Luis Peñailillo

Purpose : To assess the test–retest reliability of in vivo Achilles tendon (AT) structure and mechanical properties in youth with obesity. Methods : Participants (11 males; 12 females; age: 12.00 [2.07] y; body mass index z score: 2.93 [0.59]) were assessed for AT (1) length, (2) cross-sectional area, (3) moment arm, (4) force, (5) deformation, (6) stress, (7) strain, (8) stiffness, (9) Young’s modulus, (10) plantar flexor maximal isometric voluntary contraction, and (11) tibialis anterior co-activation. Reliability was assessed using the intraclass correlation coefficient, coefficient of variation, Bland–Altman, standard error of the measurement, and minimum detectable change. The intraclass correlation coefficient values were classified as excellent (≥.90), good (≥.75 to <.90), moderate (>.49 to <.75), and poor (≤.49). Moreover, the threshold for CV was set at < 10% to be considered excellent. Results : The intraclass correlation coefficient ranged from .88 ( P < .001) (AT stiffness) to .99 ( P < .001) (AT stress), while the CV ranged from 0.91% (AT length) to 9.98% (AT Young’s modulus). Bland–Altman (%) of mean bias ranged from 0.24% (AT length) to −6.65% (AT stiffness). The standard error of the measurement (%) ranged from 0.13% (AT length) to 2.96% (AT stiffness), and the minimum detectable change (%) of the mean ranged from 0.35% (AT length) to 8.20% (AT stiffness). Conclusion : The in vivo measurement of AT structure and mechanical properties showed a good to excellent degree of test–retest reliability in youth with obesity.

Progressive resistance exercise training (RET) enhances skeletal muscle mass in healthy postmenopausal women (HEAs) and breast cancer survivors (BCSs) undergoing endocrine therapy. MicroRNAs (miRNAs) are recognized as key epigenetic regulators of exercise-induced adaptations, functioning as tumor suppressors, oncomiRs, and modulators of skeletal muscle homeostasis. Nevertheless, the impact of RET on circulating miRNA profiles in this population remains largely unexplored. This study aimed to explore the effects of a 12-week progressive RET program on plasma miRNAs associated with tumor biology and skeletal muscle regulation in HEAs and BCSs. Five HEAs and five BCSs undergoing endocrine therapy completed a 12-week supervised progressive RET program (3 sessions/week, 60–80% 1RM). Plasma samples were collected before and after intervention, and candidate miRNA expression was quantified by qRT-PCR, normalized to hsa-miR-16-5p, and analyzed using the 2^−ΔΔCt method. At baseline, no significant differences were observed between HEA and BCS in tumor suppressor miRNAs (miR-let-7f-5p, miR-125a-5p, miR-342-3p), oncomiRs (miR-21-5p, miR-155-5p, miR-221-3p), or skeletal muscle–related miRNAs (miR-206-3p, miR-486-5p) (p > 0.05). The only exception was miR-375-3p, which showed increased expression in HEA vs BCS (p = 0.037). After 12 weeks of RET, The BCS group showed increases in miR-125a-5p (p = 0.050) and miR-342-3p (p = 0.048) with significant group × time interactions that remained significant after Benjamini–Hochberg False Discovery Rate (BH-FDR) correction (FDR-adjusted p = 0.042 for both). Both groups displayed a nominal increase in miR-375-3p (p = 0.042), which did not remain significant after FDR correction. No significant changes were detected for miR-let-7f-5p or the analyzed oncomiRs in either group. Both miR-206-3p and miR-486-5p exhibited upward trends in the BCS group (p > 0.05). In this exploratory study, 12-week RET program was associated with selective changes in plasma miRNA expression in the HEA and BCS groups, suggesting that this training regimen may act as an epigenetic modulator of circulating miRNAs involved in tumor suppression and skeletal muscle homeostasis.

