Exercise and tumor proteome: Insights from a neuroblastoma model.

BACKGROUND/AIM: The impact of exercise on pediatric tumor biology is essentially unknown. We investigated the effects of regular exercise on tumor proteome profile (as assessed with liquid chromatography with tandem mass spectrometry) in a mouse model of one of the most aggressive childhood malignancies, high-risk neuroblastoma (HR-NB). METHODS: Tumor samples of 14 male mice (aged 6-8 weeks) that were randomly allocated into an exercise (5-week combined aerobic and resistance training) or nonexercise control group (6 and 8 mice per group, respectively) were analyzed. The Search Tool for the Retrieval of Interacting Genes/Proteins database was used to generate a protein-protein interaction (PPI) network and enrichment analyses. The Systems Biology Triangle (SBT) algorithm was applied for analyses at the functional category level. RESULTS: Tumors of exercised mice showed a higher and lower abundance of 101 and 150 proteins, respectively, compared to controls [false discovery rate (FDR)<0.05], which were enriched in metabolic pathways, aminoacid metabolism, regulation of hormone levels, and peroxisome proliferator-activated receptor signaling pathway (FDR<0.05). The SBT algorithm indicated that 184 and 126 categories showed a lower and higher abundance, respectively, in the tumors of exercised mice (FDR<0.01). Categories with lower abundance were involved in energy production while those with higher abundance were related to transcription/translation, apoptosis, and tumor suppression. CONCLUSION: Regular exercise altered the abundance of hundreds of intratumoral proteins and molecular pathways, particularly those involved in energy metabolism, apoptosis, and tumor suppression. These findings provide preliminary evidence of the molecular mechanisms underlying potential effects of exercise in HR-NB.

Physical exercise: a polypill against chronic kidney disease.

We are currently facing a pandemic of physical inactivity that might contribute to the growing prevalence of chronic kidney disease (CKD). Here, we summarize currently available evidence on the association between physical activity and CKD, and also review the effects of exercise intervention in affected patients. Physical activity/exercise might act as a polypill against CKD, preventing its development or even exerting beneficial effects once it is established (i.e. improvements in patients' physical fitness and cardiovascular risk, as well as in kidney function). Exercise benefits are also found at advanced CKD stages or in patients under hemodialysis. The biological mechanisms behind the clinical evidence are also discussed. An active lifestyle appears as a cornerstone in CKD prevention and management.

Physical activity, chronic kidney disease, and cardiovascular risk: A study in half a million adults.

OBJECTIVE: There is a growing prevalence of chronic kidney disease (CKD), a condition associated with a higher cardiovascular disease (CVD) risk. We assessed the association between self-reported physical activity (PA) and CKD and also studied whether PA attenuates CKD-associated CVD risk. METHODS: A cohort of Spanish adults (18-64 years) participated in this nationwide study. Participants were categorized at baseline as being either inactive (performing no PA), regularly, or insufficiently active (meeting or not, respectively, international PA recommendations) and were followed for up to 5 years. The presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 ) and major CVD risk factors (diabetes, hypercholesterolemia, hypertension, obesity) was determined at baseline and at follow-up. RESULTS: 517 917 participants (44 ± 9 years, 67% male, CKD prevalence = 7%) were studied at baseline, with prospective analyses (median follow-up = 2 years, range = 2-5) in a subcohort of 264 581 individuals. Compared to physical inactivity, cross-sectional analyses at baseline showed that regular PA (odds ratio = 0.80; 95% confidence interval = 0.79-0.81), but not insufficient PA (1.02; 0.99-1.04) was associated with lower CKD prevalence. However, prospective analyses failed to confirm this association (p > 0.1). In turn, CKD was associated with a higher prevalence of hypertension (+3%) and diabetes (+5%) at baseline and with a greater incidence of hypertension at follow-up (+37%). Among those participants with CKD, regular PA was associated with a lower prevalence (-45% to -7%) and incidence (-38% to -4%) of all CVD risk factors. CONCLUSION: Although PA might not reduce incident CKD in the middle term (~2 years), it can attenuate the CVD risk linked to this condition.

Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study.

INTRODUCTION: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. METHODS: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. RESULTS: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2 , performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. CONCLUSIONS: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.

Effectiveness and chemical insights: Exploring interactions between nanomicelles and monoterpenoids for head lice treatment.

This study evaluates the pediculicidal activity of nanoformulations containing different binary essential oil component mixtures (eugenol:linalool, 1,8 -cineole:linalool, and eugenol:thymol) using immersion bioassays. These have allowed us to evaluate the knockdown time affecting 50% of the individuals (KT50). In addition, the type of interaction between the components in each mixture was established in terms of the combination index (IC). The KT50 values were 6.07; 8.83; 7.17 and 27.23 h for linalool, 1,8 -cineole, eugenol, and thymol, respectively. For the eugenol:linalool mixtures, the efficacy was lower or equal to that obtained for the nanoformulations of the pure compounds, with values of KT50 about 13.33, 8.16 and 6.71 h for mixtures with ratios 3:1, 1:1 and 1:3, respectively. These mixtures present IC > 1, evidencing antagonistic interaction, which is enhanced with eugenol content. In the case of the binary mixtures of 1,8 -cineole: linalool, KT50 values were similar to those obtained for eugenol:linalool mixtures with similar ratios. In this case, IC assumes values close to unity, suggesting additive interactions independently of the mixture composition. On the other side, mixtures of eugenol:thymol with 1:1 and 1:3 ratios showed values of 9.40 and 32.93 h, while the mixture with a 3:1 ratio showed the greatest effectiveness (KT50 of 4.42 h). Eugenol:thymol mixtures show synergistic interaction (IC < 1) for combinations 3:1 and 1:1, while no interaction was observed for 1:3 combination. This indicates that eugenol enhances thymol activity. These results must be considered an important step forward to the development of effective pediculicidal nanoformulations based on botanical compounds.

Acute Inflammatory Response to Eccentric Exercise in Young and Master Resistance-trained Athletes.

This study aimed to compare the acute inflammatory response following high-intensity eccentric exercise between resistance-trained young and master athletes with similar performance levels. Resistance-trained young (n=8; 22±2 years) and master (n=8; 52±4 years) male athletes of a similar performance level performed a standardized high-intensity eccentric squat exercise protocol (10 sets of half-squats at 70% of 1-repetition maximum). The serum concentration of 20 biomarkers related to tissue damage, inflammation, remodeling, and repair was measured at baseline, immediately after exercise, and over a 72 h recovery period. Both groups experienced similar muscle damage as evidenced by a comparable increase in creatine kinase activity 24 h after exercise (p<0.001). Interleukin-6 (p=0.009) and growth hormone (p<0.001) increased immediately post-exercise in both groups. Monocyte chemoattractant protein-1 increased immediately post-exercise only in young athletes (p=0.003) and then decreased 24 h later. There were no significant differences for the remaining variables, including cell markers related to neutrophil/macrophage activation or pro/anti-inflammatory cytokines. Resistance-trained young and master athletes, matched for performance level, showed an overall similar inflammatory response to eccentric exercise, possibly reflecting regulatory mechanisms or immunological adaptations to chronic stimulation in master athletes.

Time-course Changes of Field- and Laboratory-based Performance Indicators in Junior Cyclists Through a Season.

