Elucidation of the Role of L-Arginine and Nω-Nitro-L-Arginine in the Treatment of Rats with Different Levels of Hypoxic Tolerance and Exposure to Lead Nitrate.

BACKGROUND/AIMS: Individual resistance to hypoxia is an important feature of the physiological profile of an organism, particularly in relation to lead-induced toxicity. METHODS: Our study focused on evaluating parameters of mitochondrial oxygen consumption, microsomal oxidation, intensity of lipoperoxidation processes and antioxidant defences in the liver of rats with low (LR) and high (HR) resistance to hypoxia to elucidate the mechanisms of action of L-arginine and the NO synthase inhibitor L-NNA before or after exposure to lead nitrate. RESULTS: Our study suggests that the redistribution of oxygen-dependent processes towards mitochondrial processes under the influence of the nitric oxide precursor amino acid L-arginine is an important mechanism for maintaining mitochondrial respiratory chain function during per os lead nitrate exposure (3.6 mg lead nitrate/kg bw per day for 30 days). Animals were given L-arginine at a dose of 600 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate or the NO synthase inhibitor Nω-nitro-L-arginine (L-NNA) at a dose of 35 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate. Our experiments demonstrated the efficacy of using lead nitrate to simulate lead-related toxic processes via Pb levels in liver tissue; we demonstrated significantly reduced levels of nitrites and nitrates, i.e. stable metabolites of the nitric oxide system, in both LR and HR animals. The effect of the amino acid L-arginine stabilised the negative effects of lead nitrate exposure in both groups of LR and HR rats. We observed the efficiency of mitochondrial energy supply processes and showed a greater vulnerability of NADH-dependent oxidation during lead nitrate exposure in the liver of HR rats. CONCLUSION: L-arginine initiated the processes of oxidation of NADH-dependent substrates in the LR group, whereas in the HR group this directionality of processes was more effective when the role of the nitric oxide system was reduced (use of L-NNA). Our study of key antioxidant enzyme activities in rat liver tissue during lead nitrate exposure revealed changes in the catalase-peroxidase activity ratio. We found different activities of antioxidant enzymes in the liver tissue of rats treated with lead nitrate and L-arginine or L-NNA, with a significant increase in GPx activity in the LR group when L-arginine was administered both before and after exposure to lead nitrate.

Mechanical Deviations in Stride Characteristics During Running in the Severe Intensity Domain Are Associated With a Decline in Muscle Oxygenation.

We explored the impact of running in the severe intensity domain on running mechanics and muscle oxygenation in competitive runners by investigating the relationship between mechanical deviations from typical stride characteristics and muscle oxygen saturation (SmO2) in the quadriceps muscle. Sixteen youth competitive runners performed an 8-min exhaustive running test on an outdoor track. Running mechanics were continuously monitored using inertial measurement units. Rectus femoris SmO2 and total hemoglobin (a measure of blood volume) were continuously monitored by near-infrared spectroscopy. One-class support vector machine (OCSVM) modeling was employed for subject-specific analysis of the kinematic data. Statistical analysis included principal component analysis, ANOVA, and correlation analysis. Mechanical deviations from typical stride characteristics increased as the running test progressed. Specifically, the percentage of outliers in the OCSVM model rose gradually from 2.2 ± 0.8% at the start to 43.6 ± 28.2% at the end (p < 0.001, mean ± SD throughout). SmO2 dropped from 74.3 ± 8.4% at baseline to 10.1 ± 6.8% at the end (p < 0.001). A moderate negative correlation (r = -0.61, p = 0.013) was found between the average SmO2 and the percentage of outlier strides during the last 15% of the run. During high-intensity running, alterations in running biomechanics may occur, linked to decreased quadriceps muscle oxygenation. These parameters highlight the potential of using running kinematics and muscle oxygenation in training to optimize performance and reduce injury risks. Our research contributes to understanding biomechanical and physiological responses to endurance running and emphasizes the importance of individualized monitoring.

Effects of pacing strategy on metabolic responses to 2-min intense exercise in Thoroughbred horses.

