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Aim: The aim of this observational study was to determine the immune status and function in young adults with cerebral palsy (CP) in comparison to typically developing individuals. Method: Blood samples from 12 individuals with CP (five males, seven females; mean age: 25 years 1 month (5 years 9 months); age range: 19–38 years) and 17 typically developing individuals (eight males, nine females; mean age: 31 years 4 months (6 years 2 months); age range: 20–40 years) were collected before, immediately after, and 1 hour after 45 minutes of frame running or running respectively. Independent t‐tests were used to compare heart rate, level of exertion, and baseline cell proportions between groups. Mixed model analysis of variance was utilized to investigate immune cell responses to exercise across groups. Results: Baseline levels of gamma delta (TCRγδ+) T‐cells were significantly higher (absolute percentage: +2.65, p = 0.028) in the individuals with CP. Several cell populations showed similar significant changes after exercise in both CP and typically developing groups. Cytotoxic (CD8+) T‐cells were only significantly elevated immediately after exercise in the typically developing participants (p < 0.01). Individuals with CP exhibited significantly lower heart rates (−11.1%, p < 0.01), despite similar ratings of perceived exertion. Interpretation: Elevated baseline TCRγδ+ T‐cells may indicate low‐grade inflammation in adults with CP. Although most of the cell populations showed typical responses to endurance exercise, the absence of response in CD8+ T‐cells in individuals with CP may indicate the need for higher intensity during exercise. What this paper adds: TCRγδ+ T‐cell baseline levels are elevated in adults with cerebral palsy (CP).The CD8+ T‐cell response to exercise was blunted in adults with CP.Exercise intensity is decisive for CD8+ T‐cell responses in individuals with CP. [ABSTRACT FROM AUTHOR]

A recent study published in Experimental Physiology details the first Canadian study to investigate the physiological, psychological, and cognitive responses to 14 days of bed rest and the benefits of exercise during bed rest. The study involved 23 older male and female participants who completed 14 days of bed rest, followed by supervised rehabilitation. Half of the participants performed aerobic and resistance exercise during bed rest to test its effectiveness as a countermeasure. The study provides important insights into the physiological responses to inactivity and may help inform future countermeasure development. Bed rest studies are also relevant for understanding periods of hospitalization and testing countermeasures for microgravity and severe inactivity. [Extracted from the article]

Maintenance of skeletal muscle mass and function is critical to health and wellbeing throughout the lifespan. However, disuse through reduced physical activity (e.g., sedentarism), immobilisation, bed rest or microgravity has significant adverse effects on skeletal muscle health. Conversely, resistance exercise training (RET) induces positive muscle mass and strength adaptations. Several studies have employed microarray technology to understand the transcriptional basis of muscle atrophy and hypertrophy after disuse and RET, respectively, to devise fully effective therapeutic interventions. More recently, rapidly falling costs have seen RNA-sequencing (RNA-seq) increasingly applied in exploring muscle adaptations to RET and disuse. The aim of this review is to summarise the transcriptional responses to RET or disuse measured via RNA-seq in young and older adults. We also highlight analytical considerations to maximise the utility of RNA-seq in the context of skeletal muscle research. The limited number of muscle transcriptional signatures obtained thus far with RNA-seq are generally consistent with those obtained with microarrays. However, RNA-seq may provide additional molecular insight, particularly when combined with data-driven approaches such as correlation network analyses. In this context, it is essential to consider the most appropriate study design parameters as well as bioinformatic and statistical approaches. This will facilitate the use of RNA-seq to better understand the transcriptional regulators of skeletal muscle plasticity in response to increased or decreased use. [ABSTRACT FROM AUTHOR]

Although soccer is one of the most widely played sports around the world, studies about young players and the success factors in soccer are still scarce. Therefore, the purpose of this study was to offer some insight into the factors contributing to success in this sport and to describe how physiological and technical performance evolves in young soccer players. Soccer technical skills during match play, maximum voluntary isometric contraction and power of lower limbs, jumping ability and endurance parameters were assessed in 30 prepubescent male soccer players with the same experience in soccer training. Subjects were divided into 2 groups of 15 children, a younger group (YG), aged 9.4 [[+ or -]or -] 0.3 years, and an older group (OG), aged 11.8 [[+ or -]or -] 0.2 years. Correlations between technical and physiological parameters were also described. Significant difference was set at p < 0.05. Differences between YG and OG appeared in physiological performance, mainly in Vo2peak expressed in absolute values, [[??]o.sub.2] at different speeds, perceived exertion in treadmill test, jump performance, strength, and peak power of lower limbs. Among the technical skills measured, significant differences were found only in heading. The differences found between groups showed that most physical capacities that were measured here have an important increase during the first stages of puberty, pointing out that a specific training at these ages is necessary to get an appropriate basis for future performance. Besides, over 30% of the technical performance measured in this study can be explained with the physiological parameters. The data shown in this paper help to determine the most important capacities in youth soccer, which can facilitate the development of more appropriate selection models and trainings. KEY WORDS football, children, puberty, strength, endurance

