Cardiopulmonary exercise testing in interstitial lung diseases and the value of ventilatory efficiency

Interstitial lung diseases (ILDs) are diverse parenchymal pulmonary disorders, primarily characterised by alveolar and interstitial inflammation and/or fibrosis, and sharing pathophysiological similarities. Thus, patients generally harbour common respiratory symptoms, lung function abnormalities and modified exercise adaptation. The most usual and disabling complaint is exertional dyspnoea, frequently responsible for premature exercise interruption. Cardiopulmonary exercise testing (CPET) is increasingly used for the clinical assessment of patients with ILD. This is because exercise performance or dyspnoea on exertion cannot reliably be predicted by resting pulmonary function tests. CPET, therefore, provides an accurate evaluation of functional capacity on an individual basis. CPET can unmask anomalies in the integrated functions of the respiratory, cardiovascular, metabolic, peripheral muscle and neurosensory systems in ILDs. CPET uniquely provides an evaluation of all above aspects and can help clinicians shape ILD patient management. Preliminary evidence suggests that CPET may also generate valuable prognostic information in ILDs and can be used to shed light on the presence of associated pulmonary hypertension. This review aims to provide comprehensive and updated evidence concerning the clinical utility of CPET in ILD patients, with particular focus on the physiological and clinical value of ventilatory efficiency (V˙E/V˙CO2).

Epigenetic Evidence for Distinct Contributions of Resident and Acquired Myonuclei During Long-Term Exercise Adaptation Using Timed In Vivo Myonuclear Labeling

Muscle fibers are syncytial post-mitotic cells that can acquire exogenous nuclei from resident muscle stem cells, called satellite cells. Myonuclei are added to muscle fibers by satellite cells during conditions such as load-induced hypertrophy. It is difficult to dissect the molecular contributions of resident versus satellite cell-derived myonuclei during adaptation due to the complexity of labeling distinct nuclear populations in multinuclear cells without label transference between nuclei. To sidestep this barrier, we utilized a genetic mouse model where myonuclear DNA can be specifically and stably labeled via non-constitutive H2B-GFP at any point in the lifespan. Resident myonuclei (Mn) were GFP-tagged in vivo before eight weeks of progressive weighted wheel running (PoWeR) in adult mice (>4-month-old). Resident+satellite cell-derived myonuclei (Mn+SC Mn) were labeled at the end of PoWeR in a separate cohort. Following myonuclear isolation, promoter DNA methylation profiles acquired with low-input RRBS were compared to deduce epigenetic contributions of satellite cell-derived myonuclei during adaptation. Resident myonuclear DNA has hypomethylated promoters in genes related to protein turnover, while the addition of satellite cell-derived myonuclei shifts myonuclear methylation profiles to favor transcription factor regulation and cell-cell signaling. By comparing myonucleus-specific methylation profiling to previously published single-nucleus transcriptional analysis in the absence (Mn) versus presence of satellite cells (Mn+SC Mn) with PoWeR, we provide evidence that satellite cell-derived myonuclei may preferentially supply ribosomal proteins to growing myofibers and retain an epigenetic "memory" of prior stem cell identity. These data offer insights on distinct epigenetic myonuclear characteristics and contributions during adult muscle growth.

Exercise Training and Circulating Small Extracellular Vesicles: Appraisal of Methodological Approaches and Current Knowledge

In response to acute exercise, an array of metabolites, nucleic acids, and proteins are enriched in circulation. Collectively termed “exercise factors,” these molecules represent a topical area of research given their speculated contribution to both acute exercise metabolism and adaptation to exercise training. In addition to acute changes induced by exercise, the resting profile of circulating exercise factors may be altered by exercise training. Many exercise factors are speculated to be transported in circulation as the cargo of extracellular vesicles (EVs), and in particular, a sub-category termed “small EVs.” This review describes an overview of exercise factors, small EVs and the effects of exercise, but is specifically focused on a critical appraisal of methodological approaches and current knowledge in the context of changes in the resting profile small EVs induced by exercise training, and the potential bioactivities of preparations of these “exercise-trained” small EVs. Research to date can only be considered preliminary, with interpretation of many studies hindered by limited evidence for the rigorous identification of small EVs, and the conflation of acute and chronic responses to exercise due to sample timing in proximity to exercise. Further research that places a greater emphasis on the rigorous identification of small EVs, and interrogation of potential bioactivity is required to establish more detailed descriptions of the response of small EVs to exercise training, and consequent effects on exercise adaptation.

