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Ultrasound (US) imaging has been widely used in both research and clinical settings to evaluate the morphological and mechanical properties of muscle and tendon. In elite sports scenarios, a regular assessment of such properties has great potential, namely for testing the response to training, detecting athletes at higher risks of injury, screening athletes for structural abnormalities related to current or future musculoskeletal complaints, and monitoring their return to sport after a musculoskeletal injury. However, several practical and methodological aspects of US techniques should be considered when applying this technology in the elite sports context. Therefore, this narrative review aims to (1) present the principal US measures and field of applications in the context of elite sports; (2) to discuss, from a methodological perspective, the strengths and shortcomings of US imaging for the assessment of muscle and tendon properties; and (3) to provide future directions for research and application.

Background: Eccentric exercise increases muscle fascicle lengths; however, the mechanisms behind this adaptation are still unknown. This study aimed to determine whether biceps femoris long head (BFlh) fascicle length increases in response to 3 weeks of eccentric exercise training are the result of an in-series addition of sarcomeres within the muscle fibers. Methods: Ten recreationally active participants (age = 27 ± 3 years; mass = 70 ± 14 kg; height = 174 ± 9 cm; mean ± SD) completed 3 weeks of Nordic hamstring exercise (NHE) training on a custom exercise device that was instrumented with load cells. We collected in vivo sarcomere and muscle fascicle images of the BFlh in 2 regions (central and distal) by using microendoscopy and 3 dimension ultrasonography. We then estimated sarcomere length, sarcomere number, and fascicle length before and after the training intervention. Results: Eccentric knee flexion strength increased after the training (15%; p < 0.001; ηp2 = 0.75). Further, we found a significant increase in fascicle length (21%; p < 0.001; ηp2 = 0.81) and sarcomere length (17%; p < 0.001; ηp2 = 0.90) in the distal but not in the central portion of the muscle. The estimated number of sarcomeres in series did not change in either region. Conclusion: Fascicle length adaptations appear to be heterogeneous in the BFlh in response to 3 weeks of NHE training. An increase in sarcomere length, rather than the addition of sarcomeres in series, appears to underlie increases in fascicle length in the distal region of the BFlh. The mechanism driving regional increases in fascicle and sarcomere length remains unknown, but we speculate that it may be driven by regional changes in the passive tension of muscle or connective tissue adaptations.

ABSTACTAimAs the excitation-contraction coupling is inseparable during voluntary exercise, the relative contribution of the mechanical and neural input is poorly understood. Herein, we use a rat in-vivo strength training setup with an electrically induced standardized excitation pattern previously shown to lead to a load-dependent increase in myonuclear number and hypertrophy, to study acute effects of load per se on molecular signalling.MethodsAnaesthetized rats were subjected to unliteral identical electrically-paced contractions of the TA and EDL muscles under a high or low load for a duration of 2, 10 or 28-minutes. Muscle soluble proteins were extracted, and abundance and specific phosphorylations of FAK, mTOR, p70S6K and JNK were measured. Effects of exercise, load, muscle and exercise duration were assessed.ResultsSpecific phosphorylation of S2448-mTOR, T421/S424-p70S6K and T183/Y185-JNK was increased after 28-minutes of exercise under the high- and low-load protocol. Elevated phosphorylation of mTOR and JNK was detectable already after 2 and 10 minutes of exercise, respectively, but greatest after 28-minutes of exercise. T183/Y185-JNK and S2448-mTOR demonstrated a load-dependent increase in phosphorylation in the exercised muscles that for mTOR depended on muscle type. The abundance of all four kinases was higher in TA compared to EDL muscle. FAK and JNK abundance was reduced after 28 minutes of exercise in both the exercised and control muscle.ConclusionThe current study shows that JNK and mTOR activation is load-driven, and together with muscle-type specific mTOR and p70S6K effects it may drive muscle-type specific exercise and load-responses.

Background and aims: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MaVI) limits treatment options and decreases survival. Detailed data on the relationship between MaVI extension and patients' characteristics, and its impact on patients' outcome are limited. We evaluated the prevalence and extension of MaVI in a large cohort of consecutive HCC patients, analysing its association with liver disease and tumour characteristics, as well as with treatments performed and patients' survival. Methods: We analysed data of 4774 patients diagnosed with HCC recorded in the Italian Liver Cancer (ITA.LI.CA) database (2008-2018). Recursive partition analysis (RPA) was performed to evaluate interactions between MaVI, clinical variables and treatment, exploring the inter-relationship determining overall survival. Results: MaVI prevalence was 11.1%, and median survival of these patients was 6.0months (95% CI, 5.1-7.1). MaVI was associated with younger age at diagnosis, presence of symptoms, worse Performance Status (PS) and liver function, high alphafetoprotein levels and large HCCs. MaVI extension was associated with worse PS, ascites and greater impairment in liver function. RPA identified patients' categories with different treatment indications and survival, ranging from 2.4months in those with PS>1 and ascites, regardless of MaVI extension (receiving best supportive care in 90.3% of cases), to 14.1months in patients with PS 0-1, no ascites and Vp1-Vp2 MaVI (treated with surgery in 19.1% of cases). Conclusions: MaVI presence and extension, together with PS and ascites, significantly affect patients' survival and treatment selection. The decision tree based on these parameters may help assess patients' prognosis and inform therapeutic decisions.

Molecular epidemiology of circulating clinical isolates is crucial to improve prevention strategies. The Spanish Working Group on multidrug resistant tuberculosis (MDR-TB) is a network that monitors the MDR-TB isolates in Spain since 1998. The aim of this study was to present the study of the MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patterns in Spain using the different recommended genotyping methods over time by a national coordinated system. Based on the proposed genotyping methods in the European Union until 2018, the preservation of one method, MIRU-VNTR, applied to selected clustered strains permitted to maintain our study open for 20 years. The distribution of demographic, clinical and epidemiological characteristics of clustered and non-clustered cases of MDR/XDR tuberculosis with proportion differences as assessed by Pearson's chi-squared or Fisher's exact test was compared. The differences in the quantitative variables using the Student's-t test and the Mann-Whitney U test were evaluated. The results obtained showed a total of 48.4% of the cases grouped in 77 clusters. Younger age groups, having a known TB case contact (10.2% vs 4.7%) and XDR-TB (16.5% vs 1.8%) were significantly associated with clustering. The largest cluster corresponded to a Mycobacterium bovis strain mainly spread during the nineties. A total of 68.4% of the clusters detected were distributed among the different Spanish regions and six clusters involving 104 cases were grouped in 17 and 18 years. Comparison of the genotypes obtained with those European genotypes included in The European Surveillance System (TESSy) showed that 87 cases had become part of 20 European clusters. The continuity of MDR strain genotyping in time has offered a widespread picture of the situation that allows better management of this public health problem. It also shows the advantage of maintaining one genotyping method over time, which allowed the comparison between ancient, present and future samples. The molecular methods applied in this work were supported by the Carlos III Health Institute in the context of two consecutive Grants FIS15/0317 and 18/0336 and JC was awarded a scholarship by the Government of Aragon / European Social Fund, “Building Europe from Aragon”. Sí

Summary Background & aims The skeletal muscle anabolic effects of n-3 polyunsaturated fatty acids (n-3 PUFA) appear favoured towards women; a property that could be exploited in older women who typically exhibit poor muscle growth responses to resistance exercise training (RET). Here we sought to generate novel insights into the efficacy and mechanisms of n-3 PUFA alongside short-term RET in older women. Methods We recruited 16 healthy older women (Placebo n = 8 (PLA): 67±1y, n-3 PUFA n = 8: 64±1y) to a randomised double-blind placebo-controlled trial (n-3 PUFA; 3680 mg/day versus PLA) of 6 weeks fully-supervised progressive unilateral RET (i.e. 6 × 8 reps, 75% 1-RM, 3/wk−1). Strength was assessed by knee extensor 1-RM and isokinetic dynamometry ∼ every 10 d. Thigh fat free mass (TFFM) was measured by DXA at 0/3/6 weeks. Bilateral vastus lateralis (VL) biopsies at 0/2/4/6 weeks with deuterium oxide (D2O) dosing were used to determine MPS responses for 0–2 and 4–6 weeks. Further, fibre cross sectional area (CSA), myonuclei number and satellite cell (SC) number were assessed, alongside muscle anabolic/catabolic signalling via immunoblotting. Results RET increased 1-RM equally in the trained leg of both groups (+23 ± 5% n-3 PUFA vs. +25 ± 5% PLA (both P