Evidence suggests that positive pacing strategy improves exercise performance and fatigue tolerance in athletic events lasting 1-5 min. This study investigated muscle metabolic responses to positive and negative pacing strategies in Thoroughbred horses. Eight Thoroughbred horses performed 2 min treadmill running using positive (1 min at 110% maximal O2 uptake [V̇O2max], followed by 1 min at 90% V̇O2max) and negative (1 min at 90% V̇O2max, followed by 1 min at 110% V̇O2max) pacing strategies. The arterial-mixed venous O2 difference did not significantly differ between the two strategies. Plasma lactate levels increased toward 2 min, with significantly higher concentrations during positive pacing than during negative pacing. Muscle glycogen level was significantly lower at 1 and 2 min of positive pacing than those of negative pacing. Metabolomic analysis showed that the sum of glycolytic intermediates increased during the first half of positive pacing and the second half of negative pacing. Regardless of pacing strategy, the sum of tricarboxylic acid cycle metabolites increased during the first half but remained unchanged thereafter. Our data suggest that positive pacing strategy is likely to activate glycolytic metabolism to a greater extent compared to negative pacing, even though the total workload is identical.

Cardiorespiratory and aerobic demands of squat exercise.

Squatting, a traditional resistance exercise classified as strength training, relies on anaerobic pathways, but its aerobic aspects remain unclear. We examined heart rate and oxygen demand during squats, exploring variations across different strength statuses. It fills gaps in understanding the cardiorespiratory effects of squatting, especially during multiple sets. Twenty-two young healthy resistance trained men (age: 28 ± 4 years) participated. Maximal oxygen consumption (V̇O2max) and 1 repetition maximum (RM) of squat were measured. Participants performed 5 sets of squat exercises at 65% of 1RM for 10 repetitions with 3-min rest intervals. Heart rate and pulmonary gas exchange were measured during the squat exercise. Participants were divided into high strength (HS; upper 50%) and low strength (LS; lower 50%) groups based on a median split of their 1 RM squat values (normalized to their body weight). During 5 sets of squat exercise, oxygen consumption (V̇O2) increased up to 47.8 ± 8.9 ml/kg/min, corresponding to 100.6% of predetermined V̇O2max. The HS group achieved a greater highest point of V̇O2 in relation to V̇O2max than the LS group (108.0 vs. 93.7%). During the exercise intervals, V̇O2 exceeded V̇CO2, while during the rest intervals, V̇CO2 surpassed V̇O2. Our findings suggest that the oxygen demand during squatting is notably substantial, which may vary according to the training status.

Validity of the Ekblom-Bak Cycle Ergometer Test in Patients with Cardiovascular Disease.

OBJECTIVE: To assess the validity of the Ekblom-Bak cycle ergometer test in patients with cardiovascular disease admitted to cardiac rehabilitation. METHODS: Estimated peak oxygen consumption from the Ekblom-Bak test was compared with directly measured peak oxygen consumption from a treadmill cardiopulmonary exercise test. Patients completed the cardiopulmonary exercise test first, followed by the Ekblom-Bak test after 24 h rest. Pearson's correlation coefficient (r) was used to establish the correlation between estimated and measured peak oxygen consumption, and Bland-Altman plots with limits of agreement were used to determine the bias between the 2 tests. RESULTS: Twenty-six patients were included in the final analysis. The Ekblom-Bak test significantly overestimated peak oxygen consumption. Agreement between estimated and measured peak oxygen consumption was: bias = 4.3 mL/kg/min (limits of agreement: -4.0-12.6 mL/kg/min). CONCLUSION: The Ekblom-Bak test overestimated peak oxygen consumption to such an extent that it cannot accurately assess cardiorespiratory fitness in patients with cardiovascular disease. Thus, the cardiopulmonary exercise test remains the test of choice.

Cardiopulmonary exercise testing in long covid shows the presence of dysautonomia or chronotropic incompetence independent of subjective exercise intolerance and fatigue.

