Low Energy Availability Followed by Optimal Energy Availability Does Not Benefit Performance in Trained Females.

PURPOSE: Short periods of reduced energy availability are commonly undertaken by athletes to decrease body mass, possibly improve the power-to-mass ratio, and enhance physical performance. Our primary aim was to investigate the impact of 10 d of low energy availability (LEA) followed by 2 d of optimal energy availability (OEA) on physical performance parameters in trained females. Second, physiological markers at the whole-body and molecular level related to performance were evaluated. METHODS: Thirty young trained eumenorrheic females were matched in pairs based on training history and randomized to a 10-d intervention period of LEA (25 kcal·fat-free mass (FFM) -1 ·d -1 ) or OEA (50 kcal·FFM -1 ·d -1 ) along with supervised exercise training. Before the intervention, participants underwent a 5-d run-in period with OEA + supervised exercise training. After the LEA intervention, 2 d of recovery with OEA was completed. Participants underwent muscle biopsies, blood sampling, physical performance tests, body composition measurements, and resting metabolic rate measurements. A linear mixed model was used with group and time as fixed effects and subject as random effects. RESULTS: Compared with OEA, LEA resulted in reduced body mass, muscle glycogen content, repeated sprint ability, 4-min time-trial performance, and rate of force development of the knee extensors (absolute values; P < 0.05). Two days of recovery restored 4-min time-trial performance and partly restored repeated sprint ability, but performance remained inferior to the OEA group. When the performance data were expressed relative to body mass, LEA did not enhance performance. CONCLUSIONS: Ten days of LEA resulted in impaired performance (absolute values), with concomitant reductions in muscle glycogen. Two days of recovery with OEA partially restored these impairments, although physical performance (absolute values) was still inferior to being in OEA. Our findings do not support the thesis that LEA giving rise to small reductions in body mass improves the power-to-mass ratio and thus increases physical performance.

Regulation of adult stem cell function by ketone bodies.

Adult stem cells play key roles in tissue homeostasis and regeneration. Recent evidence suggests that dietary interventions can significantly impact adult stem cell function. Some of these effects depend on ketone bodies. Adult stem cells could therefore potentially be manipulated through dietary regimens or exogenous ketone body supplementation, a possibility with significant implications for regenerative medicine. In this review we discuss recent findings of the mechanisms by which ketone bodies could influence adult stem cells, including ketogenesis in adult stem cells, uptake and transport of circulating ketone bodies, receptor-mediated signaling, and changes to cellular metabolism. We also discuss the potential effects of ketone bodies on intracellular processes such as protein acetylation and post-transcriptional control of gene expression. The exploration of mechanisms underlying the effects of ketone bodies on stem cell function reveals potential therapeutic targets for tissue regeneration and age-related diseases and suggests future research directions in the field of ketone bodies and stem cells.

Usefulness of Heat Map Explanations for Deep-Learning-Based Electrocardiogram Analysis.

Deep neural networks are complex machine learning models that have shown promising results in analyzing high-dimensional data such as those collected from medical examinations. Such models have the potential to provide fast and accurate medical diagnoses. However, the high complexity makes deep neural networks and their predictions difficult to understand. Providing model explanations can be a way of increasing the understanding of "black box" models and building trust. In this work, we applied transfer learning to develop a deep neural network to predict sex from electrocardiograms. Using the visual explanation method Grad-CAM, heat maps were generated from the model in order to understand how it makes predictions. To evaluate the usefulness of the heat maps and determine if the heat maps identified electrocardiogram features that could be recognized to discriminate sex, medical doctors provided feedback. Based on the feedback, we concluded that, in our setting, this mode of explainable artificial intelligence does not provide meaningful information to medical doctors and is not useful in the clinic. Our results indicate that improved explanation techniques that are tailored to medical data should be developed before deep neural networks can be applied in the clinic for diagnostic purposes.

Low energy availability reduces myofibrillar and sarcoplasmic muscle protein synthesis in trained females.

