Neuromodulatory Contribution to Muscle Force Production after Short-Term Unloading and Active Recovery.

PURPOSE: Prior evidence has shown that neural factors contribute to the loss of muscle force after skeletal-muscle disuse. However, little is known about the specific neural mechanisms altered by disuse. Persistent inward current (PIC) is an intrinsic property of motoneurons responsible for prolonging and amplifying the synaptic input, proportionally to the level of neuromodulation, thus influencing motoneuron discharge rate and force production. Here, we hypothesized that short-term unilateral lower-limb suspension (ULLS) would reduce the neuromodulatory input associated with PICs, contributing to the reduction of force generation capacity. Additionally, we tested whether physical exercise would restore the force generation capacity by re-establishing the initial level of neuromodulatory input. METHODS: In 12 young adults, we assessed maximal voluntary contraction (MVC) pre- and post- 10 days of ULLS and following 21 days of active recovery (AR) based on resistance exercise. PIC was estimated from high-density surface electromyograms of the vastus lateralis muscle as the delta frequency (∆F) of paired motor units calculated during isometric ramped contractions. RESULTS: The values of ∆F were reduced after 10 days of ULLS (-33%, p < 0.001), but were fully re-established after the AR (+29.4%, p < 0.001). The changes in estimated PIC values were correlated (r = 0.63, p = 0.004) with the reduction in MVC after ULLS (-29%, p = 0.002) and its recovery after the AR (+28.5%, p = 0.003). CONCLUSIONS: Our findings suggest that PIC estimates are reduced by muscle disuse and may contribute to the loss of force production and its recovery with exercise. Overall, this is the first study demonstrating that, in addition to peripheral neuromuscular changes, central neuromodulation is a major contributor to the loss of force generation capacity after disuse, and can be recovered after resistance exercise.

Characterization of the in vivo transient responses of the femoral cartilage by means of quantitative ultrasound imaging techniques.

BACKGROUND: Quantitative ultrasound (QUS) techniques are new diagnostic tools able to identify changes in structural and material properties of the investigated tissue. For the first time, we evaluated the capability of QUS techniques in determining the in vivo transient changes in knee joint cartilage after a stressful task. METHODS: An ultrasound scanner collecting B-mode and radiofrequency data simultaneously was used to collect data from the femoral cartilage of the right knee in 15 participants. Cartilage thickness (CTK), ultrasound roughness index (URI), average magnitude ratio (AMR), and Nakagami parameters (NA) were evaluated before, immediately after and every 5 min up to 45 min a stressful task (30 min of running on a treadmill with a negative slope of 5%). RESULTS: CTK was affected by time (main effect: p < 0.001). Post hoc test showed significant differences with CTK at rest, which were observed up to 30 min after the run. AMR and NA were affected by time (p < 0.01 for both variables), while URI was unaffected by it. For AMR, post hoc test showed significant differences with rest values in the first 35 min of recovery, while NA was increased compared to rest values in all time points. CONCLUSION: Data suggest that a single running trial is not able to modify the integrity of the femoral cartilage, as reported by URI data. In vivo evaluation of QUS parameters of the femoral cartilage (NA, AMR, and URI) are able to characterize changes in cartilage properties over time.

Lower limb suspension induces threshold-specific alterations of motor units properties that are reversed by active recovery.

PURPOSE: This study aimed to non-invasively test the hypothesis that (a) short-term lower limb unloading would induce changes in the neural control of force production (based on motor units (MUs) properties) in the vastus lateralis muscle and (b) possible changes are reversed by active recovery (AR). METHODS: Ten young males underwent 10 days of unilateral lower limb suspension (ULLS) followed by 21 days of AR. During ULLS, participants walked exclusively on crutches with the dominant leg suspended in a slightly flexed position (15°-20°) and with the contralateral foot raised by an elevated shoe. The AR was based on resistance exercise (leg press and leg extension) and executed at 70% of each participant's 1 repetition maximum, 3 times/week. Maximal voluntary isometric contraction (MVC) of knee extensors and MUs properties of the vastus lateralis muscle were measured at baseline, after ULLS, and after AR. MUs were identified using high-density electromyography during trapezoidal isometric contractions at 10%, 25%, and 50% of the current MVC, and individual MUs were tracked across the 3 data collection points. RESULTS: We identified 1428 unique MUs, and 270 of them (18.9%) were accurately tracked. After ULLS, MVC decreased by 29.77%, MUs absolute recruitment/derecruitment thresholds were reduced at all contraction intensities (with changes between the 2 variables strongly correlated), while discharge rate was reduced at 10% and 25% but not at 50% MVC. Impaired MVC and MUs properties fully recovered to baseline levels after AR. Similar changes were observed in the pool of total as well as tracked MUs. CONCLUSION: Our novel results demonstrate, non-invasively, that 10 days of ULLS affected neural control predominantly by altering the discharge rate of lower-threshold but not of higher-threshold MUs, suggesting a preferential impact of disuse on motoneurons with a lower depolarization threshold. However, after 21 days of AR, the impaired MUs properties were fully restored to baseline levels, highlighting the plasticity of the components involved in neural control.

