Maximum Rate Research Articles

Optimizing E-Bike Controls for Human-bike Interaction to Enhance Riding Experience and Efficiency

E-bikes are now used for sports, rehabilitation, and work, not just commuting. Riders adjust power assistance and transmission to handle different conditions and reach their desired physical load. This interaction between the rider, bike, and environment can become complex due to faster speeds, shorter response times, and varying conditions, potentially leading to discomfort. A study with 21 non-athletes explored how riders manage the physical load on e-bikes during a simulated indoor riding session with 66 stages of varying slope resistance. Participants controlled the e-bike to maintain a moderate intensity, and data on latency of e-bike control, number of controls, acceptable pedaling power, heart rate, and perceived exertion were collected. On average, riders made their control adjustment 5.3 seconds after a slope change and used 2.7 control attempts to reach an acceptable pedaling power. The study found that the most acceptable pedaling power were similar across different slopes, suggesting a consistent preferred load. Participants aimed to maintain stable pedaling power despite external disturbances, targeting a moderate exercise intensity (66.9% maximal heart rate and a rate of perceived exertion of 12.1). The findings indicate that it's possible to estimate a personal preferred load, which could inform future studies on maintaining this load and improving the e-bike riding experience.

Chronotropic Response to Exercise is Decreased in Patients With Congenital Heart Disease Compared to Cardiomyopathy Following Pediatric Heart Transplantation.

Two common indications for pediatric heart transplantation are congenital heart disease and cardiomyopathy. Prior studies suggest differences in chronotropy on cardiopulmonary exercise testing outcomes depending on indication for heart transplantation. We aimed to determine whether the number of pretransplant sternotomies is associated with differences in heart rate response during exercise testing. A retrospective analysis of our institutional pediatric heart transplant data between 2004 and 2022 was performed. Patients were categorized by indication for transplantation into a cardiomyopathy (CM) group if they had a congenital or acquired cardiomyopathy or a congenital heart disease (CHD) group including all other forms of congenital cardiac anatomic abnormalities. CHD patients (n = 40) differed from CM patients (n = 53) by mean number of sternotomies prior to transplant (2.4 ± 1.8 vs. 0.5 ± 0.9, p < 0.001). There were no significant differences in echocardiographic function or catheterization hemodynamics. In cardiopulmonary exercise testing performance, the congenital heart disease group had a significantly higher resting heart rate (91.8 ± 11.2 vs. 86.4 ± 10.2 bpm, p = 0.019), lower percent predicted age-predicted maximal heart rate achieved (78.3 ± 8.5% vs. 83.2 ± 11.4%, p = 0.032), and lower heart rate reserve (68.6 ± 19.8 vs. 84.4 ± 24.0 bpm, p = 0.001) despite a similar age and average time from transplantation. Regression analysis confirmed number of pretransplant sternotomies as a main predictor of heart rate metrics. There is greater chronotropic incompetence in patients who underwent transplantation due to congenital heart disease compared to cardiomyopathy. The groups differ significantly by number of sternotomies, potentially supporting the hypothesis that prior surgical disruption of cardiac innervation may cause decreased chronotropic response to exercise following transplantation.

Age-predicted maximal heart rate reserve as an alternative prognostic parameter in patients with heart failure with preserved ejection fraction -insights from PURSUIT-HFpEF registry-

