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Simple Summary: High-impact publications have reported both the beneficial and harmful effects of catecholamines on cancer hallmarks and outcomes—a contradiction that is underappreciated and poorly explained. Here, we aimed to investigate whether differences in adrenergic receptor isoform expression can explain different cancer hallmark responses to catecholamines, since cancer cells can vary greatly in the expressions of nine adrenergic receptors. For this purpose, we cultured two cancer cell lines that systematically differ in their adrenergic receptor expressions: A673 cells, which express α1D-, α2C-, β1-, and β3-adrenergic receptors, and RD sarcoma cells, which barely express any adrenergic receptors. The cells were treated with noradrenaline to elucidate the effects of noradrenaline exposure on cell proliferation, migration, and cAMP signaling. While the A673 cells responded to noradrenaline treatment with decreased cell numbers, cell proliferation and migration, and increased cAMP signaling, the RD cells did not respond to noradrenaline. Therefore, our findings indicate that the adrenergic receptor isoform expressions might indeed explain why cancers can respond differently to increases in catecholamine concentrations due to, e.g., a bout of exercise, psychosocial stress, surgery, or drugs such as β-blockers. Background: Exercise has beneficial effects on cancer and its treatment, but the underlying mechanisms are poorly understood. Some studies have linked the positive impact of exercise to catecholamine signaling. In contrast, cancer stress studies have typically reported that catecholamines worsen cancer hallmarks and outcomes. Here, we aimed to investigate whether adrenergic receptor isoform expression can explain the contradictory effects of catecholamines in cancer. Methods: We cultured two pediatric sarcoma cancer cell lines that either express (A673 cell line) or do not express (RD cell line) adrenergic receptors. The cells were treated with a 5× dilution series of noradrenaline to assess the effects of noradrenaline on cell numbers. After these dose-finding experiments, we treated both cancer cell lines with 60 μM noradrenaline to examine its effect on cell proliferation and migration and cAMP signaling. Results: Treatment with 60 μM noradrenaline significantly decreased the cell numbers by 61.89% ± 10.36 (p ≤ 0.001), decreased cell proliferation by 15.88% ± 6.76 (p ≤ 0.05), decreased cell migration after 24 h (p ≤ 0.001), and increased cAMP concentrations 38-fold (p ≤ 0.001) in the A673 cells, which express adrenergic receptors, but not in the RD cells, which do not express adrenergic receptors. Conclusions: Our results indicate, as a proof of principle, that the effects of catecholamines on cancer progression and metastasis might depend on the expressions of the nine adrenergic receptor isoforms. As cancers express adrenergic and other receptors differentially, this has implications for the response of cancers to exercise, stress, and medication and may help to further personalize cancer treatments. [ABSTRACT FROM AUTHOR]

