Yes / 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.

Bakgrund: Generaliserat ångestsyndrom (GAD) är en vanlig diagnos med negativa konsekvenser såväl på individ- som samhällsnivå. För att som fysioterapeuter kunna fånga upp den här typen av patienter och då ha god kunskap om olika träningsformer som tillförlitlig behandling ansågs det fördelaktigt att undersöka det vetenskapliga underlaget för styrketräning som behandlingsmetod. Syfte: Syftet med denna litteraturstudie var att undersöka det vetenskapliga underlaget för effekten av styrketräning, i jämförelse med annan eller ingen intervention, som behandlingsmetod för att minska oros- och ångestsymtom hos vuxna mellan 18-64 år med GAD. Metod: En litteraturstudie av randomiserade kontrollerade studier där populationen var vuxna mellan 18-64 år med GAD. Sökningar genomfördes i databaserna PubMed, Cochrane, PEDro och Psycinfo. Fyra studier inkluderades och granskades sedan med PEDro. Den sammanvägda tillförlitligheten av resultatet av tre studier bedömdes med hjälp av GRADEstud. Resultat: Det vetenskapliga underlaget för styrketräning som behandling för personer med GAD är för begränsat för att kunna dra några starka slutsatser. Alla inkluderade studier visade dock på reducering av oros- och ångestsymtom, som båda är kännetecknande symtom för GAD. Konklusion: Det sammanvägda resultatet indikerar på att styrketräning skulle kunna vara en alternativ behandlingsmetod för denna patientgrupp. Mer forskning behövs dock för att kunna utvärdera effekten av styrketräning som behandling för personer med GAD. / Background: Generalized anxiety disorder (GAD) is a common diagnosis with negative consequences both on an individual and societal level. In order for physiotherapists to be able to catch these patients and then have good knowledge of different forms of exercise as reliable treatment, it was considered beneficial to investigate the scientific basis for resistance exercise training as a treatment method. Objective: The aim of this literature review was to investigate the scientific basis for the effect of resistance exercise training, in comparison with other or no intervention, as a treatment method to reduce worry and anxiety symptoms in adults aged 18-64 with GAD. Method: A literature review of randomized controlled trials where the population was adults between 18-64 years old with GAD. Searches were conducted in the databases PubMed, Cochrane, PEDro and Psycinfo. Four studies were included and reviewed with PEDro. The combined reliability of the results of three studies was assessed using GRADEstud. Results: The scientific basis for resistance exercise training as a treatment for people with GAD is too limited to be able to draw any strong conclusions. However, all included studies showed a reduction in worry and anxiety symptoms, both of which are characteristic symptoms of GAD. Conclusion: The combined results indicate that strength training could be an alternative treatment method for this patient group. However, more research is needed to be able to evaluate the effect of strength training as a treatment for people with GAD.

A ausência de terapias eficazes para a caquexia permanece como um problema central para o tratamento do câncer no mundo. Em contrapartida, o treinamento de força (i.e. também conhecido como treinamento resistido) tem sido amplamente utilizado como uma estratégia não farmacológica anticatabólica, prevenindo a perda da massa e da função da musculatura esquelética. Entretanto, o papel terapêutico do treinamento de força na caquexia do câncer permanece apenas especulativo. Portanto, nesse estudo avaliamos se o treinamento de força poderia atenuar a perda da massa e da função da musculatura esquelética em um severo modelo de caquexia do câncer em ratos. Para isso, ratos machos da linhagem Wistar foram randomizados em quatro grupos experimentais: 1) ratos sedentários injetados com solução salina na medula óssea (Controle); 2) ratos injetados com solução salina na medula óssea e submetidos ao treinamento de força (Controle + T); 3) ratos sedentários injetados com células do tumor Walker 256 na medula óssea (Tumor); e 4) ratos injetados com células do tumor Walker 256 na medula óssea e submetidos ao treinamento de força (Tumor + T). Foram avaliados a massa e a área de secção transversa da musculatura esquelética, marcadores de disfunção metabólica e do turnover proteico, a função da musculatura esquelética in vivo e ex vivo, o consumo alimentar, o crescimento tumoral e a sobrevida dos grupos experimentais com tumor. O grupo Tumor apresentou atrofia muscular após quinze dias da injeção das células tumorais como pode ser observado pela redução na massa dos músculos Plantaris (- 20,5%) e EDL (-20%). A atrofia no músculo EDL foi confirmada por análises histológicas, demonstrando uma redução de 43,8% na área de secção transversa. Embora o treinamento de força tenha aumentado o conteúdo proteico da lactato desidrogenase e revertido totalmente o conteúdo da forma fosforilada de 4EBP-1 (i.e. repressor da transcrição de mRNA), ele não atuou na morfologia da musculatura esquelética nos animais com tumor. Além disso, o treinamento de força não atenuou a perda de função da musculatura esquelética, a anorexia, o crescimento tumoral ou a taxa de mortalidade. Contudo, a força