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.

Effects of short-term unloading and active recovery on human motor unit properties, neuromuscular junction transmission and transcriptomic profile.

Electrophysiological alterations of the neuromuscular junction (NMJ) and motor unit potential (MUP) with unloading are poorly studied. We aimed to investigate these aspects and the underlying molecular mechanisms with short-term unloading and active recovery (AR). Eleven healthy males underwent a 10-day unilateral lower limb suspension (ULLS) period, followed by 21-day AR based on resistance exercise. Quadriceps femoris (QF) cross-sectional area (CSA) and isometric maximum voluntary contraction (MVC) were evaluated. Intramuscular electromyographic recordings were obtained during 10% and 25% MVC isometric contractions from the vastus lateralis (VL). Biomarkers of NMJ molecular instability (serum c-terminal agrin fragment, CAF), axonal damage (neurofilament light chain) and denervation status were assessed from blood samples and VL biopsies. NMJ and ion channel transcriptomic profiles were investigated by RNA-sequencing. QF CSA and MVC decreased with ULLS. Increased CAF and altered NMJ transcriptome with unloading suggested the emergence of NMJ molecular instability, which was not associated with impaired NMJ transmission stability. Instead, increased MUP complexity and decreased motor unit firing rates were found after ULLS. Downregulation of ion channel gene expression was found together with increased neurofilament light chain concentration and partial denervation. The AR period restored most of these neuromuscular alterations. In conclusion, the human NMJ is destabilized at the molecular level but shows functional resilience to a 10-day unloading period at least at relatively low contraction intensities. However, MUP properties are altered by ULLS, possibly due to alterations in ion channel dynamics and initial axonal damage and denervation. These changes are fully reversed by 21 days of AR. KEY POINTS: We used integrative electrophysiological and molecular approaches to comprehensively investigate changes in neuromuscular integrity and function after a 10-day unilateral lower limb suspension (ULLS), followed by 21 days of active recovery in young healthy men, with a particular focus on neuromuscular junction (NMJ) and motor unit potential (MUP) properties alterations. After 10-day ULLS, we found significant NMJ molecular alterations in the absence of NMJ transmission stability impairment. These findings suggest that the human NMJ is functionally resilient against insults and stresses induced by short-term disuse at least at relatively low contraction intensities, at which low-threshold, slow-type motor units are recruited. Intramuscular electromyography analysis revealed that unloading caused increased MUP complexity and decreased motor unit firing rates, and these alterations could be related to the observed changes in skeletal muscle ion channel pool and initial and partial signs of fibre denervation and axonal damage. The active recovery period restored these neuromuscular changes.

Neuromuscular junction instability and altered intracellular calcium handling as early determinants of force loss during unloading in humans.

KEY POINTS: Few days of unloading are sufficient to induce a decline of skeletal muscle mass and function; notably, contractile force is lost at a faster rate than muscle mass. The reasons behind this disproportionate loss of muscle force are still poorly understood. We provide strong evidence of two mechanisms only hypothesized until now for the rapid muscle force loss in only 10 days of bed rest. Our results show that an initial neuromuscular junction instability, accompanied by alterations in the innervation status and impairment of single fibre sarcoplasmic reticulum function contribute to the loss of contractile force in front of a preserved myofibrillar function and central activation capacity. Early onset of neuromuscular junction instability and impairment in calcium dynamics involved in excitation-contraction coupling are proposed as eligible determinants to the greater decline in muscle force than in muscle size during unloading. ABSTRACT: Unloading induces rapid skeletal muscle atrophy and functional decline. Importantly, force is lost at a much higher rate than muscle mass. We aimed to investigate the early determinants of the disproportionate loss of force compared to that of muscle mass in response to unloading. Ten young participants underwent 10 days of bed rest (BR). At baseline (BR0) and at 10 days (BR10), quadriceps femoris (QF) volume (VOL) and isometric maximum voluntary contraction (MVC) were assessed. At BR0 and BR10 blood samples and biopsies of vastus lateralis (VL) muscle were collected. Neuromuscular junction (NMJ) stability and myofibre innervation status were assessed, together with single fibre mechanical properties and sarcoplasmic reticulum (SR) calcium handling. From BR0 to BR10, QFVOL and MVC decreased by 5.2% (P = 0.003) and 14.3% (P < 0.001), respectively. Initial and partial denervation was detected from increased neural cell adhesion molecule (NCAM)-positive myofibres at BR10 compared with BR0 (+3.4%, P = 0.016). NMJ instability was further inferred from increased C-terminal agrin fragment concentration in serum (+19.2% at BR10, P = 0.031). Fast fibre cross-sectional area (CSA) showed a trend to decrease by 15% (P = 0.055) at BR10, while single fibre maximal tension (force/CSA) was unchanged. However, at BR10 SR Ca2+ release in response to caffeine decreased by 35.1% (P < 0.002) and 30.2% (P < 0.001) in fast and slow fibres, respectively, pointing to an impaired excitation-contraction coupling. These findings support the view that the early onset of NMJ instability and impairment in SR function are eligible mechanisms contributing to the greater decline in muscle force than in muscle size during unloading.