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Airborne respiratory aerosol particle transmission of pathogens such as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), influenza, or rhinoviruses plays a major role in the spread of infectious diseases. The infection risk is increased during indoor exercise, as aerosol particle emission can increase by more than 100-fold from rest to maximal exercise. Earlier studies have investigated the effect of factors such as age, sex, and body mass index (BMI), but only at rest and without taking ventilation into account. Here, we report that during both rest and exercise, subjects aged 60 to 76 y emit on average more than twice as many aerosol particles per minute than subjects aged 20 to 39 y. In terms of volume, older subjects emit on average five times as much dry volume (i.e., the residue of dried aerosol particles) than younger subjects. There was no statistically significant effect of sex or BMI within the test group. Together, this suggests that aging of the lung and respiratory tract is associated with an increased generation of aerosol particles irrespective of ventilation. Our findings demonstrate that age and exercise increase aerosol particle emission. In contrast, sex or BMI only have minor effects. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 is a multi-systemic disease which can target the lungs and the cardiovascular system and can also affect parts of the brain for prolonged periods of time. Even healthy athletes without comorbidities can be psychologically affected long-term by COVID-19. Objective: This study aimed to investigate athletes' perceived mental stress and recovery levels in daily life, and their maximal aerobic power, at three different time points, post COVID-19. Methods: In total, 99 athletes (62.6% male), who had been infected by COVID-19, filled out the Recovery Stress Questionnaire for Athletes (REST-Q-Sport) and completed cardiopulmonary exercise testing (endpoint maximal aerobic power output (Pmax)) at the initial screening (t1: 4 months after infection). Follow-up assessments occurred three (t2, n = 37) and seven months after t1 (t3, n = 19). Results: Subgroup means from the Recovery category were significantly below the reference value of four at all three time points, except "General Recovery" (3.76 (± 0.96), p = 0.275, d = 0.968) at t3."Overtiredness" (2.34 (± 1.27), p = 0.020, r = 0.224) was significantly above the reference value of two at t1, while all other Stress subgroups were not significantly different from the reference value or were significantly below the maximum threshold of two at t1, t2 and t3. Spearman's ρ revealed a negative association between Pmax and the subcategories of stress (ρ = -0.54 to ρ = -0.11, p < 0.050), and positive correlations between Pmax and "Somatic Recovery" (ρ = 0.43, p < 0.001) and "General Recovery" (ρ = 0.23, p = 0.040) at t1. Pmax (t1: 3.83 (± 0.99), t2: 3.78 (± 1.14), β = 0.06, p < 0.003) increased significantly from t1 to t2. In addition, REST-Q-Sport indicated a decrease in "Sleep" (t2 = 2.35 (± 0.62), t3 = 2.28(± 0.61), β = -0.18, p < 0.023) at t3, when compared to t2. Conclusion: The perceived recovery seems to be negatively affected in post COVID-19 athletes. Physical performance post COVID-19 correlates with both "Emotional and Somatic Stress" and "Somatic and General Recovery", indicating potential mental and physical benefits of exercise. While it is evident that COVID-19, like other viral infections, may have an influence on physical performance, monitoring stress and recovery perceptions of athletes is critical to facilitate their return-to-sports, while minimizing long-term COVID-19 induced negative effects like the athletic objective and subjective perceived recovery and stress levels. [ABSTRACT FROM AUTHOR]

Pathogens such as severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), influenza, and rhinoviruses are transmitted by airborne aerosol respiratory particles that are exhaled by infectious subjects. We have previously reported that the emission of aerosol particles increases on average 132-fold from rest to maximal endurance exercise. The aims of this study are to first measure aerosol particle emission during an isokinetic resistance exercise at 80% of the maximal voluntary contraction until exhaustion, second to compare aerosol particle emission during a typical spinning class session versus a three-set resistance training session. Finally, we then used this data to calculate the risk of infection during endurance and resistance exercise sessions with different mitigation strategies. During a set of isokinetic resistance exercise, aerosol particle emission increased 10-fold from 5,400 ± 1,200 particles/min at rest to 59,000 ± 69,900 particles/ min during a set of resistance exercise. We found that aerosol particle emission per minute is on average 4.9-times lower during a resistance training session than during a spinning class. Using this data, we determined that the simulated infection risk increase during an endurance exercise session was sixfold higher than during a resistance exercise session when assuming one infected participant in the class. Collectively, this data helps to select mitigation measures for indoor resistance and endurance exercise classes at times where the risk of aerosol-transmitted infectious disease with severe outcomes is high. [ABSTRACT FROM AUTHOR]