muscular, avaliada pelo teste de 1RM, apresentou uma correlação negativa com a sobrevida dos animais (p = 0,02), sugerindo que a perda de força prediz a mortalidade nesse modelo experimental de caquexia do câncer. Em suma, a injeção de células do tumor Walker 256 na medula óssea induz caquexia do câncer em ratos. O treinamento de força não foi eficaz em atenuar a perda de massa e função da musculatura esquelética nesse modelo. Entretanto, a força muscular prediz a sobrevida dos animais, sugerindo que novos estudos são necessários para elucidar o possível efeito terapêutico do treinamento de força para atenuar a caquexia do câncer e a progressão tumoral / The lack of therapies for cachexia is a key problem in cancer treatment. In contrast, resistance exercise training (RET) has been adopted as nonpharmacological anti-catabolic strategy, preventing muscle wasting and muscle dysfunction. However, the role of RET to counteract cancer cachexia is still speculative. Presently, we test whether RET would counteract skeletal muscle wasting in a severe cancer cachexia rat model. Methods: Male Wistar rats were randomly assigned into four experimental groups; 1) untrained control rats injected with saline solution in the bone marrow (control), 2) rats injected with saline solution in the bone marrow and submitted to RET (control + RET), 3) untrained rats injected with Walker 256 tumor cells in the bone marrow (tumor) and 4) rats injected with Walker 256 tumor cells in the bone marrow and submitted to RET (tumor + RET). Skeletal muscle mass and fiber cross sectional area, markers of metabolic and protein turnover impairment, in vivo and ex vivo skeletal muscle function, food intake, tumor growth and mortality rate were assessed. Results: Tumor group displayed skeletal muscle atrophy fifteen days post tumor cells injection as assessed by Plantaris (-20.5%) and EDL (-20.0%) muscle mass. EDL atrophy was confirmed by histological analysis, showing 43.8% decline in the fiber cross sectional area. Even though RET increased the lactate dehydrogenase protein content and fully restored phosphorylated form of 4EBP-1 (i.e. a repressor of mRNA translation) to the control levels in skeletal muscle, it failed to rescue muscle morphology in tumorbearing rats. Indeed, RET has not mitigated loss of muscle function, anorexia, tumor growth or mortality rate. However, loss of strength capacity (assessed by 1-RM test performance) demonstrated a negative correlation with rats´ survival (p = 0.02), suggesting that loss of strength capacity predicts cancer mortality. Conclusions: Bone marrow injection of Walker 256 tumor cells in rats induces cancer cachexia. RET is ineffective to mitigate cancer-induced skeletal muscle wasting in this rat model. However, strength capacity predicts cancer survival, suggesting that new studies are needed to elucidate the putative therapeutic role of different exercise training regimens in counteracting cancer cachexia and tumor progression

Highly-active antiretroviral therapy (HAART) has improved the prognosis of HIV-infected individuals. Unfortunately it has also been associated with impaired functional capacity and development of metabolic perturbations which increases health risk. This study tested the hypothesis that a combined cardiorespiratory and resistance exercise training (CARET) intervention may result in significant health benefits in HIV-infected individuals receiving HAART. Thirty-seven HIV-infected men and women, predominantly of lower socioeconomic status (SES), were recruited and randomly assigned to: 1) a group of moderate-intensity CARET for three months or 2) a control group receiving no exercise intervention for three months. At baseline and following the intervention, physical characteristics (body weight, body mass index, waist circumference, and blood pressure), physical fitness variables (estimated VO2max and one repetition maximum for upper and lower body), metabolic variables (fasting glucose and serum lipids), immune functioning (CD4+ T Cell count, CD4/CD8 ratio, and HIV RNA viral load), and quality of life (SF-36 Health Survey) were measured. Exercise participants evidenced increases in estimated VO2max (21%, p < 0.01), upper body strength (15%, p < 0.05), and lower body strength (22%, p < 0.05), while showing reductions in waist circumference (-2%, p < 0.05), and fasting glucose (-16%, p < 0.05). While the control group showed a significant decrease in CD4+ T cell count (-16%, p < 0.05) from baseline, the exercise group maintained a more stable count following training (-3%, p = 0.39). Finally, the exercise participants showed self-reported improvements in physical (11%, p < 0.03) and mental (10%, p < 0.02) quality of life. In conclusion, our study demonstrated that a three-month supervised and moderate intensity CARET program performed three times a week, can result in significant improvements in physical characteristics, physical fitness, metabolic variables, and physical and mental quality of life. Furthermore, the same intervention resulted in more favorable immunological responses following training in HIV-infected individuals of lower SES. Key words: Highly active antiretroviral therapy, HIV, combined aerobic and resistance exercise training, cardiorespiratory fitness, muscular strength, and immune functioning.