Skeletal muscle in individuals with CP also contains lower amounts of mtDNA, potentially indicating fewer mitochondria in CP skeletal muscle compared with typically developing muscle. We compared skeletal muscle samples from children with cerebral palsy (CP) and typically developing children and observed evidence of reduced mtDNA and OXPHOS protein content in CP skeletal muscle, indicating reduced mitochondrial abundance. Cerebral palsy (CP) muscle contains fewer energy-generating organelles than typically developing muscle. [Extracted from the article]

Mitochondrial-derived peptides (MDPs) humanin (HN) and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) are involved in cell survival, suppression of apoptosis, and metabolism. Circulating levels of MDPs are altered in chronic diseases such as diabetes type 2 and chronic kidney disease. Whether acute resistance (RE) or endurance (EE) exercise modulates circulating levels of HN and MOTS-c in humans is unknown. Following familiarization, subjects were randomized to EE (n = 10, 45 min cycling at 70% of estimated VO2max), RE (n = 10, 4 sets x 7RM, leg press and knee extension), or control (CON, n = 10). Skeletal muscle biopsies and blood samples were collected before and at 30 min and 3 h following exercise. Plasma concentration of HN and MOTS-c, skeletal muscle MOTS-c as well as gene expression of exercise-related genes were analyzed. Acute EE and RE promoted changes in skeletal muscle gene expression typically seen in response to each exercise modality (c-Myc, 45S prerRNA, PGC-1a-total, and PGC-1a-ex1b). At rest, circulating levels of HN were positively correlated to MOTS-c levels and age. Plasma levels of MDPs were not correlated to fitness outcomes [VO2max, leg strength, or muscle mitochondrial (mt) DNA copy number]. Circulating levels of HN were significantly elevated by acute EE but not RE. MOTS-C levels showed a trend to increase after EE. These results indicate that plasma MDP levels are not related to fitness status but that acute EE increases circulating levels of MDPs, in particular HN. [ABSTRACT FROM AUTHOR]

To evaluate the individual responses in skeletal muscle outcomes following bed rest, data from three studies (21-day PlanHab; 10-day FemHab and LunHab) were combined. Subjects (n = 35) participated in three cross-over campaigns within each study: normoxic (NBR) and hypoxic bed rest (HBR), and hypoxic ambulation (HAMB; used as control). Individual variability (SDIR) was investigated as √(SD Exp 2 –SD Con 2), where SDExp and SDCon are the standard deviations of the change score (i.e., post – pre) in the experimental (NBR and HBR) and the control (HAMB) groups, respectively. Repeatability and moderators of the individual variability were explored. Significant SDIR was detected for knee extension torque, and thigh and calf muscle area, which translated into an individual response ranging from 3 to −17% for knee extension torque, −2 to −12% for calf muscle area, and −1 to −8% for thigh muscle area. Strong correlations were found for changes in NBR vs. HBR (i.e., repeatability) in thigh and calf muscle area (r = 0.65–0.75, P < 0.0001). Change-scores in knee extension torque, and thigh and calf muscle area strongly correlated with baseline values (P < 0.001; r between −0.5 and −0.9). Orthogonal partial least squares regression analysis explored if changes in the investigated variables could predict calf muscle area alterations. This analysis indicated that 43% of the variance in calf muscle area could be attributed to changes in all of the other variables. This is the first study using a validated methodology to report clinically relevant individual variability after bed rest in knee extension torque, calf muscle area, and (to a lower extent) thigh muscle area. Baseline values emerged as a moderator of the individual response, and a global bed rest signature served as a moderately strong predictor of the individual variation in calf muscle area alterations. [ABSTRACT FROM AUTHOR]