Fully Automated Analysis of Muscle Architecture from B-Mode Ultrasound Images with DL_Track_US.

OBJECTIVE: B-mode ultrasound can be used to image musculoskeletal tissues, but one major bottleneck is analyses of muscle architectural parameters (i.e., muscle thickness, pennation angle and fascicle length), which are most often performed manually. METHODS: In this study we trained two different neural networks (classic U-Net and U-Net with VGG16 pre-trained encoder) to detect muscle fascicles and aponeuroses using a set of labeled musculoskeletal ultrasound images. We determined the best-performing model based on intersection over union and loss metrics. We then compared neural network predictions on an unseen test set with those obtained via manual analysis and two existing semi/automated analysis approaches (simple muscle architecture analysis [SMA] and UltraTrack). DL_Track_US detects the locations of the superficial and deep aponeuroses, as well as multiple fascicle fragments per image. RESULTS: For single images, DL_Track_US yielded results similar to those produced by a non-trainable automated method (SMA; mean difference in fascicle length: 5.1 mm) and human manual analysis (mean difference: -2.4 mm). Between-method differences in pennation angle were within 1.5°, and mean differences in muscle thickness were less than 1 mm. Similarly, for videos, there was overlap between the results produced with UltraTrack and DL_Track_US, with intraclass correlations ranging between 0.19 and 0.88. CONCLUSION: DL_Track_US is fully automated and open source and can estimate fascicle length, pennation angle and muscle thickness from single images or videos, as well as from multiple superficial muscles. We also provide a user interface and all necessary code and training data for custom model development.

Reliability of panoramic ultrasound imaging and agreement with magnetic resonance imaging for the assessment of lumbar multifidus anatomical cross-sectional area.

The aim of this study was to investigate the reliability of panoramic ultrasound (US) imaging and agreement with magnetic resonance imaging (MRI) for assessing the average lumbar multifidus anatomical cross-sectional area between the lumbar vertebral bodies L3-L5 (i.e., LMF ACSAL3-L5). US and MRI scans of 20 male youth competitive alpine skiers were collected. To test the intra- and interrater reliability of US, transversal panoramic scans were analyzed on two different days by the same rater and the analysis of the first day was compared with the analysis of a second rater. To examine the agreement between US and MRI, Bland-Altman analysis was performed. Intrarater reliability was excellent, and interrater reliability was weak to good for both sides. The bias between MRI and US was - 0.19 ± 0.90 cm2 (2.68 ± 12.30%) for the left side and - 0.04 ± 0.98 cm2 (- 1.11 ± 12.93%) for the right side (i.e., for both sides US slightly overestimated LMF ACSAL3-L5 on average). The limits of agreement were - 1.95 to 1.57 cm2 (- 26.70 to 21.30%) for the left side and - 1.95 to 1.88 cm2 (- 26.46 to 24.24%) for the right side. Panoramic US imaging may be considered a method with excellent intrarater and weak to good interrater reliability for assessing LMF ACSAL3-L5. Comparison with MRI showed large individual differences in some cases, but an acceptable bias between the two imaging modalities.

Ultrasonographic measurements of fascicle length overestimate adaptations in serial sarcomere number.