BACKGROUND: After COVID-19 infection, 10-20% of patients suffer from varying symptoms lasting more than 12 weeks (Long COVID, LC). Exercise intolerance and fatigue are common in LC. The aim was to measure the maximal exercise capacity of the LC patients with these symptoms and to analyze whether this capacity was related to heart rate (HR) responses at rest and during exercise and recovery, to find out possible sympathetic overactivity, dysautonomia or chronotropic incompetence. METHODS: Cardiopulmonary exercise test was conducted on 101 LC patients, who were admitted to exercise testing. The majority of them (86%) had been treated at home during their acute COVID-19 infection. Peak oxygen uptake (VO2peak), maximal power during the last 4 min of exercise (Wlast4), HRs, and other exercise test variables were compared between those with or without subjective exercise intolerance, fatigue, or both. RESULTS: The measurements were performed in mean 12.7 months (SD 5.75) after COVID-19 infection in patients with exercise intolerance (group EI, 19 patients), fatigue (group F, 31 patients), their combination (group EI + F, 37 patients), or neither (group N, 14 patients). Exercise capacity was, in the mean, normal in all symptom groups and did not significantly differ among them. HRs were higher in group EI + F than in group N at maximum exercise (169/min vs. 158/min, p = 0.034) and 10 min after exercise (104/min vs. 87/min, p = 0.028). Independent of symptoms, 12 patients filled the criteria of dysautonomia associated with slightly decreased Wlast4 (73% vs. 91% of sex, age, height, and weight-based reference values p = 0.017) and 13 filled the criteria of chronotropic incompetence with the lowest Wlast4 (63% vs. 93%, p < 0.001), VO2peak (70% vs. 94%, p < 0.001), the lowest increase of systolic blood pressure (50 mmHg vs. 67 mmHg, p = 0.001), and the greatest prevalence of slight ECG-findings (p = 0.017) compared to patients without these features. The highest prevalence of chronotropic incompetence was seen in the group N (p = 0.022). CONCLUSIONS: This study on LC patients with different symptoms showed that cardiopulmonary exercise capacity was in mean normal, with increased sympathetic activity in most patients. However, we identified subgroups with dysautonomia or chronotropic incompetence with a lowered exercise capacity as measured by Wlast4 or VO2peak. Subjective exercise intolerance and fatigue poorly foresaw the level of exercise capacity. The results could be used to plan the rehabilitation from LC and for selection of the patients suitable for it.

Metabolic features of neutrophilic differentiation of HL-60 cells in hyperglycemic environments.

INTRODUCTION: Chronic hyperglycemia affects neutrophil functions, leading to reduced pathogen killing and increased morbidity. This impairment has been directly linked to increased glycemia, however, how this specifically affects neutrophils metabolism and their differentiation in the bone marrow is unclear and difficult to study. RESEARCH DESIGN AND METHODS: We used high-resolution respirometry to investigate the metabolism of resting and activated donor neutrophils, and flow cytometry to measure surface CD15 and CD11b expression. We then used HL-60 cells differentiated towards neutrophil-like cells in standard media and investigated the effect of doubling glucose concentration on differentiation metabolism. We measured the oxygen consumption rate (OCR), and the enzymatic activity of carnitine palmitoyl transferase 1 (CPT1) and citrate synthase during neutrophil-like differentiation. We compared the surface phenotype, functions, and OCR of neutrophil-like cells differentiated under both glucose concentrations. RESULTS: Donor neutrophils showed significant instability of CD11b and OCR after phorbol 12-myristate 13-acetate stimulation at 3 hours post-enrichment. During HL-60 neutrophil-like cell differentiation, there was a significant increase in surface CD15 and CD11b expression together with the loss of mitochondrial mass. Differentiated neutrophil-like cells also exhibited higher CD11b expression and were significantly more phagocytic. In higher glucose media, we measured a decrease in citrate synthase and CPT1 activities during neutrophil-like differentiation. CONCLUSIONS: HL-60 neutrophil-like differentiation recapitulated known molecular and metabolic features of human neutrophil differentiation. Increased glucose concentrations correlated with features described in hyperglycemic donor neutrophils including increased CD11b and phagocytosis. We used this model to describe metabolic features of neutrophil-like cell differentiation in hyperglycemia and show for the first time the downregulation of CPT1 and citrate synthase activity, independently of mitochondrial mass.

