Nanoplastics Penetrate Human Bronchial Smooth Muscle and Small Airway Epithelial Cells and Affect Mitochondrial Metabolism.

Micro- and nanoplastic particles, including common forms like polyethylene and polystyrene, have been identified as relevant pollutants, potentially causing health problems in living organisms. The mechanisms at the cellular level largely remain to be elucidated. This study aims to visualize nanoplastics in bronchial smooth muscle (BSMC) and small airway epithelial cells (SAEC), and to assess the impact on mitochondrial metabolism. Healthy and asthmatic human BSMC and SAEC in vitro cultures were stimulated with polystyrene nanoplastics (PS-NPs) of 25 or 50 nm size, for 1 or 24 h. Live cell, label-free imaging by holotomography microscopy and mitochondrial respiration and glycolysis assessment were performed. Furthermore, 25 and 50 nm NPs were shown to penetrate SAEC, along with healthy and diseased BSMC, and they impaired bioenergetics and induce mitochondrial dysfunction compared to cells not treated with NPs, including changes in oxygen consumption rate and extracellular acidification rate. NPs pose a serious threat to human health by penetrating airway tissues and cells, and affecting both oxidative and glycolytic metabolism.

Re-evaluating the Need for Routine Maximal Aerobic Capacity Testing within Fighter Pilots.

INTRODUCTION: There is a current belief in aviation suggesting that aerobic training may reduce G-tolerance due to potential negative impacts on arterial pressure response. Studies indicate that increasing maximal aerobic capacity (V˙o2 max) through aerobic training does not hinder G-tolerance. Moreover, sustained centrifuge training programs revealed no instances where excessive aerobic exercise compromised a trainee's ability to complete target profiles. The purpose of this review article is to examine the current research in the hope of establishing the need for routine V˙o2-max testing in air force pilot protocols.METHODS: A systematic search of electronic databases including Google Scholar, PubMed, the Aerospace Medical Association, and Military Medicine was conducted. Keywords related to "human performance," "Air Force fighter pilots," "aerobic function," and "maximal aerobic capacity" were used in various combinations. Articles addressing exercise physiology, G-tolerance, physical training, and fighter pilot maneuvers related to human performance were considered. No primary data collection involving human subjects was conducted; therefore, ethical approval was not required.RESULTS: The V˙o2-max test provides essential information regarding a pilot's ability to handle increased Gz-load. It assists in predicting G-induced loss of consciousness by assessing anti-G straining maneuver performance and heart rate variables during increased G-load.DISCUSSION: V˙o2-max testing guides tailored exercise plans, optimizes cardiovascular health, and disproves the notion that aerobic training hampers G-tolerance. Its inclusion in air force protocols could boost readiness, reduce health risks, and refine training for fighter pilots' safety and performance. This evidence-backed approach supports integrating V˙o2-max testing for insights into fitness, risks, and tailored exercise.Zeigler Z, Acevedo AM. Re-evaluating the need for routine maximal aerobic capacity testing within fighter pilots. Aerosp Med Hum Perform. 2024; 95(5):273-277.

Are incremental exercise relationships between rating of perceived exertion and oxygen uptake or heart rate reserve valid during steady-state exercises?