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 PIC, contributing to the reduction of force generation capacity. In addition, we tested whether physical exercise would restore the force generation capacity by reestablishing the initial level of neuromodulatory input. METHODS: In 12 young adults, we assessed maximal voluntary contraction pre- and post-10 d of ULLS and after 21 d 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 (Δ F ) of paired motor units calculated during isometric ramped contractions. RESULTS: The values of Δ F were reduced after 10 d of ULLS (-33%, P < 0.001), but were fully reestablished 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 maximal voluntary contraction 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.

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.

Neuromuscular impairment at different stages of human sarcopenia.

BACKGROUND: Degeneration of the motoneuron and neuromuscular junction (NMJ) and loss of motor units (MUs) contribute to age-related muscle wasting and weakness associated with sarcopenia. However, these features have not been comprehensively investigated in humans. This study aimed to compare neuromuscular system integrity and function at different stages of sarcopenia, with a particular focus on NMJ stability and MU properties. METHODS: We recruited 42 young individuals (Y) (aged 25.98 ± 4.6 years; 57% females) and 88 older individuals (aged 75.9 ± 4.7 years; 55% females). The older group underwent a sarcopenia screening according to the revised guidelines of the European Working Group on Sarcopenia in Older People 2. In all groups, knee extensor muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and MU potential properties by intramuscular electromyography (iEMG). MU number estimate (iMUNE) and blood samples were obtained. Muscle biopsies were collected in a subgroup of 16 Y and 52 older participants. RESULTS: Thirty-nine older individuals were non-sarcopenic (NS), 31 pre-sarcopenic (PS) and 18 sarcopenic (S). A gradual decrease in quadriceps force, cross-sectional area and appendicular lean mass was observed across the different stages of sarcopenia (for all P < 0.0001). Handgrip force and the Short Physical Performance Battery score also showed a diminishing trend. iEMG analyses revealed elevated near fibre segment jitter in NS, PS and S compared with Y (Y vs. NS and S: P < 0.0001; Y vs. PS: P = 0.0169), suggestive of age-related impaired NMJ transmission. Increased C-terminal agrin fragment (P < 0.0001) and altered caveolin 3 protein expression were consistent with age-related NMJ instability in all the older groups. The iMUNE was lower in all older groups (P < 0.0001), confirming age-related loss of MUs. An age-related increase in MU potential complexity was also observed. These observations were accompanied by increased muscle denervation and axonal damage, evinced by the increase in neural cell adhesion molecule-positive fibres (Y vs. NS: P < 0.0001; Y vs. S: P = 0.02) and the increase in serum concentration of neurofilament light chain (P < 0.0001), respectively. Notably, most of these MU and NMJ parameters did not differ when comparing older individuals with or without sarcopenia. CONCLUSIONS: Alterations in MU properties, axonal damage, an altered innervation profile and NMJ instability are prominent features of the ageing of the neuromuscular system. These neuromuscular alterations are accompanied by muscle wasting and weakness; however, they appear to precede clinically diagnosed sarcopenia, as they are already detectable in older NS individuals.

Risk Factors for Disabling and Nondisabling Neck Pain in a Large Cohort of Adolescents.