Abstract Background Heart rate reserve (HRR), a measure of chronotropic response, is a prognostic parameter in patients with heart failure with preserved ejection fraction (HFpEF). However, exercise testing and measuring maximum heart rate (HR) are sometimes difficult in patients with heart failure with preserved ejection fraction (HFpEF). Assessing age-predicted maximal HRR (APHRR), defined as the difference between the resting HR and the age-predicted maximum HR (220 - age), would be a simple alternative to HRR. Purpose To assess the impact of APHRR at discharge on prognosis in patients with HFpEF. Methods An analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 1231 patients hospitalized for acute heart failure (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction ≥50% and brain natriuretic peptide level ≥100 pg/ml. Excluding patients with permanent pacemakers, we enrolled 918 patients (age, 81 ± 9 years; men, 45%; atrial fibrillation, 38%) whose follow-up data after survival discharge were available. Results There was a moderate correlation between HR (median 69, interquartile range [IQR] 61-79 beats per minute [bpm]) and APHRR at discharge (71, 59-81 bpm) (r² = 0.68, p &amp;lt;0.001). During the median follow-up period of 23.8 months [IQR, 12.5-36.3] after discharge, 267 patients (15.4%) died, and the mortality rates incrementally decreased according to the APHRR quartiles (Q1, 44.6%; Q2, 26.6%; Q3, 26.2%; Q4, 18.4%; p &amp;lt;0.001). Cox regression analysis revealed that both the resting HR (hazard ratio per quartile increase, 1.16; 95% confidence interval, 1.04-1.30, p = 0.008) and APHRR (0.67; 0.60-0.75, p &amp;lt;0.001) were associated with mortality. However, the diagnostic accuracy was significantly superior in the APHRR than in resting HR (area under the curve; 0.628 vs. 0.552, p &amp;lt;0.001). Conclusions Assessment of the APHRR at discharge was a simple and useful method for risk stratification of patients with HFpEF. An incremental favorable prognosis indicated the prognostic importance of having a functional reserve during physiologic stress.

Temporal relationship between high-intensity training sessions and episodes of atrial fibrillation among previously inactive patients with paroxysmal or persistent AF

Abstract Background Exercise is considered beneficial for managing comorbidities in atrial fibrillation (AF) patients in the long term, and emerging evidence also indicate that high-intensity interval training (HIIT) may reduce AF burden and symptoms. However, more data on the impact of individual training sessions on recurrence of AF is needed to understand mechanisms and tailor exercise recommendations. Purpose To assess the temporal relationship between training sessions and recurrent AF episodes among previously inactive patients with paroxysmal or persistent AF being introduced to HIIT. Methods The Norwegian Exercise in Atrial Fibrillation Trial is a multi centre randomized controlled trial including inactive patients with paroxysmal or persistent AF, who are randomly assigned to either a structured exercise intervention or control for 12 months. We analysed AF episodes and training data from the initial weeks with introduction to structured exercise in the intervention group (8 supervised sessions of HIIT at 85-95% of maximal heart rate). AF episodes lasting ≥30 seconds were registered using implantable cardiac monitors (ICM). Training sessions were registered using sports watches and manual logs. We report event rates and rate ratios for recurrent AF episodes during HIIT compared to episodes occurring outside HIIT. Due to non-normal data distribution statistical comparisons were performed using the Wilcoxon sign-ranked test. Results 81 patients (24 female, 57 male), mean age of 64.2 years (range 35-78), were included. 57 patients had paroxysmal and 24 had persistent AF. The combined duration of monitoring was 5272 days (median 53, range 30 – 163). The participants performed a total of 418 hours of HIIT (median 5.3 hours, range 0.67 – 6.58) during 615 training sessions (median 8, range 1 – 8). In total 4528 AF episodes (median 4, range 0 – 1693) were registered, of which 18 occurred during HIIT. The mean AF rate per 24 hours was 0.69 outside HIIT, 1.20 during HIIT, 0.92 for the periods 1 – 3 hours and 4-6 hours after HIIT (Figure 1). The rate ratio for AF during HIIT compared to outside HIIT was 1.73 (p=0.002). In the 52 participants with at least one episode of AF during follow-up, the rate ratio for AF during HIIT compared to outside HIIT was 10.4 (bootstrapped 95% CI 0.2 to 30.3). Conclusion Among previously inactive patients with paroxysmal or persistent AF, the rate of recurrent AF episodes was significantly higher during high-intensity exercise than outside exercise. Given the few AF episodes, this mechanism of trigging AF by high-intensity exercise needs further investigation.Mean AF per 24 hours

Study on the Dynamic Evolution of Mining-Induced Stress and Displacement in the Floor Coal-Rock Induced by Protective Layer Mining