A ausência de terapias eficazes para a caquexia permanece como um problema central para o tratamento do câncer no mundo. Em contrapartida, o treinamento de força (i.e. também conhecido como treinamento resistido) tem sido amplamente utilizado como uma estratégia não farmacológica anticatabólica, prevenindo a perda da massa e da função da musculatura esquelética. Entretanto, o papel terapêutico do treinamento de força na caquexia do câncer permanece apenas especulativo. Portanto, nesse estudo avaliamos se o treinamento de força poderia atenuar a perda da massa e da função da musculatura esquelética em um severo modelo de caquexia do câncer em ratos. Para isso, ratos machos da linhagem Wistar foram randomizados em quatro grupos experimentais: 1) ratos sedentários injetados com solução salina na medula óssea (Controle); 2) ratos injetados com solução salina na medula óssea e submetidos ao treinamento de força (Controle + T); 3) ratos sedentários injetados com células do tumor Walker 256 na medula óssea (Tumor); e 4) ratos injetados com células do tumor Walker 256 na medula óssea e submetidos ao treinamento de força (Tumor + T). Foram avaliados a massa e a área de secção transversa da musculatura esquelética, marcadores de disfunção metabólica e do turnover proteico, a função da musculatura esquelética in vivo e ex vivo, o consumo alimentar, o crescimento tumoral e a sobrevida dos grupos experimentais com tumor. O grupo Tumor apresentou atrofia muscular após quinze dias da injeção das células tumorais como pode ser observado pela redução na massa dos músculos Plantaris (- 20,5%) e EDL (-20%). A atrofia no músculo EDL foi confirmada por análises histológicas, demonstrando uma redução de 43,8% na área de secção transversa. Embora o treinamento de força tenha aumentado o conteúdo proteico da lactato desidrogenase e revertido totalmente o conteúdo da forma fosforilada de 4EBP-1 (i.e. repressor da transcrição de mRNA), ele não atuou na morfologia da musculatura esquelética nos animais com tumor. Além disso, o treinamento de força não atenuou a perda de função da musculatura esquelética, a anorexia, o crescimento tumoral ou a taxa de mortalidade. Contudo, a força muscular, avaliada pelo teste de 1RM, apresentou uma correlação negativa com a sobrevida dos animais (p = 0,02), sugerindo que a perda de força prediz a mortalidade nesse modelo experimental de caquexia do câncer. Em suma, a injeção de células do tumor Walker 256 na medula óssea induz caquexia do câncer em ratos. O treinamento de força não foi eficaz em atenuar a perda de massa e função da musculatura esquelética nesse modelo. Entretanto, a força muscular prediz a sobrevida dos animais, sugerindo que novos estudos são necessários para elucidar o possível efeito terapêutico do treinamento de força para atenuar a caquexia do câncer e a progressão tumoral / The lack of therapies for cachexia is a key problem in cancer treatment. In contrast, resistance exercise training (RET) has been adopted as nonpharmacological anti-catabolic strategy, preventing muscle wasting and muscle dysfunction. However, the role of RET to counteract cancer cachexia is still speculative. Presently, we test whether RET would counteract skeletal muscle wasting in a severe cancer cachexia rat model. Methods: Male Wistar rats were randomly assigned into four experimental groups; 1) untrained control rats injected with saline solution in the bone marrow (control), 2) rats injected with saline solution in the bone marrow and submitted to RET (control + RET), 3) untrained rats injected with Walker 256 tumor cells in the bone marrow (tumor) and 4) rats injected with Walker 256 tumor cells in the bone marrow and submitted to RET (tumor + RET). Skeletal muscle mass and fiber cross sectional area, markers of metabolic and protein turnover impairment, in vivo and ex vivo skeletal muscle function, food intake, tumor growth and mortality rate were assessed. Results: Tumor group displayed skeletal muscle atrophy fifteen days post tumor cells injection as assessed by Plantaris (-20.5%) and EDL (-20.0%) muscle mass. EDL atrophy was confirmed by histological analysis, showing 43.8% decline in the fiber cross sectional area. Even though RET increased the lactate dehydrogenase protein content and fully