This study aimed to assess the seasonal evolution of field-based and laboratory-based performance indicators in cyclists. Thirteen Junior male road cyclists (age 17.4±0.5 years) were followed up during a season, which was divided in three phases: early season (involving mainly training sessions), mid-season (including the first competitions), and late season (including the major competitions of the season). During each phase, field-based power output data were registered for the assessment of maximum mean power values, and laboratory-based endurance (ramp test and simulated 8-minute time trial), muscle strength/power (squat, lunge, hip thrust) and body composition indicators (dual-energy X-ray absorptiometry) were also assessed. A progressive (p<0.01) increase in maximum mean power values (e.g., 3.8±0.3 and 4.5±0.4 watts/kg in early and late season, respectively, for 60-minute efforts) and on 8-minute time trial performance (i.e., 5.3±0.3 and 5.6±0.4 watts/kg, respectively) was observed through the season. Yet, more "traditional" endurance indicators (i.e., ventilatory threshold, respiratory compensation point, or maximum oxygen uptake) seemed to show a ceiling effect beyond the mid-season. In addition, neither peak power output, body composition, nor muscle strength indicators followed a similar pattern to the aforementioned field-based indicators. In summary, in Junior cyclists field-based indicators seem more sensitive to monitor endurance cyclists' changes in actual fitness and performance capacity than more "traditional" laboratory-based markers in Junior cyclists.

Exercise benefits in cardiovascular diseases: from mechanisms to clinical implementation.

There is a pandemic of physical inactivity that appears to parallel the widespread prevalence of cardiovascular disease (CVD). Yet, regular physical activity (PA) and exercise can play an important role not only in primary cardiovascular prevention but also in secondary prevention. This review discusses some of the main cardiovascular effects of PA/exercise and the mechanisms involved, including a healthier metabolic milieu with attenuation of systemic chronic inflammation, as well as adaptations at the vascular (antiatherogenic effects) and heart tissue (myocardial regeneration and cardioprotection) levels. The current evidence for safe implementation of PA and exercise in patients with CVD is also summarized.

Prevention of cardiorenal damage: importance of albuminuria.

Chronic kidney disease (CKD) is projected to become a leading global cause of death by 2040, and its early detection is critical for effective and timely management. The current definition of CKD identifies only advanced stages, when kidney injury has already destroyed >50% of functioning kidney mass as reflected by an estimated glomerular filtration rate <60 mL/min/1.73 m2 or a urinary albumin/creatinine ratio >six-fold higher than physiological levels (i.e. > 30 mg/g). An elevated urinary albumin-excretion rate is a known early predictor of future cardiovascular events. There is thus a 'blind spot' in the detection of CKD, when kidney injury is present but is undetectable by current diagnostic criteria, and no intervention is made before renal and cardiovascular damage occurs. The present review discusses the CKD 'blind spot' concept and how it may facilitate a holistic approach to CKD and cardiovascular disease prevention and implement the call for albuminuria screening implicit in current guidelines. Cardiorenal risk associated with albuminuria in the high-normal range, novel genetic and biochemical markers of elevated cardiorenal risk, and the role of heart and kidney protective drugs evaluated in recent clinical trials are also discussed. As albuminuria is a major risk factor for cardiovascular and renal disease, starting from levels not yet considered in the definition of CKD, the implementation of opportunistic or systematic albuminuria screening and therapy, possibly complemented with novel early biomarkers, has the potential to improve cardiorenal outcomes and mitigate the dismal 2040 projections for CKD and related cardiovascular burden.

Intrasession Caffeine Intake and Cycling Performance After Accumulated Work: A Field-Based Study.

BACKGROUND: Preexercise caffeine intake has proven to exert ergogenic effects on cycling performance. However, whether these benefits are also observed under fatigue conditions remains largely unexplored. We aimed to assess the effect of caffeine ingested during prolonged cycling on subsequent time-trial performance in trained cyclists. METHODS: The study followed a triple-blinded, randomized, placebo-controlled cross-over design. Eleven well-trained junior cyclists (17 ± 1 years) performed a field-based 8-min time trial under "fresh" conditions (i.e., after their usual warm-up) or after two work-matched steady-state cycling sessions (total energy expenditure∼20 kJ/kg and ∼100 min duration). During the latter sessions, participants consumed caffeine (3 mg/kg) or a placebo ∼60 min before the time trial. We assessed power output, heart rate, and rating of perceived exertion during the time trial and mood state (Brunel Mood Scale) before and after each session. RESULTS: No significant condition effect was found for the mean power output attained during the time trial (365 ± 25, 369 ± 31, and 364 32 W for "fresh," caffeine, and placebo condition, respectively; p = .669). Similar results were found for the mean heart rate (p = .100) and rating of perceived exertion (p = 1.000) during the time trial and for the different mood domains (all p > .1). CONCLUSIONS: Caffeine intake during prolonged exercise seems to exert no ergogenic effects on subsequent time-trial performance in junior cyclists. Future studies should determine whether significant effects can be found with larger caffeine doses or after greater fatigue levels.

Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease.

Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by complete blockade of muscle glycogen metabolism, compared to healthy controls. Nine patients (three women, aged 36 ± 12 years) and 12 healthy controls (four women, aged 40 ± 13 years) were studied. Several molecular markers of lipid transport/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (Pygm p.50R*/p.50R*) and wild-type male mice. Peak oxygen uptake ( V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ ), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate-associated workload were determined by indirect calorimetry during an incremental cycle-ergometer test. Despite having a much lower V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ (24.7 ± 4 vs. 42.5 ± 11.4 mL kg-1  min-1 , respectively; P < 0.0001), patients showed considerably higher values for the MFO rate (0.53 ± 0.12 vs. 0.33 ± 0.10 g min-1 , P = 0.001), and for the FATmax (94.4 ± 7.2 vs. 41.3 ± 9.1 % of V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ , P < 0.0001) and MFO rate-associated workload (1.33 ± 0.35 vs. 0.81 ± 0.54 W kg-1 , P = 0.020) than controls. No between-group differences were found overall in molecular markers of lipid transport/metabolism in mice. In summary, patients with McArdle disease show an exceptionally high MFO rate, which they attained at near-maximal exercise capacity. Pending more mechanistic explanations, these findings support the influence of glycogen availability on MFO rate and suggest that these patients develop a unique fat oxidation capacity, possibly as an adaptation to compensate for the inherited blockade in glycogen metabolism, and point to MFO rate as a potential limiting factor of exercise tolerance in this disease. KEY POINTS: Physically active McArdle patients show an exceptional fat oxidation capacity. Maximal fat oxidation rate occurs near-maximal exercise capacity in these patients. McArdle patients' exercise tolerance might rely on maximal fat oxidation rate capacity. Hyperpnoea might cloud substrate oxidation measurements in some patients. An animal model revealed overall no higher molecular markers of lipid transport/metabolism.

Combined exercise intervention in a mouse model of high-risk neuroblastoma: effects on physical, immune, tumor and clinical outcomes.

Background: Exercise might exert anti-tumoral effects in adult cancers but this question remains open in pediatric tumors, which frequently show a different biology compared to adult malignancies. We studied the effects of an exercise intervention on physical function, immune variables and tumoral response in a preclinical model of a highly aggressive pediatric cancer, high-risk neuroblastoma (HR-NB). Methods: 6-8-week-old male mice with orthotopically-induced HR-NB were assigned to a control (N = 13) or exercise (5-week combined [aerobic+resistance]) group (N = 17). Outcomes included physical function (cardiorespiratory fitness [CRF] and muscle strength), as well as related muscle molecular indicators, blood and tumor immune cell and molecular variables, tumor progression, clinical severity, and survival. Results: Exercise attenuated CRF decline (p=0.029 for the group-by-time interaction effect), which was accompanied by higher muscle levels of oxidative capacity (citrate synthase and respiratory chain complexes III, IV and V) and an indicator of antioxidant defense (glutathione reductase) in the intervention arm (all p≤0.001), as well as by higher levels of apoptosis (caspase-3, p=0.029) and angiogenesis (vascular endothelial growth factor receptor-2, p=0.012). The proportion of 'hot-like' (i.e., with viable immune infiltrates in flow cytometry analyses) tumors tended to be higher (p=0.0789) in the exercise group (76.9%, vs. 33.3% in control mice). Exercise also promoted greater total immune (p=0.045) and myeloid cell (p=0.049) infiltration within the 'hot' tumors, with a higher proportion of two myeloid cell subsets (CD11C+ [dendritic] cells [p=0.049] and M2-like tumor-associated macrophages [p=0.028]), yet with no significant changes in lymphoid infiltrates or in cirulating immune cells or chemokines/cytokines. No training effect was found either for muscle strength or anabolic status, cancer progression (tumor weight and metastasis, tumor microenvironment), clinical severity, or survival. Conclusions: Combined exercise appears as an effective strategy for attenuating physical function decline in a mouse model of HR-NB, also exerting some potential immune benefits within the tumor, which seem overall different from those previously reported in adult cancers.