Protective layer mining is the most effective means to prevent and control coal and gas outbursts. In order to deeply understand the dynamic evolution law of mining stress and displacement of the bottom plate coal rock body in the process of protective layer mining, the effects of upper protective layer mining on stress variation and displacement deformation in the underlying coal seam were studied using the similar experiment and FLAC3D simulations. The results reveal that mining in the 82# coal seam notably alleviates pressure in the 9# coal seam below, with an average relief rate of 86.2%, demonstrated by the maximal strike expansion deformation rate of 11.3‰ in the 9# coal seam post-mining. Stress monitoring data indicates a stress concentration zone within 32 m ahead of the working face, and a pressure relief zone within 51 m behind it. The research provides a scientific foundation for pressure-relief gas extraction techniques, affirming the substantial impact of upper protective layer mining on alleviating pressure in underlying coal seams, enhancing safety, and optimizing mining efficiency.

The effect of afterload on right ventricular pacing-induced left ventricular dysfunction: a translational study

Abstract Introduction Right ventricular (RV) pacing (RVP) impairs left ventricular (LV) function. Nevertheless, the interaction between arterial afterload and RVP-associated LV dysfunction has not been investigated yet. Purpose We sought to examine the effect of afterload on RVP-evoked LV hemodynamic changes in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) as well as in a small animal model of sustained LV pressure overload (PO). Methods Thirty-five patients with AS and a previously implanted pacemaker underwent detailed echocardiographic examination immediately before TAVI and also on the second postoperative day. The ultrasound measurements were carried out during intrinsic, narrow QRS rhythm and during frequency-matched RVP as well. Global myocardial work index (GMWI) was calculated to assess LV contractility. In parallel, LV pressure-volume analysis was performed in Wistar rats with transverse aortic constriction (TAC) or sham operation (Sham) during intrinsic narrow QRS rhythm (termed as TAC-Vsense and Sham-Vsense) as well as during RVP (termed as TAC-Vpace and Sham-Vpace). RVP was achieved in rats by an octopolar electrophysiology catheter placed in the RV. Results RVP decreased LV contractility in AS patients before and after TAVI as well. Nevertheless, the extent of RVP-evoked LV dysfunction was alleviated following pressure unloading (ΔGMWI: -37±7 vs. -25±8%, before TAVI vs. after TAVI, P&amp;lt;0.05). Similarly, although RVP was associated with reduced LV contractility in both the TAC (the slope of the maximum rate of LV pressure rise-end-diastolic volume relation [dPdtmax-EDV]: 92±8 vs. 53±6mmHg/s/µl, TAC-Vsense vs. TAC-Vpace; P&amp;lt;0.05) and Sham groups (dPdtmax-EDV: 74±5 vs. 60±9 mmHg/s/µl, Sham-Vsense vs. Sham-Vpace; P&amp;lt;0.05), the negative inotropic effect of RVP was found to be stronger in the TAC compared to the Sham group (ΔdPdtmax-EDV: -42±4 vs. -19±6%; TAC vs. Sham, P&amp;lt;0.01). Furthermore, reduction of the maximal rate of LV pressure decrease (ΔdPdtmin: -20±3 vs. -5±5%, TAC vs. Sham, P&amp;lt;0.01) and prolongation of the active relaxation time constant (Δτ: 22±3 vs. 6±3%, TAC vs. Sham, P&amp;lt;0.01) also occurred to a greater extent in case of sustained LV PO, indicating augmented diastolic dysfunction. Conclusion Our translational results indicate that RVP-induced LV dysfunction might be afterload dependent.