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

Space analogs, such as bed rest, are used to reproduce microgravity-induced morphological and physiological changes and can be used as clinical models of prolonged inactivity. Nevertheless, nonuniform decreases in muscle mass and function have been frequently reported, and peripheral nerve adaptations have been poorly studied, although some of these mechanisms may be explained. Ten young healthy males (18–33 yr) underwent 10 days of horizontal bed rest. Peripheral neurophysiological assessments were performed bilaterally for the dominant (DL) and nondominant upper and lower limbs (N-DL) on the 1st and 10th day of bed rest, including ultrasound of the median, deep peroneal nerve (DPN), and common fibular nerve (CFN) , as well as a complete nerve conduction study (NCS) of the upper and lower limbs. Consistently, reduced F waves, suggesting peripheral nerve dysfunction, of both the peroneal (DL: P = 0.005, N-DL: P = 0.013) and tibial nerves (DL: P = 0.037, N-DL: P = 0.005) were found bilaterally, whereas no changes were observed in nerve ultrasound or other parameters of the NCS of both the upper and lower limbs. In these young healthy males, only the F waves, known to respond to postural changes, were significantly affected by short-term bed rest. These preliminary results suggest that during simulated microgravity, most changes occur at the muscle or central nervous system level. Since the assessment of F waves is common in clinical neurophysiological examinations, caution should be used when testing individuals after prolonged immobility.

We investigated the validity of panoramic ultrasound (US) compared to magnetic resonance imaging (MRI) for the assessment of hamstrings cross-sectional area (CSA) and volume. Hamstrings CSA were acquired with US (by an expert operator) at four different sites of femur length (FL) in 85 youth competitive alpine skiers (14.8 ± 0.5 years), and successively compared to corresponding scans obtained by MRI, analyzed by a trained vs. a novice rater. The agreement between techniques was assessed by Bland–Altman analyses. Statistical analysis was carried out using Pearson’s product moment correlation coefficient (r). US-derived CSA showed a very good agreement compared to MRI-based ones. The best sites were 40% FL (0 = mid patellar point) for biceps femoris long head (r = 0.9), 50% for semitendinosus (r = 0.9), and 30% for semimembranosus (r = 0.86) and biceps femoris short head (BFsh, r = 0.8). US-based vs. MRI-based hamstrings volume showed an r of 0.96. Poorer r values were observed for the novice compared to the trained rater, with the biggest difference observed for BFsh at 50% (r = 0.001 vs. r = 0.50, respectively) and semimembranosus at 60% (r = 0.23 vs. r = 0.42, respectively). Panoramic US provides valid CSA values and volume estimations compared to MRI. To ensure optimal US-vs.-MRI agreement, raters should preferably possess previous experience in imaging-based analyses.

The aim was to investigate the potential differences in muscle (vastus lateralis) and cerebral (prefrontal cortex) oxygenation levels as well as in the number of repetitions and total work output between isokinetic eccentric and concentric exercise at a moderate relative intensity until exhaustion. Ten recreationally active young men underwent two isokinetic exercise sessions either concentric or eccentric, one on each randomly selected leg. The protocols were performed at 60°/s and an intensity corresponding to 60% of the maximal voluntary contraction (MVC) of each contraction type. Concentric torque was significantly lower compared to eccentric torque in both peak values and at values corresponding to 60% of MVC [230 ± 18 Nm vs. 276 ± 19 Nm (P = .014) and 137 ± 12 Nm vs. 168 ± 11 Nm, respectively (P = .010)]. The participants performed 40% more contractions during eccentric compared to concentric exercise [122 ± 15 vs. 78 ± 7, respectively]. No differences were found in the levels of oxyhaemoglobin, deoxyhemoglobin, total haemoglobin and tissue saturation index when eccentric and eccentric exercise regimes were compared (all P > .05). Our results demonstrate that eccentric exercise of moderate intensity leads to greater resistance to fatigue and more work output compared to concentric exercise, despite the comparable muscle and cerebral oxygenation levels.

During COVID-19 home confinement, athletes are likely exposed to some level of detraining (i.e. the partial or complete loss of training-induced morphological and physiological adaptations), as a consequence of insufficient and/or inappropriate training stimuli. Such changes may result in impaired performance and increased injury risk if, upon restart, an appropriate sport-specific reconditioning cannot be granted. With this editorial, we aim to recommend extreme caution in sports programming after the COVID-19 emergency

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.

International audience; BackgroundThe assessment of muscle mass is a key determinant of the diagnosis of sarcopenia. We introduce for the first time an ultrasound imaging method for diagnosing sarcopenia based on changes in muscle geometric proportions.MethodsVastus lateralis muscle fascicle length (Lf) and thickness (Tm) were measured at 35% distal femur length by ultrasonography in a population of 279 individuals classified as moderately active elderly (MAE), sedentary elderly (SE) (n = 109), mobility impaired elderly (MIE) (n = 43), and in adult young controls (YC) (n = 60). The ratio of Lf/Tm was calculated to obtain an ultrasound index of the loss of muscle mass associated with sarcopenia (USI). In a subsample of elderly male individuals (n = 76) in which corresponding DXA measurements were available (MAE, n = 52 and SE, n = 24), DXA-derived skeletal muscle index (SMI, appendicular limb mass/height2) was compared with corresponding USI values.ResultsFor both young and older participants, USI values were found to be independent of sex, height and body mass. USI values were 3.70 ± 0.52 for YC, 4.50 ± 0.72 for the MAE, 5.05 ± 1.11 for the SE and 6.31 ± 1.38 for the MIE, all significantly different between each other (P < 0.0001). Based on the USI Z-scores, with reference to the YC population, the 219 elderly participants were stratified according to their muscle sarcopenic status. Individuals with USI values within a range of 3.70 < USI ≥ 4.23 were classified as non-sarcopenic (prevalence 23.7%), those with USI values within 4.23 < USI ≥ 4.76 were classified as pre-sarcopenic (prevalence 23.7%), those with USI values within 4.76 < USI ≥ 5.29 were classified as moderately sarcopenic (prevalence 15.1%), those with USI values within range 5.29 < USI ≥ 5.82 were classified as sarcopenic (prevalence 27.9%), and those with USI values >5.82 were classified as severely sarcopenic (prevalence 9.6%). The DXA-derived SMI was found to be significantly correlated with USI (r = 0.61, P < 0.0001). Notably, the USI cut-off value for moderate sarcopenia (4.76 a.u.) was found to coincide with the DXA cut-off value of sarcopenia (7.26 kg/m2).ConclusionsWe propose a novel, practical, and inexpensive imaging marker of the loss of muscle mass associated with sarcopenia, called the ultrasound sarcopenic index (USI), based on changes in muscle geometric proportions. These changes provide a useful ‘signature of sarcopenia’ and allow the stratification of individuals according to the presence and severity of muscle sarcopenia. We are convinced that the USI will be a useful clinical tool for confirming the diagnosis of sarcopenia, of which the assessment of muscle mass is a key-component.

