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ImportanceThere is a growing interest in understanding whether cardiovascular magnetic resonance (CMR) myocardial tissue characterization helps identify risk of cancer therapy–related cardiac dysfunction (CTRCD).ObjectiveTo describe changes in CMR tissue biomarkers during breast cancer therapy and their association with CTRCD.Design, Setting, and ParticipantsThis was a prospective, multicenter, cohort study of women with ERBB2 (formerly HER2)–positive breast cancer (stages I-III) who were scheduled to receive anthracycline and trastuzumab therapy with/without adjuvant radiotherapy and surgery. From November 7, 2013, to January 16, 2019, participants were recruited from 3 University of Toronto–affiliated hospitals. Data were analyzed from July 2021 to June 2022.ExposuresSequential therapy with anthracyclines, trastuzumab, and radiation.Main Outcomes and MeasuresCMR, high-sensitivity cardiac troponin I (hs-cTnI), and B-type natriuretic peptide (BNP) measurements were performed before anthracycline treatment, after anthracycline and before trastuzumab treatment, and at 3-month intervals during trastuzumab therapy. CMR included left ventricular (LV) volumes, LV ejection fraction (EF), myocardial strain, early gadolinium enhancement imaging to assess hyperemia (inflammation marker), native/postcontrast T1 mapping (with extracellular volume fraction [ECV]) to assess edema and/or fibrosis, T2 mapping to assess edema, and late gadolinium enhancement (LGE) to assess replacement fibrosis. CTRCD was defined using the Cardiac Review and Evaluation Committee criteria. Fixed-effects models or generalized estimating equations were used in analyses.ResultsOf 136 women (mean [SD] age, 51.1 [9.2] years) recruited from 2013 to 2019, 37 (27%) developed CTRCD. Compared with baseline, tissue biomarkers of myocardial hyperemia and edema peaked after anthracycline therapy or 3 months after trastuzumab initiation as demonstrated by an increase in mean (SD) relative myocardial enhancement (baseline, 46.3% [16.8%] to peak, 56.2% [18.6%]), native T1 (1012 [26] milliseconds to 1035 [28] milliseconds), T2 (51.4 [2.2] milliseconds to 52.6 [2.2] milliseconds), and ECV (25.2% [2.4%] to 26.8% [2.7%]), with P Conclusions and RelevanceIn women with ERBB2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy, CMR tissue biomarkers suggest inflammation and edema peaking early during therapy and were associated with ventricular remodeling and BNP elevation. However, the increases in CMR biomarkers were transient, were not associated with LVEF or myocardial strain, and were not useful in identifying traditional CTRCD risk.

Resistance training induces skeletal muscle hypertrophy via the summated effects of postexercise elevations in myofibrillar protein synthesis (MyoPS) that persist for up to 48 h, although research in females is currently lacking. MyoPS is regulated by mTOR translocation and colocalization; however, the effects of resistance training on these intracellular processes are unknown. We hypothesized that MyoPS would correlate with hypertrophy only after training in both sexes and would be associated with intracellular redistribution of mTOR.Recreationally active males and females (n = 10 each) underwent 8 wk of whole-body resistance exercise three times a week. Fasted muscle biopsies were obtained immediately before (REST) and 24 and 48 h after acute resistance exercise in the untrained (UT) and trained (T) states to determine integrated MyoPS over 48 h (D2O ingestion) and intracellular mTOR colocalization (immunofluorescence microscopy).Training increased (P0.01) muscle strength (~20%-126%), muscle thickness (~8%-11%), and average fiber cross-sectional area (~15%-20%). MyoPS increased above REST in UT (P = 0.032) and T (P0.01), but to a greater extent in males (~23%; P = 0.023), and was positively (P0.01) associated with muscle thickness and fiber cross-sectional area at T only in both males and females. mTOR colocalization with the cell periphery increased (P0.01) in T, irrespective of sex or acute exercise. Training increased (P ≤ 0.043) total mTOR, LAMP2 (lysosomal marker), and their colocalization (P0.01), although their colocalization was greater in males at 24 and 48 h independent of training status (P0.01).MyoPS during prolonged recovery from exercise is greater in males but related to muscle hypertrophy regardless of sex only in the trained state, which may be underpinned by altered mTOR localization.