Background: Rating of perceived exertion (RPE) is considered a valid method for prescribing prolonged aerobic steady-state exercise (SSE) intensity due to its association with physiological indicators of exercise intensity, such as oxygen uptake (V̇O2) or heart rate (HR). However, these associations between psychological and physiological indicators of exercise intensity were found during graded exercise tests (GXT) but are currently used to prescribe SSE intensity even though the transferability and validity of the relationships found during GXT to SSE were not investigated. The present study aims to verify whether (a) RPE-HR or RPE-V̇O2 relations found during GXTs are valid during SSEs, and (b) the duration and intensity of SSE affect these relations. Methods: Eight healthy and physically active males (age 22.6 ± 1.2 years) were enrolled. On the first visit, pre-exercise (during 20 min standing) and maximal (during a GXT) HR and V̇O2 values were measured. Then, on separate days, participants performed 4 SSEs on the treadmill by running at 60% and 80% of the HR reserve (HRR) for 15 and 45 min (random order). Individual linear regressions between GXTs' RPE (dependent variable) and HRR and V̇O2 reserve (V̇O2R) values (computed as the difference between maximal and pre-exercise values) were used to predict the RPE associated with %HRR (RPEHRR) and %V̇O2R (RPEV̇O2R) during the SSEs. For each relation (RPE-%HRR and RPE-%V̇O2R), a three-way factorial repeated measures ANOVA (α = 0.05) was used to assess if RPE (dependent variable) was affected by exercise modality (i.e., RPE recorded during SSE [RPESSE] or GXT-predicted), duration (i.e., 15 or 45 min), and intensity (i.e., 60% or 80% of HRR). Results: The differences between RPESSE and GXT-predicted RPE, which were assessed by evaluating the effect of modality and its interactions with SSE intensity and duration, showed no significant differences between RPESSE and RPEHRR. However, when RPESSE was compared with RPEV̇O2R, although modality or its interactions with intensity were not significant, there was a significant (p = 0.020) interaction effect of modality and duration yielding a dissociation between changes of RPESSE and RPEV̇O2R over time. Indeed, RPESSE did not change significantly (p = 0.054) from SSE of 15 min (12.1 ± 2.0) to SSE of 45 min (13.5 ± 2.1), with a mean change of 1.4 ± 1.8, whereas RPEV̇O2R decreased significantly (p = 0.022) from SSE of 15 min (13.7 ± 3.2) to SSE of 45 min (12.4 ± 2.8), with a mean change of -1.3 ± 1.5. Conclusion: The transferability of the individual relationships between RPE and physiological parameters found during GXT to SSE should not be assumed as shown by the results of this study. Therefore, future studies modelling how the exercise prescription method used (e.g., RPE, HR, or V̇O2) and SSE characteristics (e.g., exercise intensity, duration, or modality) affect the relationships between RPE and physiological parameters are warranted.

Life's Essential 8 Cardiovascular Health Score and Cardiorespiratory Fitness in the Community.

BACKGROUND: The relation of cardiorespiratory fitness (CRF) to lifestyle behaviors and factors linked with cardiovascular health remains unclear. We aimed to understand how the American Heart Association's Life's Essential 8 (LE8) score (and its changes over time) relate to CRF and complementary exercise measures in community-dwelling adults. METHODS AND RESULTS: Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise testing for direct quantification of peak oxygen uptake (V̇O2). A 100-point LE8 score was constructed as the average across 8 factors: diet, physical activity, nicotine exposure, sleep, body mass index, lipids, blood glucose, and blood pressure. We related total LE8 score, score components, and change in LE8 score over 8 years with peak V̇O2 (log-transformed) and complementary CRF measures. In age- and sex-adjusted linear models (N=1838, age 54±9 years, 54% women, LE8 score 76±12), a higher LE8 score was associated favorably with peak V̇O2, ventilatory efficiency, resting heart rate, and blood pressure response to exercise (all P<0.0001). A clinically meaningful 5-point higher LE8 score was associated with a 6.0% greater peak V̇O2 (≈1.4 mL/kg per minute at sample mean). All LE8 components were significantly associated with peak V̇O2 in models adjusted for age and sex, but blood lipids, diet, and sleep health were no longer statistically significant after adjustment for all LE8 components. Over an ≈8-year interval, a 5-unit increase in LE8 score was associated with a 3.7% higher peak V̇O2 (P<0.0001). CONCLUSIONS: Higher LE8 score and improvement in LE8 over time was associated with greater CRF, highlighting the importance of the LE8 factors in maintaining CRF.

Comparable Ventilatory Inefficiency at Maximal and Submaximal Performance in COPD vs. CHF subjects: An Innovative Approach. / Ineficiência Ventilatória Comparável no Desempenho Máximo e Submáximo em Indivíduos com DPOC e ICC: Uma Abordagem Inovadora.

BACKGROUND: Currently, excess ventilation has been grounded under the relationship between minute-ventilation/carbon dioxide output ( V ˙ E - V ˙ CO 2 ). Alternatively, a new approach for ventilatory efficiency ( η E V ˙ ) has been published. OBJECTIVE: Our main hypothesis is that comparatively low levels of η E V ˙ between chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are attainable for a similar level of maximum and submaximal aerobic performance, conversely to long-established methods ( V ˙ E - V ˙ CO 2 slope and intercept). METHODS: Both groups performed lung function tests, echocardiography, and cardiopulmonary exercise testing. The significance level adopted in the statistical analysis was 5%. Thus, nineteen COPD and nineteen CHF-eligible subjects completed the study. With the aim of contrasting full values of V ˙ E - V ˙ CO 2 and η V ˙ E for the exercise period (100%), correlations were made with smaller fractions, such as 90% and 75% of the maximum values. RESULTS: The two groups attained matched characteristics for age (62±6 vs. 59±9 yrs, p>.05), sex (10/9 vs. 14/5, p>0.05), BMI (26±4 vs. 27±3 Kg m2, p>0.05), and peak V ˙ O 2 (72±19 vs. 74±20 %pred, p>0.05), respectively. The V ˙ E - V ˙ CO 2 slope and intercept were significantly different for COPD and CHF (27.2±1.4 vs. 33.1±5.7 and 5.3±1.9 vs. 1.7±3.6, p<0.05 for both), but η V ˙ E average values were similar between-groups (10.2±3.4 vs. 10.9±2.3%, p=0.462). The correlations between 100% of the exercise period with 90% and 75% of it were stronger for η V ˙ E (r>0.850 for both). CONCLUSION: The η V ˙ E is a valuable method for comparison between cardiopulmonary diseases, with so far distinct physiopathological mechanisms, including ventilatory constraints in COPD.