OBJECTIVES: Neck pain is extremely common and represents a substantial economic burden to our society. We aimed to investigate risk factors for nondisabling and disabling neck pain in a large cohort of Italian adolescents with a cross-sectional study. DESIGN: Six thousand two hundred eighty-one students (14-19 yrs old) answered an online questionnaire, investigating the following: anthropometric data, lifestyle-related items, neck pain frequency and intensity, need for medical examination, and several risk factors. Students who had to give up social activities because of neck complaints constituted the disabling neck pain group. RESULTS: Our findings revealed that sex, age, sports practice, hours of sleep, and family history were risk factors ( P < 0.001) for neck pain in our cohort. Moreover, disabling neck pain group experienced neck pain more frequently ( P < 0.001) and with higher levels of pain ( P < 0.001) compared with the nondisabling group. The number of hours of sleep was the only risk factor that showed a trend to differ comparing the disabling neck pain group with the nondisabling neck pain one ( P = 0.057). CONCLUSIONS: Different risk factors for neck pain were detected in a very large cohort of adolescents. This study may pave the way for future prospective studies and for the development of preventive strategies for neck pain in adolescents. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Identify different risk factors for neck pain in adolescents; (2) Determine the differences between adolescents with nondisabling neck pain and disabling neck pain; and (3) Recognize that most risk factors for disabling neck pain are still unknown, but insufficient sleep quantity could potentially contribute to the development of this condition. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

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.

Lower back pain in young climbers: a retrospective cross-sectional study.

Objective: The popularity of sport climbing has been growing since its inclusion in the Olympic Games program, which led to more people practicing it on recreational, amateur, and professional levels. Strenuous climbing training sessions and competitions might lead to frequent and serious musculoskeletal injuries and complaints among competitive climbers. This study aimed to investigate the prevalence of low back pain (LBP) and to explore the influence of various risk factors on LBP in adolescent climbers. Methods: The sample included 180 competitive climbers (46.6% males) aged 13-19 years competing in under-16 (48.3%) or under-20 categories. Data collection was carried out using the Nordic Musculoskeletal Questionnaire (NMQ) and the Graded Chronic Pain Scale (GCPS). Results: A total of 74.4% of the entire sample of participants (male = 75%; female = 74%) reported lower back complaints throughout the past twelve months, and only 15.5% during the last seven days. A major part of complaints was classified as low intensity-low disability (Grade I, 62.8%; male = 72.6%; female = 54.2%). Under-20 competitors reported a small but significantly higher percentage of almost all NMQ measures compared to under-16 athletes. Conclusions: This study found a relatively high prevalence of LBP, although complaints were of limited severity and did not affect climbers' regular training practice. Moreover, climbers did not differ in LBP prevalence according to sex, while climbers from the older age group reported higher complaints and seeking medical attention than younger climbers. Future studies should prospectively monitor the influence of climbing on LBP in youth climbers.

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.

C-terminal agrin fragment as a biomarker of muscle wasting and weakness: a narrative review.

Ageing is accompanied by an inexorable loss of muscle mass and functionality and represents a major risk factor for numerous diseases such as cancer, diabetes and cardiovascular and pulmonary diseases. This progressive loss of muscle mass and function may also result in the insurgence of a clinical syndrome termed sarcopenia, exacerbated by inactivity and disease. Sarcopenia and muscle weakness yield the risk of falls and injuries, heavily impacting on health and social costs. Thus, screening, monitoring and prevention of conditions inducing muscle wasting and weakness are essential to improve life quality in the ageing modern society. To this aim, the reliability of easily accessible and non-invasive blood-derived biomarkers is being evaluated. C-terminal agrin fragment (CAF) has been widely investigated as a neuromuscular junction (NMJ)-related biomarker of muscle dysfunction. This narrative review summarizes and critically discusses, for the first time, the studies measuring CAF concentration in young and older, healthy and diseased individuals, cross-sectionally and in response to inactivity and physical exercise, providing possible explanations behind the discrepancies observed in the literature. To identify the studies investigating CAF in the above-mentioned conditions, all the publications found in PubMed, written in English and measuring this biomarker in blood from 2013 (when CAF was firstly measured in human serum) to 2022 were included in this review. CAF increases with age and in sarcopenic individuals when compared with age-matched, non-sarcopenic peers. In addition, CAF was found to be higher than controls in other muscle wasting conditions, such as diabetes, COPD, chronic heart failure and stroke, and in pancreatic and colorectal cancer cachectic patients. As agrin is also expressed in kidney glomeruli, chronic kidney disease and transplantation were shown to have a profound impact on CAF independently from muscle wasting. CAF concentration raises following inactivity and seems to be lowered or maintained by exercise training. Finally, CAF was reported to be cross-sectionally correlated to appendicular lean mass, handgrip and gait speed; whether longitudinal changes in CAF are associated with those in muscle mass or performance following physical exercise is still controversial. CAF seems a reliable marker to assess muscle wasting in ageing and disease, also correlating with measurements of appendicular lean mass and muscle function. Future research should aim at enlarging sample size and accurately reporting the medical history of each patient, to normalize for any condition, including chronic kidney disease, that may influence the circulating concentration of this biomarker.