Introduction: Understanding the impact of lockdown upon RT, and how people adapted their RT behaviours, is expected to have implications for strategies to maintain engagement in positive health behaviours such as this during- restrictive pandemic-related public health measures. Further, doing so will provide a baseline for investigation of the long-term effects of these measures upon behaviours and perceptions and facilitate future follow-up study.Objectives: To determine how the onset of coronavirus (COVID-19), and the associated ‘lockdown’, affected resistance training (RT) behaviours, in addition to motivation, perceived effectiveness, enjoyment, and intent to continue, in those who regularly performed resistance training RT prior to the pandemic.Methods: We conducted an observational, cross-sectional study using online surveys in multiple languages (English, Danish, French, German, Italian, Portuguese, Slovakian, Swedish, and Japanese) distributed across social media platforms and through authors professional and personal networks. Adults (n = 5389 after data cleaning; median age = 31 years [interquartile range (IQR) = 25, 38]), who were previously engaged in RT prior to lockdown (median prior RT experience = 7 years [IQR = 4, 12]) participated. Outcomes were self-reported RT behaviours including: continuation of RT during lockdown, location of RT, purchase of specific equipment for RT, method of training (e.g. alone, supervision etc.), full-body or split routine, types of training, repetition ranges, exercise number, set volumes (per exercise and muscle group), weekly frequency of training, perception of effort, whether training was planned/recorded, time of day, and training goals. Secondary outcomes included motivation, perceived effectiveness, enjoyment, and intent to continue RT.Results: A majority of individuals (82.8%) maintained participation in some form of RT during- lockdown. Marginal probabilities from generalised linear models and generalised estimating equations of engaging in certain RT behaviours were largely similar from pre- to during- lockdown (particularly numbers of exercises, sets per exercise or muscle group, and weekly frequencies). There was reduced probability of training in privately owned gyms (~59% to ~7%) and increased probability of training at home (~18% to ~89%); greater probability of training using a full-body routine (~38% to ~51%); reduced probability of resistance machines (~66% to ~13%) and free weight use (~96% to ~81%), and increased probability of bodyweight training (~62% to ~82%); reduced probability of moderate repetition ranges (~62-82% to ~55-66%) and greater probability of higher repetition ranges (~27% to ~49%); and moderate reduction in the perception of effort experienced during- training (r = 0.31). Further, individuals were slightly less likely to plan or record training during- lockdown and many changed their training goals as a result of lockdown. Additionally, perceived effectiveness, enjoyment, and likelihood of continuing current training were all lower during- lockdown.Conclusions: Those engaged in RT prior to lockdown appeared mostly able to maintain these behaviours with only slight adaptations in both the location and types of training performed. However, people employed less effort, had lower motivation, and perceived training as less effective and enjoyable, reporting that their likelihood of continuing current training was similar or lower than pre- lockdown. These results have implications for strategies to maintain engagement in positive health behaviours such as RT during- restrictive pandemic-related public health measures.

Competitive alpine skiers are subject to substantial risks of injury, especially concerning the anterior cruciate ligament (ACL). During “landing back weighted” episodes, hamstrings may partially counteract the anterior shear force acting on the tibia by eccentrically resisting the boot-induced drawer of the tibia relative to the femur. The aim of the present study was to provide novel descriptive data and sport-specific reference values on maximal eccentric hamstrings strength (MEHS) in competitive alpine skiers from youth to elite level, and to explore potential relationships with sex, age and biological maturation. 170 competitive alpine skiers were investigated: 139 youth athletes (51 females, 88 males; age: 13.8 ± 0.59 years) and 31 elite athletes (19 females, 12 males; age: 21.7 ± 2.8 years). MEHS was assessed by the (Vald Performance, Newstead, Australia). U15 female skiers presented lower MEHS compared to female elite skiers for both limbs (R = 210 ± 44 N vs. 340 ± 48 N, respectively, p < 0.001, and L = 207 ± 46 N vs. 303 ± 35 N, respectively, p < 0.001). Similarly, lower MEHS was observed in U15 male skiers compared to male elite skiers for both limbs (R = 259 ± 51 N vs. 486 ± 62 N, respectively, p < 0.001, and L = 258 ± 57 N vs. 427 ± 54 N, respectively, p < 0.001). Correlations between MEHS and chronological age were modestly significant only for the U15 group (r = 0.37 and p < 0.001). When the correlations for the U15 group were performed between MHES and maturity offset (obtained from the calculation of biological age, i.e., age at peak height velocity), statistical significance was reached by all the correlations run for 3 variables (Males < 0: r = 0.59, p < 0.0001; Males > 0: r = 0.70, p < 0.0001; and Females > 0: r = 0.46, p < 0.0001, start of maturity offset = 0). This cross-sectional description of MEHS in alpine skiers from youth to elite level highlights the importance of biological maturation for MEHS values in youth athletes and presents novel data that may offer insights into new approaches for injury prevention.

Resistance exercise training (RET) is well-known to counteract negative age-related changes in both muscle and tendon tissue. Traditional RET consists of both concentric (CON) and eccentric (ECC) contractions; nevertheless, isolated ECC contractions are metabolically less demanding and, thus, may be more suitable for older populations. However, whether submaximal (60% 1RM) CON or ECC contractions differ in their effectiveness is relatively unknown. Further, whether the time course of muscle and tendon adaptations differs to the above is also unknown. Therefore, this study aimed to establish the time course of muscle and tendon adaptations to submaximal CON and ECC RET. Twenty healthy young (24.5 ± 5.1 years) and 17 older males (68.1 ± 2.4 years) were randomly allocated to either isolated CON or ECC RET which took place 3/week for 8 weeks. Tendon biomechanical properties, muscle architecture and maximal voluntary contraction were assessed every 2 weeks and quadriceps muscle volume every 4 weeks. Positive changes in tendon Young’s modulus were observed after 4 weeks in all groups after which adaptations in young males plateaued but continued to increase in older males, suggesting a dampened rate of adaptation with age. However, both CON and ECC resulted in similar overall changes in tendon Young’s modulus, in all groups. Muscle hypertrophy and strength increases were similar between CON and ECC in all groups. However, pennation angle increases were greater in CON, and fascicle length changes were greater in ECC. Notably, muscle and tendon adaptations appeared to occur in synergy, presumably to maintain the efficacy of the muscle–tendon unit.

Background: Conventional forms of endurance training based on shortening contractions improve aerobic capacity but elicit a detriment of muscle strength. We hypothesized that eccentric interval training, loading muscle during the lengthening phase of contraction, overcome this interference and potentially adverse cardiovascular reactions, enhancing both muscle metabolism and strength, in association with the stress experienced during exercise. Methods: Twelve healthy participants completed an eight-week program of work-matched progressive interval-type pedaling exercise on a soft robot under predominately concentric or eccentric load. Results: Eccentric interval training specifically enhanced the peak power of positive anaerobic contractions (+28%), mitigated the strain on muscle&rsquo, s aerobic metabolism, and lowered hemodynamic stress during interval exercise, concomitant with a lowered contribution of positive work to the target output. Concentric training alone lowered blood glucose concentration during interval exercise and mitigated heart rate and blood lactate concentration during ramp exercise. Training-induced adjustments for lactate and positive peak power were independently correlated (p &lt, 0.05, |r| &gt, 0.7) with indices of metabolic and mechanical muscle stress during exercise. Discussion: Task-specific improvements in strength and muscle&rsquo, s metabolic capacity were induced with eccentric interval exercise lowering cardiovascular risk factors, except for blood glucose concentration, possibly through altered neuromuscular coordination.