FUNDAMENTO: Atualmente, o excesso de ventilação tem sido fundamentado na relação entre ventilação-minuto/produção de dióxido de carbono ( V ˙ E − V ˙ CO 2 ). Alternativamente, uma nova abordagem para eficiência ventilatória ( η E V ˙ ) tem sido publicada. OBJETIVO: Nossa hipótese principal é que níveis comparativamente baixos de η E V ˙ entre insuficiência cardíaca crônica (ICC) e doença pulmonar obstrutiva crônica (DPOC) são atingíveis para um nível semelhante de desempenho aeróbico máximo e submáximo, inversamente aos métodos estabelecidos há muito tempo (inclinação V ˙ E − V ˙ CO 2 e intercepto). MÉTODOS: Ambos os grupos realizaram testes de função pulmonar, ecocardiografia e teste de exercício cardiopulmonar. O nível de significância adotada na análise estatística foi 5%. Assim, dezenove indivíduos elegíveis para DPOC e dezenove indivíduos elegíveis para ICC completaram o estudo. Com o objetivo de contrastar valores completos de V ˙ E − V ˙ CO 2 e η E V ˙ para o período de exercício (100%), correlações foram feitas com frações menores, como 90% e 75% dos valores máximos. RESULTADOS: Os dois grupos tiveram características correspondentes para a idade (62±6 vs 59±9 anos, p>.05), sexo (10/9 vs 14/5, p>0,05), IMC (26±4 vs 27±3 Kg m2, p>0,05), e pico V ˙ O 2 (72±19 vs 74±20 % pred, p>0,05), respectivamente. A inclinação V ˙ E − V ˙ CO 2 e intercepto foram significativamente diferentes para DPOC e ICC (207,2±1,4 vs 33,1±5,7 e 5,3±1,9 vs 1,7±3,6, p<0,05 para ambas), mas os valores médios da η E V ˙ foram semelhantes entre os grupos (10,2±3,4 vs 10,9±2,3%, p=0,462). As correlações entre 100% do período do exercício com 90% e 75% dele foram mais fortes para η E V ˙ (r>0,850 para ambos). CONCLUSÃO: A η E V ˙ é um método valioso para comparação entre doenças cardiopulmonares, com mecanismos fisiopatológicos até agora distintos, incluindo restrições ventilatórias na DPOC.

Respiratory symptom perception during exercise in patients with heart failure with preserved ejection fraction.

We investigated whether central or peripheral limitations to oxygen uptake elicit different respiratory sensations and whether dyspnea on exertion (DOE) provokes unpleasantness and negative emotions in patients with heart failure with preserved ejection fraction (HFpEF). 48 patients were categorized based on their cardiac output (Q̇c)/oxygen uptake (V̇O2) slope and stroke volume (SV) reserve during an incremental cycling test. 15 were classified as centrally limited and 33 were classified as peripherally limited. Ratings of perceived breathlessness (RPB) and unpleasantness (RPU) were assessed (Borg 0-10 scale) during a 20 W cycling test. 15 respiratory sensations statements (1-10 scale) and 5 negative emotions statements (1-10) were subsequently rated. RPB (Central: 3.5±2.0 vs. Peripheral: 3.4±2.0, p=0.86), respiratory sensations, or negative emotions were not different between groups (p>0.05). RPB correlated (p<0.05) with RPU (r=0.925), "anxious" (r=0.610), and "afraid" (r=0.383). While DOE provokes elevated levels of negative emotions, DOE and respiratory sensations seem more related to a common mechanism rather than central and/or peripheral limitations in HFpEF.

Maximal cardiopulmonary exercise testing in glioblastoma patients undergoing chemotherapy: assessment of feasibility, safety, and physical fitness status.