Bioenergetic and Inflammatory Alterations in Regressed and Non-Regressed Patients with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is associated with multiple physiological abnormalities. Current laboratory and clinical evidence most commonly report mitochondrial dysfunction, oxidative stress, and immunological imbalance in almost every cell type of the body. The present work aims to evaluate oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and inflammation-related molecules such as Cyclooxygenase-2 (COX-2), chitinase 3-like protein 1 (YKL-40), Interleukin-1 beta (IL-1ß), Interleukin-9 (IL-9) in ASD children with and without regression compared to healthy controls. Children with ASD (n = 56) and typically developing children (TDC, n = 12) aged 1.11 to 11 years were studied. Mitochondrial activity was examined in peripheral blood mononuclear cells (PBMCs) isolated from children with ASD and from the control group, using a metabolic analyzer. Gene and protein levels of IL-1ß, IL-9, COX-2, and YKL-40 were investigated in parallel. Our results showed that PBMCs of the ASD subgroup of regressed patients (ASD R(+), n = 21) had a specific pattern of mitochondrial activity with significantly increased maximal respiration, respiratory spare capacity, and proton leak compared to the non-regressed group (ASD R(-), n = 35) and TDC. Furthermore, we found an imbalance in the studied proinflammatory molecules and increased levels in ASD R(-) proving the involvement of inflammatory changes. The results of this study provide new evidence for specific bioenergetic profiles of immune cells and elevated inflammation-related molecules in ASD. For the first time, data on a unique metabolic profile in ASD R(+) and its comparison with a random group of children of similar age and sex are provided. Our data show that mitochondrial dysfunction is more significant in ASD R(+), while in ASD R(-) inflammation is more pronounced. Probably, in the group without regression, immune mechanisms (immune dysregulation, leading to inflammation) begin initially, and at a later stage mitochondrial activity is also affected under exogenous factors. On the other hand, in the regressed group, the initial damage is in the mitochondria, and perhaps at a later stage immune dysfunction is involved.

Characteristics of 16-17-year-old young males' physical development in the process of judo club activities.

OBJECTIVE: Aim: To investigate the influence of judo club activities on the physical development indicators of 16-17-year-old young males. PATIENTS AND METHODS: Materials and Methods: The research, conducted in 2022-2024, involved 54 young males aged 16-17, who were divided into experimental (EG) and control (CG) groups of 27 each. The physical development was assessed by body weight, hand dynamometry, lung capacity, heart rate, and blood pressure indicators. Cooper, Rufier, Stange, Genchi, vital, strength, body weight, Robinson, and maximum oxygen consumption indices were calculated. RESULTS: Results: The positive influence of judo club activities on the physical development of 16-17-year-old young males was revealed: all studied indicators significantly improved in the EG young males during the experiment. Judo training sessions had the most effective impact on the indicators characterizing the development of the muscular system and the level of strength qualities. At the end of the experiment, young males of the EG showed significantly better physical development than the CG representatives in terms of strength index (by 6.33 %), static endurance of stronger (by 2.07 s) and weaker (2.03 s) hands. According to the indicators characterizing the state of cardiovascular and respiratory systems, the indicators of young males of both groups were significantly the same. CONCLUSION: Conclusions: It has been established that judo club activities, which were conducted taking into account the age characteristics of 16-17-year-old young males, create the most favorable conditions for the harmonious physical development of boys, promoting their health and preparing them for future educational and professional activities.

The effect of tart cherry juice compared to a sports drink on cycling exercise performance, substrate metabolism, and recovery.

Tart cherries have low glycemic index, antioxidant and anti-inflammatory properties, and therefore may benefit performance and recovery from exercise. We determined the effects of consuming tart cherry juice versus a high-glycemic index sports drink on cycling performance, substrate oxidation, and recovery of low-frequency fatigue. Using a randomized, counter-balanced cross-over design, with one-month washout, 12 recreational cyclists (8 males and 4 females; 35±16y; VO2peak 38.2±7.4 ml/kg/min) consumed cherry juice or sports drink twice a day (300mL/d) for 4d before and 2d after exercise. On the exercise day, beverages (providing 1g/kg carbohydrate) were consumed 45min before 90min of cycling at 65%VO2peak, followed by a 10km time trial. Blood glucose, lactate, carbohydrate and fat oxidation, respiratory exchange ratio (RER), O2 cost of cycling, and rating of perceived exertion (RPE) were measured during the initial 90min of cycling. Muscle soreness, maximal voluntary contraction (MVC) and low-frequency fatigue were determined at baseline and after the time trial on the exercise day, and 30min after beverage consumption 24 and 48h later. There were no differences for time trial performance (17±3min cherry juice vs. 17±2min sports drink, p = 0.27) or any other measures between drink conditions. There were time main effects (p<0.05) for isometric MVC (decreasing) and low-frequency fatigue (increasing; i.e. decreased force at low relative to high stimulation frequencies), changing significantly from baseline to post-exercise and then returning to baseline at 24h post-exercise. Tart cherry juice was not effective for improving performance, substrate oxidation during exercise, and recovery from exercise, compared to a high-glycemic index sports drink.