Effects of a 2-year exercise training on neuromuscular system health in older individuals with low muscle function.

BACKGROUND: Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, potentially determining the insurgence of sarcopenia. Evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration contribute to sarcopenia pathogenesis. Seeking for strategies able to slow down sarcopenia insurgence and progression, we investigated whether a 2-year mixed-model training involving aerobic, strength and balance exercises would be effective for improving or preserving motoneuronal health and NMJ stability, together with muscle mass, strength and functionality in an old, sarcopenic population. METHODS: Forty-five sarcopenic elderly (34 females; 11 males) with low dual-energy X-ray absorptiometry (DXA) lean mass and Short Physical Performance Battery (SPPB) score <9 were randomly assigned to either a control group [Healthy Aging Lifestyle Education (HALE), n = 21] or an intervention group [MultiComponent Intervention (MCI), n = 24]. MCI trained three times per week for 2 years with a mix of aerobic, strength and balance exercises matched with nutritional advice. Before and after the intervention, ultrasound scans of the vastus lateralis (VL), SPPB and a blood sample were obtained. VL architecture [pennation angle (PA) and fascicle length (Lf)] and cross-sectional area (CSA) were measured. As biomarkers of neuronal health and NMJ stability status, neurofilament light chain (NfL) and C-terminal agrin fragment (CAF) concentrations were measured in serum. Differences in ultrasound parameters, NfL and CAF concentration and physical performance between baseline and follow-up were tested with mixed ANOVA or Wilcoxon test. The relationship between changes in physical performance and NfL or CAF concentration was assessed through correlation analyses. RESULTS: At follow-up, MCI showed preserved VL architecture (PA, Lf) despite a reduced CSA (-8.4%, P < 0.001), accompanied by maintained CAF concentration and ameliorated overall SPPB performance (P = 0.007). Conversely, HALE showed 12.7% decrease in muscle CSA (P < 0.001), together with 5.1% and 5.5% reduction in PA and Lf (P < 0.001 and P = 0.001, respectively), and a 6.2% increase in CAF (P = 0.009) but improved SPPB balance score (P = 0.007). NfL concentration did not change in either group. In the population, negative correlations between changes in CAF concentration and SPPB total score were found (P = 0.047), whereas no correlation between NfL and SPPB variations was observed. CONCLUSIONS: The present findings suggest that our 2-year mixed aerobic, strength and balance training seemed effective for preventing the age and sarcopenia-related increases in CAF concentration, preserving NMJ stability as well as muscle structure (PA and Lf) and improving physical performance in sarcopenic older individuals.

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.

Early Changes of Hamstrings Morphology and Contractile Properties during 10 d of Complete Inactivity.