Low energy availability (LEA) describes a state where the energy intake is insufficient to cover the energy costs of both exercise energy expenditure and basal physiological body functions. LEA has been associated with various physiological consequences, such as reproductive dysfunction. However, the effect of LEA on skeletal muscle protein synthesis in females performing exercise training is still poorly understood. We conducted a randomized controlled trial to investigate the impact of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in trained females. Thirty eumenorrheic females were matched based on training history and randomized to undergo 10 days of LEA (25 kcal · kg fat-free mass (FFM)-1  · day-1 ) or optimal energy availability (OEA, 50 kcal · kg FFM-1  · day-1 ). Before the intervention, both groups underwent a 5-day 'run-in' period with OEA. All foods were provided throughout the experimental period with a protein content of 2.2 g kg lean mass-1  · day-1 . A standardized, supervised combined resistance and cardiovascular exercise training programme was performed over the experimental period. Daily integrated muscle protein synthesis was measured by deuterium oxide (D2 O) consumption along with changes in body composition, resting metabolic rate, blood biomarkers and 24 h nitrogen balance. We found that LEA reduced daily integrated myofibrillar and sarcoplasmic muscle protein synthesis compared with OEA. Concomitant reductions were observed in lean mass, urinary nitrogen balance, free androgen index, thyroid hormone concentrations and resting metabolic rate following LEA. These results highlight that LEA may negatively affect skeletal muscle adaptations in females performing exercise training. KEY POINTS: Low energy availability (LEA) with potential health and performance impairments is widespread among female athletes. We investigated the impact of 10 days of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in young, trained females. We show that LEA impairs myofibrillar and sarcoplasmic muscle protein synthesis in trained females performing exercise training. These findings suggest that LEA may have negative consequences for skeletal muscle adaptations and highlight the importance of ensuring adequate energy availability in female athletes.

Lowered muscle glycogen reduces body mass with no effect on short-term exercise performance in men.

Performance in short-duration sports is highly dependent on muscle glycogen, but the total degradation is only moderate and considering the water-binding property of glycogen, unnecessary storing of glycogen may cause an unfavorable increase in body mass. To investigate this, we determined the effect of manipulating dietary carbohydrates (CHO) on muscle glycogen content, body mass, and short-term exercise performance. In a randomized and counterbalanced cross-over design, twenty-two men completed two maximal cycle tests of either 1-min (n = 10) or 15-min (n = 12) duration with different pre-exercise muscle glycogen levels. Glycogen manipulation was initiated three days prior to the tests by exercise-induced glycogen depletion followed by ingestion of a moderate (M-CHO) or high (H-CHO) CHO-diet. Subjects were weighed before each test, and muscle glycogen content was determined in biopsies from m. vastus lateralis before and after each test. Pre-exercise muscle glycogen content was lower following M-CHO than H-CHO (367 mmol · kg-1 DW vs. 525 mmol · kg-1 DW, p < 0.00001), accompanied by a 0.7 kg lower body mass (p < 0.00001). No differences were observed in performance between diets in neither the 1-min (p = 0.33) nor the 15-min (p = 0.99) test. In conclusion, pre-exercise muscle glycogen content and body mass were lower after ingesting moderate compared with high amounts of CHO, while short-term exercise performance was unaffected. This demonstrates that adjusting pre-exercise glycogen levels to the requirements of competition may provide an attractive weight management strategy in weight-bearing sports, particularly in athletes with high resting glycogen levels.

Force potentiation during eccentric contractions in rat skeletal muscle.

Postactivation potentiation refers to an acute enhancement of contractile properties following muscle activity. Previously, the effects of prior muscle activation on eccentric force at tetanic activation frequencies have only been sparsely reported. This paper aimed to study acute activity-induced effects on eccentric force of slow and fast-twitch muscles and characterize them in relation to postactivation potentiation. We elicited eccentric contractions in isolated rat extensor digitorum longus and soleus muscles by actively lengthening muscles at a constant velocity. We assessed contractile properties by measuring force over shortly interspaced, identical eccentric, and isometric contractions. We then analyzed stretch force, isometric peak force, rate of force development, and relaxation times. Finally, we compared the time courses for the development and cessation of changes in stretch force to known features of postactivation potentiation. In extensor digitorum longus, muscles stretch force consistently increased in a contraction-to-contraction manner by up to 49% [95% confidence interval (CI): 35-64%] whereas isometric peak force simultaneously showed minor declines (8%, 95% CI: 5-10%). The development and cessation of eccentric force potentiation coincided with the development of twitch potentiation and increases in rate of force development. In soleus muscles we found no consistent eccentric potentiation. Characterization of the increase in eccentric force revealed that force only increased in the very beginning of an active stretch. Eccentric force at tetanic activation frequencies potentiates substantially in extensor digitorum longus muscles over consecutive contractions with a time course coinciding with postactivation potentiation. Such eccentric potentiation may be important in sport performance.NEW & NOTEWORTHY Force during eccentric contractions can increase to a magnitude that may have profound consequences for our understanding of skeletal muscle locomotion. This increase in eccentric force occurs over consecutive, shortly interspaced, tetanic contractions in rat extensor digitorum longus muscles-not in rat soleus muscles-and coincides with well-known traits of postactivation potentiation. Eccentric force potentiation may significantly enhance muscle performance in activities involving stretch-shortening cycles.