Pathophysiology of Cerebellar Degeneration in Mitochondrial Disorders: Insights from the Harlequin Mouse.

By means of a proteomic approach, we assessed the pathways involved in cerebellar neurodegeneration in a mouse model (Harlequin, Hq) of mitochondrial disorder. A differential proteomic profile study (iTRAQ) was performed in cerebellum homogenates of male Hq and wild-type (WT) mice 8 weeks after the onset of clear symptoms of ataxia in the Hq mice (aged 5.2 ± 0.2 and 5.3 ± 0.1 months for WT and Hq, respectively), followed by a biochemical validation of the most relevant changes. Additional groups of 2-, 3- and 6-month-old WT and Hq mice were analyzed to assess the disease progression on the proteins altered in the proteomic study. The proteomic analysis showed that beyond the expected deregulation of oxidative phosphorylation, the cerebellum of Hq mice showed a marked astroglial activation together with alterations in Ca2+ homeostasis and neurotransmission, with an up- and downregulation of GABAergic and glutamatergic neurotransmission, respectively, and the downregulation of cerebellar "long-term depression", a synaptic plasticity phenomenon that is a major player in the error-driven learning that occurs in the cerebellar cortex. Our study provides novel insights into the mechanisms associated with cerebellar degeneration in the Hq mouse model, including a complex deregulation of neuroinflammation, oxidative phosphorylation and glutamate, GABA and amino acids' metabolism.

Is the Record Power Profile Repeatable? A Practical Analysis and Interpretation in Professional Cyclists.

ABSTRACT: Muriel, X, Hernández-Belmonte, A, Mateo-March, M, Valenzuela, PL, Zabala, M, Barranco-Gil, D, Lucia, A, and Pallares, JG. Is the record power profile repeatable? A practical analysis and interpretation in professional cyclists. J Strength Cond Res 37(5): 1131-1134, 2023-This study assessed the repeatability of the Record Power Profile (RPP, i.e., the highest power output that a cyclist can attain for different effort durations under field-based conditions). We registered the RPP of 12 professional cyclists (age 32 ± 5 years) for efforts lasting between 30 seconds and 60 minutes during 3 periods of a season, each of 23-day duration: preparation (including training data only), specific (training and competition data), and competition (competition data only) periods. Repeatability was assessed using the highest 2 (RPP 2 ), 3 (RPP 3 ), and 5 (RPP 5 ) values of mean maximum power obtained by the cyclists for each effort duration in each of the 3 periods. Smaller standard errors of measurement ( SEM ) were found as the competitive period approached, especially for short-duration efforts (i.e., 30 seconds, 1 minute, and 5 minutes, where SEM ranged from 4.3 to 12.5%, 4.1-8.5%, and 2.6-7.0% in the preparation, specific, and competition periods, respectively). However, similar SEM values were found in the 3 periods for RPP 2 , RPP 3 , or RPP 5. In conclusion, the RPP appears as a repeatable parameter for monitoring field-based performance within the different phases of the season in professional cyclists.

Laboratory-based determinants of simulated time trial performance in cyclists.