Breaking up prolonged sitting with intermittent walking breaks can improve glycemic control. Here, we demonstrated that interrupting prolonged sitting every 30 min with 1 min of repeated chair stands was as effective as 2-min treadmill walks for lowering postprandial insulinemia in healthy adults. Markers of contraction- and insulin-mediated muscle glucose uptake were unchanged. Repeated chair stands as a form of body-weight resistance activity may represent a cost- and space-efficient activity break for mitigating cardiometabolic-disease risk.

Satellite cells (SC) play an integral role in the recovery from skeletal muscle damage and supporting muscle hypertrophy. Acute resistance exercise typically elevates type I and type II SC content 24-96 h post exercise in healthy young males, although comparable research in females is lacking. We aimed to elucidate whether sex-based differences exist in fiber type-specific SC content after resistance exercise in the untrained (UT) and trained (T) states. Ten young males (23.0 ± 4.0 yr) and females (23.0 ± 4.8 yr) completed an acute bout of resistance exercise before and after 8 wk of whole body resistance training. Muscle biopsies were taken from the vastus lateralis immediately before and 24 and 48 h after each bout to determine SC and myonuclear content by immunohistochemistry. Males had greater SC associated with type II fibers (

BACKGROUND Acute exercise increases the incorporation of dietary amino acids into de novo myofibrillar proteins after a single meal in controlled laboratory studies in males. It is unclear whether this extends to free-living settings or is influenced by training or sex. OBJECTIVES We determined the effects of exercise, training status, and sex on 24-hour free-living dietary phenylalanine incorporation into skeletal muscle proteins. METHODS In a parallel group design, recreationally active males (mean ± SD age, 23 ± 3 years; BMI. 23.4 ± 2.9 kg/m2; n = 10) and females (age 24 ± 5 years; BMI, 23.1 ± 3.9 kg/m2; n = 9) underwent 8 weeks of whole-body resistance exercise 3 times a week. Controlled diets containing 1.6 g/kg-1/d-1 (amino acids modelled after egg), enriched to 10% with [13C6] or [2H5]phenylalanine, were consumed before and after an acute bout of resistance exercise. Fasted muscle biopsies were obtained before [untrained, pre-exercise condition (REST ] and 24 hours after an acute bout of resistance exercise in untrained (UT) and trained (T) states to determine dietary phenylalanine incorporation into myofibrillar (ΔMyo) and sarcoplasmic (ΔSarc) proteins, intracellular mechanistic target of rapamycin (mTOR) colocalization with ulex europaeus agglutinin-1 (UEA-1; capillary marker; immunofluorescence), and amino acid transporter expression (Western blotting). RESULTS The ΔMyo values were ∼62% greater (P

Protein recommendations for resistance-trained athletes are generally lower than their habitual intakes. Excess protein consumption increases the capacity to oxidize amino acids, which can attenuate post-exercise anabolism and may impact protein requirements determined by stable isotope techniques predicated on amino acid tracer oxidation. We aimed to determine the impact of an acute (5d) reduction in dietary protein intake on post-exercise anabolism in high habitual consumers using the indicator amino acid oxidation (IAAO) technique. Resistance trained men [n = 5; 25 ± 7 y; 73.0 ± 5.7 kg; 9.9 ± 2.9% body fat; 2.69 ± 0.38 g·kg−1·d−1 habitual protein intake) consumed a high (H; 2.2 g·kg−1·d−1) and moderate (M; 1.2 g·kg−1·d−1) protein diet while training every other day. During the High protein phase, participants consumed a 2d controlled diet prior to determining whole body phenylalanine turnover, net balance (NB), and 13CO2 excretion (F13CO2) after exercise via oral [13C]phenylalanine. During the Moderate phase, participants consumed 2.2 g protein·kg−1·d−1 for 2d prior to consuming 1.2 g protein·kg−1·d−1 for 5d. Phenylalanine metabolism was measured on days 1, 3, and 5 (M1, M3, and M5, respectively) of the moderate intake. F13CO2, the primary outcome for IAAO, was ~72 and ~55% greater on the 1st day (M1, P < 0.05) and the third day of the moderate protein diet (M3, P = 0.07), respectively, compared to the High protein trial. Compared to the High protein trial, NB was ~25% lower on the 1st day (M1, P < 0.01) and 15% lower on the third day of the moderate protein diet (M3, P = 0.09). High habitual protein consumption may bias protein requirements determined by traditional IAAO methods that use only a 2d pre-trial controlled diet. Post-exercise whole body anabolism is attenuated following a reduction in protein intake in resistance trained men and may require ~3–5d to adapt. This trial is registered at clinicaltrials.gov as NCT03845569.