Key points: Ribosome biogenesis and MYC transcription are associated with acute resistance exercise (RE) and are distinct from endurance exercise in human skeletal muscle throughout a 24 h time course of recovery.A PCR‐based method for relative ribosomal DNA (rDNA) copy number estimation was validated by whole genome sequencing and revealed that rDNA dosage is positively correlated with ribosome biogenesis in response to RE.Acute RE modifies rDNA methylation patterns in enhancer, intergenic spacer and non‐canonical MYC‐associated regions, but not the promoter.Myonuclear‐specific rDNA methylation patterns with acute mechanical overload in mice corroborate and expand on rDNA findings with RE in humans.A genetic predisposition for hypertrophic responsiveness may exist based on rDNA gene dosage. Ribosomes are the macromolecular engines of protein synthesis. Skeletal muscle ribosome biogenesis is stimulated by exercise, although the contribution of ribosomal DNA (rDNA) copy number and methylation to exercise‐induced rDNA transcription is unclear. To investigate the genetic and epigenetic regulation of ribosome biogenesis with exercise, a time course of skeletal muscle biopsies was obtained from 30 participants (18 men and 12 women; 31 ± 8 years, 25 ± 4 kg m–2) at rest and 30 min, 3 h, 8 h and 24 h after acute endurance (n = 10, 45 min cycling, 70% V̇O2max) or resistance exercise (n = 10, 4 × 7 × 2 exercises); 10 control participants underwent biopsies without exercise. rDNA transcription and dosage were assessed using quantitative PCR and whole genome sequencing. rDNA promoter methylation was investigated using massARRAY EpiTYPER and global rDNA CpG methylation was assessed using reduced‐representation bisulphite sequencing. Ribosome biogenesis and MYC transcription were associated primarily with resistance but not endurance exercise, indicating preferential up‐regulation during hypertrophic processes. With resistance exercise, ribosome biogenesis was associated with rDNA gene dosage, as well as epigenetic changes in enhancer and non‐canonical MYC‐associated areas in rDNA, but not the promoter. A mouse model of in vivo metabolic RNA labelling and genetic myonuclear fluorescence labelling validated the effects of an acute hypertrophic stimulus on ribosome biogenesis and Myc transcription, and also corroborated rDNA enhancer and Myc‐associated methylation alterations specifically in myonuclei. The present study provides the first information on skeletal muscle genetic and rDNA gene‐wide epigenetic regulation of ribosome biogenesis in response to exercise, revealing novel roles for rDNA dosage and CpG methylation. Key points: Ribosome biogenesis and MYC transcription are associated with acute resistance exercise (RE) and are distinct from endurance exercise in human skeletal muscle throughout a 24 h time course of recovery.A PCR‐based method for relative ribosomal DNA (rDNA) copy number estimation was validated by whole genome sequencing and revealed that rDNA dosage is positively correlated with ribosome biogenesis in response to RE.Acute RE modifies rDNA methylation patterns in enhancer, intergenic spacer and non‐canonical MYC‐associated regions, but not the promoter.Myonuclear‐specific rDNA methylation patterns with acute mechanical overload in mice corroborate and expand on rDNA findings with RE in humans.A genetic predisposition for hypertrophic responsiveness may exist based on rDNA gene dosage. [ABSTRACT FROM AUTHOR]

The current study explored whether the marked hypertrophic response noted with a short-term unilateral concurrent exercise paradigm was associated with more prominent changes in myonuclei accretion, ribosome biogenesis, and capillarization compared with resistance exercise alone (RE). Ten men (age 25 ± 4 yr) performed aerobic and resistance exercise (AE + RE) for one leg while the other leg did RE. Muscle biopsies were obtained before and after 5 wk of training and subjected to fiber-type specific immunohistochemical analysis, and quantification of total RNA content and mRNA/rRNA transcript abundance. Type II fiber cross-sectional area (CSA) increased with both AE + RE (22%) and RE (16%), while type I fiber CSA increased mainly with AE + RE (16%). The change score tended to differ between legs for type I CSA (P = 0.099), and the increase in smallest fiber diameter was greater in AE + RE than RE (P = 0.029). The number of nuclei per fiber increased after AE + RE in both fiber types, and this increase was greater (P = 0.027) than after RE. A strong correlation was observed between changes in number of nuclei per fiber and fiber CSA in both fiber types, for both AE + RE and RE (r > 0.8, P < 0.004). RNA content increased after AE + RE (24%, P = 0.019), but the change-scores did not differ across legs. The capillary variables generally increased in both fiber types, with no difference across legs. In conclusion, the accentuated hypertrophic response to AE + RE was associated with more pronounced myonuclear accretion, which was strongly correlated with the degree of fiber hypertrophy. This suggests that myonuclear accretion could play a role in facilitating muscle hypertrophy also during very short training periods. [ABSTRACT FROM AUTHOR]