Simple Summary: Exercise can counteract some of the adverse effects of cancer and its treatment. Epidemiological and mechanistic data suggest that exercise can influence cancer hallmarks, survival, and recurrence. Our pilot study aimed to assess the feasibility and safety of a single bout of high-intensity interval training (HIIT) in childhood cancer patients. The predefined feasibility criteria included recruitment rate, acceptability, practicability, and data acquisition. Very strict inclusion criteria and surveillance guaranteed safety, and no severe adverse events occurred. Our HIIT protocol is applicable only in a small number of childhood cancer patients. Blood lactate concentrations and heart rates significantly increased after HIIT, indicating that the patients achieved the targeted high exercise intensity. In conclusion, our preliminary data suggest that HIIT is safe and feasible in a small number of childhood cancer patients who do not suffer from severe side effects of treatment. Additional exercise protocols should be developed for patients with pronounced cancer-related impairments and health restrictions. Low- and moderate-intensity exercise is safe and feasible during childhood cancer treatment. The feasibility of a bout of high-intensity interval training (HIIT) in this population has not been analyzed to date. Pediatric cancer patients aged between 6 and 18 years were selected based on clinical conditions to perform ten sets of 15 s HIIT (>90% of estimated maximal heart rate (HRmax)) and 1 min active recovery on a bicycle ergometer within the first three chemotherapy courses. We assessed safety and feasibility criteria and the following parameters: perceived exertion rate, heart rate, and lactate and adrenaline concentrations. Out of 212 eligible patients, 11 patients aged 13.9 ± 3.6 years (n = 7 ♂) with lymphoma, leukemia, rhabdomyosarcoma, nephroblastoma, and synovial sarcoma completed the bout of HIIT without serious adverse events. During exercise, patients reached a BORG value maxima of 16 ± 1.2, and their heart rates rose from 78 ± 17 beats per minute (bpm) at rest to 178 ± 12 bpm after exercise (90 ± 6% estimated HRmax). The power-to-weight ratio was 2 ± 0.5 W/kg (watt per kilogram). Blood lactate concentrations increased from 1.09 ± 0.50 mmol/L (millimole per liter) at rest to 5.05 ± 1.88 mmol/L post-exercise. Our preliminary data suggest that HIIT is applicable only in a small number of childhood cancer patients. Individually adapted exercise protocols for patients with multiple impairments are needed. [ABSTRACT FROM AUTHOR]

Micro ribonucleic acids (miRNAs) are small non-coding RNA molecules that control gene expression by translational inhibition. Exercise has been shown to affect several miRNAs' expression in healthy subjects, but this has not yet been studied in patients with coronary artery disease (CAD). Since exercise training confers beneficial long-term effects and may also trigger acute coronary events, it is of utmost interest to be able to identify those who are risk for untoward effects. Therefore, we set out to assess miRNA expression in response to maximal ergospirometry in patients with CAD. Total RNA was extracted from blood drawn immediately before and 5 min after maximal cycle-ergospirometry (10 male and 10 female CAD patients). A qRT-PCR was performed for 187 target miRNAs associated with endothelial function/dysfunction, cardiovascular disease, myocardial infarction, and sudden cardiac death. In response to a maximal ergospirometry, 33 miRNAs significantly changed their expression levels. Of these miRNAs 16 were significantly differently expressed between gender. Using multi-variance analysis, nine miRNAs (let-7e-5p; miR-1; miR-19b-1-5p; miR-103a-3p; miR-148b-3p; miR-181b-5p; miR-188-5p; miR-423-5p; miR-874-3p) showed significantly different responses to maximal ergospirometry between genders. We report for the first time that in patients with CAD, miRNA expression is amenable to maximal ergospirometry and that the extent of changes differs between genders. Affected by exercise and gender were miRNAs that are associated, among others, with pathways for glucose metabolism, oxidative stress, and angiogenesis. Future studies should assess whether disease-specific miRNA expression in response to maximal exercise might serve as a marker for patient outcome. [ABSTRACT FROM AUTHOR]

Human metabolism is highly variable. At one end of the spectrum, defects of enzymes, transporters, and metabolic regulation result in metabolic diseases such as diabetes mellitus or inborn errors of metabolism. At the other end of the spectrum, favorable genetics and years of training combine to result in physiologically extreme forms of metabolism in athletes. Here, we investigated how the highly glycolytic metabolism of sprinters, highly oxidative metabolism of endurance athletes, and highly anabolic metabolism of natural bodybuilders affect their serum metabolome at rest and after a bout of exercise to exhaustion. We used targeted mass spectrometry‐based metabolomics to measure the serum concentrations of 151 metabolites and 43 metabolite ratios or sums in 15 competitive male athletes (6 endurance athletes, 5 sprinters, and 4 natural bodybuilders) and 4 untrained control subjects at fasted rest and 5 minutes after a maximum graded bicycle test to exhaustion. The analysis of all 194 metabolite concentrations, ratios and sums revealed that natural bodybuilders and endurance athletes had overall different metabolite profiles, whereas sprinters and untrained controls were more similar. Specifically, natural bodybuilders had 1.5 to 1.8‐fold higher concentrations of specific phosphatidylcholines and lower levels of branched chain amino acids than all other subjects. Endurance athletes had 1.4‐fold higher levels of a metabolite ratio showing the activity of carnitine‐palmitoyl‐transferase I and 1.4‐fold lower levels of various alkyl‐acyl‐phosphatidylcholines. When we compared the effect of exercise between groups, endurance athletes showed 1.3‐fold higher increases of hexose and of tetradecenoylcarnitine (C14:1). In summary, physiologically extreme metabolic capacities of endurance athletes and natural bodybuilders are associated with unique blood metabolite concentrations, ratios, and sums at rest and after exercise. Our results suggest that long‐term specific training, along with genetics and other athlete‐specific factors systematically change metabolite concentrations at rest and after exercise. [ABSTRACT FROM AUTHOR]