PURPOSE: The hamstrings (HS) muscle group plays a fundamental role in maintaining knee stability, thus contributing to the prevention and rehabilitation of lower limb musculoskeletal injuries. However, little is known about HS structural and functional adaptations after periods of prolonged inactivity. Our purpose was to investigate the HS morphological and contractile properties changes during 10 d of bed rest (BR). METHODS: Ten young healthy males underwent a 10-d BR. HS cross-sectional area (CSA) (at 30%, 50%, and 70% of femur length) and biceps femoris long head (BFlh) architecture were assessed by ultrasound imaging after 0 d (BR0), 2 d (BR2), 4 d (BR4), 6 d (BR6), and 10 d (BR10) of BR, whereas BFlh contractile properties (radial twitch displacement [Dm] and contraction time [Tc]) were evaluated at the same time points by tensiomyography. HS muscle volume was assessed by magnetic resonance imaging at BR0 and BR10. RESULTS: A reduction in muscle volume was observed in BFlh ( P = 0.002; Δ = -3.53%), biceps femoris short head ( P = 0.002; Δ = -3.54%), semitendinosus ( P = 0.002; Δ = -2.63%), semimembranosus ( P = 0.002; Δ = -2.01%), and HS pooled together ( P < 0.001; Δ = -2.78%). Early changes in CSA were detected at 30% femur length already at BR6 for BFlh ( P = 0.009; Δ = -2.66%) and biceps femoris short head ( P = 0.049; Δ = -1.96%). We also found a reduction in fascicle length at BR6 ( P = 0.035; Δ = -2.44%) and BR10 ( P < 0.001; Δ = -2.84%). Dm and Tc increased at BR2 ( P = 0.010; Δ = 30.0%) and B10 ( P = 0.019; Δ = 19.7%), respectively. CONCLUSIONS: Despite being a nonpostural muscle group, HS exhibited a moderate reduction in muscle dimensions in response to a short unloading period. Small changes in BFlh fascicle length were also observed, accompanied by alterations in BFLh contractile properties. These HS modifications should not be ignored from a clinical perspective.

DeepACSA: Automatic Segmentation of Cross-Sectional Area in Ultrasound Images of Lower Limb Muscles Using Deep Learning.

PURPOSE: Muscle anatomical cross-sectional area (ACSA) can be assessed using ultrasound and images are usually evaluated manually. Here, we present DeepACSA, a deep learning approach to automatically segment ACSA in panoramic ultrasound images of the human rectus femoris (RF), vastus lateralis (VL), gastrocnemius medialis (GM) and lateralis (GL) muscles. METHODS: We trained three muscle-specific convolutional neural networks (CNN) using 1772 ultrasound images from 153 participants (age = 38.2 yr, range = 13-78). Images were acquired in 10% increments from 30% to 70% of femur length for RF and VL and at 30% and 50% of muscle length for GM and GL. During training, CNN performance was evaluated using intersection-over-union scores. We compared the performance of DeepACSA to manual analysis and a semiautomated algorithm using an unseen test set. RESULTS: Comparing DeepACSA analysis of the RF to manual analysis with erroneous predictions removed (3.3%) resulted in intraclass correlation (ICC) of 0.989 (95% confidence interval = 0.983-0.992), mean difference of 0.20 cm 2 (0.10-0.30), and SEM of 0.33 cm 2 (0.26-0.41). For the VL, ICC was 0.97 (0.96-0.968), mean difference was 0.85 cm 2 (-0.4 to 1.31), and SEM was 0.92 cm 2 (0.73-1.09) after removal of erroneous predictions (7.7%). After removal of erroneous predictions (12.3%), GM/GL muscles demonstrated an ICC of 0.98 (0.96-0.99), a mean difference of 0.43 cm 2 (0.21-0.65), and an SEM of 0.41 cm 2 (0.29-0.51). Analysis duration was 4.0 ± 0.43 s (mean ± SD) for analysis of one image in our test set using DeepACSA. CONCLUSIONS: DeepACSA provides fast and objective segmentation of lower limb panoramic ultrasound images comparable with manual segmentation. Inaccurate model predictions occurred predominantly on low-quality images, highlighting the importance of high-quality image for accurate prediction.

Physical active lifestyle promotes static and dynamic balance performance in young and older adults.