This study explored the muscle genome‐wide response to long‐term unloading (84‐day bed rest) in 21 men. We hypothesized that a part of the bed rest‐induced gene expression signature would be resilient to a concurrent flywheel resistance exercise (RE) countermeasure. Using DNA microarray technology analyzing 35 345 gene‐level probe‐sets, we identified 335 annotated probe‐sets that were downregulated, and 315 that were upregulated after bed rest (P <.01). Besides a predictable differential expression of genes and pathways related to mitochondria (downregulation; false‐discovery rates (FDR) <1E‐04), ubiquitin system (upregulation; FDR = 3E‐02), and skeletal muscle energy metabolism and structure (downregulation; FDR ≤ 3E‐03), 84‐day bed rest also altered circadian rhythm regulation (upregulation; FDR = 3E‐02). While most of the bed rest‐induced changes were counteracted by RE, 209 transcripts were resilient to the exercise countermeasure. Genes upregulated after bed rest were particularly resistant to training (P <.001 vs downregulated, non‐reversed genes). Specifically, "Translation Factors," "Proteasome Degradation," "Cell Cycle," and "Nucleotide Metabolism" pathways were not normalized by RE. This study provides an unbiased high‐throughput transcriptomic signature of one of the longest unloading periods in humans to date. Classical disuse‐related changes in structural and metabolic genes/pathways were identified, together with a novel upregulation of circadian rhythm transcripts. In the context of previous bed rest campaigns, the latter seemed to be related to the duration of unloading, suggesting the transcriptomic machinery continues to adapt throughout extended disuse periods. Despite that the RE training offset most of the bed rest‐induced muscle‐phenotypic and transcriptomic alterations, we contend that the human skeletal muscle also displays a residual transcriptomic signature of unloading that is resistant to an established exercise countermeasure. [ABSTRACT FROM AUTHOR]

Because manual immunohistochemical analysis of features such as skeletal muscle fiber typing, capillaries, myonuclei, and fiber size-related parameters is time consuming and prone to user subjectivity, automatic computational methods could allow for faster and more objective evaluation. Here, we developed Muscle2View, a free CellProfiler-based pipeline that integrates all key fiber-morphological variables, including the novel quantification of the capillary-to-fiber interface, in one single tool. Provided that the images are of sufficient quality and the settings are configured for the specific study, the pipeline allows for automatic and unsupervised analysis of fiber borders, myonuclei, capillaries, and morphometric parameters in a fiber type-specific manner from large batches of images in <10 min/tissue sample. The novel identification of the capillary-to-fiber interface allowed for the calculation of microvascular factors such as capillary contacts (CC), individual capillary-to-fiber ratio (C/Fi), and capillary-to-fiber perimeter exchange (CFPE) index. When comparing the Muscle2View pipeline to manual or semiautomatic analysis, overall the results revealed strong correlations. For several variables, however, there were differences (5-15%) between values computed by manual counting and Muscle2View, suggesting that the methods should not necessarily be used interchangeably. Collectively, we demonstrate that the Muscle2View pipeline can provide unbiased and high-content analysis of muscle cross-sectional immunohistochemistry images. In addition to the classical morphological measurements, the Muscle2View can identify the complex capillary-to-fiber network and myonuclear density in a fiber type-specific manner. This robust analysis is done in one single run within a user-friendly and flexible environment based on the free and widely used image software CellProfiler. [ABSTRACT FROM AUTHOR]

This study aimed to analyse whether increasing the eccentric overload (EO) during resistance training, in terms of range of motion and/or velocity using an electric-motor device, would induce different muscle adaptations than conventional flywheel-EO resistance training. Forty physically active university students (21.7 ± 3.4 years) were randomly placed into one of the three training groups (EX1, EX2, FW) and a control group without training (n = 10 per group). Participants in the training groups completed 12 sessions (4 sets of 7 repetitions) of iso-inertial single-leg squat training over 6 weeks for the dominant leg. Resistance was generated either by an electric-motor device at two different velocities for the eccentric phase; 100% (EX1) or 150% (EX2) of concentric speed, or by a conventional flywheel device (FW). Thigh lean tissue mass, unilateral leg press one-repetition maximum (1-RM), unilateral muscle power at different percentages of the 1-RM and bilateral/unilateral vertical jump were assessed before and after the 6-week training. There were significant (p < 0.05–0.001) main effects of time in the 3 training groups, indicating increased thigh lean tissue mass (2.5–5.8%), 1-RM load (22.4–30.2%), vertical jump performance (9.1–32.9%) and muscle power (8.8–21.7%), without differences across experimental groups. Participants in the control group did not improve any of the variables measured. In addition, EX2 showed greater gains in eccentric average peak power during training than EX1 and FW (p < 0.001). Despite the different EO offered, 6 weeks of resistance training using flywheel or electric-motor devices induced similar significant gains in muscle mass, strength, muscle power and vertical jump. [ABSTRACT FROM AUTHOR]