Aim Skeletal muscles of Body Builders (BB) represent an interesting model to study muscle mass gains in response to high volume resistance training. It is debated whether muscle contractile performance improves in proportion to mass. Here, we aim to assess whether muscle hypertrophy does not occur at the expense of performance. Methods Six BB and Six untrained controls (CTRL) were recruited. Cross-sectional area (CSA) and maximum voluntary contraction (MVC) of quadriceps femoris muscle (QF) and CSA and architecture of vastus lateralis (VL) were determined. Moreover, a biopsy was taken from VL mid-portion and single fibres were analysed. Results QF CSA and MVC were 32% (n.s., P = .052) and 58% (P = .009) higher in BB than in CTRL, respectively. VL CSA was 37% higher in BB (P = .030). Fast 2A fibres CSA was 24% (P = .048) greater in BB than in CTRL, when determined in immunostained sections of biopsy samples. Single permeabilized fast fibres CSA was 37% (n.s., P = .052) higher in BB than in CTRL, and their force was slightly higher in BB (n.s.), while specific tension (P0 ) was 19% (P = .024) lower. The lower P0 was not explained either by lower myosin content or by impaired calcium diffusion. Conversely, the swelling caused by skinning-induced permeabilization was different and, when used to correct P0 , differences between populations disappeared. Conclusions The results show that high degree of muscle hypertrophy is not detrimental for force generation capacity, as increases in fibre size and force are strictly proportional once the differential swelling response is accounted for.

PurposeTo investigate the time-course of changes in knee-extensors muscle mass, architecture and function in response to plyometric training (PLT) performed on a novel training device, the Tramp-Trainer. This machine consists in a trampoline connected to an inclined sledge which allows the performance of repeated jumps while the subject is sitting on a chair.MethodsEight healthy males (173.6 ± 4.7 cm, 69.7 ± 13.5 kg, 25.3 ± 4.6 years) underwent 6 weeks of bilateral PLT on the tramp-trainer machine. Training was performed three times per week (between 120 and 150 bounces per session). Knee-extensor maximum voluntary torque (MVT) and power, quadriceps femoris (QF) volume (VOL), cross-sectional area from the 20% to the 60% of femur length and CSAmean, together with vastus lateralis (VL) architecture (fascicle length, Lf, and pennation angle, PA) were assessed after 2, 4, and 6 weeks of PLT.ResultsAll results are presented as changes versus baseline values. MVT increased by 17.8% (week 2, p < 0.001) and 22.2% (week 4, p < 0.01), respectively, and declined to 13.3% (p < 0.05) at week 6 of PLT. Power increased by 18.2% (week 4, p < 0.05) and 19.7% (week 6, p < 0.05). QF VOL increased by 4.7% (week 4, p < 0.05) and 5.8% (week 6, p < 0.01); VL VOL increased by 5.2%, (p < 0.05), 8.2%, (p < 0.01), and 9.6% (p < 0.05) at weeks 2, 4, and 6, respectively. An increase in Lf was detected already at wk 2 (2.2%, p < 0.05), with further increase at 4 and 6 weeks of PLT (4 and 4.4%, respectively, p < 0.01). PA increased by 5.8% (p < 0.05) at week 6. Significant positive correlations were found between CSAmean and Power (R2 = 0.46, p < 0.001) and between QF VOL and Power (R2 = 0.44, p < 0.024).ConclusionsPLT induced rapid increases in muscle volume, fascicle length, pennation angle, torque and power in healthy younger adults. Notably, changes in VL VOL and Lf were detectable already after 2 weeks, followed by increases in knee extensors VOL and power from week 4 of PLT. Since the increase in CSAmean and QF VOL cannot fully explain the increment in muscle power, it is likely that other factors (such as adaptations in neural drive or tendon mechanical properties) may have contributed to such fucntional changes.

The COVID-19 pandemic is an unprecedented health crisis as entire populations have been asked to self-isolate and live in home-confinement for several weeks to months, which in itself represents a physiological challenge with significant health risks. This paper describes the impact of sedentarism on the human body at the level of the muscular, cardiovascular, metabolic, endocrine and nervous systems and is based on evidence from several models of inactivity, including bed rest, unilateral limb suspension, and step-reduction. Data form these studies show that muscle wasting occurs rapidly, being detectable within two days of inactivity. This loss of muscle mass is associated with fibre denervation, neuromuscular junction damage and upregulation of protein breakdown, but is mostly explained by the suppression of muscle protein synthesis. Inactivity also affects glucose homeostasis as just few days of step reduction or bed rest, reduce insulin sensitivity, principally in muscle. Additionally, aerobic capacity is impaired at all levels of the O2 cascade, from the cardiovascular system, including peripheral circulation, to skeletal muscle oxidative function. Positive energy balance during physical inactivity is associated with fat deposition, associated with systemic inflammation and activation of antioxidant defences, exacerbating muscle loss. Importantly, these deleterious effects of inactivity can be diminished by routine exercise practice, but the exercise dose–response relationship is currently unknown. Nevertheless, low to medium-intensity high volume resistive exercise, easily implementable in home-settings, will have positive effects, particularly if combined with a 15–25% reduction in daily energy intake. This combined regimen seems ideal for preserving neuromuscular, metabolic and cardiovascular health. Highlights This paper describes the impact of sedentarism, caused by the COVID-19 home confinement on the neuromuscular, cardiovascular, metabolic and endocrine systems. Just few days of sedentary lifestyle are sufficient to induce muscle loss, neuromuscular junction damage and fibre denervation, insulin resistance, decreased aerobic capacity, fat deposition and low-grade systemic inflammation. Regular low/medium intensity high volume exercise, together with a 15-25% reduction in caloric intake are recommended for preserving neuromuscular, cardiovascular, metabolic and endocrine health.

PurposeEccentric exercise is widely used to increase muscle fascicle lengths and thus decrease the risk of muscle strain injuries. However, the mechanisms behind this protection are still unknown. The aim of this study was to determine whether Biceps femoris long head (BFlh) fascicle length increases in response to three weeks of eccentric exercise training are the result of addition of in-series sarcomeres within muscle fibres.MethodsTen recreationally active participants (age: 27 ± 3 years, mass: 70 ± 14 kg, height: 174 ± 9 cm) completed three weeks of Nordic hamstring exercise (NHE) training. We collected in vivo sarcomere and muscle fascicle images of the BFlh in two regions (central and distal), utilising microendoscopy and 3D ultrasonography. These images allowed us to estimate sarcomere length, sarcomere number and fascicle lengths before and after the training intervention.ResultsEccentric knee flexion strength increased after the training (15%, P < 0.001, ηp2= 0.75). Further, we found a significant increase in fascicle (21%, P < 0.001, ηp2 = 0.81) and sarcomere (17%, P < 0.001, ηp2 = 0.9) lengths in the distal but not in the central portion of the muscle. The estimated number of in series sarcomeres did not change in either region.ConclusionFascicle length adaptations appear to be heterogeneous in the BFlf in response to three weeks of NHE training. An increase in sarcomere length, rather than the addition of sarcomeres in series, appears to be underlying this adaptation. The mechanism driving regional increases in fascicle and sarcomere length remain unknown, but we speculate it may be driven by regional changes in the passive tension of muscle or connective tissue adaptations.

Schoenfeld, BJ, Ogborn, DI, Vigotsky, AD, Franchi, MV, and Krieger, JW. Hypertrophic effects of concentric vs. eccentric muscle actions: A systematic review and meta-analysis. J Strength Cond Res 31(9): 2599-2608, 2017-Controversy exists as to whether different dynamic muscle actions produce divergent hypertrophic responses. The purpose of this paper was to conduct a systematic review and meta-analysis of randomized controlled trials comparing the hypertrophic effects of concentric vs. eccentric training in healthy adults after regimented resistance training (RT). Studies were deemed eligible for inclusion if they met the following criteria: (a) were an experimental trial published in an English-language refereed journal; (b) directly compared concentric and eccentric actions without the use of external implements (i.e., blood pressure cuffs) and all other RT variables equivalent; (c) measured morphologic changes using biopsy, imaging (magnetic resonance imaging, computerized tomography, or ultrasound), bioelectrical impedance, and/or densitometry; (d) had a minimum duration of 6 weeks; and (e) used human participants without musculoskeletal injury or any health condition that could directly, or through the medications associated with the management of said condition, be expected to impact the hypertrophic response to resistance exercise. A systematic literature search determined that 15 studies met inclusion criteria. Results showed that eccentric muscle actions resulted in a greater effect size (ES) compared with concentric actions, but results did not reach statistical significance (ES difference = 0.25 ± 0.13; 95% confidence interval: -0.03 to 0.52; p = 0.076). The mean percent change in muscle growth across studies favored eccentric compared with concentric actions (10.0% vs. 6.8, respectively). The findings indicate the importance of including eccentric and concentric actions in a hypertrophy-oriented RT program, as both have shown to be effective in increasing muscle hypertrophy.

