18 g protein, 17 g fat) or egg whites (18 g protein, 0 g fat). Muscle biopsies were obtained before exercise and at 120 and 300 min after egg ingestion to assess, by immunofluorescence, protein colocalization of key anabolic signaling molecules. After resistance exercise, tuberous sclerosis 2-Ras homolog enriched in brain (Rheb) colocalization decreased ( P < 0.01) at 120 and 300 min after whole egg and egg white ingestion with concomitant increases ( P < 0.01) in mTOR-Rheb colocalization. After resistance exercise, mTOR-lysosome-associated membrane protein 2 (LAMP2) colocalization significantly increased at 120 and 300 min only after whole egg ingestion ( P < 0.01), and mTOR-LAMP2 colocalization correlated with rates of MPS at rest and after exercise ( r = 0.40, P < 0.05). We demonstrated that the greater postexercise MPS response with whole egg ingestion is related in part to an enhanced recruitment of mTORC1-Rheb complexes to the lysosome during recovery. These data suggest nonprotein dietary factors influence the postexercise regulation of mRNA translation in human skeletal muscle.

Introduction: Skeletal muscle loss is common in patients with renal failure who receive maintenance hemodialysis (MHD) therapy. Regular ingestion of protein-rich meals are recommended to help offset muscle protein loss in MHD patients, but little is known about the anabolic potential of this strategy., Methods: Eight MHD patients (age: 56 ± 5 years; body mass index [BMI]: 32 ± 2 kg/m 2 ) and 8 nonuremic control subjects (age: 50 ± 2 years: BMI: 31 ± 1 kg/m 2 ) received primed continuous L-[ ring - 2 H 5 ]phenylalanine and L-[1- 13 C]leucine infusions with blood and muscle biopsy sampling on a nondialysis day. Participants consumed a mixed meal (546 kcal; 20-g protein, 59-g carbohydrates, 26-g fat) with protein provided as L-[5,5,5- 2 H 3 ]leucine-labeled eggs., Results: Circulating dietary amino acid availability was reduced in MHD patients (41 ± 5%) versus control subjects (61 ± 4%; P  = 0.03). Basal muscle caspase-3 protein content was elevated ( P  = 0.03) and large neutral amino acid transporter 1 (LAT1) protein content was reduced ( P = 0.02) in MHD patients versus control subjects. Basal muscle protein synthesis (MPS) was ∼2-fold higher in MHD patients (0.030 ± 0.005%/h) versus control subjects (0.014 ± 0.003%/h) ( P  = 0.01). Meal ingestion failed to increase MPS in MHD patients (absolute change from basal: 0.0003 ± 0.007%/h), but stimulated MPS in control subjects (0.009 ± 0.002%/h; P = 0.004)., Conclusions: MHD patients demonstrated muscle anabolic resistance to meal ingestion. This blunted postprandial MPS response in MHD patients might be related to high basal MPS, which results in a stimulatory ceiling effect and/or reduced plasma dietary amino acid availability after mixed-meal ingestion.

Translocation and colocalization of mechanistic target of rapamycin complex 1 (mTORC1) with regulatory proteins represents a critical step in translation initiation of protein synthesis in vitro. However, mechanistic insight into the control of postprandial skeletal muscle protein synthesis rates at rest and after an acute bout of endurance exercise in humans is lacking. In crossover trials, eight endurance-trained men received primed-continuous infusions of L-[ring- 2 H 5 ]phenylalanine and consumed a mixed-macronutrient meal (18 g protein, 60 g carbohydrates, 17 g fat) at rest (REST) and after 60 min of treadmill running at 70% VO 2peak (EX). Skeletal muscle biopsies were collected to measure changes in phosphorylation and colocalization in the mTORC1-pathway, in addition to rates of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis. MyoPS increased (P < 0.05) above fasted in REST (~2.1-fold) and EX (~twofold) during the 300 min postprandial period, with no corresponding changes in MitoPS (P > 0.05). TSC2/Rheb colocalization decreased below fasted at 60 and 300 min after feeding in REST and EX (P < 0.01). mTOR colocalization with Rheb increased above fasted at 60 and 300 min after feeding in REST and EX (P < 0.01), which was consistent with an increased phosphorylation 4E-BP1 Thr37/46 and rpS6 ser240/244 at 60 min. Our data suggest that MyoPS, but not MitoPS, is primarily nutrient responsive in trained young men at rest and after endurance exercise. The postprandial increase in MyoPS is associated with an increase in mTOR/Rheb colocalization and a reciprocal decrease in TSC2/Rheb colocalization and thus likely represent important regulatory events for in vivo skeletal muscle myofibrillar mRNA translation in humans., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Purpose: Endurance exercise increases indices of small intestinal damage and leucine oxidation, which may attenuate dietary amino acid appearance and postprandial leucine balance during postexercise recovery. Therefore, the purpose of this study was to examine the effect of an acute bout of endurance exercise on postprandial leucine kinetics and net leucine balance., Methods: In a crossover design, seven trained young men (age = 25.6 ± 2.3 yr; V˙O2peak = 61.4 ± 2.9 mL·kg·min; mean ± SEM) received a primed constant infusion of L-[1-C]leucine before and after ingesting a mixed macronutrient meal containing 18 g whole egg protein intrinsically labeled with L-[5,5,5-H3]leucine, 17 g fat, and 60 g carbohydrate at rest and after 60 min of treadmill running at 70% V˙O2peak., Results: Plasma intestinal fatty acid binding protein concentrations and leucine oxidation both increased (P < 0.01) to peaks that were ~2.5-fold above baseline values during exercise with a concomitant decrease (P < 0.01) in nonoxidative leucine disposal. Meal ingestion attenuated (P < 0.01) endogenous leucine rates of appearance at rest and after exercise. There were no differences (both, P > 0.05) in dietary leucine appearance rates or in the amount of dietary protein-derived leucine that appeared into circulation over the 5-h postprandial period at rest and after exercise (62% ± 2% and 63% ± 2%, respectively). Leucine balance over the 5-h postprandial period was positive (P < 0.01) in both conditions but was negative (P < 0.01) during the exercise trial after accounting for exercise-induced leucine oxidation., Conclusions: We demonstrate that endurance exercise does not modulate dietary leucine availability from a mixed meal but attenuates postprandial whole-body leucine balance in trained young men.