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The current study examined the effects of a preceding bout of aerobic exercise (AE) on subsequent molecular signaling to resistance exercise (RE) of the elbow extensors. Eleven men performed unilateral elbow-extensor AE (~45 min at 70% peak workload) followed by unilateral RE (4 × 7 maximal repetitions) for both arms. Thus, one arm performed AE+RE interspersed with 15 min recovery, whereas the other arm conducted RE alone. Muscle biopsies were taken from the triceps brachii of each arm immediately before (PRE) and 15 min (POST1) and 3 h (POST2) after RE. Molecular markers involved in translation initiation, protein breakdown, mechanosignaling, and ribosome biogenesis were analyzed. Peak power during RE was reduced by 24% (±19%) when preceded by AE (P < 0.05). Increases in PGC1a and MuRF1 expression were greater from PRE to POST2 in AE+RE compared with RE (18-vs. 3.5- and 4- vs. 2-fold, respectively, interaction, P < 0.05). Myostatin mRNA decreased in both arms (P < 0.05). Phosphorylation of AMPK (Thr172) increased (2.5-fold), and 4E-BP1 (Thr37/46) decreased (2.0-fold), after AE (interactions, P < 0.05). p70 S6K, yesassociated protein, and c-Jun NH2-terminal kinase phosphorylation were unaltered, whereas focal adhesion kinase decreased ~1.5-fold, and β1- integrin increased ~1.3- to 1.5-fold, (time effect, P < 0.05). Abundance of 45S pre-ribosomal (r)RNA (internally transcribed spacer, ITS) decreased (~30%) after AE (interaction, P < 0.05), whereas CMYC mRNA was greater in AE+RE compared with RE (12-fold, P < 0.05). POLR1B abundance increased after both AE+RE and RE. All together, our results suggest that a single bout of AE leads to an immediate decrease in signaling for translation initiation and ribosome biogenesis. Yet, this did not translate into altered RE-induced signaling during the 3-h postexercise recovery period. [ABSTRACT FROM AUTHOR]

Our understanding of skeletal muscle structural and functional alterations during unloading has increased in recent decades, yet the molecular mechanisms underpinning these changes have only started to be unraveled. The purpose of the current investigation was to assess changes in skeletal muscle gene expression after 21 days of bed rest, with a particular focus on predicting upstream regulators of muscle disuse. Additionally, the association between differential microRNA expression and the transcriptome signature of bed rest were investigated. mRNAs from musculus vastus lateralis biopsies obtained from 12 men before and after the bed rest were analyzed using a microarray. There were 54 significantly upregulated probesets after bed rest, whereas 103 probesets were downregulated (false discovery rate 10%; fold-change cutoff ≥1.5). Among the upregulated genes, transcripts related to denervation-induced alterations in skeletal muscle were identified, e.g., acetylcholine receptor subunit delta and perinatal myosin. The most downregulated transcripts were functionally enriched for mitochondrial genes and genes involved in mitochondrial biogenesis, followed by a large number of contractile fiber components. Upstream regulator analysis identified a robust inhibition of the myocyte enhancer factor-2 (MEF2) family, in particular MEF2C, which was suggested to act upstream of several key downregulated genes, most notably peroxisome proliferator-activated receptor ɣ coactivator 1- (PGC-1α)/peroxisome proliferator-activated receptors (PPARs) and CRSP3. Only a few microRNAs were identified as playing a role in the overall transcriptome picture induced by sustained bed rest. Our results suggest that the MEF2 family is a key regulator underlying the transcriptional signature of bed rest and, hence, ultimately also skeletal muscle alterations induced by systemic unloading in humans. [ABSTRACT FROM AUTHOR]

Although immune dysfunction by space conditions has been reported postflight, as well as during ground-based experiments, the cause(s) and nature of the immunological changes are not completely understood. Microgravity has been suggested as one of the factors responsible for the observed immune dysregulation. The goal of this study was to assess immune changes in simulated microgravity (s-μG) using an in vitro cytokine release assay. The effect of s-μG provided by the desktop random positioning machine on cell-mediated immunity was examined by analyzing interleukin 2 (IL-2), interferon-γ (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10), in response to immune cell stimulation in whole blood samples ( n = 10). Stimuli used were bacterial recall antigens, pokeweed mitogen (PWM), lipopolysaccharide (LPS), or heat-killed Listeria monocytogenes (HKLM). S-μG caused an overall inhibition of the IL-2 and IFN-γ responses to recall antigen and mitogen stimulation. More specifically, s-μG most strongly influenced the levels of all four cytokines elicited by bacterial recall antigen stimulation. In contrast, HKLM-induced TNF-α secretion was elevated. The average concentrations of TNF-α in response to PWM and LPS and IL-10 release stimulated by PWM, LPS, and HKLM were not significantly altered by s-μG. However, a variable response between individual subjects could be observed. In conclusion, our results demonstrate that the in vitro cytokine release assay can detect gravity-related immune alterations. Furthermore, the use of multiple stimuli and the associated changes in cytokine secretion has the potential to reveal information on the underlying mechanisms affected by s-μG. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this meta-analysis was to examine the effect of flywheel (FW) resistance training with Eccentric Overload (FW-EOT) on muscle size and functional capacities (i.e. strength and power) in athletes and healthy subjects, and to compare FW-induced adaptations with those triggered by traditional resistance exercise interventions.Design: A systematic review and meta-analysis of randomised controlled trials.Methods: A search of electronic databases [PubMed, MEDLINE (SportDiscus), Web of Science, Scopus and PEDro] was conducted to identify all publications employing FW-EOT up to April 30, 2016. Outcomes were analyzed as continuous outcomes using a random effects model to calculate a standardized mean difference (SMD) and 95% CI. A total of 9 studies with 276 subjects and 92 effect sizes met the inclusion criteria and were included in the statistical analyses.Results: The overall pooled estimate from the main effects analysis was 0.63 (95% CI 0.49-0.76) with a significant (p<0.001) Z overall effect of 9.17. No significant heterogeneity (p value=0.78) was found. The meta-analysis showed significant differences between FW-EOT vs. conventional resistance training in concentric and eccentric strength, muscle power, muscle hypertrophy, vertical jump height and running speed, favoring FW-EOT.Conclusions: This meta-analysis provides evidence supporting the superiority of FW-EOT, compared with traditional weight-stack exercise, to promote skeletal muscle adaptations in terms of strength, power and size in healthy subjects and athletes. [ABSTRACT FROM AUTHOR]