Ultrasound-derived measurements of muscle fascicle length (FL) are often used to infer increases (chronic stretch or training) or decreases (muscle disuse or aging) in serial sarcomere number (SSN). Whether FL adaptations measured via ultrasound can truly approximate SSN adaptations has not been investigated. We casted the right hindlimb of 15 male Sprague-Dawley rats in a dorsiflexed position (i.e., stretched the plantar flexors) for 2 weeks, with the left hindlimb serving as a control. Ultrasound images of the soleus, lateral gastrocnemius (LG), and medial gastrocnemius (MG) were obtained with the ankle at 90° and full dorsiflexion for both hindlimbs pre and post-cast. Following post-cast ultrasound measurements, legs were fixed in formalin with the ankle at 90°, then muscles were dissected and fascicles were teased out for measurement of sarcomere lengths via laser diffraction and calculation of SSN. Ultrasound detected an 11% increase in soleus FL, a 12% decrease in LG FL, and an 8-11% increase in MG FL for proximal fascicles and at full dorsiflexion. These adaptations were partly reflected by SSN adaptations, with a 6% greater soleus SSN in the casted leg than the un-casted leg, but no SSN differences for the gastrocnemii. Weak relationships were observed between ultrasonographic measurements of FL and measurements of FL and SSN from dissected fascicles. Our results showed that ultrasound-derived FL measurements can overestimate an increase in SSN by ∼5%. Future studies should be cautious when concluding a large magnitude of sarcomerogenesis from ultrasound-derived FL measurements, and may consider applying a correction factor. NEW FINDINGS: What is the central question of this study? Measurements of muscle fascicle length via ultrasound are often used to infer changes in serial sarcomere number, such as increases following chronic stretch or resistance training, and decreases with ageing: does ultrasound-derived fascicle length accurately depict adaptations in serial sarcomere number? What is the main finding and its importance? Ultrasound detected an ∼11% increase in soleus fascicle length, but measurements on dissected fascicles showed the actual serial sarcomere number increase was only ∼6%; therefore, measurements of ultrasound-derived fascicle length can overestimate serial sarcomere number adaptations by as much as 5%.

The importance of serial sarcomere addition for muscle function and the impact of aging.

During natural aging, skeletal muscle experiences impairments in mechanical performance due, in part, to changes in muscle architecture and size, notably with a loss of muscle cross-sectional area (CSA). Another important factor that has received less attention is the shortening of fascicle length (FL), potentially reflective of a decrease in serial sarcomere number (SSN). Interventions that promote the growth of new serial sarcomeres, such as chronic stretching and eccentric-biased resistance training, have been suggested as potential ways to mitigate age-related impairments in muscle function. Although current research suggests it is possible to stimulate serial sarcomerogenesis in muscle in old age, the magnitude of sarcomerogenesis may be less than in young muscle. This blunted effect may be partly due to age-related impairments in the pathways regulating mechanotransduction, muscle gene expression, and protein synthesis, as some have been implicated in SSN adaptation. The purpose of this review was to investigate the impact of aging on the ability for serial sarcomerogenesis and elucidate the molecular pathways that may limit serial sarcomerogenesis in old age. Age-related changes in mechanistic target of rapamycin (mTOR), insulin-like growth factor 1 (IGF-1), myostatin, and serum response factor signaling, muscle ring finger protein (MuRFs), and satellite cells may hinder serial sarcomerogenesis. In addition, our current understanding of SSN in older humans is limited by assumptions based on ultrasound-derived fascicle length. Future research should explore the effects of age-related changes in the identified pathways on the ability to stimulate serial sarcomerogenesis, and better estimate SSN adaptations to gain a deeper understanding of the adaptability of muscle in old age.

Myoelectric activity during electromagnetic resistance alone and in combination with variable resistance or eccentric overload.

The purpose of this study was to compare the effects of electromagnetic resistance alone, as well as in combination with variable resistance or accentuated eccentric methods, with traditional dynamic constant external resistance exercise on myoelectric activity during elbow flexion. The study employed a within-participant randomized, cross-over design whereby 16 young, resistance-trained male and female volunteers performed elbow flexion exercise under each of the following conditions: using a dumbbell (DB); using a commercial electromagnetic resistance device (ELECTRO); variable resistance (VR) using a setting on the device that attempts to match the level of resistance to the human strength curve, and; eccentric overload (EO) using a setting on the device that increases the load by 50% on the eccentric portion of each repetition. Surface electromyography (sEMG) was obtained for the biceps brachii, brachioradialis and anterior deltoid on each of the conditions. Participants performed the conditions at their predetermined 10 repetition maximum. " The order of performance for the conditions was counterbalanced, with trials separated by a 10-min recovery period. The sEMG was synced to a motion capture system to assess sEMG amplitude at elbow joint angles of 30°, 50°, 70°, 90°, 110°, with amplitude normalized to the maximal activation. The anterior deltoid showed the largest differences in amplitude between conditions, where median estimates indicated greater concentric sEMG amplitude (~ 7-10%) with EO, ELECTRO and VR compared with DB. Concentric biceps brachii sEMG amplitude was similar between conditions. In contrast, results indicated a greater eccentric amplitude with DB compared to ELECTRO and VR, but unlikely to exceed a 5% difference. Data indicated a greater concentric and eccentric brachioradialis sEMG amplitude with DB compared to all other conditions, but differences were unlikely to exceed 5%. The electromagnetic device tended to produce greater amplitudes in the anterior deltoid, while DB tended to produce greater amplitudes in the brachioradialis; amplitude for the biceps brachii was relatively similar between conditions. Overall, any observed differences were relatively modest, equating to magnitudes of ~ 5% and not likely greater than 10%. These differences would seem to be of minimal practical significance.