miR-181c level predicts response to exercise training in patients with heart failure and preserved ejection fraction: an analysis of the OptimEx-Clin trial

Aims In patients with heart failure with preserved ejection fraction (HFpEF), exercise training improves the quality of life and aerobic capacity (peakV·O2). Up to 55% of HF patients, however, show no increase in peakV·O2 despite adequate training. We hypothesized that circulating microRNAs (miRNAs) can distinguish exercise low responders (LR) from exercise high responders (HR) among HFpEF patients. Methods and results We selected HFpEF patients from the Optimizing Exercise Training in Prevention and Treatment of Diastolic HF (OptimEx) study which attended ≥70% of training sessions during 3 months (n = 51). Patients were defined as HR with a change in peakV·O2 above median (6.4%), and LR as below median (n = 30 and n = 21, respectively). Clinical, ergospirometric, and echocardiographic characteristics were similar between LR and HR. We performed an miRNA array (n = 377 miRNAs) in 14 age- and sex-matched patients. A total of 10 miRNAs were upregulated in LR, of which 4 correlated with peakV·O2. Validation in the remaining 37 patients indicated that high miR-181c predicted reduced peakV·O2 response (multiple linear regression, β = −2.60, P = 0.011), and LR status (multiple logistic regression, odds ratio = 0.48, P = 0.010), independent of age, sex, body mass index, and resting heart rate. Furthermore, miR-181c decreased in LR after exercise training (P-group = 0.030, P-time = 0.048, P-interaction = 0.037). An in silico pathway analysis identified several downstream targets involved in exercise adaptation. Conclusions Circulating miR-181c is a marker of the response to exercise training in HFpEF patients. High miR-181c levels can aid in identifying LR prior to training, providing the possibility for individualized management.

Signals from the Circle: Tricarboxylic Acid Cycle Intermediates as Myometabokines

Regular physical activity is an effective strategy to prevent and ameliorate aging-associated diseases. In particular, training increases muscle performance and improves whole-body metabolism. Since exercise affects the whole organism, it has countless health benefits. The systemic effects of exercise can, in part, be explained by communication between the contracting skeletal muscle and other organs and cell types. While small proteins and peptides known as myokines are the most prominent candidates to mediate this tissue cross-talk, recent investigations have paid increasing attention to metabolites. The purpose of this review is to highlight the potential role of tricarboxylic acid (TCA) metabolites as humoral mediators of exercise adaptation processes. We focus on TCA metabolites that are released from human skeletal muscle in response to exercise and provide an overview of their potential auto-, para- or endocrine health-promoting effects.

Fear of Covid-19: Associations with Trait Anxiety and Life Satisfaction

Aim: Present study aimed to analyze perceived fear of COVID-19 among Turkish people and investigate its associations with trait anxiety and life satisfaction. Methods: The online snowball research sampling method was used to collect data, and 1129 subjects participated in the study. As data collection tools, the Fear of COVID-19 scale, Trait Anxiety Scale, and Satisfaction with Life Scale were used. In the adaptation and validation process of the Fear of COVID-19 Scale, confirmatory factor analysis was applied. Convergent validity of the model resulting from CFA was evaluated with Average Variance Extracted (AVE) and Composite Reliability (CR) based on the factor load values. The reliability of the scale was assessed with Cronbach's alpha method. Independent samples t-test and Two-Way ANOVA analysis were used to compare the differences in the perception of fear of COVID-19, trait anxiety and life satisfaction. Multiple regression was applied to predict anxiety based on fear of COVID-19 and life satisfaction. Results: Analyze results confirmed the unidimensionality of the 7-item scale on a Turkish sample, and the results indicated satisfactory reliability coefficients. According to independent t-test and Two Way Anova results, females, non-athletes, participants with the worry of gaining weight, who did not care about their nutrition, and who followed media news more often scored higher fear of COVID-19 and anxiety. Multiple regression analysis identified a negative correlation between fear of COVID-19 and life satisfaction and a positive correlation with anxiety. Conclusion: Although the present study revealed the associations of the fear of Covid-19 with life satisfaction and anxiety, further research is still recommended to explore these associations in more depth. Keywords: COVID-19; Fear; Anxiety; Satisfaction with Life; Athlete; Exercise; Adaptation