Exercise load is a key component in determining end-point adaptations to resistance exercise. Yet, there is no information regarding the use of different inertia (i.e., loads) during isoinertial flywheel resistance exercise, a very popular high-intensity training model. Thus, this study examined power, work, force, and eccentric overload produced during flywheel resistance exercise with different inertial settings in men and women. Twenty-two women (n = 11) and men (n = 11) performed unilateral (in both legs) isolated concentric (CON) and coupled CON and eccentric (ECC) exercise in a flywheel knee extension device employing 6 inertias (0.0125, 0.025, 0.0375, 0.05, 0.075, 0.1 kg⋅m-2). Power decreased as higher inertias were used, with men showing greater (p ≤ 0.05) decrements than women (-36 vs. -29% from lowest to highest inertia). In contrast, work increased as higher inertias were employed, independent of sex (p ≤ 0.05; ~48% from lowest to highest inertia). Women increased CON and ECC mean force (46-55%, respectively) more (p ≤ 0.05) than men (34-50%, respectively) from the lowest to the highest inertia evaluated, although the opposite was found for peak force data (i.e., peak force increased more in men than in women as inertia was increased). Men, but not women, increased ECC overload from inertia 0.0125 to 0.0375 kg⋅m². Although estimated stretch-shorting cycle use during flywheel exercise was higher (p ≤ 0.05) in men (6.6%) than women (4.9%), values were greater for both sexes when using low-to-medium inertias. The information gained in this study could help athletes and sport and health professionals to better understand the impact of different inertial settings on skeletal muscle responses to flywheel resistance exercise. [ABSTRACT FROM AUTHOR]

In the quest for a viable non-gravity dependent method to "lift weights" in space, our laboratory introduced iso-inertial resistance (YoYo™) exercise using spinning flywheel(s), more than 25 years ago. After being thoroughly tested in individuals subjected to various established spaceflight analogs, a multi-mode YoYo™ exercise apparatus was eventually installed on the International Space Station in 2009. The method, applicable to any muscle group, provides accommodated resistance and optimal muscle loading through the full range of motion of concentric actions, and brief episodes of eccentric overload. This exercise intervention has found terrestrial applications and shown success in enhancing sports performance and preventing injury and aiding neurological or orthopedic rehabilitation. Research has proven that this technique offers unique physiological responses not possible with other exercise hardware solutions. This paper provides a brief overview of research that has made use, and explored the efficacy, of this method in healthy sedentary or physically active individuals and populations suffering from muscle wasting, disease or injury. While the collective evidence to date suggests YoYo™ offers a potent stimulus to optimize the benefits of resistance exercise, systematic research to support clinical use of this method has only begun to emerge. Thus, we also offer perspectives on unresolved issues, unexplored applications for clinical conditions, and how this particular exercise paradigm could be implemented in future clinical research and eventually being prescribed. Fields of particular interest are those aimed at promoting muscle health by preventing injury or combating muscle wasting and neurological or metabolic dysfunction due to aging or illness, or those serving in rehabilitation following trauma and/or surgery. [ABSTRACT FROM AUTHOR]

Despite the generalized use of photon-based radiation (i.e., gamma rays and X-rays) to treat different cancer types, particle radiotherapy (i.e., protons and carbon ions) is becoming a popular, and more effective tool to treat specific tumors due to the improved physical properties and biological effectiveness. Current scientific evidence indicates that conventional radiation therapy affects the tumor immunological profile in a particular manner, which in turn, might induce beneficial effects both at local and systemic (i.e., abscopal effects) levels. The interaction between radiotherapy and the immune system is being explored to combine immune and radiation (including particles) treatments, which in many cases have a greater clinical effect than any of the therapies alone. Contrary to localized, clinical irradiation, astronauts are exposed to whole body, chronic cosmic radiation, where protons and heavy ions are an important component. The effects of this extreme environment during long periods of time, e.g., a potential mission to Mars, will have an impact on the immune system that could jeopardize the health of the astronauts, hence the success of the mission. To this background, the purpose of this mini review is to briefly present the current knowledge in local and systemic immune alterations triggered by particle irradiation and to propose new lines of future research. Immune effects induced by particle radiation relevant to clinical applications will be covered, together with examples of combined radiotherapy and immunotherapy. Then, the focus will move to outer space, where the immune system alterations induced by cosmic radiation during spaceflight will be discussed. [ABSTRACT FROM AUTHOR]