Background: Protein in the diet is commonly ingested from whole foods that contain various macro- and micronutrients. However, the effect of consuming protein within its natural whole-food matrix on postprandial protein metabolism remains understudied in humans. Objective: We aimed to compare the whole-body and muscle protein metabolic responses after the consumption of whole eggs with egg whites during exercise recovery in young men. Design: In crossover trials, 10 resistance-trained men [aged 21 ± 1 y; 88 ± 3 kg; body fat: 16% ± 1% (means ± SEMs)] received primed continuous l-[ ring - 2 H 5 ]phenylalanine and l-[1- 13 C]leucine infusions and performed a single bout of resistance exercise. After exercise, participants consumed intrinsically l-[5,5,5- 2 H 3 ]leucine-labeled whole eggs (18 g protein, 17 g fat) or egg whites (18 g protein, 0 g fat). Repeated blood and muscle biopsy samples were collected to assess whole-body leucine kinetics, intramuscular signaling, and myofibrillar protein synthesis. Results: Plasma appearance rates of protein-derived leucine were more rapid after the consumption of egg whites than after whole eggs ( P = 0.01). Total plasma availability of leucine over the 300-min postprandial period was similar ( P = 0.75) between the ingestion of whole eggs (68% ± 1%) and egg whites (66% ± 2%), with no difference in whole-body net leucine balance ( P = 0.27). Both whole-egg and egg white conditions increased the phosphorylation of mammalian target of rapamycin complex 1, ribosomal protein S6 kinase 1, and eukaryotic translation initiation factor 4E-binding protein 1 during postexercise recovery (all P < 0.05). However, whole-egg ingestion increased the postexercise myofibrillar protein synthetic response to a greater extent than did the ingestion of egg whites ( P = 0.04). Conclusions: We show that the ingestion of whole eggs immediately after resistance exercise resulted in greater stimulation of myofibrillar protein synthesis than did the ingestion of egg whites, despite being matched for protein content in young men. Our data indicate that the ingestion of nutrient- and protein-dense foods differentially stimulates muscle anabolism compared with protein-dense foods. This trial was registered at clinicaltrials.gov as NCT03117127., (© 2017 American Society for Nutrition.)