Nuclear factor erythroid 2-related factor 2 activation in streptozotocin-induced diabetic rats normalize renal hemodynamics and oxygen consumption.

Background: Diabetic kidney disease is a major contributor to end stage renal disease. A change in kidney oxygen homeostasis leading to decreased tissue oxygen tension is an important factor initiating alterations in kidney function in diabetes. However, the mechanism contributing to changed oxygen homeostasis is still unclear. Hyperglycemia-induced production of reactive oxygen species and an altered response to them have previously been demonstrated. In the present study, chronic treatment with DL-sulforaphane to induce nuclear factor erythroid 2-related factor 2 (Nrf2) expression, a master transcriptional regulator binding to antioxidant response elements inducing increased protection against reactive oxygen species, is studied. Methods: Sprague-Dawley rats were made diabetic using streptozotocin and either left untreated or received daily subcutaneous injections of DL-sulforaphane for 4 weeks. Age-matched non-diabetic rats served as controls. After 4 weeks of treatment, rats were anesthetized using thiobutabarbital, and kidney functions were studied in terms of glomerular filtration rate (GFR), renal blood flow (RBF), sodium transport, kidney oxygen consumption, and kidney oxygen tension. Mitochondria was isolated from kidney cortical tissue and investigated using high-resolution respirometry. Results: GFR was increased in diabetics but not RBF resulting in increased filtration fraction in diabetics. DL-sulforaphane treatment did not affect RBF and GFR in controls but decreased the same parameters in diabetics. Increased GFR resulted in increased sodium transport and oxygen consumption, hence decreased efficiency in diabetics compared to controls. Increased oxygen consumption in diabetics resulted in decreased cortical tissue oxygen tension. DL-sulforaphane treatment decreased oxygen consumption in diabetics, whereas transport efficiency was not significantly affected. DL-sulforaphane treatment increased cortical pO2 in diabetics. Conclusions: DL-sulforaphane treatment affects renal hemodynamics, improving cortical oxygen tension but not mitochondrial efficiency.

Effect of real-time oxygen consumption versus fixed flow-based low flow anesthesia on oxygenation and perfusion: a randomized, single-blind study.

Although low-flow anesthesia is widely used due to its various advantages, there are concerns about potential and relative hypoxia. Furthermore, oxygen is also a drug with benefits and adverse effects. We aimed to evaluate and compare the effect of real-time oxygen consumption versus fixed flow-based low flow anesthesia on oxygenation and perfusion and to compare the economic benefits. With ethical approvals and informed consent, participants were randomly assigned to a dynamic group (13 males, and 27 females) receiving fresh gas flows depending on real-time oxygen consumption (dynamic O2: N2O), and a fixed group (20 males, and 13 females) receiving fixed fresh gas flows of 600 mL/min (with O2: N2O of 1:1). Oxygen partial pressure and serum lactate were comparable between groups. However, isoflurane consumed and costs incurred were significantly different. Total oxygen consumption per minute was also significantly lower in the dynamic group than the fixed group. No episodes of hypoxia were observed in either group. Real-time oxygen consumption-based low flow anesthesia is feasible and cost-effective without affecting the patient's global perfusion and outcome.

The Glucose-Glutamine Metabolic Interplay in MCF-7 Cells, a Hormone-Sensitive Breast Cancer Model.

BACKGROUND: Selective deprivation of glutamine has been shown to accelerate the generation of reactive oxygen species (ROS) and to impair the activity of a specific pentose phosphate pathway (PPP) located within the endoplasmic reticulum (ER). The consequent oxidative damage suggests that glucose flux through this reticular pathway might contribute to the redox stress of breast cancer cells. We thus evaluated whether this response is reproduced when the glutamine shortage is coupled with the glucose deprivation. METHODS: Cancer growth, metabolic plasticity and redox status were evaluated under saturating conditions and after 48 h starvation (glucose 2.5 mM, glutamine 0.5 mM). The Seahorse technology was used to estimate adenosine triphosphate (ATP)-linked and ATP-independent oxygen consumption rate (OCR) as well as proton efflux rate (PER). 18F-fluoro-deoxy-glucose (FDG) uptake was evaluated through the LigandTracer device. Proliferation rate was estimated by the carboxyfluorescein-diacetate-succinimidyl ester (CFSE) staining, while cell viability by the propidium iodide exclusion assay. RESULTS: Starvation reduced the proliferation rate of MCF-7 cells without affecting their viability. It also decreased lactate release and PER. Overall OCR was left unchanged although ATP-synthase dependent fraction was increased under nutrient shortage. Glutaminolysis inhibition selectively impaired the ATP-independent and the oligomycin-sensitive OCR in control and starved cultures, respectively. The combined nutrient shortage decreased the cytosolic and mitochondrial markers of redox stress. It also left unchanged the expression of the reticular unfolded protein marker GRP78. By contrast, starvation decreased the expression of hexose-6P-dehydrogenase (H6PD) thus decreasing the glucose flux through the ER-PPP as documented by the profound impairment in the uptake rate of FDG. CONCLUSIONS: When combined with glucose deprivation, glutamine shortage does not elicit the expected enhancement of ROS generation in the studied breast cancer cell line. Combined with the decreased activity of ER-PPP, this observation suggests that glutamine interferes with the reticular glucose metabolism to regulate the cell redox balance.