As metabolic changes in human skeletal muscle after long-term (simulated) spaceflight are not well understood, this study examined the effects of long-term microgravity, with and without concurrent resistance exercise, on skeletal muscle oxidative and glycolytic capacity. Twenty-one men were subjected to 84 days head-down tilt bed rest with (BRE; n = 9) or without (BR; n = 12) concurrent flywheel resistance exercise. Activity and gene expression of glycogen synthase, glycogen phosphorylase (GPh), hexokinase, phosphofructokinase- 1 (PFK-1), and citrate synthase (CS), as well as gene expression of succinate dehydrogenase (SDH), vascular endothelial growth factor (VEFG), peroxisome proliferator-activated receptor gamma coactivator- 1 (PGC-1α), and myostatin, were analyzed in samples from m. vastus lateralis collected before and after bed rest. Activity and gene expression of enzymes controlling oxidative metabolism (CS, SDH) decreased in BR but were partially maintained in BRE. Activity of enzymes regulating anaerobic glycolysis (GPh, PFK-1) was unchanged in BR. Resistance exercise increased the activity of GPh. PGC-1α and VEGF expression decreased in both BR and BRE. Myostatin increased in BR but decreased in BRE after bed rest. The analyses of these unique samples indicate that long-term microgravity induces marked alterations in the oxidative, but not the glycolytic, energy system. The proposed flywheel resistance exercise was effective in counteracting some of the metabolic alterations triggered by 84-day bed rest. Given the disparity between gene expression vs. enzyme activity in several key metabolic markers, posttranscriptional mechanisms should be explored to fully evaluate metabolic adaptations to long-term microgravity with/without exercise countermeasures in human skeletal muscle. [ABSTRACT FROM AUTHOR]

The present study examined site-specific hamstring muscles use with functional magnetic resonance imaging (MRI) in elite soccer players during strength training. Thirty-six players were randomized into four groups, each performing either Nordic hamstring, flywheel leg-curl, Russian belt or the hip-extension conic-pulley exercise. The transverse relaxation time (T2) shift from pre- to post-MRI were calculated for the biceps femoris long (BFl) and short (BFs) heads, semitendinosus (ST) and semimembranosus (SM) muscles at proximal, middle and distal areas of the muscle length. T2 values increased substantially after flywheel leg-curl in all regions of the BFl (from 9±8 to 16±8%), BFs (41±6–71±11%), and ST (60±1–69±7%). Nordic hamstring induced a substantial T2 increase in all regions of the BFs (13±8–16±5%) and ST (15±7–17±5%). T2 values after the Russian belt deadlift substantially increased in all regions of the BFl (6±4–7±5%), ST (8±3–11±2%), SM (6±4–10±4%), and proximal and distal regions of BFs (6±6–8±5%). T2 values substantially increased after hip-extension conic-pulley only in proximal and middle regions of BFl (11±5–7±5%) and ST (7±3–12±4%). The relevance of such MRI-based inter- and intra-muscle use in designing more effective resistance training for improving hamstring function and preventing hamstring injuries in elite soccer players should be explored with more mechanistic studies. [ABSTRACT FROM AUTHOR]

Recent reports suggest that aerobic exercise may boost the hypertrophic response to short-term resistance training. This study explored the effects of an acute aerobic exercise bout on the transcriptional response to subsequent resistance exercise. Ten moderately trained men performed ~45 min cycling on one leg followed by 4 x 7 maximal knee extensions for each leg, 15 min later. Thus, one limb performed aerobic and resistance exercise (AE + RE) while the opposing leg did resistance exercise only (RE). Biopsies were obtained from the vastus lateralis muscle of each leg 3 h after the resistance exercise bout. Using DNA microarray, we analyzed differences [≥1.5-fold, false discovery rate (FDR) ≤10%] in gene expression profiles for the two modes of exercise. There were 176 genes up (127)- or downregulated (49) by AE + RE compared with RE. Among the most significant differentially expressed genes were established markers for muscle growth and oxidative capacity, novel cytokines, transcription factors, and micro-RNAs (miRNAs). The most enriched functional categories were those linked to carbohydrate metabolism and transcriptional regulation. Upstream analysis revealed that vascular endothelial growth factor, cAMP-response element-binding protein, Tet methylcytosine dioxygenase, and mammalian target of rapamycin were regulators highly activated by AE + RE, whereas JnK, NF-κβ, MAPK, and several miRNAs were inhibited. Thus, aerobic exercise alters the skeletal muscle transcriptional signature of resistance exercise to initiate important gene programs promoting both myofiber growth and improved oxidative capacity. These results provide novel insight into human muscle adaptations to diverse exercise modes and offer the very first genomic basis explaining how aerobic exercise may augment, rather than compromise, muscle growth induced by resistance exercise. [ABSTRACT FROM AUTHOR]