Circulating progenitor cells (CPCs) are a heterogeneous population of stem/progenitor cells in peripheral blood that includes hematopoietic stem and progenitor cells (HSPCs and HSCs), endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs) that are involved in tissue repair and adaptation. CPC mobilization during exercise remains uncharacterized in young adults. The purpose of this study was to investigate the kinetics of CPC mobilization during and after submaximal treadmill running and their relationship to mobilization factors. Seven men [age = 25.3 ± 2.4 yr, body mass index = 23.5 ± 1.0 kg/m 2 , peak O 2 uptake (V̇o 2peak ) = 60.9 ± 2.74 ml·kg -1 ·min -1 ] ran on a treadmill for 60 min at 70% V̇o 2peak Blood sampling occurred before (Pre), during [20 min (20e), 40 min (40e), 60 min (60e)], and after exercise [15 min (15p), 60 min (60p), 120 min (120p)] for quantification of CPCs (CD34 + ), HSPCs (CD34 + /CD45 low ), HSCs (CD34 + /CD45 low /CD38 - ), CD34 + MSCs (CD45 - /CD34 + /CD31 - /CD105 + ), CD34 - MSCs (CD45 - /CD34 - /CD31 - /CD105 + ), and EPCs (CD45 - /CD34 + /CD31 + ) via flow cytometry. CPC concentration increased compared with Pre at 20e and 40e (2.7- and 2.4-fold, respectively, P < 0.05). HSPCs and HSCs increased at 20e compared with 60p (2.7- and 2.8-fold, respectively, P < 0.05), whereas EPCs and both MSC populations did not change. CXC chemokine ligand (CXCL) 12 (1.5-fold; P < 0.05) and stem cell factor (1.3-fold; P < 0.05) were increased at 40e and remained elevated postexercise. The peak increase in CPCs was positively correlated to concentration of endothelial cells during exercise with no relationship to CXCL12 and SCF. Our data show the kinetics of progenitor cell mobilization during exercise that could provide insight into cellular mediators of exercise-induced adaptations, and have implication for the use of exercise as an adjuvant therapy for CPC collection in hematopoietic stem cell transplant. NEW & NOTEWORTHY Using a comprehensive evaluation of circulating progenitor cells (CPCs), we show that CPC mobilization during exercise is related to tissue damage, and not plasma concentrations of CXC chemokine ligand 12 and stem cell factor. These data have implications for the use of exercise interventions as adjuvant therapy for CPC mobilization in the context of hematopoietic stem cell transplant and also support the role of mobilized progenitor cells as cellular mediators of systemic adaptations to exercise., (Copyright © 2017 the American Physiological Society.)

Background: Excess body fat diminishes muscle protein synthesis rates in response to hyperinsulinemic-hyperaminoacidemic clamps. However, muscle protein synthetic responses after the ingestion of a protein-dense food source across a range of body mass indexes (BMIs) have not been compared., Objective: We compared the myofibrillar protein synthetic response and underlying nutrient-sensing mechanisms after the ingestion of lean pork between obese, overweight, and healthy-weight adults., Design: Ten healthy-weight [HW; BMI (in kg/m 2 ): 22.7 ± 0.4], 10 overweight (OW; BMI: 27.1 ± 0.5), and 10 obese (OB; BMI: 35.9 ± 1.3) adults received primed continuous l-[ring- 13 C 6 ]phenylalanine infusions. Blood and muscle biopsy samples were collected before and after the ingestion of 170 g pork (36 g protein and 3 g fat) to assess skeletal muscle anabolic signaling, amino acid transporters [large neutral and small neutral amino acid transporters (LAT1, SNAT2) and CD98], and myofibrillar protein synthesis., Results: At baseline, OW and OB groups showed greater relative amounts of mammalian target of rapamycin complex 1 (mTORC1) protein than the HW group. Pork ingestion increased mTORC1 phosphorylation only in the HW group (P = 0.001). LAT1 and SNAT2 protein content increased during the postprandial period in all groups (time effect, P < 0.05). Basal myofibrillar protein synthetic responses were similar between groups (P = 0.43). However, myofibrillar protein synthetic responses (0-300 min) were greater in the HW group (1.6-fold; P = 0.005) after pork ingestion than in the OW and OB groups., Conclusions: There is a diminished myofibrillar protein synthetic response to the ingestion of protein-dense food in overweight and obese adults compared with healthy-weight controls. These data indicate that impaired postprandial myofibrillar protein synthetic response may be an early defect with increasing fat mass, potentially dependent on altered anabolic signals, that reduces muscle sensitivity to food ingestion. This trial was registered at clinicaltrials.gov as NCT02613767., (© 2016 American Society for Nutrition.)