Different laboratory-based variables are individually associated with cycling performance, but scarce evidence exists on which of them, when all assessed in combination, could best explain cycling performance. The present study aimed to examine the combined association between laboratory-based endurance, strength/power and body composition indicators with time trial performance in high-level cyclists. Ninety-four male cyclists were recruited (age: 20 ± 3.5 years, maximum oxygen uptake [V̇O2max]: 77.7 ± 5.4 ml · kg-1 · min-1). Participants performed a maximal incremental cycling test for the assessment of endurance indicators (peak power output [PPO], V̇O2max, ventilatory threshold [VT] and respiratory compensation point [RCP]), and an incremental loading test to assess muscle strength and power-related outcomes (1-repetition maximum, mean maximal power) in the squat, lunge and hip-thrust exercises. Body composition was assessed by dual energy X-ray absorptiometry. On a separate visit, participants performed a simulated 8-minute time trial to assess cycling performance (determined as the mean power output attained). Strong-to-very-strong correlations were found between all endurance indicators and time trial performance (most r-values ranging between 0.68-0.92), whereas weaker correlations were found for strength/power (r-values < 0.5) or body composition (r-values < 0.7) indicators. Multivariate regression analyses revealed that VT, RCP and PPO explained together 92% of the variance in time trial performance (p < 0.001), with no significant contribution of the remaining variables. Although different endurance, strength/power and body composition individually correlate with simulated time trial performance in high-level cyclists, the former (and particularly VT, RCP and PPO) show the strongest association when all studied in combination. These findings underscore the importance of endurance capabilities (above strength/power or body composition) for maximizing time trial performance.

Poor self-reported sleep is associated with risk factors for cardiovascular disease: A cross-sectional analysis in half a million adults.

BACKGROUND: Sleep is known to affect cardiovascular health, but some controversy exists on the independent association between different sleep characteristics (duration, restfulness, difficulties falling asleep) and specific risk factors for cardiovascular disease (CVD). We aimed to assess the association between self-reported sleep characteristics and the likelihood of major CVD risk factors. METHODS: Totally, 521,364 Spanish workers (32% female, 44 ± 9 years [18-64]) insured by an occupational risk prevention company participated in this nationwide cross-sectional study. Participants' sleep was considered 'poor' if they reported having ≥1 of the following conditions: excessively short (<6 h/d) or long (>9 h/d) sleep, unrestful sleep, or difficulties to fall asleep. We assessed the independent association between aforementioned sleep characteristics and the prevalence of hypertension, diabetes, hypercholesterolaemia, obesity and physical inactivity. RESULTS: Poor sleep (reported by 33% of participants) was associated with a higher likelihood of presenting all CVD risk factors individually, particularly physical inactivity (which prevalence was ~3-fold higher in the poor sleep group compared with participants reporting no sleep abnormality). In separate analyses, all the different sleep characteristics were associated with the likelihood of ≥2 CVD risk factors. Participants with optimal sleep, normal sleep duration, no difficulties falling sleep and restful sleep showed a lower total CVD risk score than their peers with poor sleep, short sleep duration, difficulties falling sleep and unrestful sleep, respectively (all p < .001). CONCLUSIONS: Poor sleep was associated with a higher likelihood of presenting major CVD risk factors. These findings might support the importance of monitoring and improving sleep patterns for primary CVD prevention.

Identification of Potential Muscle Biomarkers in McArdle Disease: Insights from Muscle Proteome Analysis.

Glycogen storage disease type V (GSDV, McArdle disease) is a rare genetic myopathy caused by deficiency of the muscle isoform of glycogen phosphorylase (PYGM). This results in a block in the use of muscle glycogen as an energetic substrate, with subsequent exercise intolerance. The pathobiology of GSDV is still not fully understood, especially with regard to some features such as persistent muscle damage (i.e., even without prior exercise). We aimed at identifying potential muscle protein biomarkers of GSDV by analyzing the muscle proteome and the molecular networks associated with muscle dysfunction in these patients. Muscle biopsies from eight patients and eight healthy controls showing none of the features of McArdle disease, such as frequent contractures and persistent muscle damage, were studied by quantitative protein expression using isobaric tags for relative and absolute quantitation (iTRAQ) followed by artificial neuronal networks (ANNs) and topology analysis. Protein candidate validation was performed by Western blot. Several proteins predominantly involved in the process of muscle contraction and/or calcium homeostasis, such as myosin, sarcoplasmic/endoplasmic reticulum calcium ATPase 1, tropomyosin alpha-1 chain, troponin isoforms, and alpha-actinin-3, showed significantly lower expression levels in the muscle of GSDV patients. These proteins could be potential biomarkers of the persistent muscle damage in the absence of prior exertion reported in GSDV patients. Further studies are needed to elucidate the molecular mechanisms by which PYGM controls the expression of these proteins.