PURPOSE: Maximal cardiopulmonary exercise testing (max. CPET) provides the most accurate measurement of cardiorespiratory fitness. However, glioblastoma (GBM) patients often undergo less intensive tests, e.g., 6-min walk test or self-rating scales. This study aims to demonstrate feasibility and safety of max. CPET in GBM patients, concurrently evaluating their physical fitness status. METHODS: Newly diagnosed GBM patients undergoing adjuvant chemotherapy were offered participation in an exercise program. At baseline, max. CPET assessed cardiorespiratory fitness including peak oxygen consumption (VO2peak), peak workload, and physical work capacity (PWC) at 75% of age-adjusted maximal heart rate (HR). Criteria for peak workload were predefined based on threshold values in HR, respiratory quotient, respiratory equivalent, lactate, and rate of perceived effort. Data were compared to normative values. Adverse events were categorized according to standardized international criteria. Further, self-reported exercise data pre- and post-diagnosis were gathered. RESULTS: All 36 patients (median-aged 60; 21 men) met the predefined criteria for peak workload. Mean absolute VO2peak was 1750 ± 529 ml/min, peak workload averaged 130 ± 43 W, and mean PWC was 0.99 ± 0.38 W/kg BW, all clinically meaningful lower than age- and sex-predicted normative values (87%, 79%, 90%, resp.). Only once (3%) a minor, transient side effect occurred (post-test dizziness, no intervention needed). Self-reported exercise decreased from 15.8 MET-h/week pre-diagnosis to 7.2 MET-h/week post-diagnosis. CONCLUSION: Max. CPET in this well-defined population proved feasible and safe. GBM patients exhibit reduced cardiorespiratory fitness, indicating the need for tailored exercise to enhance health and quality of life. CPET could be essential in establishing precise exercise guidelines.

Energy metabolism and respirometry of lambs fed sun or shade dried hays of banana crop residues.

We aimed to evaluate the effects of different drying methods for banana residues on the energy metabolism and respirometry of growing lambs. Twenty Santa Inês x Dorper lambs were fed five experimental diets: Tifton 85 grass hay (Control), shade-dried banana leaf hay (LH Shade), shade-dried pseudostem banana hay (PH Shade), sun-dried banana leaf hay (LH Sun), and sun-dried banana pseudostem hay (PH Sun). Nutrient intake and digestibility were assessed in metabolic cages, whereas O2 consumption and CO2, methane, and heat production were measured in a respirometry chamber with animals fed at maintenance and ad libitum levels. Nutrient and energy intake was not influenced by diet. Pseudostem hay had higher apparent digestibility of dry matter (71.5%), organic matter (72.4%), and neutral detergent fiber (58.0%). However, this led to greater energy loss in the form of methane (12.1%). The banana residue hays and drying methods did not alter oxygen consumption, CO2 production, or heat production of animals fed ad libitum or during maintenance. On the other hand, the use of leaf hay resulted in a reduction of 24.7% in enteric methane production of animals fed ad libitum. The inclusion of pseudostem hay is recommended in sheep feedlot diet. This residue provided greater use of DM, however promoted a greater loss of energy in the form of methane, resulting in similar energy consumption. The drying methods did not reduce the availability of nutrients and the sun drying method is recommended, since it is a faster drying method.

Reference values for leg effort during incremental cycle ergometry in non-trained healthy men and women, aged 19-85.

Heightened sensation of leg effort contributes importantly to poor exercise tolerance in patient populations. We aim to provide a sex- and age-adjusted frame of reference to judge symptom's normalcy across progressively higher exercise intensities during incremental exercise. Two-hundred and seventy-five non-trained subjects (130 men) aged 19-85 prospectively underwent incremental cycle ergometry. After establishing centiles-based norms for Borg leg effort scores (0-10 category-ratio scale) versus work rate, exponential loss function identified the centile that best quantified the symptom's severity individually. Peak O2 uptake and work rate (% predicted) were used to threshold gradually higher symptom intensity categories. Leg effort-work rate increased as a function of age; women typically reported higher scores at a given age, particularly in the younger groups (p < 0.05). For instance, "heavy" (5) scores at the 95th centile were reported at ~200 W (<40 years) and ~90 W (≥70 years) in men versus ~130 W and ~70 W in women, respectively. The following categories of leg effort severity were associated with progressively lower exercise capacity: ≤50th ("mild"), >50th to <75th ("moderate"), ≥75th to <95th ("severe"), and ≥ 95th ("very severe") (p < 0.05). Although most subjects reporting peak scores <5 were in "mild" range, higher scores were not predictive of the other categories (p > 0.05). This novel frame of reference for 0-10 Borg leg effort, which considers its cumulative burden across increasingly higher exercise intensities, might prove valuable to judging symptom's normalcy, quantifying its severity, and assessing the effects of interventions in clinical populations.