Reduced autonomic function in patients with long-COVID-19 syndrome is mediated by cardiorespiratory fitness.

BACKGROUND: Long-COVID-19 syndrome (LCS) exhibits neurological problems such as peripheral neuropathy and autonomic nervous system (ANS) dysfunction. Exercise intolerance and, consequently, low cardiorespiratory fitness (CRF) are some of the most common symptoms of LCS. We describe a series of individuals exhibiting LCS symptoms compared to a control group and posit that this condition may be related to the exercise capacity-mediated disruption of the ANS resulting particularly in exercise intolerance. METHODS: This study included 87 individuals with LCS and 71 control participants without COVID-19 diagnoses. Heart rate variability (HRV) in supine position is commonly measured to diagnose autonomic dysregulation and subsequently analyzed using the Kubios software (Kuopio, Finland). CRF (peak VO2), post-COVID-19 patient-reported symptoms, maximal muscle strength (grip strength, bilateral leg press, leg extension, pectoral press, and back press exercises), and body composition were also measured. Analysis of covariance (ANCOVA) and mediation analysis were employed to assess the associations among LCS, peak VO2, and HRV indicators. Two-sided p < 0.05 was considered as significant. RESULTS: The HRV parameters-RR interval, RMSSD, SDNN, PNS index, LF, HF, total power, SD1, and SD2-were significantly elevated (p < 0.05) in the control group when compared to the LCS patients. In contrast, the HR, stress index, and SNS index parameters were significantly higher (p < 0.05) in the LCS group. When adjusted for RR intervals, these parameters remained statistically significant (p < 0.05). A partially mediated effect was found between peak VO2 and RMSSD (mediation effect = 24.4%) as well as peak VO2 and SDNN (mediation effect = 25.1%) in the LCS patients. CONCLUSIONS: These findings contribute new insights on the interplay between CRF and HRV indicators as well as endorse that dysautonomia may be related to the low peak VO2 observed in long COVID-19 patients.

Autonomous Oscillatory Mitochondrial Respiratory Activity: Results of a Systematic Analysis Show Heterogeneity in Different In Vitro-Synchronized Cancer Cells.

Circadian oscillations of several physiological and behavioral processes are an established process in all the organisms anticipating the geophysical changes recurring during the day. The time-keeping mechanism is controlled by a transcription translation feedback loop involving a set of well-characterized transcription factors. The synchronization of cells, controlled at the organismal level by a brain central clock, can be mimicked in vitro, pointing to the notion that all the cells are endowed with an autonomous time-keeping system. Metabolism undergoes circadian control, including the mitochondrial terminal catabolic pathways, culminating under aerobic conditions in the electron transfer to oxygen through the respiratory chain coupled to the ATP synthesis according to the oxidative phosphorylation chemiosmotic mechanism. In this study, we expanded upon previous isolated observations by utilizing multiple cell types, employing various synchronization protocols and different methodologies to measure mitochondrial oxygen consumption rates under conditions simulating various metabolic stressors. The results obtained clearly demonstrate that mitochondrial respiratory activity undergoes rhythmic oscillations in all tested cell types, regardless of their individual respiratory proficiency, indicating a phenomenon that can be generalized. However, notably, while primary cell types exhibited similar rhythmic respiratory profiles, cancer-derived cell lines displayed highly heterogeneous rhythmic changes. This observation confirms on the one hand the dysregulation of the circadian control of the oxidative metabolism observed in cancer, likely contributing to its development, and on the other hand underscores the necessity of personalized chronotherapy, which necessitates a detailed characterization of the cancer chronotype.