restored phosphorylated form of 4EBP-1 (i.e. a repressor of mRNA translation) to the control levels in skeletal muscle, it failed to rescue muscle morphology in tumorbearing rats. Indeed, RET has not mitigated loss of muscle function, anorexia, tumor growth or mortality rate. However, loss of strength capacity (assessed by 1-RM test performance) demonstrated a negative correlation with rats´ survival (p = 0.02), suggesting that loss of strength capacity predicts cancer mortality. Conclusions: Bone marrow injection of Walker 256 tumor cells in rats induces cancer cachexia. RET is ineffective to mitigate cancer-induced skeletal muscle wasting in this rat model. However, strength capacity predicts cancer survival, suggesting that new studies are needed to elucidate the putative therapeutic role of different exercise training regimens in counteracting cancer cachexia and tumor progression

Ribosomes are the essential machinery for cellular protein synthesis. Ribosome content is hypothesized to support muscle growth and is suggested that those with more ribosomes may better respond to resistance training. Aerobic training also elicits distinct physiological adaptations; however, no direct measures of ribosome content following aerobic training have been measured. Ribosomes interact with mitochondria for mitochondrial protein synthesis and import. Mitochondria may also provide cellular energy to ribosomes. We hypothesized that aerobic and resistance training would increase ribosome content and that ribosome content following aerobic training would correspond to changes in mitochondrial-related protein content and gene expression. Fourteen young men and women performed 6 weeks of single-legged aerobic followed by 10 weeks of bilateral resistance training. Muscle biopsies were taken following aerobic (Pre RT) and resistance training (Post RT) in the aerobically trained (EX) and control (CTL) legs. Pre RT, EX had greater COXIV staining intensity in Type 1 (1.17-fold; p=0.020) and Type 2 (1.22-fold; p=0.015) fibres compared to CTL; however, no differences in whole-muscle mitochondrial-related protein content or gene expression were observed (p>0.05). No differences in regulatory (UBF, Cyclin D1, TIF-1A, POLR-1B), cytosolic (45S, 5.8S, 18S, 28S rRNAs) or mitochondrial (12S rRNA) ribosome-related gene expression were observed (p>0.05), except for c-Myc (CTL>EX; p=0.034) and 5S rRNA (Pre RT CTL<Pre RT EX; p=0.076). When stratified for leg-lean soft tissue mass (LLSTM), legs with greater LLSTM had lower expression in 3/13 ribosome-related genes (p<0.10). When stratified for ΔLLSTM following resistance training, legs with the greatest ΔLLSTM had lower expression in 11/13 ribosome-related genes prior to (p<0.10) and less change or decrease in expression in 9/13 genes following resistance training (p<0.05). These results indicate that baseline ribosome content was sufficient to support aerobic adaptations (capillarization, VO2 peak) that were previously observed and that ribosome’s efficiency, rather than content, is likely more important to support increases in muscle hypertrophy following resistance training. / Thesis / Master of Science in Kinesiology / Ribosomes are essential in making proteins within the cell, and their content has been hypothesized to support the adaptive responses observed with exercise training. Ribosome content has previously been shown to increase following resistance training likely to support skeletal muscle growth. However as aerobic training also influences cellular adaptations, it is plausible that ribosome content also supports these training adaptations. We hypothesized that both aerobic and resistance training would increase ribosome content. Contrary to our hypotheses, no changes in ribosome content were observed following aerobic or resistance training despite previously observing adaptations characteristic of each respective training stimulus. However, those with the greatest increases in muscle mass had lower baseline ribosome content and less change in content following resistance training. These results suggest that baseline ribosome content is sufficient for aerobic adaptations and that ribosome’s efficiency is likely more important than content to elicit resistance training adaptations.