The unilateral lower limb suspension (ULLS) method was developed, introduced, and validated in the quest for a simple, effective, and highly reliable human analog to study the consequences of spaceflight on muscle size and function. Because withdrawal of weight bearing for no more than 2-3 days is sufficient to inflict disturbances in protein metabolism of postural muscles, it is imperative ULLS serves as a very powerful method to manifest skeletal muscle adaptations similar to those experienced in 0 g. Thus the rate of global muscle loss appears rather constant over the first 2 mo, amounting to about 2-3% per week. At the microscopic level, these changes are accompanied by a corresponding decrease in individual muscle fiber size. ULLS alters metabolism favoring more carbohydrate over fat substrate utilization. Altogether, these changes result in impaired work and endurance capacity of muscles being subjected to ULLS. Maximal voluntary force decreases out of proportion to the muscle loss, suggesting motor control is modified. Past reviews offer near exhaustive information on ULLS-induced responses with regard to the above changes. Hence, the current brief review describes more broadly the evolution of the ULLS model, from issues of subject recruitment and compliance control, to recent advances unraveling molecular mechanisms facilitating unloading-induced muscle wasting. Such knowledge is critical in designing future studies aimed at exploring and developing exercise countermeasures or other means to combat the debilitating effects on muscle experienced by astronauts during longhaul missions in Orbit. [ABSTRACT FROM AUTHOR]

Background: Resistance exercise (RE) improves neuromuscular function and physical performance after stroke. Yet, the effects of RE emphasizing eccentric (ECC; lengthening) actions on muscle hypertrophy and cognitive function in stroke patients are currently unknown. Thus, this study explored the effects of ECC-overload RE training on skeletal muscle size and function, and cognitive performance in individuals with stroke. Methods: Thirty-two individuals with chronic stroke (≥6 months post-stroke) were randomly assigned into a training group (TG; n = 16) performing ECC-overload flywheel RE of the more-affected lower limb (12 weeks, 2 times/week; 4 sets of 7 maximal closed-chain knee extensions; <2 min of contractile activity per session) or a control group (CG; n = 16), maintaining daily routines. Before and after the intervention, quadriceps femoris volume, maximal force and power for each leg were assessed, and functional and dual task performance, and cognitive functions were measured. Results: Quadriceps femoris volume of the more-affected leg increased by 9.4 % in TG. Muscle power of the more-affected, trained (48.2 %), and the less-affected, untrained limb (28.1 %) increased after training. TG showed enhanced balance (8.9 %), gait performance (10.6 %), dual-task performance, executive functions (working memory, verbal fluency tasks), attention, and speed of information processing. CG showed no changes. Conclusion: ECC-overload flywheel resistance exercise comprising 4 min of contractile activity per week offers a powerful aid to regain muscle mass and function, and functional performance in individuals with stroke. While the current intervention improved cognitive functions, the cause-effect relationship, if any, with the concomitant neuromuscular adaptations remains to be explored. Trial Registration: Clinical Trials NCT02120846. [ABSTRACT FROM AUTHOR]

This study examined the effects of a high-speed power training program in peak muscle power and maximal voluntary isometric contraction (MVIC) of knee extensors in patients with relapsing-remitting multiple sclerosis (MS). Forty patients, 20 women (age 42.8 +/- 10.3 yr) and 20 men (age 44.0 +/- 8.7 yr) diagnosed with relapsing-remitting MS were randomly assigned, with respect to sex, to either an exercise group or a control group. Participants from the exercise group performed 12 wk of supervised muscle power training of knee extensors. All subjects were tested for MVIC and peak muscle power at baseline and after the training intervention. A strain gauge was used to measure the MVIC, and peak muscle power was assessed with a linear encoder at five relative loads. The training-related effects were assessed using a t-test. The results showed no significant changes in the control group from baseline to postintervention evaluation. In contrast, the exercise group significantly increased MVIC (10.8%; p < 0.05) and muscle power at 40, 50, 60, 70, and 80% of the MVIC by 21.8, 14.5, 17.3, 19.4, and 22.3%, respectively (p < 0.01), after the training. These findings suggest that 12 wk of high-speed power training improve both MVIC and muscle power at five different loads in patients with relapsing-remitting MS. [ABSTRACT FROM AUTHOR]