A physical fitness-evaluation system for outstanding Chinese male boxers.

Background: We sought to create a system to evaluate the physical fitness of outstanding Chinese male boxers that included an evaluation index, fitness level criteria, and modeling. This system was then used to assess athletes' physical fitness and development. Methods: Documentation, expert interviews, questionnaires, measurements, and statistical analyses were used in this study. Results: The physical fitness evaluation system included the following three components: (1) body shape indexes (n = 4) including the backhand upper arm circumference differential, finger span height, Cottrell index, and pelvic width/shoulder width × 100; (2) body function indexes (n = 4) including relative maximum anaerobic power, relative maximal oxygen uptake, and creatine kinase and testosterone concentrations; and (3) athletic quality indexes (n = 9) including the speed strength index, the backhand straight punch strength, 3-min cumulative punching force, backhand straight punch reaction time, backhand straight punch speed, 30-m sprint, 9-min double shake jump rope, 1-min double shake jump rope, and sitting forward bend tests. A five-point grading system to evaluate physical fitness was established and an evaluation model was proposed. Conclusions: The reference values were determined to be objective and effective using a back substitution process. Individual and differential assessments reflected the athletes' level of physical fitness. The critical values were established under the best and worst conditions and the optimal values were found to be valid and effective.

A comparison of the effects of two protocols of concurrent resistance and aerobic training on physical fitness in middle school students.

Objective: This study aimed to compare the effects of two concurrent training (CT) protocols on the physical fitness of middle school students. Method: A 12-week quasi-experimental pre-test/post-test study was conducted with 157 middle school students (age = 12.48 ± 0.34, n = 90 females) divided into three groups: CT group A (CT-0h) received combined resistance training (RT) and aerobic training (AT) in each physical education session, CT group B (CT-48h) received RT and AT across two separate physical education classes 48 h apart, and a control group (Con) received no training. Training occurred twice a week. Test indicators included cardiorespiratory fitness (CRF) measured by estimated VO2max and 20 m shuttle run (laps), as well as muscle strength assessed through long jump, vertical jump, and handgrip strength. Results: The intervention groups exhibited significant increases in estimated VO2max and muscle strength compared to their baseline values (p < 0.05). Both CT-0h and CT-48h groups demonstrated significant improvements in 20 m shuttle run (laps) (mean difference: 8.88 laps, p < 0.01; mean difference: 4.81 laps, p < 0.01, respectively), standing long jump (mean difference: 6.20 cm, p < 0.01; mean difference: 3.68 cm, p < 0.01, respectively), vertical jump (mean difference: 4.95 cm, p < 0.01; mean difference: 4.04 cm, p < 0.01, respectively), and handgrip strength (mean difference: 11.17 kg, p < 0.01; mean difference: 6.99 kg, p < 0.01, respectively). CT-0h group exhibited significantly increased estimated VO2max (mean difference: 1.47 ml/kg/min, p < 0.01) compared to the CT-48h group. Conclusion: Both CT programs effectively improved adolescents' physical fitness indicators. However, the program that integrated RT and AT within the same physical education class demonstrated superior enhancement in adolescents' CRF.

Acute interval running induces greater excess post-exercise oxygen consumption and lipid oxidation than isocaloric continuous running in men with obesity.

Studies seem to show that high-intensity interval training (HIIT) is a more time-efficient protocol for weight loss, compared with moderate-intensity continuous training (MICT). Our aim was to compare the acute effects of energy expenditure (EE) matched HIIT vs. MICT on excess post-exercise oxygen consumption (EPOC) and substrate metabolism in male college students with obesity. Twenty-one untrained male college students (age, 22 ± 3 years; body fat, 28.4 ± 4.5%) completed two acute interventions (~ 300 kcal) on a treadmill in a randomized order: (1) HIIT: 3 min bouts at 90% of maximal oxygen uptake (VO2max) with 2 min of recovery at 25% of VO2max; (2) MICT: 60% of VO2max continuous training. EPOC and substrate metabolism were measured by indirect calorimetry during and 30 min after exercise. Results showed that EPOC was higher after HIIT (66.20 ± 14.36 kcal) compared to MICT (53.91 ± 12.63 kcal, p = 0.045), especially in the first 10 min after exercise (HIIT: 45.91 ± 9.64 kcal and MICT: 34.39 ± 7.22 kcal, p = 0.041). Lipid oxidation rate was higher after HIIT (1.01 ± 0.43 mg/kg/min) compared to MICT (0.76 ± 0.46 mg/kg/min, p = 0.003). Moreover, the percentage of energy from lipid was higher after HIIT (37.94 ± 14.21%) compared to MICT (30.09 ± 13.54%, p = 0.020). We conclude that HIIT results in greater total EE and EPOC, as well as higher percentage of energy from lipid during EPOC than EE matched MICT in male college students with obesity.