Background The ability to rapidly generate and transfer muscle force is essential for effective corrective movements in order to prevent a fall. The aim of this study was to establish the muscle and tendon contributions to differences in rate of torque development (RTD) between younger (YM) and older males (OM). Method Twenty-eight young males (23.9 years ± 1.1) and 22 old males (68.5 years ± 0.5) were recruited for assessment of Quadriceps Anatomical CSA (ACSA), maximal voluntary contraction (MVC), rate of torque development (RTD), and tendon biomechanical properties. Activation capacity (AC), maximal muscle twitch df/dt) and time to peak EMG amplitude (TTPE) were also assessed. Results Absolute RTD (aRTD) was lower in OM (577.5 ± 34.6 Nm/s vs 881.7 ± 45.6 Nm/s, p < .0001). RTD remained lower in OM following normalization (nRTD) for muscle ACSA (9.93 ± 0.7 Nm/s/cm2 vs 11.9 ± 0.6 Nm/s/cm2, p < .05). Maximal muscle twitch df/dt (1,086 Nm∙s−1 vs 2,209 Nm∙s−1, p < .0001), TTPE (109.2 ± 8.6ms vs 154.6 ± 16.6 ms, p < .05), and AC (75.8 ± 1.5% vs 80.1 ± 0.9%, p < .01) were all affected in OM. Tendon stiffness was found to be lower in OM (1,222 ± 78.4 N/mm vs 1,771 ± 154.1 N/mm, p < .004). nRTD was significantly correlated with tendon stiffness (R2 = .15). Conclusion These observations provide evidence that in absolute terms, a lower RTD in the elderly adults is caused by slower muscle contraction speeds, slower TTPE, reduced ACSA, reduced MVC, and a decrease in tendon stiffness. Once the RTD is normalized to quadriceps ACSA, only MVC and tendon stiffness remain influential. This strongly reinforces the importance of both muscle and tendon characteristics when considering RTD.

This study sought to investigate the electromyographic activity of the vastus lateralis (VL) muscle during concentric-eccentric exercise using a new concept leg press machine enabling a preset overloading in the eccentric phase. Ten young males familiar with resistive exercise were recruited for this study. Tests were performed on a Leg-press Biostrength® (Technogym S.p.A., Italy). The load was set to 70% and 80% of one-repetition maximum (1-RM). The participants performed 2 sets of 6 repetitions at each relative load with (ECC +) and without (ISOW) an eccentric overload equivalent to 150% of the concentric load. A metronome was employed to maintain the selected cadence. Sets were separated by a 5-min rest. Surface electromyography (EMG) of VL was recorded and integrated (iEMG). Results showed a higher iEMG in ECC + with respect to ISOW at both intensities (+ 29% for 70% 1-RM, p

High-load eccentric training reputedly produces greater muscle hypertrophy than concentric training, possibly due to greater loading and/or inflammation. We quantified the temporal impact of combined maximal concentric-eccentric training vs maximal concentric training on muscle cross-sectional area (CSA), volume, and targeted mRNA expression (93 transcripts). Eight recreationally active males (24 ± 5 years, BMI 23.5 ± 2.5 kg/m2 ) performed 3 x 30 maximal eccentric isokinetic knee extensions and 2 x 30 maximal concentric knee extensions in dominant limb (ECC + CON) and 5 x 30 maximal concentric contractions (CON) in the non-dominant limb for 12 weeks (all 90°/s, 3x/wk). Quadriceps muscle CSA and volume were measured at baseline, 28 days (d), and 84 d in both limbs (3T MRI). Resting vastus lateralis biopsies were obtained from both limbs at baseline, 24 hours (h), 7, 28, and 84 d for mRNA abundance measurements (RT-PCR microfluidic cards). Work output was greater throughout training in ECC + CON vs CON (20.8 ± 9.7%, P < .001). Muscle CSA increased from baseline in both limbs at 28 d (CON 4.3 ± 2.6%, ECC + CON 4.0 ± 1.9%, both P < .001) and 84d (CON 3.9 ± 2.3%, ECC + CON 4.0 ± 3.1%, both P < .001), and muscle volume and isometric strength at 84 d (CON 44.8 ± 40.0%, P < .001; ECC + CON 36.9 ± 40.0%, P < .01), but no between-limb differences existed in any parameter. Ingenuity Pathway Analysis identified several cellular functions associated with regulation of muscle mass and metabolism as altered by both modalities at 24 h and 7 d, but particularly with ECC + CON. However, mRNA responses waned thereafter, regardless of modality. Initial muscle mRNA responses to training did not reflect chronic training-induced hypertrophy. Moreover, ECC + CON did not produce greater hypertrophy than CON, despite greater loading throughout and a differential mRNA response during the initial training week.

© 2019 by the authors. The purpose of this short review is to discuss the effects of eccentric exercise in modifying the properties of tendon tissue in healthy individuals. The tendon provides a mechanical link between muscle and bone, allowing force transmission to the skeleton, and thus, its properties have significant functional implications. Chronic resistance training has long been shown to increase the stiffness and Young’s modulus of the tendon and even tendon cross-sectional area. However, as the tendon responds to the amount and/or frequency of strain, it has been previously suggested that eccentric training may result in greater adaptations due to the potential for greater training loads. Thus, this review discusses the effects of eccentric training upon healthy tendon tissue and compares these to other training modalities. Furthermore, it has been reported that the tendon may undergo adverse age-related changes. Thus, this review also discusses the potential application of eccentric resistance training as a preferential modality for counteracting these age-related changes. We conclude that while there may be no difference between contraction types for overall tendon adaptation, the lower demands of eccentric contractions may make it more appealing for the elderly population.

The preservation of muscle power is crucial in aging for maintaining mobility and performing daily tasks. Resistance training involving high movement velocities represents a valid strategy to slow down the rate of sarcopenia, counteracting the loss of muscle mass and muscle power. Plyometric exercise may represent an effective training modality for increasing muscle power; however, its application in older populations has been sparingly investigated, as the high impact actions involved may reduce its feasibility for older individuals. By adopting a safer modality of plyometric training, we investigated if a 6-week plyometric training intervention could increase knee extensor muscle size, architecture, force and power in 14 young (YM, age = 25.4 ± 3.5 y; means ± SD) and nine older males (OM, age = 69.7 ± 3.4 y). Volunteers trained 3 times/week using a device similar to a leg press machine where the user was required to bounce against his body mass on a trampoline. Pre-to-post training changes in isometric maximum voluntary torque (MVT), leg extension power and vastus lateralis (VL) architecture were assessed. Muscle power increased in both groups (+27% OM -P < 0.001, 20% YM -P < 0.001), although the total external work performed during the training period was significantly lower for OM (i.e., ~-47%). Both groups showed significant increases in muscle thickness (MT) (+5.8 OM -P < 0.01 vs. +3.8% YM -P < 0.01), fascicle length (Lf) (+8% OM -P < 0.001 vs. +6% YM -P < 0.001), and pennation angle (PA) (+7.5% OM -P < 0.001 vs. +4.1% YM -P < 0.001). The current study shows that trampoline-based plyometric training is an effective intervention producing a rapid increase in muscle mass and power in both young and older individuals. The training modality used in this study seems to particularly benefit the older population, targeting the morphological and functional effects of sarcopenia in human muscle.