Background The cross-education effect after unilateral resistance training (CE-URT) describes force production gains in a contralateral non-trained homologous muscle. While CE-URT is established in healthy populations, its role in clinical populations has not been systematically assessed. The CE-URT magnitude may be influenced by training parameters (i.e. contraction type, intensity, anatomical region and training–testing contraction specificity), but their contribution remains unclear in experimental models of immobilisation in healthy immobilised participants (HIP) and clinical populations, particularly in patients with musculoskeletal conditions (PMC) and hemiparesis after stroke (PHAS), where CE-URT has been primarily applied. Objective We aimed to assess the CE-URT on force production capacity in HIP, PMC and PHAS, to examine the modulatory role of key URT prescription parameters. Methods PubMed, Scopus, CINAHL and Web of Science were searched for randomised and non-randomised controlled trials (≥ 3 weeks) assessing CE-URT compared to control conditions (immobilisation, conventional rehabilitation or within-subject control periods) on contralateral force production capacity. Risk of bias (Downs & Black) and certainty of evidence (Grading of Recommendations Assessment, Development and Evaluation [GRADE]) were assessed. A three-level random-effects meta-analysis with subgroup analyses was conducted according to population (HIP/PMC/PHAS), contraction type (eccentric/concentric/isometric/concentric-eccentric-coupled), training intensity (maximal/submaximal), training–testing contraction specificity (specific/non-specific) and anatomical region (upper/lower limb). Effect sizes (ESs) were expressed as standardised mean differences with 95% confidence intervals (95% CIs). Results Twenty-four studies (low to very-low risk of bias) were included. Compared with control conditions, CE-URT induced a moderate effect on maximal strength (ES [95% CI] = 0.654 [0.393, 0.915], P < 0.001; Q(52) = 163.14, P < 0.001; moderate-GRADE) and a small effect on rapid force production (ES [95% CI] = 0.367 [0.115, 0.619], P = 0.007; Q(17) = 7.59, P = 0.97; low-GRADE). Large effects were observed in PHAS (ES [95% CI] = 1.263 [0.439, 2.087], P = 0.008; Q(9) = 48.28, P < 0.001; moderate-GRADE) and HIP models (ES [95% CI] = 0.845 [0.533, 1.158], P < 0.001; Q(20) = 18.63, P = 0.546; high-GRADE). Large effects were found in isometric (ES [95% CI] = 1.080 [0.286, 1.873], P = 0.014; Q(8) = 41.22, P < 0.001; moderate-GRADE), testing-training contraction specific (ES [95% CI] = 1.072 [0.449, 1.695], P = 0.003; Q(10) = 42.04, P < 0.001; moderate-GRADE), upper-limb (ES [95% CI] = 0.857 [0.529, 1.185], P < 0.001; Q(32) = 76.35, P < 0.001) and eccentric protocols (ES [95% CI] = 0.831 [0.491, 1.171], P < 0.001; Q(13) = 10.62, P = 0.64; high-GRADE). Moderate effects were observed after maximal (ES [95% CI] = 0.759 [0.256, 1.262], P = 0.005; Q(17) = 67.54, P < 0.001; very low-GRADE) or submaximal intensity protocols (ES [95% CI] = 0.587 [0.273, 0.902], P = 0.001; Q(34) = 91.05, P < 0.001; low-GRADE), and training–testing contraction non-specific protocols (ES [95% CI] = 0.542 [0.280, 0.805], P < 0.001, Q(41) = 97.667, P = 0.008; low-GRADE). No significant effect was observed in PMC (P = 0.150), concentric (P = 0.411) or lower-limb protocols (P = 0.093). Conclusions The CE-URT was shown in experimental models of disuse in HIP and clinical conditions with PHAS. The CE-URT appears promising for recovery of force production capacity in clinical scenarios. However, further research is needed to optimise intervention protocols and increase certainty of the evidence, particularly in PMC.

Background: Resistance training has been shown to activate the protein synthesis pathway, leading to muscle growth in humans. However, this type of exercise has shown equivocal results in animal studies due to the difficulty of mimicking muscle overload in vivo. This study aimed to determine whether ladder‐based exercise in mice induces canonical molecular, cellular, and functional adaptations to training. Methods: Mice performed a single exercise session or 6 weeks of training in the ladder climb. Acute responses included mTOR phosphorylation, puromycin incorporation, and mRNA levels of myogenic regulatory factors (MRF). Chronic adaptations were assessed by strength, fat‐free mass, physical performance, and blood lactate levels to confirm the training load. Sarcomeric proteins were analyzed using Western blot, while histology measured muscle fiber diameter and satellite cell (SC) fusion. The SC amount was quantified by flow cytometry. Results: After a single exercise bout, mTOR phosphorylation increased at one and 3 h, with puromycin incorporation and MRF mRNA levels elevated at 8 h. After 6 weeks of training, the mice showed increased skeletal muscle strength and fat‐free mass, with no changes in physical performance. Muscle‐specific adaptations included increases in sarcomeric proteins and fiber diameters. SC adaptations were associated with an increased pool and enhanced capacity to fuse with muscle fibers. Conclusions: Our results demonstrate that ladder‐based resistance exercise in mice induces molecular, cellular, and functional responses that are directionally consistent with adaptations reported after human resistance training, supporting its value for investigating the molecular and cellular mechanisms underlying this training.