Captivity affects mitochondrial aerobic respiration and carotenoid metabolism in the house finch (Haemorhous mexicanus).

In many species of animals, red carotenoid-based coloration is produced by metabolizing yellow dietary pigments, and this red ornamentation can be an honest signal of individual quality. However, the physiological basis for associations between organism function and the metabolism of red ornamental carotenoids from yellow dietary carotenoids remains uncertain. A recent hypothesis posits that carotenoid metabolism depends on mitochondrial performance, with diminished red coloration resulting from altered mitochondrial aerobic respiration. To test for an association between mitochondrial respiration and red carotenoids, we held wild-caught, molting male house finches in either small bird cages or large flight cages to create environmental challenges during the period when red ornamental coloration is produced. We predicted that small cages would present a less favorable environment than large flight cages and that captivity itself would decrease both mitochondrial performance and the abundance of red carotenoids compared with free-living birds. We found that captive-held birds circulated fewer red carotenoids, showed increased mitochondrial respiratory rates, and had lower complex II respiratory control ratios - a metric associated with mitochondrial efficiency - compared with free-living birds, though we did not detect a difference in the effects of small cages versus large cages. Among captive individuals, the birds that circulated the highest concentrations of red carotenoids had the highest mitochondrial respiratory control ratio for complex II substrate. These data support the hypothesis that the metabolism of red carotenoid pigments is linked to mitochondrial aerobic respiration in the house finch, but the mechanisms for this association remain to be established.

The C-terminus of the prototypical M2 muscarinic receptor localizes to the mitochondria and regulates cell respiration under stress conditions.

Muscarinic acetylcholine receptors are prototypical G protein-coupled receptors (GPCRs), members of a large family of 7 transmembrane receptors mediating a wide variety of extracellular signals. We show here, in cultured cells and in a murine model, that the carboxyl terminal fragment of the muscarinic M2 receptor, comprising the transmembrane regions 6 and 7 (M2tail), is expressed by virtue of an internal ribosome entry site localized in the third intracellular loop. Single-cell imaging and import in isolated yeast mitochondria reveals that M2tail, whose expression is up-regulated in cells undergoing integrated stress response, does not follow the normal route to the plasma membrane, but is almost exclusively sorted to the mitochondria inner membrane: here, it controls oxygen consumption, cell proliferation, and the formation of reactive oxygen species (ROS) by reducing oxidative phosphorylation. Crispr/Cas9 editing of the key methionine where cap-independent translation begins in human-induced pluripotent stem cells (hiPSCs), reveals the physiological role of this process in influencing cell proliferation and oxygen consumption at the endogenous level. The expression of the C-terminal domain of a GPCR, capable of regulating mitochondrial function, constitutes a hitherto unknown mechanism notably unrelated to its canonical signaling function as a GPCR at the plasma membrane. This work thus highlights a potential novel mechanism that cells may use for controlling their metabolism under variable environmental conditions, notably as a negative regulator of cell respiration.

(Non)-Exertional Variables of Cardiopulmonary Exercise Testing in Heart Failure with and Without Cardiac Amyloidosis.

PURPOSE OF REVIEW: Cardiac amyloidosis (CA) constitutes an important etiology of heart failure with preserved ejection fraction (HFpEF) or heart failure with mildly reduced ejection fraction (HFmrEF). Since patients with CA show early exhaustion, we aimed to investigate whether non-exertional variables of cardiopulmonary exercise testing (CPET) provide additional information in comparison to traditional peak oxygen consumption (VO2peak). RECENT FINDINGS: We retrospectively investigated CPET variables of patients with HFpEF and HFmrEF with (n = 21) and without (n = 21, HF) CA at comparable age and ejection fraction. Exertional and non-exertional CPET variables as well as laboratory and echocardiographic markers were analyzed. The primary outcome was the difference in CPET variables between groups. The secondary outcome was rehospitalization in patients with CA during a follow-up of 24 months. Correlations between CPET, NTproBNP, and echocardiographic variables were calculated to detect patterns of discrimination between the groups. HF patients with CA were inferior to controls in most exertional and non-exertional CPET variables. Patients with CA were hospitalized more often (p = 0.002), and rehospitalization was associated with VE/VCO2 (p = 0.019), peak oxygen pulse (p = 0.042), the oxygen equivalent at the first ventilatory threshold (p = 0.003), circulatory (p = 0.024), and ventilatory power (p < .001), but not VO2peak (p = 0.127). Higher performance was correlated with lower E/e' and NTproBNP as well as higher resting heart rate and stroke volume in CA. Patients with CA displayed worse non-exertional CPET performance compared to non-CA HF patients, which was associated with rehospitalization. Differences between correlations of resting echocardiography and CPET variables between groups emphasize different properties of exercise physiology despite comparable ejection fraction.