Regional muscle features and their association with knee extensors force production at a single joint angle.

This study aimed (i) to investigate the role of regional characteristics of the knee extensors muscles (vastus lateralis: VL, vastus intermedius: VI and rectus femoris: RF) in determining maximum-voluntary force (MVF); and (ii) to understand which regional parameter of muscle structure would best predict MVF. Muscle architecture (e.g., pennation angle and fascicle length), muscle volume (Vol), anatomical (ACSA) and physiological cross-sectional-area (PCSA) were measured in the proximal (0-33% of the muscle length), middle (33-66% of the muscle length) and distal (66-100% of the muscle length) portions of each muscle in fifteen healthy males using ultrasound and Magnetic Resonance Imaging (MRI). Knee extensors force was calculated in isometric condition at a single knee joint angle of 90 degrees. Regional ACSA, Vol and PCSA were correlated with MVF production. Regional muscle geometry showed no significant correlations with MVF. Among regions, the middle portion of each muscle was largely correlated with MVF compared to all the other regions (distal and proximal). To understand which regional structural parameter best predicted MVF, a stepwise multiple linear regression was performed. This model showed a significant explanatory power (P < 0.001, R2 = 0.76, adjusted R2 = 0.71), including muscle Vol collected in the mid portions of VL and RF. Even if no significant differences were reported between Vol, PCSA and ACSA in determining MVF, our results showed that the RF and VL volume collected in the middle portion of the muscle length are strong determinants of MVF produced by the knee extensors at 90 degrees joint angle.

Pathophysiological mechanisms of reduced physical activity: Insights from the human step reduction model and animal analogues.

Physical inactivity represents a heavy burden for modern societies and is spreading worldwide, it is a recognised pandemic and is the fourth cause of global mortality. Not surprisingly, there is an increasing interest in longitudinal studies on the impact of reduced physical activity on different physiological systems. This narrative review focuses on the pathophysiological mechanisms of step reduction (SR), an experimental paradigm that involves a sudden decrease in participants' habitual daily steps to a lower level, mimicking the effects of a sedentary lifestyle. Analogous animal models of reduced physical activity, namely, the "wheel-lock" and the "cage reduction" models, which can provide the foundation for human studies, are also discussed. The empirical evidence obtained thus far shows that even brief periods of reduced physical activity can lead to substantial alterations in skeletal muscle health and metabolic function. In particular, decrements in lean/muscle mass, muscle function, muscle protein synthesis, cardiorespiratory fitness, endothelial function and insulin sensitivity, together with an increased fat mass and inflammation, have been observed. Exercise interventions seem particularly effective for counteracting these pathophysiological alterations induced by periods of reduced physical activity. A direct comparison of SR with other human models of unloading, such as bed rest and lower limb suspension/immobilisation, is presented. In addition, we propose a conceptual framework aiming to unravel the mechanisms of muscle atrophy and insulin resistance in the specific context of reduced ambulatory activity. Finally, methodological considerations, knowledge gaps and future directions for both animal and human models are also discussed in the review.

Study of the link between hemotopoietic and skeletal systems in patients attending a referral center for osteoporosis.