(S)-2-Hydroxyisovalerate Production from d-Xylose with CO-Converting Clostridium ragsdalei

Clostridium ragsdalei was found to produce (S)-2-hydroxyisovalerate (2-HIV) as a novel product in addition to acetate, ethanol, and d-2,3-butanediol in heterotrophic (d-xylose), autotrophic (CO), and mixotrophic (d-xylose + CO) conditions. Mixotrophic batch processes in stirred-tank bioreactors with continuous gassing resulted in improved production of this alpha-hydroxy acid compared to batch processes solely with either d-xylose or CO. The maximal CO uptake rate was considerably reduced in mixotrophic compared to autotrophic processes, resulting in a concomitant decreased total CO2 production. Simultaneous conversion of 9.5 g L−1 d-xylose and 320 mmol CO enabled the production of 1.8 g L−1 2-HIV in addition to 1.1 g L−1 d-2,3-butanediol, 2.0 g L−1 ethanol, and 1.8 g L−1 acetate. With reduced initial d-xylose (3.1 g L−1), l-valine production started when d-xylose was depleted, reaching a maximum of 0.4 g L−1 l-valine. Using l-arabinose or d-glucose instead of d-xylose in mixotrophic batch processes reduced the 2-HIV production by C. ragsdalei. Considerable amounts of meso-2,3-butanediol (0.9–1.3 g L−1) were produced instead, which was not observed with d-xylose. The monomer 2-HIV can form polyesters that make the molecule attractive for application as bioplastic (polyhydroxyalkanoates) or new composite material.

Plasma Lipidomic Profiles Improve upon Traditional Risk Factors for the Prediction of Arterial Stiffness Among Patients with Type 2 Diabetes Mellitum: A Randomized, Placebo-Controlled Trial

Background: Exercise or vitamin D intervention can reduce the risk of arterial stiffness; however, the underlying mechanisms of lipid metabolism remain unexplored. To examine the effects of a 12-week moderate and vigorous exercise program (65–80% maximal heart rate, 60 min/time, 2~3 times/week) with or without vitamin D supplementation (1000 IU/day) on the reduction in arterial stiffness and further explore whether the effects of interventions could be associated with the basal lipidome among patients with Type 2 diabetes mellitum (T2DM). Method: 61 patients with T2DM were randomly assigned to the following groups: control (CON, n = 15), exercise (EX, n = 14), vitamin D (VD, n = 16), and exercise + vitamin D (EX + VD, n = 16). Arterial stiffness risk factors (ankle–brachial index (ABI); brachial–ankle pulse wave velocity (baPWV), systolic blood pressure (SBP), and diastolic blood pressure (DBP)) were evaluated before and after the intervention. The plasma lipidome was determined using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Machine learning was applied to establish prediction models for the responsiveness to arterial stiffness. Result: Vitamin D supplementation could inhibit the decrease in the ankle–brachial index (mean ± SD: EX + VD and VD, −0.001 ± 0.058; EX + CON, −0.047 ± −0.089; p = 0.03). We observed high inter-individual variability in the arterial stiffness risk factors in response to the interventions. We also found that optimally selecting the lipid predictors at baseline, such as SM d44:6, LPE 18:2, and Hex2Cer 29:0, could enhance the predictive power by 100% for arm SBP changes in the exercise group. Basal levels of Cer (33:1) and GM3 (44:4) could enhance the predictive power by 100% for changes in baPWV in the vitamin D group. Conclusions: A 12-week vitamin D supplementation was beneficial in preventing arterial stiffness. Compared with traditional clinical risk factors, specific lipids at baseline could significantly improve the ability to predict intervention-induced changes in the reduction of arterial stiffness.

Unbiased complexome profiling and global proteomics analysis reveals mitochondrial impairment and potential changes at the intercalated disk in presymptomatic R14Δ/+ mice hearts.