Increased Retinal Metabolism Induced by Flicker in the Isolated Mouse Retina.

Both the retina and brain exhibit neurovascular coupling, increased blood flow during increased neural activity. In the retina increased blood flow can be evoked by flickering light, but the magnitude of the metabolic change that underlies this is not known. Local changes in oxygen consumption (QO2) are difficult to measure in vivo when both supply and demand are changing. Here we isolated the C57BL/6J mouse retina and supplied it with oxygen from both sides of the tissue. Microelectrode recordings of PO2 were made in darkness and during 20 s of high scotopic flickering light at 1 Hz. Flicker led to a PO2 increase in the outer retina and a decrease in the inner retina, indicating that outer retinal QO2 (QOR) decreased and inner retinal QO2 (QIR) increased. A four-layer oxygen diffusion model was fitted to PO2 values obtained in darkness and at the end of flicker to determine the values of QOR and QIR. QOR in flicker was 76 ± 14% (mean and SD, n = 10) of QOR in darkness. The increase in QIR was smaller, 6.4 ± 5.0%. These metabolic changes are likely smaller than the maximum changes, because with no regeneration of pigment in the isolated retina, we limited the illumination. Further modeling indicated that at high illumination, QIR could increase by up to 45%, which is comparable to the magnitude of flow changes. This suggests that the blood flow increase is at least roughly matched to the increased metabolic demands of activity in the retina.

Effects of pre-exercise glycerol supplementation on dehydration, metabolic, kinematic, and thermographic variables in international race walkers.

BACKGROUND: Due to the increase in global temperature, it is necessary to investigate solutions so that athletes competing in hot conditions can perform in optimal conditions avoiding loss of performance and health problems. Therefore, this study aims to evaluate the effect of pre-exercise glycerol supplementation during a rectangular test at ambient temperature mid (28.2ºC) on dehydration variables in international race walkers. METHODS: Eight international male race walkers (age: 28.0 years (4.4); weight: 65.6 kg (6.6); height: 180.0 cm (5.0); fat mass: 6.72% (0.66); muscle mass: 33.3 kg (3.3); VO2MAX: 66.5 ml · kg-1·min-1 (1.9)) completed this randomized crossover design clinical trial. Subjects underwent two interventions: they consumed placebo (n = 8) and glycerol (n = 8) acutely, before a rectangular test where dehydration, RPE, metabolic, kinematic, and thermographic variables were analyzed before, during and after the test. RESULTS: After the intervention, significant differences were found between groups in body mass in favor of the placebo (Placebo: -2.23 kg vs Glycerol: -2.48 kg; p = 0.033). For other variables, no significant differences were found. CONCLUSION: Therefore, pre-exercise glycerol supplementation was not able to improve any dehydration, metabolic, kinematic, or thermographic variables during a rectangular test at temperature mid in international race walkers. Possibly, a higher environmental temperature could have generated a higher metabolic and thermoregulatory stress, generating differences between groups like other previous scientific evidence.

Correlations of Aerobic Capacity with External and Internal Load of Young Football Players during Small-Sided Games.

Aerobic capacity plays a crucial role in football performance, making it a focal point in training processes. Small-sided games (SSGs) are widely used in football training, but the relationship between aerobic capacity and running performance during SSGs remains unclear. The aim of this study was to investigate possible correlations between maximum oxygen uptake (VO2max) and running performance in youth football players in SSGs (4:4, 3:3, 2:2, 1:1) with three different pitch sizes per player (150, 100, 75 m2/player). Sixteen male U15 football players participated in the study. Players underwent the Yo-Yo intermittent recovery test level 1, and their VO2max was estimated based on their performance. Subsequently, players participated in SSGs wearing GPS devices to measure internal and external load. Pearson or Spearman correlation was applied for statistical analysis depending on the normal distribution of the data. The results reveal that, for 4:4 and 3:3 relationships, larger pitches led to a greater impact of aerobic capacity (total distance (TD): 4:4, 150 m2/pl, r = 0.715, p = 0.002; 100 m2/pl, r = 0.656, p = 0.006; 75 m2/pl, r = 0.586, p = 0.017). In the 2:2 relationship, the opposite was observed, with more correlations appearing on smaller pitches (TD: 2:2, 100 m2/pl, r = 0.581, p = 0.018; 75 m2/pl, r = 0.747, p < 0.001). In the 1:1 relationship, correlations with VO2max, total distance, and speed were observed only on the larger pitch. In conclusion, the aerobic capacity of young football players can influence running performance indicators in SSGs. Therefore, aerobic capacity could serve as a criterion for team composition, making SSGs more competitive. Additionally, the variation in correlations in the 2:2 relationship and their limited presence in the 1:1 relationship may be attributed to technical-tactical factors, such as increased ball contacts and one-on-one situations typically occurring in smaller setups.