Accuracy of a non-exercise method using seismocardiography for the estimation of V̇O2peak in sub-elite football players.

A non-exercise method equation using seismocardiography for estimating V̇O2peak (SCG V̇O2peak) has previously been validated in healthy subjects. However, the performance of the SCG V̇O2peak within a trained population is unknown, and the ability of the model to detect changes over time is not well elucidated. Forty-seven sub-elite football players were tested at the start of pre-season (SPS) and 36 players completed a test after eight weeks at the end of the pre-season (EPS). Testing included an SCG V̇O2peak estimation at rest and a graded cardiopulmonary exercise test (CPET) on a treadmill for determination of V̇O2peak. Agreement between SCG V̇O2peak and CPET V̇O2peak showed a large underestimation at SPS (bias ± 95% CI: -9.9 ± 1.8, 95% Limits of Agreement: 2.2 to -22.0 mL·min-1 kg-1). At EPS no interaction (p = 0.3590) but a main effect of time (p < 0.0001) and methods (p < 0.0001) was observed between SCG and CPET V̇O2peak. No correlation in V̇O2peak changes was observed between SCG and CPET (r = -20.0, p = 0.2484) but a fair agreement in classifying the correct directional change in V̇O2peak with the SCG method was found (Cohen's κ coefficient = 0.28 ± 0.25). Overall, the SCG V̇O2peak method lacks accuracy and despite being able to estimate group changes, it was incapable of detecting individual changes in V̇O2peak following a pre-season period in sub-elite football players. The SCG algorithm needs to be further adjusted and the accuracy and precision improved for the method to be applicable for use within a trained population.

Aerobic high-intensity interval training and maximal strength training in patients with unspecific musculoskeletal disorders improve V̇O2peak and maximal strength more than moderate training.

Improving peak oxygen uptake (V̇O2peak) and maximal strength are key objectives of rehabilitation for patients with unspecific musculoskeletal disorders (MSDs). Although high-intensity training yield superior outcomes for these factors, patients with MSDs may not tolerate high-intensity due to pain and fear. Therefore, we examined the effect and feasibility of incorporating aerobic high-intensity intervals (HIITs) and maximal strength training (MST) in a standard clinical rehabilitation program for patients with unspecific MSDs. 73 patients (45 ± 10 years) with MSDs partaking in a standard, public, and 4-week rehabilitation program were randomized to high-intensity training (HG: 4 × 4 minutes intervals at ∼90% of maximal heart rate; HRmax, and 4 × 4 repetitions leg press at ∼90% of 1 repetition maximum; 1RM, with maximal intended velocity) or keep todays treatment of low-to moderate-intensity training (MG: various cycling, walking, and/or running activities at ∼70%-80% of HRmax and 3 × 8 - 10 repetitions leg press at ∼75% of 1RM without maximal intended velocity). HG improved V̇O2peak (12 ± 7%) and leg press 1RM (43 ± 34%) more than moderate-intensity group (V̇O2peak; 5 ± 6%, 1RM; 19 ± 18%, both p < 0.001). We observed that no adverse events and no between-group differences in dropout rate or self-reported quality of life (both p > 0.05). There were positive correlations between improved V̇O2peak and improved physical (p = 0.024) and emotional (0.016) role functioning. We conclude that both high-intensity interval training and MST are feasible and improve V̇O2peak and maximal strength more than standard low-to moderate-intensity treatment of patients with unspecific MSDs. Our findings suggest that high-intensity training should be implemented as a part of standard clinical care of this patient population.

Adjunctive hiking bouts during 8 weeks regular sailing training improves cardiorespiratory and muscular responses during hiking emulation in highly trained sailors.