Phospholamban (PLN) is a sarco-endoplasmic reticulum (SER) membrane protein that regulates cardiac contraction/relaxation by reversibly inhibiting the SERCA2a Ca2+-reuptake pump. The R14Δ-PLN mutation causes severe cardiomyopathy that is resistant to conventional treatment. Protein complexes and higher-order supercomplexes such as intercalated disk components and Ca+2-cycling domains underlie many critical cardiac functions, a subset of which may be disrupted by R14Δ-PLN. Complexome profiling (CP) is a proteomics workflow for systematic analysis of high molecular weight (MW) protein complexes and supercomplexes. We hypothesize that R14Δ-PLN may alter a subset of these assemblies, and apply CP workflows to explore these changes in presymptomatic R14Δ/+ mice hearts. Ventricular tissues from presymptomatic 28wk-old WT and R14Δ/+ mice were homogenized under non-denaturing conditions, fractionated by size-exclusion chromatography (SEC) with a linear MW-range exceeding 5 MDa, and subjected to quantitative data-independent acquisition mass spectrometry (DIA-MS) analysis. Unfortunately, current workflows for the systematic analysis of CP data proved ill-suited for use in cardiac samples. Most rely upon curated protein complex databases to provide ground-truth for analysis; however, these are derived primarily from cancerous or immortalized cell lines and, consequently, cell-type specific complexes (including cardiac-specific machinery potentially affected in R14Δ-PLN hearts) are poorly covered. We thus developed PERCOM: a novel CP data-analysis strategy that does not rely upon these databases and can, furthermore, be implemented on widely available spreadsheet software. Applying PERCOM to our CP dataset resulted in the identification of 296 proteins with disrupted elution profiles. Hits were significantly enriched for mitochondrial and intercalated disk (ICD) supercomplex components. Changes to mitochondrial supercomplexes were associated with reduced expression of mitochondrial proteins and maximal oxygen consumption rate. The observed alterations to mitochondrial and ICD supercomplexes were replicated in a second cohort of "juvenile" 9wk-old mice. These early-stage changes to key cardiac machinery may contribute to R14Δ-PLN pathogenesis.

Heterogeneous Engineering Strategy Derived In Situ Carbon-Encased Nickel Selenides Enabling Superior LIBs/SIBs with High Thermal Safety.

Nowadays, the extended usage of lithium/sodium ion batteries (LIBs/SIBs) encounters nerve-wracking issues, including a lack of suitable reservoirs and high thermal runaway hazards. Although using TiO2 and Li4Ti5O12 has been confirmed to be effective in improving battery safety, their low theoretical capacities inevitably cause damage to the electrochemical performance of the battery. Achieving win-win results has become an urgent necessity. This study designed a metal-organic framework (MOF)-derived in situ carbon-coated metal selenide (Ni-Se@G@C) as the anode. When the current density is 0.1-0.3 A g-1, the initial capacity of LIBs reaches 993.2 mAh g-1, which increases to 1478.9 mAh g-1 after running 800 cycles. When running at 2 A g-1, the cell also offers a relatively high capacity of 458.3 mAh g-1 after 1500 cycles. After the replacement of graphite with Ni-Se@G@C, the self-heating temperature (T0) and thermal runaway triggering temperature (T1) of half and full cells are significantly increased. Meanwhile, the maximum thermal runaway temperature (T2) and maximal heating release rate (HRRmax) are significantly reduced. Of note, the usage of Ni-Se@G@C enables the battery with superior cycling and rate performance. When used in SIBs, the cell gives an initial discharge capacity of 624.9 mAh g-1, which still remains at 269.4 mAh g-1 after running 200 cycles at 1 A g-1. Notably, Ea of the Ni-Se@G@C cell is 5.6 times higher than that of the graphite cell, corroborating the promoted safety performance. This work provides a new paradigm for MOF-derived micro/nanostructures, enabling the battery with an excellent electrochemical and safety performance portfolio.

The relationship between maximal lactate accumulation rate and sprint performance parameters in male competitive swimmers

This study aimed to examine the relationship between the maximal lactate accumulation rate (ċLamax) and sprint performance parameters in male competitive swimmers. Seventeen male competitive swimmers volunteered to perform a 20 m maximal front crawl sprint without pushing off the wall from a floating position. ċLamax was determined by the 20-m sprint time and blood lactate measured before and after the 20 m sprint. For the sprint performance parameter, a 50 m time trial with the front crawl swimming stroke was conducted, and the times taken from 0 to 15 m, 15–25 m, 25–35 m, and 35–45 m were analyzed. A semi-tethered swimming test was conducted to investigate the load-velocity profile of each swimmer. From the load-velocity profile, theoretical maximal velocity (V0), maximal load (L0) and relative maximal load (rL0) were examined. The slope of the load-velocity profile was also determined. According to the results, ċLamax correlated with 50 m front crawl performance (r = −.546, p &amp;lt; .05). Moreover, a higher ċLamax was related to faster 0–35 m section time. Furthermore, ċLamax correlated with L0 (r = .837, p &amp;lt; .01), rL0 (r = .820, p &amp;lt; .01), and load-velocity slope (r = .804, p &amp;lt; .01). ċLamax is a good indicator of 50 m front crawl performance in male swimmers, and higher glycolytic power contributes to the faster time at the beginning of the sprint race. ċLamax could also evaluate the ability of a swimmer to apply force to the water during high-intensity swimming.