Although regular physical activity exposure leads to positive postural balance control (PBC) adaptations, few studies investigated its effects, or the one of inactivity, on PBC in populations of different age groups. Thus, this study investigated the impact of a physically active lifestyle on static and dynamic PBC in young and older adults. Thirty-five young physically active subjects (YA), 20 young sedentary subjects (YS), 16 physically active older adults (OA), and 15 sedentary older adults (OS) underwent a static and a dynamic PBC assessment. A force platform and an instrumented proprioceptive board were employed to measure the center of pressure (COP) trajectory and the anteroposterior oscillations, respectively. In static conditions, no significant differences were detected among groups considering the overall postural balance performance represented by the area of confidence ellipse values. Conversely, the YA highlighted a higher efficiency (i.e., lower sway path mean velocity) in PBC maintenance compared to the other groups (YA vs OA: p = 0.0057, Cohen's d = 0.94; YA vs OS p = 0.043, d = 1.07; YA vs YS p = 0.08, d = 0.67). OS exhibited an overall worse performance in dynamic conditions than YA and YS. Surprisingly, no differences were found between YS and OA for all the static and dynamic parameters considered. In conclusion, our results suggest that a physically active lifestyle may promote static and dynamic balance performance in young and older adults, thus with potentially positive effects on the age-related decline of postural balance performance. Dynamic PBC assessment seems more sensitive in detecting differences between groups than the static evaluation.

Changes in Biceps Femoris Long Head Fascicle Length after 10-d Bed Rest Assessed with Different Ultrasound Methods.

PURPOSE: This study aimed to investigate the changes in fascicle length (Lf) of biceps femoris long head (BFlh) after 10 d of bed rest (BR) by comparing four different ultrasound (US) methods. METHODS: Ten healthy men participated in 10-d BR. Before (BR0) and after (BR10) the BR period, BFlh Lf values were obtained using 1) extended-field-of-view (EFOV) technique, 2) the manual linear extrapolation (MLE) method, and 3) two trigonometric equations (equations A and B) from a single US image. RESULTS: After BR10, decreased Lf values were observed by EFOV (P < 0.001; Hedges' g = 0.29) and MLE (P = 0.0082; g = 0.22) methods, but not with equations A and B. Differences between equation A and the other US methods were detected at both time points. The percentage of changes in Lf between BR0 and BR10 was influenced by the US methods applied, with difference detected between the changes measured by EFOV and the ones estimated by equation A (P = 0.04; g = 0.53). Bland-Altman analyses revealed relevant average absolute biases in Lf between EFOV and other methods at both time points (range BR0-BR10: MLE, 0.3-0.37 cm (3.4%-4.32%); equation B, 0.3-0.48 cm (3.24%-5.41%); equation A, 2.44-2.97 cm (24.05%-29.2%)). A significant correlation (r = 0.83) in percentage of change in Lf values was observed only between EFOV and MLE. CONCLUSIONS: We showed that four distinct US methods lead to different results in the assessment of BFlh Lf changes after a short-term period of unloading. The implementation of EFOV technique (or alternatively MLE) to assess Lf changes in BFlh during longitudinal studies is warranted.

Lifetime Prevalence of Nonspecific Low Back Pain in Adolescents: A Cross-sectional Epidemiologic Survey.

BACKGROUND: Many nonconclusive studies have been conducted on low back pain (LBP) in adolescents and associated factors. OBJECTIVE: The aim was to assess the lifetime prevalence and associated factors of LBP in adolescents. MATERIALS AND METHODS: A questionnaire was administered in high school students (14-19-yr-old participants) in Veneto region (Italy). The self-administered, structured questionnaire included anthropometric data; psychologic factors and lifestyle; presence, intensity, and family history of LBP; referral to professional health care for LBP; and a short version of the International Physical Activity Questionnaire. RESULTS: A total of 6281 adolescents were recruited; 5204 questionnaires were included in the final analysis. A total of 2549 (48.98%) students reported one or more LBP episodes and 723 (13.89%) reported nonspecific disabling lumbar pain (i.e., no underlying pathology); 1040 (41.11%) subjects with LBP consulted a healthcare professional. A significant association emerged for LBP with sex (female), positive family history, time spent sitting or using electronic devices, sleep deprivation (<5 hrs/night), and low level of physical activity. CONCLUSION: In a large sample of adolescents, LBP lifetime prevalence is high and often associated with disabling pain and sedentary lifestyle, requiring professional care. These findings may support the development of prevention and treatment strategies of LBP in adolescents, reducing the risk of developing chronic pain.