Background/Objectives: Cancer pathophysiology involves metabolic disturbances, and exercise improves muscle metabolism, but little is known about the effect of concurrent high-intensity interval plus resistance training (CT_HIIT+RT) on the resting and exercise metabolism of breast cancer survivors with risk factors related to metabolic syndrome (MetS). The purpose of this study was to determine the effects of 8 weeks of CT_HIIT+RT on the fat and carbohydrate (CHO) metabolism during rest and progressive exercise post-exercise intervention in breast cancer survivors with histories of high- and low-volume chemotherapy. Methods: An experimental study was conducted in which (n = 21) women breast cancer survivors (age: 58.7 ± 8.7 years) were divided by history of high- (HV_chemo, ≥8 to 16 sessions, n = 10) or low-volume (LV_chemo, ≤7 chemo sessions, n = 11) chemotherapy. The fat (RFAT_ox) and CHO oxidation during 10 min of resting was measured (i.e., including the area under curve [AUC] points within this time), as well as the fat (ExFAT_ox) and CHO (ExCHO_ox) oxidation during progressive exercise, before and after 8 weeks of CT_HIIT+RT by indirect calorimetry. Additionally, risk factors related to MetS were described from pre- to post-intervention. Results: At rest, the HV_chemo group showed significant increases in the AUC of RFAT_ox (∆ + 23.7, p < 0.0001), similar to the LV_chemo group (∆ + 14.0, p < 0.0001). The HV_chemo group showed significant increases in the AUC of RCHO_ox (∆ + 109.7, p < 0.0001), similar to the LV_chemo group (∆ + 107.5, p < 0.0001). During progressive exercise, the ExFAT_ox was increased in the HV_chemo group (∆ + 0.12 g/min, p = 0.006), similar to the ExCHO_ox (∆ + 0.52 g/min, p = 0.013) of this group. The proportion of subjects categorized with MetS were significantly reduced in blood pressure, Glu and triglyceride components. Conclusions: Eight weeks of CT_HIIT+RT may promote favorable metabolic and cardiometabolic adaptations in breast cancer survivors regardless of the chemotherapy exposure volume. However, these findings should be interpreted cautiously due to the small sample size and lack of a true non-exercise control group.

Eccentric exercise-induced muscle damage (EIMD) impairs muscle function and recovery. While omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has shown promise in mitigating EIMD, the role of their oxidation products (oxylipins) remains unclear. This study investigated the effects of 8-week n-3 PUFA supplementation on muscle recovery and its relationship with blood oxylipin profiles after EIMD in healthy men. Eighteen participants were randomly assigned into two groups: OMEGA (n = 9 28.0 ± 2.5 y; 2.5 g/d of DHA and 0.5 g/d of EPA) and PLACEBO (n = 9 21.4 ± 0.6 y; maltodextrin). Participants performed one bout of 100 unilateral isokinetic eccentric maximal voluntary contractions of the knee extensor muscles before and after an 8-week supplementation period. N-3 PUFA supplementation augmented plasma EPA- and DHA-derived oxylipins (p < 0.05) in the OMEGA group, which showed an attenuation of peak muscle maximum voluntary contraction loss (-15.4 ± 5.2%; p = 0.05) post-exercise compared to the PLACEBO group (1.3 ± 6.0%). There were no differences in muscles soreness between groups. Multivariate analyses identified body fat percentage and specific n-3 and n-6 PUFA-derived oxylipins as predictors of MVC loss after EIMD. In conclusion, the increased plasma levels of n-3 PUFA derived oxylipins following supplementation suggest a possible role for these lipid mediators in promoting muscle recovery.