PURPOSE: To investigate the link between hematopoietic and skeletal tissues in patients with fragility fractures. METHODS: We retrospectively analyzed the medical records of women older than 40 years who attended the Bone Disease Unit of "Sapienza" University of Rome for their first visit for osteoporosis from January 2020 to June 2022. RESULTS: Fragility fractures were found in 61.8% of the sample. In particular, vertebral fractures in 35.5%, femoral fractures in 6.3%, Colles fractures in 16.5% and non-vertebral non-hip in 42.5%. Fractured patients were significantly older compared to non-fractured, had lower mean values of lumbar spine (p = 0.01), and femoral neck BMD (p = 0.007). A red blood cell distribution width (RDW) value higher than 15% was observed four times more in those with fractures compared to non-fractured patients (8.9% vs 2%, p = 0.01) and was associated with vertebral fracture after adjusting for age, BMI, menopause, nutritional status, smoking, osteoporosis and anemia (OR = 4.1, 95% CI 1.6-11.4, p = 0.003). Hematocrit was negatively associated with hip fracture also adjusting for age, BMI, menopause, nutritional status, smoking, osteoporosis (p = 0.025). CONCLUSION: Our study demonstrates that RDW values were significantly associated with vertebral fracture and hematocrit with hip fracture. Since both parameters are included in the initial evaluation of patients with suspected bone fragility, our results should push doctors to look at these values with no incremental cost for national health services.

Upregulation of Sarcolemmal Hemichannels and Inflammatory Transcripts with Neuromuscular Junction Instability during Lower Limb Unloading in Humans.

Human skeletal muscle atrophy and a disproportionate force loss occur within a few days of unloading in space and on Earth, but the underlying mechanisms are not fully understood. Disruption of neuromuscular junction homeostasis has been proposed as one of the possible causes. Here, we investigated the potential mechanisms involved in this neuromuscular disruption induced by a 10-day unilateral lower limb suspension (ULLS) in humans. Specifically, we investigated hemichannels' upregulation, neuromuscular junction and axonal damage, neurotrophins' receptor downregulation and inflammatory transcriptional signatures. Biomarkers were evaluated at local and systemic levels. At the sarcolemmal level, changes were found to be associated with an increased expression of connexin 43 and pannexin-1. Upregulation of the inflammatory transcripts revealed by deep transcriptomics was found after 10 days of ULLS. The destabilisation of the neuromuscular junction was not accompanied by changes in the secretion of the brain-derived neurotrophic factor and neurotrophin-4, while their receptor, BDNF/NT growth factors receptor (TrkB), decreased. Furthermore, at 5 days of ULLS, there was already a significant upregulation of the serum neurofilament light chain concentration, an established clinical biomarker of axonal injury. At 10 days of ULLS, other biomarkers of early denervation processes appeared. Hence, short periods of muscle unloading induce sarcolemmal hemichannels upregulation, inflammatory transcripts upregulation, neuromuscular junction instability and axonal damage.

More than just a side effect: Dynamic knee valgus and deadbug bridging performance in youth soccer players and alpine skiers have similar absolute values and asymmetry magnitudes but differ in terms of the direction of laterality.

From a preventative perspective, leg axis and core stabilization capacities are important for soccer players and alpine skiers; however, due to different sport-specific demands, the role of laterality clearly differs and may result in functional long-term adaptations. The aims of this study are 1) to determine whether there are differences in leg axis and core stability between youth soccer players and alpine skiers and 2) between dominant and non-dominant sides, and 3) to explore the outcomes of applying common sport-specific asymmetry thresholds to these two distinct cohorts. Twenty-one highly trained/national-level soccer players (16.1 years, 95% CI: 15.6, 16.5) and 61 alpine skiers (15.7 years, 95% CI: 15.6, 15.8) participated in this study. Using a marker-based 3D motion capture system, dynamic knee valgus was quantified as the medial knee displacement (MKD) during drop jump landings, and core stability was quantified as the vertical displacement during deadbug bridging exercise (DBB displacement ). For the analysis of sports and side differences, a repeated-measures multivariate analysis of variance was used. For the interpretation of laterality, coefficients of variation (CV) and common asymmetry thresholds were applied. There were no differences in MKD or DBB displacement between soccer players and skiers or between the dominant and non-dominant sides, but there was an interaction effect side*sports for both variables (MKD: p = 0.040, η2 p = 0.052; DBB displacement : p = 0.025, η2 p = 0.061). On average, MKD was larger on the non-dominant side and DBB displacement laterality on the dominant side in soccer players, whereas this pattern was reversed in alpine skiers. Despite similar absolute values and asymmetry magnitudes of dynamic knee valgus and deadbug bridging performance in youth soccer players and alpine skiers, the effect on the direction of laterality was opposite even though much less pronounced. This may imply that sport-specific demands and potential laterality advantages should be considered when dealing with asymmetries in athletes.