Transfer learning for non-image data in clinical research: A scoping review.

BACKGROUND: Transfer learning is a form of machine learning where a pre-trained model trained on a specific task is reused as a starting point and tailored to another task in a different dataset. While transfer learning has garnered considerable attention in medical image analysis, its use for clinical non-image data is not well studied. Therefore, the objective of this scoping review was to explore the use of transfer learning for non-image data in the clinical literature. METHODS AND FINDINGS: We systematically searched medical databases (PubMed, EMBASE, CINAHL) for peer-reviewed clinical studies that used transfer learning on human non-image data. We included 83 studies in the review. More than half of the studies (63%) were published within 12 months of the search. Transfer learning was most often applied to time series data (61%), followed by tabular data (18%), audio (12%) and text (8%). Thirty-three (40%) studies applied an image-based model to non-image data after transforming data into images (e.g. spectrograms). Twenty-nine (35%) studies did not have any authors with a health-related affiliation. Many studies used publicly available datasets (66%) and models (49%), but fewer shared their code (27%). CONCLUSIONS: In this scoping review, we have described current trends in the use of transfer learning for non-image data in the clinical literature. We found that the use of transfer learning has grown rapidly within the last few years. We have identified studies and demonstrated the potential of transfer learning in clinical research in a wide range of medical specialties. More interdisciplinary collaborations and the wider adaption of reproducible research principles are needed to increase the impact of transfer learning in clinical research.

Early effects of eccentric contractions on muscle glucose uptake.

Muscle-damaging eccentric exercise impairs muscle glucose uptake several hours to days after exercise. Little, however, is known about the acute effects of eccentric exercise on contraction- and insulin-induced glucose uptake. This study compares glucose uptake rates in the first hours following eccentric, concentric, and isometric contractions with and without insulin present. Isolated rat extensor digitorum longus muscles were exposed to either an eccentric, concentric, or isometric contraction protocol, and muscle contractions were induced by electric stimulation that was identical between contraction protocols. In eccentric and concentric modes, length changes of 0.6 or 1.2 mm were used during contractions. Both contraction- and insulin-induced glucose uptake were assessed immediately and 2 h after contractions. Glucose uptake increased significantly following all modes of contraction and was higher after eccentric contractions with a stretch of 1.2 mm compared with the remaining contraction groups when assessed immediately after contractions [eccentric (1.2 mm) > eccentric (0.6 mm), concentric (1.2 mm), concentric (0.6 mm), isometric > rest; P < 0.05]. After 2 h, contraction-induced glucose uptake was still higher than noncontracting levels, but with no difference between contraction modes. The presence of insulin increased glucose uptake markedly, but this response was blunted by, respectively, 39-51% and 29-36% ( P < 0.05) immediately and 2 h after eccentric contractions stretched 1.2 mm compared with concentric and isometric contractions. The contrasting early effects of eccentric contractions on contraction- and insulin-induced glucose uptake suggest that glucose uptake is impaired acutely following eccentric exercise because of reduced insulin responsiveness. NEW & NOTEWORTHY This study shows that, in isolated rat muscle, muscle-damaging eccentric contractions result in a transient increase in contraction-induced glucose uptake compared with isometric and concentric contractions induced by identical muscle activation protocols. Furthermore, our results demonstrate that, in contrast, the insulin-stimulated glucose uptake is impaired immediately following muscle-damaging eccentric contractions.