To investigate the effects of 8-week hiking bench training on cardiorespiratory and muscular responses of highly trained sailors during hiking emulation. Twenty-four sailors were assigned into two groups: the hiking bench training group (HTG, n = 12) and the control group (CG, n = 12). Both groups maintained their regular training with the HTG performed two additional hiking bench training sessions per week for 8 weeks, while the CG performed an equivalent duration of on-water sailing training. Physiological responses were assessed by performing four successive 3-min hiking bouts on a sailing emulation ergometer before and after the 8-week training period. Comparing the pretest, both groups exhibited a significant decrease (p < 0.05) in the percentage of maximal oxygen uptake (%VO2max) and maximal heart rate (%HRmax); the HTG experienced a greater decrease in %VO2max in bouts 2 and 3. The root mean square (RMS) of rectus femoris (RF), vastus lateralis (VL), rectus abdominis (RA), and external oblique decreased significantly (p < 0.05), whereas the mean power frequency (MPF) of RF, VL, and RA exhibited an increasing trend. The RMS of RF and RA in HTG were lower than those in CG in the initial three bouts; VL and EA in HTG were lower than those in CG in bouts 1 and 2 (p < 0.05). The MPF of RA in HTG was significantly increased in bouts 2, 3, and 4 (p < 0.05). Eight-week hiking bench training could improve hiking economy and the activation of lower limb and trunk muscles delaying the onset of fatigue in sailors.

Workload and spirometry associated with untethered swimming in horses.

BACKGROUND: Swimming has been used empirically for rehabilitation and conditioning of horses. However, due to challenges imposed by recording physiological parameters in water, the intensity of free swimming effort is unknown. OBJECTIVES: Measure the physiological workload associated with untethered swimming in horses. Five fit Arabian endurance horses were assessed while swimming in a 100 m-long indoor pool. Horses were equipped with a modified ergospirometry facemask to measure oxygen consumption (V̇O2) and ventilatory parameters (inspired/expired volumes, VI, VE; peak inspiratory/expiratory flows, PkVI, PkVE; respiratory frequency, Rf; minute ventilation, VE; inspiratory/expiratory durations and ratios, tI, tE, tI/ttot, tE/ttot); and an underwater electrocardiogram that recorded heart rate (HR). Postexercise venous blood lactate and ammonia concentrations were measured. Data are reported as median (interquartile ranges). RESULTS: Horses showed bradypnea (12 breaths/min (10-16)) for the first 30 s of swimming. V̇O2 during swimming was 43.2 ml/(kg.min) (36.0-56.6). Ventilatory parameters were: VI = 16.7 L (15.3-21.8), VE = 14.7 L (12.4-18.9), PkVI = 47.8 L/s (45.8-56.5), PkVE = 55.8 L/s (38.3-72.5), Rf = 31.4 breaths/min (20.0-33.8), VE = 522.9 L/min (414.7-580.0), tI = 0.5 s (0.5-0.6), tE = 1.2 s (1.1-1.6), tI/ttot = 0.3 (0.2-0.4), tE/ttot = 0.7 (0.6-0.8). Expiratory flow tracings showed marked oscillations that coincided with a vibrating expiratory sound. HR was 178.0 bpm (148.5-182.0), lactate = 1.5 mmol/L (1.0-1.9) and ammonia = 41.0 µmol/L (36.5-43.5). CONCLUSIONS: Free (untethered) swimming represents a submaximal, primarily aerobic exercise in horses. The breathing pattern during swimming is unique, with a relatively longer apneic period at the beginning of the exercise and an inspiratory time less than half that of expiration.

Multi-omic analysis of bat versus human fibroblasts reveals altered central metabolism.

Bats have unique characteristics compared to other mammals, including increased longevity and higher resistance to cancer and infectious disease. While previous studies have analyzed the metabolic requirements for flight, it is still unclear how bat metabolism supports these unique features, and no study has integrated metabolomics, transcriptomics, and proteomics to characterize bat metabolism. In this work, we performed a multi-omics data analysis using a computational model of metabolic fluxes to identify fundamental differences in central metabolism between primary lung fibroblast cell lines from the black flying fox fruit bat (Pteropus alecto) and human. Bat cells showed higher expression levels of Complex I components of electron transport chain (ETC), but, remarkably, a lower rate of oxygen consumption. Computational modeling interpreted these results as indicating that Complex II activity may be low or reversed, similar to an ischemic state. An ischemic-like state of bats was also supported by decreased levels of central metabolites and increased ratios of succinate to fumarate in bat cells. Ischemic states tend to produce reactive oxygen species (ROS), which would be incompatible with the longevity of bats. However, bat cells had higher antioxidant reservoirs (higher total glutathione and higher ratio of NADPH to NADP) despite higher mitochondrial ROS levels. In addition, bat cells were more resistant to glucose deprivation and had increased resistance to ferroptosis, one of the characteristics of which is oxidative stress. Thus, our studies revealed distinct differences in the ETC regulation and metabolic stress responses between human and bat cells.