Effects of various living-low and training-high modes with distinct training prescriptions on sea-level performance: A network meta-analysis.

This study aimed to separately compare and rank the effect of various living-low and training-high (LLTH) modes on aerobic and anaerobic performances in athletes, focusing on training intensity, modality, and volume, through network meta-analysis. We systematically searched PubMed, Web of Science, Embase, EBSCO, and Cochrane from their inception date to June 30, 2023. Based on the hypoxic training modality and the intensity and duration of work intervals, LLTH was divided into intermittent hypoxic exposure, continuous hypoxic training, repeated sprint training in hypoxia (RSH; work interval: 5-10 s and rest interval: approximately 30 s), interval sprint training in hypoxia (ISH; work interval: 15-30 s), short-duration high-intensity interval training (s-IHT; short work interval: 1-2 min), long-duration high-intensity interval training (l-IHT; long work interval: > 5 min), and continuous and interval training under hypoxia. A meta-analysis was conducted to determine the standardized mean differences (SMDs) among the effects of various hypoxic interventions on aerobic and anaerobic performances. From 2,072 originally identified titles, 56 studies were included in the analysis. The pooled data from 53 studies showed that only l-IHT (SMDs: 0.78 [95% credible interval; CrI, 0.52-1.05]) and RSH (SMDs: 0.30 [95% CrI, 0.10-0.50]) compared with normoxic training effectively improved athletes' aerobic performance. Furthermore, the pooled data from 29 studies revealed that active intermittent hypoxic training compared with normoxic training can effectively improve anaerobic performance, with SMDs ranging from 0.97 (95% CrI, 0.12-1.81) for l-IHT to 0.32 (95% CrI, 0.05-0.59) for RSH. When adopting a program for LLTH, sufficient duration and work intensity intervals are key to achieving optimal improvements in athletes' overall performance, regardless of the potential improvement in aerobic or anaerobic performance. Nevertheless, it is essential to acknowledge that this study incorporated merely one study on the improvement of anaerobic performance by l-IHT, undermining the credibility of the results. Accordingly, more related studies are needed in the future to provide evidence-based support. It seems difficult to achieve beneficial adaptive changes in performance with intermittent passive hypoxic exposure and continuous low-intensity hypoxic training.

Evaluation of calibrated and uncalibrated optical imaging approaches for relative cerebral oxygen metabolism measurements in awake mice.

Objective. The continuous delivery of oxygen is critical to sustain brain function, and therefore, measuring brain oxygen consumption can provide vital physiological insight. In this work, we examine the impact of calibration and cerebral blood flow (CBF) measurements on the computation of the relative changes in the cerebral metabolic rate of oxygen consumption (rCMRO2) from hemoglobin-sensitive intrinsic optical imaging data. Using these data, we calculate rCMRO2, and calibrate the model using an isometabolic stimulus.Approach. We used awake head-fixed rodents to obtain hemoglobin-sensitive optical imaging data to test different calibrated and uncalibrated rCMRO2models. Hypercapnia was used for calibration and whisker stimulation was used to test the impact of calibration.Main results. We found that typical uncalibrated models can provide reasonable estimates of rCMRO2with differences as small as 7%-9% compared to their calibrated models. However, calibrated models showed lower variability and less dependence on baseline hemoglobin concentrations. Lastly, we found that supplying the model with measurements of CBF significantly reduced error and variability in rCMRO2change calculations.Significance. The effect of calibration on rCMRO2calculations remains understudied, and we systematically evaluated different rCMRO2calculation scenarios that consider including different measurement combinations. This study provides a quantitative comparison of these scenarios to evaluate trade-offs that can be vital to the design of blood oxygenation sensitive imaging experiments for rCMRO2calculation.