Altered regional 3D shear wave velocity patterns in youth competitive alpine skiers suffering from patellar tendon complaints - a prospective case-control study.

Patellar tendon (PT) complaints are frequent throughout the population, with increased occurrence in athletes and, particularly, in youth competitive alpine skiers. Timely detection and treatment might improve prospects of recovery. Diagnostic modalities in clinical use to date rely on pain symptoms, manual palpation, and potentially, magnetic resonance imaging (MRI); however, MRI-based imaging yields limited sensitivity. Quantitatively measuring the morphological and mechanical properties of PTs by means of B-mode ultrasound and shear wave elastography (SWE), instead, may allow improved diagnosis or even early detection. We performed B-mode scans and three-dimensional ultrasound shear wave velocity (SWV) mapping and MRI of the PT in 106 youth skiers. A prospective one-year survey on health problems combined with clinical assessments served to categorize symptomatic and asymptomatic youth skiers. Skiers suffering from distal or proximal tendon complaints showed lower SWV in the respective tendon region than asymptomatic skiers (p = 0.035 and p = 0.019, respectively). Youth skiers with distal tendon complaints additionally exhibited decreased SWV in the proximal region compared to asymptomatic counterparts (p = 0.020). Cross-validated analysis of retrospective prediction indicated sensitivity and specificity in detecting tendon complaints in the range of 0.606-0.621 and 0.536-0.650, respectively. MRI detected distal tendon complaints with a sensitivity of 0.410 (12/29) but failed to detect any proximal cases. This study agrees with the most recent literature in that SWE holds promise as a valuable adjunct modality for the diagnosis of PT complaints or even the detection of subclinical prestages. However, to evaluate its prospective predictive value, long-term studies are warranted.Highlights Patellar tendon complaints are a frequent complaint in athletes, particularly in youth competitive alpine skiers, but timely quantitative detection of related tendon properties remains challenging.Quantitative B-mode US and three-dimensional ultrasound shear wave elastography assessments and magnetic resonance imaging were performed in youth competitive alpine skiers.Three-dimensional shear wave elastography was able to discern symptomatic from asymptomatic patellar tendons both in the distal and proximal tendon regions, whereas magnetic resonance imaging failed to detect any proximal cases.

Neuromuscular Aging: A Case for the Neuroprotective Effects of Dancing.

AIM: We planned a cross-sectional investigation (study 1) and a longitudinal training intervention (study 2) to investigate whether recreational dancing affords greater neuroprotective effects against age-related neuromuscular junction (NMJ) degeneration compared to general fitness exercise training. METHODS: In study 1, we recruited 19 older volunteers regularly practising dancing (older dancers [OD]) and 15 recreationally physically active older individuals (OA) and physical performance, muscle morphology, muscle function, and NMJ stability (from serum C-terminal agrin fragment [CAF] concentration) were assessed. In study 2, employing a longitudinal study design in a different cohort (composed of 37 older adults), we aimed to study whether a 6-month dancing intervention decreased CAF concentration compared to general fitness exercise training in older adults. RESULTS: Our findings show that OD had a lower CAF concentration (suggesting an increased NMJ stability) compared to OA. This result was accompanied by superior functional performance despite no differences in muscle size. In study 2, we observed a reduction in CAF concentration only in the dancing group. CONCLUSION: Overall, these findings suggest that dancing is an effective training modality to promote neuroprotection and increase muscle function in healthy older individuals.

Metabolic and molecular responses of human patellar tendon to concentric- and eccentric-type exercise in youth and older age.

Exercise training can induce adaptive changes to tendon tissue both structurally and mechanically; however, the underlying compositional changes that contribute to these alterations remain uncertain in humans, particularly in the context of the ageing tendon. The aims of the present study were to determine the molecular changes with ageing in patellar tendons in humans, as well as the responses to exercise and exercise type (eccentric (ECC) and concentric (CON)) in young and old patellar tendon. Healthy younger males (age 23.5 ± 6.1 years; n = 27) and older males (age 68.5 ± 1.9 years; n = 27) undertook 8 weeks of CON or ECC training (3 times per week; at 60% of 1 repetition maximum (1RM)) or no training. Subjects consumed D2O throughout the protocol and tendon biopsies were collected after 4 and 8 weeks for measurement of fractional synthetic rates (FSR) of tendon protein synthesis and gene expression. There were increases in tendon protein synthesis following 4 weeks of CON and ECC training (P < 0.01; main effect by ANOVA), with no differences observed between young and old males, or training type. At the transcriptional level however, ECC in young adults generally induced greater responses of collagen and extracellular matrix-related genes than CON, while older individuals had reduced gene expression responses to training. Different training types did not appear to induce differential tendon responses in terms of protein synthesis, and while tendons from older adults exhibited different transcriptional responses to younger individuals, protein turnover changes with training were similar for both age groups.