Skeletal muscle structural assembly (and its remodeling in response to loading-unloading states) can be investigated macroscopically by assessing muscle architecture, described as fascicle geometric disposition within the muscle. Over recent decades, various medical imaging techniques have been developed to facilitate the in vivo assessment of muscle architecture. However, the main advantages and limitations of these methodologies have been fragmentally discussed. In the present article, the main techniques used for the evaluation of muscle architecture are presented: conventional B-mode ultrasonography, extended-field-of-view ultrasound, 3-D ultrasound and magnetic resonance imaging-based diffusion tensor imaging. By critically discussing potentials and shortcomings of each methodology, we aim to provide readers with an overview of both established and new techniques for the in vivo assessment of muscle architecture. This review may serve as decision guidance facilitating selection of the appropriate technique to be applied in biomedical research or clinical routine.

Introduction Gene polymorphisms are associated with athletic phenotypes relying on maximal or continued power production and affect the specialization of skeletal muscle composition with endurance or strength training of untrained subjects. We tested whether prominent polymorphisms in genes for angiotensin converting enzyme (ACE), tenascin-C (TNC), and actinin-3 (ACTN3) are associated with the differentiation of cellular hallmarks of muscle metabolism and contraction in high level athletes. Methods Muscle biopsies were collected from m. vastus lateralis of three distinct phenotypes; endurance athletes (n = 29), power athletes (n = 17), and untrained non-athletes (n = 63). Metabolism-, and contraction-related cellular parameters (such as capillary-to-fiber ratio, capillary length density, volume densities of mitochondria and intramyocellular lipid, fiber mean cross sectional area (MCSA) and volume densities of myofibrils) and the volume densities of sarcoplasma were analyzed by quantitative electron microscopy of the biopsies. Gene polymorphisms of ACE (I/D (insertion/deletion), rs1799752), TNC (A/T, rs2104772), and ACTN3 (C/T, rs1815739) were determined using high-resolution melting polymerase chain reaction (HRM-PCR). Genotype distribution was assessed using Chi$^{2}$ tests. Genotype and phenotype effects were analyzed by univariate or multivariate analysis of variance and post hoc test of Fisher. P-values below 0.05 were considered statistically significant. Results The athletes demonstrated the specialization of metabolism- and contraction-related cellular parameters. Differences in cellular parameters could be identified for genotypes rs1799752 and rs2104772, and localized post hoc when taking the interaction with the phenotype into account. Between endurance and power athletes these concerned effects on capillary length density for rs1799752 and rs2104772, fiber type distribution and volume densities of myofibrils (rs1799752), and MSCA (rs2104772). Endurance athletes carrying the I-allele of rs1799752 demonstrated 50%-higher volume densities of mitochondria and sarcoplasma, when power athletes that carried only the D-allele showed the highest fiber MCSAs and a lower percentage of slow type muscle fibers. Discussion ACE and tenascin-C gene polymorphisms are associated with differences in cellular aspects of muscle metabolism and contraction in specifically-trained high level athletes. Quantitative differences in muscle fiber type distribution and composition, and capillarization in knee extensor muscle explain, in part, identified associations of the insertion/deletion genotypes of ACE (rs1799752) with endurance- and power-type Sports.

We investigated molecular and cellular parameters which set metabolic and mechanical functioning of knee extensor muscles in the operated and contralateral control leg of 9 patients with a chronically insufficient anterior cruciate ligament (ACL; 26.6 ± 8.3 years, 8 males, 1 female) after open reconstructive surgery (week 0), after ambulant physiotherapy under cast immobilization (week 9), succeeding rehabilitation training (up to week 26), and subsequent voluntary physical activity (week 260). Clinical indices of knee function in the operated leg were improved at 52 weeks and remained at a comparable level at week 260. CSA of the quadriceps (-18%), MCSA of muscle fibers (-24%), and capillary-to-fiber ratio (-24%) in m. vastus lateralis from the ACL insufficient leg were lower at week 0 than reference values in the contralateral leg at week 260. Slow type fiber percentage (-35%) and mitochondrial volume density (-39%) were reduced in m. vastus lateralis from the operated leg at weeks 9 and 26. Composition alterations in the operated leg exceeded those in the contralateral leg and, with the exception of the volume density of subsarcolemmal mitochondria, returned to the reference levels at week 260. Leg-specific deterioration of metabolic characteristics in the vasti from the operated leg was reflected by the down-regulation of mitochondrial respiration complex I-III markers (-41–57%) at week 9. After rehabilitation training at week 26, the specific Y397 phosphorylation of focal adhesion kinase (FAK), which is a proxy for mechano-regulation, was elevated by 71% in the operated leg but not in the contralateral leg, which had performed strengthening type exercise during ambulant physiotherapy. Total FAK protein and Y397 phosphorylation levels were lowered in both legs at week 26 resulting in positive correlations with mitochondrial volume densities and mitochondrial protein levels. The findings emphasize that a loss of mechanical and metabolic characteristics in knee extensor muscle remains detectable years after untreated ACL rupture, which may be aggravated in the post-operative phase by the deterioration of slow-oxidative characteristics after reconstruction due to insufficient load-bearing muscle activity. The reestablishment of muscle composition subsequent to years of voluntary physical activity reinforces that slow-to-fast fiber transformation is reversible in humans., Frontiers in Physiology, 9, ISSN:1664-042X

Non-specific chronic low back pain (nsCLBP) is a multifactorial condition of unknown etiology and pathogenesis. Physical and genetic factors may influence the predisposition of individuals to CLBP, which in many instances share a musculoskeletal origin. A reduced pain level in low back pain patients that participate in exercise therapy highlights that disuse-related muscle deconditioning may predispose individuals to nsCLBP. In this context, musculoskeletal pain may be the consequence of capillary rarefaction in inactive muscle as this would lower local tissue drainage and washing out of toxic waste. Muscle activity is translated into an angio-adaptative process, which implicates angiogenic-gene expression and individual response differences due to heritable modifications of such genes (gene polymorphisms). The pathophysiologic mechanism underlying nsCLBP is still largely unaddressed. We hypothesize that capillary rarefaction due to a deconditioning of dorsal muscle groups exacerbates nsCLBP by increasing noxious sensation, reducing muscle strength and fatigue resistance by initiating a downward spiral of local deconditioning of back muscles which diminishes their load-bearing capacity. We address the idea that specific factors such as angiotensin-converting enzyme and Tenascin-C might play an important role in altering susceptibility to nsCLBP via their effects on microvascular perfusion and vascular remodeling of skeletal muscle, inflammation, and pain sensation. The genetic profile may help to explain the individual predisposition to nsCLBP, thus identifying subgroups of patients, which could benefit from ad hoc treatment types. Future therapeutic approaches aimed at relieving the pain associated with nsCLBP should be based on the verification of mechanistic processes of activity-induced angio-adaptation and muscle-perfusion.