Physical exercise effects on metastasis: a systematic review and meta-analysis in animal cancer models.

Physical exercise is considered a well-tolerated adjuvant therapy to mitigate cancer-related side effects, but its impact on metastasis is unclear. The present systematic review and meta-analysis aimed to summarize the evidence on the effects of exercise on metastasis in animal cancer models. A systematic search was conducted to identify controlled studies in animals analyzing the impact of exercise interventions on any marker of metastasis incidence or severity. The pooled mean differences (PMD) were calculated for those endpoints for which a minimum of three studies used the same assessment method. We also calculated the pooled odds ratio (OR) of metastases. Twenty-six articles were included in the systematic review, of which 12 could be meta-analyzed. Exercise training in murine cancer models did not significantly modify the number of metastatic foci (PMD = - 3.18; 95% confidence interval [CI] - 8.32, 1.97; p = 0.23), the weight of metastatic tumors (PMD = - 0.03; 95% CI - 0.10, 0.04; p = 0.41), or the risk of developing metastasis (OR = 0.64; 95% CI 0.10, 4.12; p = 0.64). These findings suggest that exercise has no overall influence on any marker of cancer metastasis incidence or severity in animal models. However, the wide methodological heterogeneity observed between studies might be taken into account and the potential exercise effects on metastasis development remain to be determined in pediatric tumors.

What are the effects of exercise training in childhood cancer survivors? A systematic review.

This systematic review aimed to summarize evidence on the effects of physical exercise interventions in childhood cancer survivors (CCS) who had finished anticancer therapy ≥ 1 year before the study. Relevant articles were identified in the electronic databases PubMed, Web of Science, and SPORTDiscus (from inception to June 27, 2019). The PEDro scale was used to assess methodological quality. Twelve studies including 109 CCS met all inclusion criteria and were included in the systematic review. The quality of the included studies was overall low. Physical exercise improved endothelial function, reduced waist circumference, and waist-to-hip ratio and increased physical activity levels. Preliminary evidence was found regarding benefits on brain volume and structure after exercise interventions in childhood brain tumor survivors. Only two studies reported exercise-related adverse events. Physical exercise seems to be safe and effective for improving several health markers in CCS, but further high-quality research and especially randomized controlled trials are needed to confirm these results.

Obesity can offset the cardiometabolic benefits of gestational exercise.

Pregnancy exercise can prevent excessive gestational weight gain (EGWG), gestational diabetes mellitus (GDM) and hypertension (GH), but inter-individual variability has not been explored. We aimed to analyze the prevalence--and potential sociodemographic and medical predictors of--non-responsiveness to gestational exercise, and the association of non-responsiveness with adverse pregnancy outcomes. Among 688 women who completed a supervised light-to-moderate intensity exercise program (three ~1-h sessions/week including aerobic, resistance, and pelvic floor muscle training) until near-term, those who showed EGWG, GDM or GH were considered 'non-responders'. A low prevalence of non-responders was observed for GDM (3.6%) and GH (3.4%), but not for EGWG (24.2%). Pre-pregnancy obesity was the strongest predictor of non-responsiveness for GH (odds ratio 8.40 [95% confidence interval 3.10-22.78] and EGWG (5.37 [2.78-10.39]), whereas having a highest education level attenuated the risk of being non-responder for GDM (0.10 [0.02-0.49]). Non-responsiveness for EGWG was associated with a higher risk of prolonged labor length, instrumental/cesarean delivery, and macrosomia, and of lower Apgar scores. No association with negative delivery outcomes was found for GDM/GH. In summary, women with pre-pregnancy obesity might require from additional interventions beyond light-to-moderate intensity gestational exercise (e.g., diet and/or higher exercise loads) to ensure cardiometabolic benefits.