Background: Stable isotope amino acids are regularly used as tracers to examine whole-body and muscle protein metabolism in humans. To accurately assess in vivo dietary protein digestion and absorption kinetics, the amino acid tracer is required to be incorporated within the dietary protein food source (i.e., intrinsically labeled protein)., Objective: We assessed the practicality of producing eggs and poultry meat intrinsically labeled with l-[5,5,5-(2)H3]leucine through noninvasive oral tracer administration., Methods: A specifically formulated diet containing 0.52% leucine was supplemented with 0.3% l-[5,5,5-(2)H3]leucine and subsequently fed to 3 laying hens (Lohmann LSL Whites) for 55 d. On day 55, the hens were slaughtered and their meat, bones, and organs were harvested to determine tissue labeling. In Expt. 1, 2 healthy young men [mean ± SEM age: 22 ± 1.5 y; mean ± SEM body mass index (BMI; in kg/m(2)): 23.7 ± 0.5] ingested 18 g l-[5,5,5-(2)H3]leucine-labeled egg protein. In Expt. 2, 2 healthy young men (mean ± SEM age: 20.0 ± 0.0 y; mean ± SEM BMI: 26.4 ± 3.1) ingested 28 g l-[5,5,5-(2)H3]leucine-labeled poultry meat protein. Plasma samples (Expts. 1 and 2) and muscle biopsies (Expt. 1) were collected before and after labeled-food ingestion., Results: High tracer labeling [>20 mole percent excess (MPE)] in the eggs was obtained after 7 d and maintained throughout the feeding protocol (P < 0.05). Over a 55-d period, ∼850 g egg protein (145 eggs) was produced, with a mean ± SEM tracer enrichment of 22.0 ± 0.8 MPE. Mean ± SEM l-[5,5,5-(2)H3]leucine enrichment in the meat was 9.6 ± 0.1 MPE. In Expts. 1 and 2, the consumption of labeled eggs and poultry meat protein increased plasma l-[5,5,5-(2)H3]leucine enrichment, with mean ± SEM peak values of 6.7 ± 0.1 MPE and 4.0 ± 0.9 MPE, respectively. The mean ± SEM 5-h postprandial increase in myofibrillar l-[5,5,5-(2)H3]leucine enrichment after egg ingestion in healthy young men was 0.051 ± 0.008 MPE (Expt. 1)., Conclusion: We demonstrated the feasibility of producing intrinsically labeled eggs and poultry meat for use in human metabolic research., (© 2016 American Society for Nutrition.)

The larynx and surrounding soft tissues are vulnerable to injury during athletics despite protective equipment and rule modifications. Laryngeal injuries are uncommon but potentially fatal conditions that pose risks to the voice, airway, and esophagus of athletes who sustain blunt or penetrating neck trauma. Common symptoms and signs of laryngeal trauma include hoarseness, dyspnea, hemoptysis, dysphonia, respiratory distress, anterior neck tenderness, subcutaneous emphysema, and loss of normal laryngeal architecture. Diagnostic evaluation includes plain radiographs, computed tomography, and fibroscopic endoscopy. Most athletes with laryngeal injuries will require surgical treatment to restore normal regional anatomy and vocal quality. Less severe injuries may be treated with close observation, serial endoscopy, medications, and vocal rest.

Caffeine is the most commonly consumed drug in the world, and athletes frequently use it as an ergogenic aid. It improves performance and endurance during prolonged, exhaustive exercise. To a lesser degree it also enhances short-term, high-intensity athletic performance. Caffeine improves concentration, reduces fatigue, and enhances alertness. Habitual intake does not diminish caffeine's ergogenic properties. Several mechanisms have been proposed to explain the physiologic effects of caffeine, but adenosine receptor antagonism most likely accounts for the primary mode of action. It is relatively safe and has no known negative performance effects, nor does it cause significant dehydration or electrolyte imbalance during exercise. Routine caffeine consumption may cause tolerance or dependence, and abrupt discontinuation produces irritability, mood shifts, headache, drowsiness, or fatigue. Major sport governing bodies ban excessive use of caffeine, but current monitoring techniques are inadequate, and ethical dilemmas persist regarding caffeine intake by athletes.

Background and Objectives: Studies have shown that female and male residents see disproportionately few patients of the opposite gender. Such an imbalance may be detrimental to the quality of residency training. This study examined residents' levels of comfort in caring for patients of the same and opposite genders and their assessments of the adequacy of the number of same- and opposite-gender patients they saw during residency training., Methods: Data were collected from four family practice residency programs in the Midwest. All current family practice residents at the four sites surveyed were given a questionnaire asking them to rate their perceptions of the gender distributions of their patient panels and comfort with several areas of health care, some gender specific. The questionnaire used a five-point Likert scale., Results: Ninety-four surveys (83% response rate) were collected. Ninety-three percent of female residents reported seeing enough female patients, but only 54% reported seeing enough male patients. Seventy-six percent of male residents reported seeing enough male patients, but only 31% reported seeing enough female patients. More females than males (88% versus 48%) felt comfortable with women's health, but more males than females (70% versus 31%) felt comfortable with men's health. Male residents were significantly more comfortable than female residents in performing or managing prostate exams, testicular exams, and prostatitis. Female residents were significantly more comfortable with clinical breast exams and breast disease., Conclusions: Male and female residents perceive disproportionate experiences in their exposure to patients of the opposite gender. Significant differences between male and female residents were also apparent regarding their relative comfort in managing some gender-specific health care topics. These results have implications for residency education.