Plasma proteome profiling of healthy subjects undergoing bed rest reveals unloading-dependent changes linked to muscle atrophy.

BACKGROUND: Inactivity and unloading induce skeletal muscle atrophy, loss of strength and detrimental metabolic effects. Bed rest is a model to study the impact of inactivity on the musculoskeletal system. It not only provides information for bed-ridden patients care, but it is also a ground-based spaceflight analogue used to mimic the challenges of long space missions for the human body. In both cases, it would be desirable to develop a panel of biomarkers to monitor muscle atrophy in a minimally invasive way at point of care to limit the onset of muscle loss in a personalized fashion. METHODS: We applied mass spectrometry-based proteomics to measure plasma protein abundance changes in response to 10 days of bed rest in 10 young males. To validate the correlation between muscle atrophy and the significant hits emerging from our study, we analysed in parallel, with the same pipeline, a cohort of cancer patients with or without cachexia and age-matched controls. Our analysis resulted in the quantification of over 500 proteins. RESULTS: Unloading affected plasma concentration of proteins of the complement cascade, lipid carriers and proteins derived from tissue leakage. Among the latter, teneurin-4 increased 1.6-fold in plasma at bed rest day 10 (BR10) compared with BR0 (6.E9 vs. 4.3E9, P = 0.02) and decreased to 0.6-fold the initial abundance after 2 days of recovery at normal daily activity (R + 2, 2.7E9, P = 3.3E-4); the extracellular matrix protein lumican was decreased to 0.7-fold (1.2E9 vs. 8.5E8, P = 1.5E-4) at BR10 and remained as low at R + 2. We identified six proteins distinguishing subjects developing unloading-mediated muscle atrophy (decrease of >4% of quadriceps cross-sectional area) from those largely maintaining their initial muscle mass. Among them, transthyretin, a thyroid hormone-binding protein, was significantly less abundant at BR10 in the plasma of subjects with muscle atrophy compared with those with no atrophy (1.6E10 vs. 2.6E10, P = 0.001). Haptoglobin-related protein was also significantly reduced in the serum of cancer patients with cachexia compared with that of controls. CONCLUSIONS: Our findings highlight a combination or proteomic changes that can be explored as potential biomarkers of muscle atrophy occurring under different conditions. The panel of significant proteomic differences distinguishing atrophy-prone and atrophy-resistant subjects after 10 days of bed rest need to be tested in a larger cohort to validate their potential to predict inactivity-triggered muscle loss in humans.

Lumbar Multifidus Morphology in Youth Competitive Alpine Skiers and Associated Sex, Age, Biological Maturation, Trunk Stability, and Back Complaints.

BACKGROUND: The lumbar multifidus (LMF), as a dynamic stabilizer of the lumbar spine, may play an important role in the prevention of overuse-related back complaints. HYPOTHESIS: LMF morphology is associated with trunk stability and differs between symptomatic and asymptomatic skiers. STUDY DESIGN: Cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 85 youth skiers (28 females, mean age, 14.7 ± 0.7 years; 57 males, mean age, 14.9 ± 0.5 years) underwent anthropometric assessments, an estimation of biological maturation, a magnetic resonance imaging- and ultrasound-based examination of LMF morphology, and a biomechanical quantification of deadbug bridging stabilization performance. Athletes were categorized as symptomatic if they had registered at least 1 significant overuse-related back complaint episode in the 12 months before the main examination. RESULTS: Male skiers showed a greater LMF size (ie, anatomical cross-sectional area [ACSA]) than female skiers, except for vertebral body L5, where no difference was found (8.8 ± 1.8 cm2 vs 8.3 ± 1.4 cm2, P = 0.18). Conversely, female skiers displayed longer fascicles than male skiers (5.8 ± 0.8 cm vs 5.4 ± 0.8 cm, P = 0.03). Skiers aged under 16 years (U16) skiers had greater values for LMF size and fascicle length than U15 skiers. Maturity offset was associated with L5 LMF size (R2 = 0.060, P = 0.01), fascicle length (R2 = 0.038, P = 0.04), and muscle thickness (R2 = 0.064, P = 0.02). L5 LMF size was associated with trunk stability (R2 = 0.068, P = 0.01). Asymptomatic skiers showed on average a 12.8% greater value for L5 LMF size compared with symptomatic skiers (P = 0.04). CONCLUSION: There are sex- and age-related differences in LMF morphology in youth competitive alpine skiers. Moreover, the ACSA at the level of the lumbar vertebral body L5 undergoes changes during biological maturation, shows a small, but significant association with trunk stability, and differs between symptomatic and asymptomatic skiers with back complaints. CLINICAL RELEVANCE: The observed association of muscle structure (ie, L5 LMF ACSA) with functional aspects (ie, trunk stabilization capacity) and clinical representation (ie, overuse-related back complaints) further highlights the important role of the multifidus muscle for training and injury prevention in youth competitive alpine skiers around the growth spurt.