Quantification of muscle protein synthesis (MPS) remains a cornerstone for understanding the control of muscle mass. Traditional [13C]amino acid tracer methodologies necessitate sustained bed rest and intravenous cannulation(s), restricting studies to ∼12 h, and thus cannot holistically inform on diurnal MPS. This limits insight into the regulation of habitual muscle metabolism in health, aging, and disease while querying the utility of tracer techniques to predict the long-term efficacy of anabolic/anticatabolic interventions. We tested the efficacy of the D2O tracer for quantifying MPS over a period not feasible with13C tracers and too short to quantify changes in mass. Eight men (22 ± 3.5 yr) undertook one-legged resistance exercise over an 8-day period (4 × 8–10 repetitions, 80% 1RM every 2nd day, to yield “nonexercised” vs. “exercise” leg comparisons), with vastus lateralis biopsies taken bilaterally at 0, 2, 4, and 8 days. After day 0 biopsies, participants consumed a D2O bolus (150 ml, 70 atom%); saliva was collected daily. Fractional synthetic rates (FSRs) of myofibrillar (MyoPS), sarcoplasmic (SPS), and collagen (CPS) protein fractions were measured by GC-pyrolysis-IRMS and TC/EA-IRMS. Body water initially enriched at 0.16–0.24 APE decayed at ∼0.009%/day. In the nonexercised leg, MyoPS was 1.45 ± 0.10, 1.47 ± 0.06, and 1.35 ± 0.07%/day at 0–2, 0–4, and 0–8 days, respectively (∼0.05–0.06%/h). MyoPS was greater in the exercised leg (0–2 days: 1.97 ± 0.13%/day; 0–4 days: 1.96 ± 0.15%/day, P < 0.01; 0–8 days: 1.79 ± 0.12%/day, P < 0.05). CPS was slower than MyoPS but followed a similar pattern, with the exercised leg tending to yield greater FSRs (0–2 days: 1.14 ± 0.13 vs. 1.45 ± 0.15%/day; 0–4 days: 1.13 ± 0.07%/day vs. 1.47 ± 0.18%/day; 0–8 days: 1.03 ± 0.09%/day vs. 1.40 ± 0.11%/day). SPS remained unchanged. Therefore, D2O has unrivaled utility to quantify day-to-day MPS in humans and inform on short-term changes in anabolism and presumably catabolism alike.

Skeletal muscle contracts either by shortening or lengthening (concentrically or eccentrically, respectively); however, the two contractions substantially differ from one another in terms of mechanisms of force generation, maximum force production and energy cost. It is generally known that eccentric action s generate greater force than isometric and concentric contractions and at a lower metabolic cost. Hence, by virtue of the greater mechanical loading involved in active lengthening, eccentric resistance training (ECC RT) is assumed to produce greater hypertrophy than concentric resistance training (CON RT). Nonetheless, prevalence of either ECC RT or CON RT in inducing gains in muscle mass is still an open issue, with some studies reporting greater hypertrophy with eccentric, some with concentric and some with similar hypertrophy within both training modes. Recent observations suggest that such hypertrophic responses to lengthening vs. shortening contractions are achieved by different adaptations in muscle architecture. Whilst the changes in muscle protein synthesis in response to acute and chronic concentric and eccentric exercise bouts seem very similar, the molecular mechanisms regulating the myogenic adaptations to the two distinct loading stimuli are still incompletely understood. Thus, the present review aims to, (a) critically discuss the literature on the contribution of eccentric vs. concentric loading to muscular hypertrophy and structural remodeling, and, (b) clarify the molecular mechanisms that may regulate such adaptations. We conclude that, when matched for either maximum load or work, similar increase in muscle size is found between ECC and CON RT. However, such hypertrophic changes appear to be achieved through distinct structural adaptations, which may be regulated by different myogenic and molecular responses observed between lengthening and shortening contractions.

AIMS We assessed focal adhesion kinase (FAK) response to concentric (CON) versus eccentric (ECC) resistance training (RT) at two vastus lateralis (VL) sites, and the relationships between FAK, muscle protein synthesis (MPS), and morphological remodeling. METHODS Six young males trained both legs unilaterally 3 times/week for 8 weeks; one leg performed CON RT, the contralateral performed ECC RT. Muscle biopsies were collected after training from VL midbelly (MID) and distal (Distal) sites at 0, 4, 8 weeks. FAK content and activation were evaluated by immunoblotting. MPS was assessed by deuterium-oxide tracer; morphological adaptations were evaluated by ultrasound and DXA. RESULTS pY397-FAK 8 weeks levels were ~4-fold greater after ECC at the Distal site compared to CON (p

Dear Editor: Morphological adaptations of skeletal muscle to resistance exercise training (RET) have been the subject of many studies: essentially, muscle hypertrophy is achieved by a structural remodelling of the contractile machinery, which can be assessed macroscopically by investigating changes in muscle architecture (i.e. fascicle length, Lf; pennation angle, PA; muscle thickness, MT) (Gans 1982; Narici 1999; Lieber and Friden 2000, 2001; Reeves et al. 2004, 2005). A thorough understanding of muscle architecture is indeed fundamental when interpreting training-induced changes in muscle function given its key role as determinant of muscle mechanical properties (Narici et al. 2015; Lieber and Friden 2000). In a recent study by Fukutani and Kurihara (2015) published in SpringerPlus (2015, 4:341), the authors investigated differences in Lf between resistance trained and untrained individuals using a cross-sectional design: the main conclusion being made was that Lf was not associated with muscle hypertrophy on the basis that no significant differences in Lf were found between the groups. The authors claimed that fascicle length does not increase with resistance training. Some fundamental considerations arise from these findings. Skeletal muscle hypertrophy in response to RET is mainly accomplished with the addition of new contractile material as a result of enhanced muscle myofibrillar protein synthesis after exercise (Glass 2003; Atherton and Smith 2012). Moreover, it is well established that the longitudinal post-natal growth of mammal muscle is associated with the increased in length and size of muscle fibres (Goldspink 1968; Williams and Goldspink 1971; Russell et al. 2000). Seminal pre-clinical studies previously showed that skeletal muscle responds to passive and intermittent stretch by adding new sarcomeres in-series (Holly et al. 1980; Goldspink 1985; Williams et al. 1988; Williams 1990), a phenomenon that occurs also in response to exercise regimes/overload, especially when including lengthening muscle actions (Goldspink 1999; Proske and Morgan 2001). Greater addition of serial sarcomeres was found in rats after downhill compared to uphill running (Lynn and Morgan 1994; Butterfield et al. 2005), reinforcing the concept of muscle longitudinal growth being intimately related to lengthening contractions. Indeed, the addition of sarcomeres in series (and thus increased Lf) appears to be one of the main “protective” mechanisms after eccentric exercise induced muscle damage (Morgan and Talbot 2002). Further support to these observations on animal muscle can be found in numerous studies investigating architectural responses to RET, directly in humans. Interestingly, Fukutani and Kurihara stated it as controversial as to whether Lf increases after RET: however the number of reports showing no increases in Lf in response to exercise is limited (Blazevich et al. 2007b; Erskine et al. 2010; Ema et al. 2013) compared to those that demonstrated an increase in Lf after either conventional resistance, isokinetic, isoinertial or even marathon training (Morgan and Proske 2004; Seynnes et al. 2007; Blazevich et al. 2007a; Potier et al. 2009; Reeves et al. 2009; Baroni et al. 2013; Franchi et al. 2014, 2015; Sharifnezhad et al. 2014; McMahon et al. 2014; Murach et al. 2015). But, most importantly, it was recently reported by our group that, in both young and older populations, architectural changes, such as increases in Lf, are somewhat contraction-specific (Reeves et al. 2009; Franchi et al. 2014, 2015). That is, concentric loading promotes increases in PA, reflecting preferential addition of sarcomeres in parallel, whereas eccentric training favours the increase of Lf through the addition of sarcomeres in series. It is our opinion that these investigations should have been cited in Fukutani and Kurihara’s manuscript. Furthermore, considering the substantial number of longitudinal studies that have showed significant changes in Lf and muscle architecture after RET, the adoption of such a cross-sectional study design calls into question the validity of these conclusions. Moreover, the investigation was performed on recreationally active volunteers (the untrained group, with “no experience in regular RET”) compared to a group of “resistance exercise trained” participants, either body builders or rugby players (i.e. the number of bodybuilders/rugby players was not specified). Taking into account the aforementioned considerations on the contraction-specificity of architectural responses, the individual history of resistance training in both groups should have been accounted for. Kawakami and colleagues (1993) previously reported that PA and MT are greater in bodybuilders compared to untrained and moderately trained subjects (Lf was not investigated), but Abe et al. (2000, 2001), showed that Lf is greater in elite male 100 m-sprinters compared to elite long-distance runners and to non-sprinters. Rather than being innate factors, as Fukutani and Kurihara argue, architectural adaptations such as increases in Lf are indeed detectable longitudinally and are training/contraction-specific (Blazevich et al. 2003; Franchi et al. 2014, 2015). In addition, Lf was measured as a straight line in Fukutani and Kurihara’s study: while this might not represent a problem in the untrained group, in hypertrophied muscle, instead, fascicles show a significantly greater curvature, which partially explains the increased pennation occurring with hypertrophy (clearly visible in bodybuilders muscle) (Kawakami et al. 1993). Since the fascicle curvature was neglected by the methodological approach used to measure Lf, the true Lf values could have been underestimated in the resistance-trained group. Therefore, Lf may have gone undetected as a result of the simplicity of the morphometric analyses implemented. Thus, the chances are that Fukutani and Kurihara’s results were biased by the non-longitudinal study design and by the possible underestimation of Lf due to specific methodological approach. We agree that in some cases “muscle hypertrophy is not necessarily accompanied with increase in Lf” (Fukutani and Kurihara 2015), but these cases can only be truly determined by tightly controlled longitudinal studies. We are of the opinion that the nature of fascicle length (Lf) increase is highly dependent on which type of contraction and mechanical stimulus is predominant in specific RET programmes: thus, data on muscle architecture features should be cautiously interpreted, as crucial in the understanding of muscle structural remodelling and its functional characteristics.