Background: The COVID-19 pandemic left numerous patients with post-intensive care syndrome (PICS) that resulted in prolonged physical and health impairment. Compared to standard rehabilitation (STD REHAB), eccentric cycling (ECC) has lower cardiopulmonary demands while inducing greater functional performance improvements after training, which could be ideal for individuals with PICS. Aim: To compare the effects of eight weeks of ECC versus STD REHAB on functional performance and quality of life of patients after hospitalization. Methods: Randomised crossover design study (clinicaltrial.gov: NCT06895850). Twenty survivors of the COVID-19 infection (50.8 ± 8.8 years old) recruited six months after hospitalization were involved. Participants were initially randomized into ECC (n = 10) or STD REHAB (n = 10). Both groups trained for eight weeks, rested for two weeks, and performed the crossover with the remaining training modality. Exercise time was 20−30 min for ECC and 60 min for STD REHAB. Cardiopulmonary demand was measured during training. Body composition, whole-body manual and handgrip strength, functional performance (6-min walking test; 6MWT, timed up and go; TUG, 1-min sit to stand), cognitive (MoCa and Barthel Index), and quality of life and symptoms (QoL; Patient Health Questionnaire; PHQ and Post-COVID-19 Functional Status Scale; PCFS) were measured before and after interventions. Results: Cardiopulmonary demand during training was lesser during STD REHAB than ECC. All variables improved after both interventions, but ECC showed larger improvements in 6MWT, TUG, and Barthel Index compared to STD REHAB. Conclusion: Eccentric cycling training induced greater functional and cognitive improvements than standard rehabilitation.

Background and Objectives: Aging is associated with functional decline and multimorbidity, highlighting the need for holistic biomarkers to monitor healthy aging. The aim of this study was to validate intrinsic capacity age (IC-age) as a biomarker of aging and to examine its association with multimorbidity and geroprotective agents. Research Design and Methods: A cross-sectional study was conducted with data from 48,068 participants aged ≥60 years from the 9th wave of the Survey of Health, Ageing and Retirement in Europe (2021–2022). Random forest regression was used to train a model predicting IC-age based on biomarkers (cognitive, psychological, sensory, vitality, locomotion) and demographic factors. Results: IC-age showed a prediction error of 5.3 years (r = 0.55). Biomarkers for vitality (handgrip strength), cognitive (verbal fluency and memory), and sensory (hearing aid use) domains were important contributors. General linear models assessed associations with multimorbidity, physical activity, and smoking. Intrinsic capacity age was significantly higher in individuals with multimorbidity and smokers compared with healthy individuals. Physical activity exhibited a protective effect on IC-age, with vigorous activity showing a particularly pronounced benefit in women. Discussion and Implications: This model demonstrates that IC domains can estimate biological age and distinguish individuals based on their comorbidities. It also underscores the role of physical activity as a key geroprotective factor, with vigorous physical activity in females with comorbidities showing the most pronounced protective effect on IC-age. These results validate the concept of IC-age as a comprehensive measure of aging and highlight its potential to inform personalized interventions and public health strategies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition characterized by altered liver function due to fatty accumulation, which can lead to liver inflammation and, in advanced stages, liver carcinoma. MASLD is closely linked to several metabolic alterations, such as obesity and insulin resistance, which directly affect skeletal muscles and contribute to the development of sarcopenia. Sarcopenia is the loss of muscle mass and strength, leading to decreased physical performance in severe stages. Skeletal muscles secrete molecules known as myokines under various conditions, such as exercise or diseases like MASLD. These myokines modulate communication between the skeletal muscle and other tissues. These myokines regulate muscle mass and, in pathological conditions, contribute to the development of sarcopenia. Emerging evidence highlights the crucial role of myokines in regulating skeletal muscle metabolism and function in MASLD. Myokines influence muscle metabolism, inflammation, and insulin sensitivity, offering potential therapeutic targets for managing muscle atrophy and sarcopenia in the context of MASLD. Understanding the interaction between myokines and skeletal muscle may lead to novel interventions to mitigate MASLD progression and sarcopenia. This review examines the mechanisms by which myokines regulate skeletal muscle metabolism and function in the context of MASLD.