Loss of neuromuscular junction integrity and muscle atrophy in skeletal muscle disuse.

Physical inactivity (PI) is a major risk factor of chronic diseases. A major aspect of PI is loss of muscle mass and strength. The latter phenomenon significantly impacts daily life and represent a major issue for global health. Understandably, skeletal muscle itself has been the major focus of studies aimed at understanding the mechanisms underlying loss of mass and strength. Relatively lesser attention has been given to the contribution of alterations in somatomotor control, despite the fact that these changes can start very early and can occur at multiple levels, from the cortex down to the neuromuscular junction (NMJ). It is well known that exposure to chronic inactivity or immobilization causes a disproportionate loss of force compared to muscle mass, i.e. a loss of specific or intrinsic whole muscle force. The latter phenomenon may be partially explained by the loss of specific force of individual muscle fibres, but several other players are very likely to contribute to such detrimental phenomenon. Irrespective of the length of the disuse period, the loss of force is, in fact, more than two-fold greater than that of muscle size. It is very likely that somatomotor alterations may contribute to this loss in intrinsic muscle force. Here we review evidence that alterations of one component of somatomotor control, namely the neuromuscular junction, occur in disuse. We also discuss some of the novel players in NMJ stability (e.g., homer, bassoon, pannexin) and the importance of new established and emerging molecular markers of neurodegenerative processes in humans such as agrin, neural-cell adhesion molecule and light-chain neurofilaments.

Three-dimensional mapping of ultrasound-derived skeletal muscle shear wave velocity.

Introduction: The mechanical properties of skeletal muscle are indicative of its capacity to perform physical work, state of disease, or risk of injury. Ultrasound shear wave elastography conducts a quantitative analysis of a tissue's shear stiffness, but current implementations only provide two-dimensional measurements with limited spatial extent. We propose and assess a framework to overcome this inherent limitation by acquiring numerous and contiguous measurements while tracking the probe position to create a volumetric scan of the muscle. This volume reconstruction is then mapped into a parameterized representation in reference to geometric and anatomical properties of the muscle. Such an approach allows to quantify regional differences in muscle stiffness to be identified across the entire muscle volume assessed, which could be linked to functional implications. Methods: We performed shear wave elastography measurements on the vastus lateralis (VL) and the biceps femoris long head (BFlh) muscle of 16 healthy volunteers. We assessed test-retest reliability, explored the potential of the proposed framework in aggregating measurements of multiple subjects, and studied the acute effects of muscular contraction on the regional shear wave velocity post-measured at rest. Results: The proposed approach yielded moderate to good reliability (ICC between 0.578 and 0.801). Aggregation of multiple subject measurements revealed considerable but consistent regional variations in shear wave velocity. As a result of muscle contraction, the shear wave velocity was elevated in various regions of the muscle; showing pre-to-post regional differences for the radial assessement of VL and longitudinally for BFlh. Post-contraction shear wave velocity was associated with maximum eccentric hamstring strength produced during six Nordic hamstring exercise repetitions. Discussion and Conclusion: The presented approach provides reliable, spatially resolved representations of skeletal muscle shear wave velocity and is capable of detecting changes in three-dimensional shear wave velocity patterns, such as those induced by muscle contraction. The observed systematic inter-subject variations in shear wave velocity throughout skeletal muscle additionally underline the necessity of accurate spatial referencing of measurements. Short high-effort exercise bouts increase muscle shear wave velocity. Further studies should investigate the potential of shear wave elastography in predicting the muscle's capacity to perform work.