Sarcopenia, the progressive loss of muscle mass and strength, is a phenomenon characterizing human aging whose etiology is still not clear. While there is increasing evidence for the influence of inter-muscular adipose tissue infiltration in the development of sarcopenia, much less is known about a possible role for intra-muscular triglycerides (IMTG). IMTG accumulate in form of lipid droplets decorated by proteins such as Perilipins (Plins). In skeletal muscle the most abundant are Plin2 and Plin5. In this study we compared the expression of these two Plins in Vastus lateralis muscle samples of subjects of different age, both healthy donors (HD) and patients with limited lower limb mobility (LLMI). These latter are characterized by a condition of chronic physical inactivity. Plin2 expression resulted higher in old age for both HD and LLMI patients, while Plin5 slightly decreased only in LLMI patients. Moreover, in these patients, only Plin2 was associated with the decrease of muscle strength and the expression of factors related to muscle atrophy (MuRF1, Atrogin and p53). An increase in Plin2 and a concomitant decrease of Plin5 was also observed when we considered animal model of disuse-induced muscle atrophy. As a whole, these data indicate that Plin2 and Plin5 have a different expression pattern during muscle aging and inactivity, and only Plin2 appears to be associated with functional alterations of the muscle.

Aim We investigated architectural, functional and molecular responses of human skeletal muscle to concentric (CON) or eccentric (ECC) resistance training (RT). Methods Twelve young males performed 10 weeks of concentric (CON) or eccentric (ECC) resistance training (RT) (n = 6 CON, 6 ECC). An additional 14 males were recruited to evaluate acute muscle fascicle behaviour and molecular signalling in biopsies collected from vastus lateralis (VL) after 30 min of single bouts of CON or ECC exercise. VL volume was measured by magnetic resonance imaging. Muscle architecture (fascicle length, Lf; pennation angle, PA) was evaluated by ultrasonography. Muscle remodelling signals to CON or ECC loading [MAPK/AKT-mammalian target of rapamycin (mTOR) signalling] and inflammatory pathway (TNFαMurf-1-MAFbx) were evaluated by immunoblotting. Results Despite the ~1.2-fold greater load of the ECC group, similar increases in muscle volume (+8% CON and +6% ECC) and in maximal voluntary isometric contraction (+9% CON and +11% ECC) were found after RT. However, increases in Lf were greater after ECC than CON (+12 vs. +5%) while increases in PA were greater in CON than ECC (+30 vs. +5%). Distinct architectural adaptations were associated with preferential growth in the distal regions of VL for ECC (+ECC +8% vs. +CON +2) and mid belly for CON (ECC +7 vs. CON +11%). While MAPK activation (p38MAPK, ERK1/2, p90RSK) was specific to ECC, neither mode affected AKT-mTOR or inflammatory signalling 30 min after exercise. Conclusion Muscle growth with CON and ECC RT occurs with different morphological adaptations reflecting distinct fibre fascicle behaviour and molecular responses.

We recently reported that the greatest distinguishing feature between eccentric (ECC) and concentric (CON) muscle loading lays in architectural adaptations: ECC favors increases in fascicle length (Lf), associated with distal vastus lateralis muscle (VL) hypertrophy, and CON increases in pennation angle (PA). Here, we explored the interactions between structural and morphological remodeling, assessed by ultrasound and dual x-ray absorptiometry (DXA), and long-term muscle protein synthesis (MPS), evaluated by deuterium oxide (D2O) tracing technique. Ten young males (23 ± 4 years) performed unilateral resistance exercise training (RET) three times/week for 4 weeks; thus, one-leg trained concentrically while the contralateral performed ECC exercise only at 80% of either CON or ECC one repetition maximum (1RM). Subjects consumed an initial bolus of D2O (150 mL), while a 25-mL dose was thereafter provided every 8 days. Muscle biopsies from VL midbelly (MID) and distal myotendinous junction (MTJ) were collected at 0 and 4-weeks. MPS was then quantified via GC–pyrolysis–IRMS over the 4-week training period. Expectedly, ECC and CON RET resulted in similar increases in VL muscle thickness (MT) (7.5% vs. 8.4%, respectively) and thigh lean mass (DXA) (2.3% vs. 3%, respectively), albeit through distinct remodeling: Lf increasing more after ECC (5%) versus CON (2%) and PA increasing after CON (7% vs. 3%). MPS did not differ between contractile modes or biopsy sites (MID-ECC: 1.42 vs. MID-CON: 1.4% day−1; MTJ-ECC: 1.38 vs. MTJ-CON: 1.39% day−1). Muscle thickness at MID site increased similarly following ECC and CON RET, reflecting a tendency for a contractile mode-independent correlation between MPS and MT (P = 0.07; R2 = 0.18). We conclude that, unlike MT, distinct structural remodeling responses to ECC or CON are not reflected in MPS; the molecular mechanisms of distinct protein deposition, and/or the role of protein breakdown in mediating these responses remain to be defined.

The relationship between muscle structure and function has been a matter of investigation since the Renaissance period. Extensive use of anatomical dissections and the introduction of the scientific method enabled early scholars to lay the foundations of muscle physiology and biomechanics. Progression of knowledge in these disciplines led to the current understanding that muscle architecture, together with muscle fibre contractile properties, has a major influence on muscle mechanical properties. Recently, advances in laser diffraction, optical microendoscopy and ultrasonography have enabled in vivo investigations into the behaviour of human muscle fascicles and sarcomeres with varying joint angle and muscle contraction intensity. With these technologies it has become possible to identify the length region over which fascicles and sarcomeres develop maximum isometric force in vivo as well as the operating ranges of fascicles and sarcomeres during real-life activities such as walking. Also, greater insights into the remodelling of muscle architecture in response to overloading and unloading, and in ageing, have been obtained by the use of ultrasonography; these have led to the identification of clinical biomarkers of disuse atrophy and sarcopenia. Recent evidence also shows that the pattern of muscle hypertrophy in response to chronic loading is contraction-mode dependent (eccentric versus concentric), as similar gains in muscle mass, but through differing addition of sarcomeres in series and in parallel (as indirectly inferred from changes in fascicle length and pennation angle), have been found. These innovative observations prompted a new set of investigations into the molecular mechanisms regulating this contraction-specific muscle growth.