Time trajectories in the transcriptomic response to exercise - a meta-analysis

Exercise training prevents multiple diseases, yet the molecular mechanisms that drive exercise adaptation are incompletely understood. To address this, we create a computational framework comprising data from skeletal muscle or blood from 43 studies, including 739 individuals before and after exercise or training. Using linear mixed effects meta-regression, we detect specific time patterns and regulatory modulators of the exercise response. Acute and long-term responses are transcriptionally distinct and we identify SMAD3 as a central regulator of the exercise response. Exercise induces a more pronounced inflammatory response in skeletal muscle of older individuals and our models reveal multiple sex-associated responses. We validate seven of our top genes in a separate human cohort. In this work, we provide a powerful resource (www.extrameta.org) that expands the transcriptional landscape of exercise adaptation by extending previously known responses and their regulatory networks, and identifying novel modality-, time-, age-, and sex-associated changes.

Changes in Plasma Bioactive Lipids and Inflammatory Markers during a Half-Marathon in Trained Athletes

Background: Exercise may affect lipid profile which in turn is related to inflammation, although changes of ceramides, diacylglycerols-DAG and sphingomyelin-SM and their relationship with inflammatory parameters following a half-marathon have never been examined. Methods: Ceramides, DAG and SM, and markers of inflammation (soluble fractalkine-CX3CL1, vascular endothelial growth factor-VEGF, interleukin6-IL-6 and tumor necrosis factorα-TNFα) were evaluated in trained half-marathoners before, post-race (withdrawal within 20 min after the race end) and 24 h after. Results: IL-6 and CX3CL1 increased immediately after the race, returning to baseline after 24 h. Total ceramides and total DAG significantly decreased post-race. Several ceramide classes decreased after exercise, while only one of the DAG (36:3) changed significantly. Total SM and specific species did not significantly change. Conclusion: Some inflammatory parameters (IL-6 and CX3CL1) transiently increased after the race, and, being reversible, these changes might represent a physiological response to acute exercise rather than a damage-related response. The decrease of specific lipid classes, i.e., DAGs and ceramides, and the lack of their relationship with inflammatory parameters, suggest their involvement in beneficial training effects, opening promising research perspectives to identify additional mechanisms of aerobic exercise adaptation.

The Differences of Pulse on The Day of Training Based on Hours Sleep

The quality of rest will give a good result for the adaptation of the exercise. Exercise is carried out, so that physical condition has improved. The pulse rate is an indicator that can be used to see the process or results of exercise adaptation. If the waking pulse rate is still high, it can be assumed that time is still needed to rest. This study aims to determine the difference in the pulse rate of waking up from samples who sleep more than 6 hours and 6 hours below. The research was carried out by experiment. The sample was given 75% weight training with 12 tools for 12 meetings. Pulse measurement is done independently before and upon waking. Data were analyzed using the T-test. Based on the results, it was reported that 25 people were trying to rest 6 hours down and 47 times resting above 6 hours. Based on the T-test analysis, it was found that there was a significant difference between respondents who slept less than 6 hours and more than 6 hours with a significance of .002 with a mean of -0.8 for those who rested 6 hours and less and 4.6 for those who slept more than 6 hours. This research can be replicated by considering several variables related to the acceleration of recovery, including Vo2Max, blood HB, and it is necessary to consider the differences between sons and daughters.