Exercise is recommended for the healthy population as it increases fitness and prevents diseases. Moreover, exercise is also applied as an adjunct therapy for patients with various chronic diseases including cancer. Childhood cancer is a rare, heterogeneous disease that differs from adult cancer. Improved therapeutic strategies have increased childhood cancer survival rates to above 80% in developed countries. Although this is higher than the average adult cancer survival rate of about 50%, therapy results often in substantial long-term side effects in childhood cancer survivors. Exercise in adult cancer patients has many beneficial effects and may slow down tumor progression and improve survival in some cancer types, suggesting that exercise may influence cancer cell behavior. In contrast to adults, there is not much data on general effects of exercise in children. Whilst it seems possible that exercise might delay cancer progression or improve survival in children as well, there is no reliable data yet to support this hypothesis. Depending on the type of cancer, animal studies of adult cancer types show that the exercise-induced increase of the catecholamines epinephrine and norepinephrine, have suppressive as well as promoting effects on cancer cells. The diverse effects of exercise in adult cancer patients require investigating whether these results can be achieved in children with cancer. [ABSTRACT FROM AUTHOR]

Skeletal muscle mass differs greatly in mice and humans and this is partially inherited. To identify muscle hypertrophy candidate genes we conducted a systematic review to identify genes whose experimental loss or gain-of-function results in significant skeletal muscle hypertrophy in mice. We found 47 genes that meet our search criteria and cause muscle hypertrophy after gene manipulation. They are from high to small effect size: Ski, Fst, Acvr2b, Akt1, Mstn, Klf10, Rheb, Igf1, Pappa, Ppard, Ikbkb, Fstl3, Atgr1a, Ucn3, Mcu, Junb, Ncor1, Gprasp1, Grb10, Mmp9, Dgkz, Ppargc1a (specifically the Ppargc1a4 isoform), Smad4, Ltbp4, Bmpr1a, Crtc2, Xiap, Dgat1, Thra, Adrb2, Asb15, Cast, Eif2b5, Bdkrb2, Tpt1, Nr3c1, Nr4a1, Gnas, Pld1, Crym, Camkk1, Yap1, Inhba, Tp53inp2, Inhbb, Nol3, Esr1. Knock out, knock down, overexpression or a higher activity of these genes causes overall muscle hypertrophy as measured by an increased muscle weight or cross sectional area. The mean effect sizes range from 5 to 345% depending on the manipulated gene as well as the muscle size variable and muscle investigated. Bioinformatical analyses reveal that Asb15, Klf10, Tpt1 are most highly expressed hypertrophy genes in human skeletal muscle when compared to other tissues. Many of the muscle hypertrophy-regulating genes are involved in transcription and ubiquitination. Especially genes belonging to three signaling pathways are able to induce hypertrophy: (a) Igf1-Akt-mTOR pathway, (b) myostatin-Smad signaling, and (c) the angiotensin-bradykinin signaling pathway. The expression of several muscle hypertrophy-inducing genes and the phosphorylation of their protein products changes after human resistance and high intensity exercise, in maximally stimulated mouse muscle or in overloaded mouse plantaris. [ABSTRACT FROM AUTHOR]