Quantitative Evaluations of Pumping-Induced Land Subsidence and Mitigation Strategies by Integrated Remote Sensing and Site-Specific Hydrogeological Observations

Land subsidence is an environmental hazard occurring gradually over time, potentially posing significant threats to the structural stability of civilian buildings and essential infrastructures. This study presented a workflow using the SBAS-PSInSAR approach to analyze surface deformation in the Choushui River Fluvial Plain (CRFP) based on Sentinel-1 SAR images and validated against precise leveling. Integrating the InSAR results with hydrogeological data, such as groundwater levels (GWLS), multilayer compactions, and borehole loggings, a straightforward model was proposed to estimate appropriate groundwater level drops to minimize further subsidence. The results showed a huge subsidence bowl centered in Yunlin, with maximal sinking at an average 60 mm/year rate. High-resolution subsidence maps enable the quantitative analyses of safety issues for Taiwan High-Speed Rail (THSR) across the areas with considerable subsidence. In addition, the analysis of hydrogeological data revealed that half of the major compaction in the study area occurred at shallow depths that mainly included the first and second aquifers. Based on a maximal subsidence control rate of 40 mm/year specified in the CRFP, the model results indicated that the groundwater level drops from wet to dry seasons needed to be maintained from 3 to 5 m for the shallowest aquifer and 4–6 m for Aquifers 3 and 4. The workflow demonstrated the compatibility of InSAR with traditional geodetic methods and the effectiveness of integrating multiple data sources to assess the complex nature of land subsidence in the CRFP.

Acute Effect of Three Aerobic Exercise Intensities on Glomerular Filtration Rate in Healthy Older Adults.

To assess the immediate effects of three aerobic exercise intensities on the estimated glomerular filtration rate (eGFR) in healthy, sedentary older adults. Eighteen healthy, sedentary older adults (ten men and eight women) voluntarily participated in this study. The participants underwent three standardized aerobic exercise tests (100%, 80%, and 60% of the maximal heart rate) on a bicycle ergometer. Blood samples were collected to determine cholesterol, triacylglycerols, glucose, serum creatinine (Cr), Cystatin C (CysC) concentrations, and eGFR. eGFR and serum concentrations of Cr and CysC were not modified at any exercise intensity. There was a negative correlation between blood total cholesterol vs. eGFR (R = -0.512, R = -0.582, R = -0.531; p < 0.05) at rest, 60%, and 100% of the maximal heart rate, respectively. In addition, a negative correlation existed for age vs. eGFR at 60% of the maximal heart rate (R = -0.516; p < 0.05). Short-duration aerobic exercise of low, moderate, and vigorous intensity did not significantly affect eGFR and is considered safe for kidney function in healthy, sedentary older adults. However, regular monitoring of kidney function in older people engaged in moderate- and high-intensity exercise is advised.

Effects of acetazolamide on exercise performance in patients with COPD going to high altitude: randomised controlled trial

BackgroundIn patients with chronic obstructive pulmonary disease (COPD), preventive treatment with acetazolamide reduces adverse health effects during altitude travel. We investigated whether preventive acetazolamide treatment modifies exercise performance in COPD patients going to high altitude.MethodsIn this randomized, double-blind trial, lowlanders with COPD, FEV1 40–80%predicted, were assigned to acetazolamide (375 mg/24 h) or placebo treatment starting 24 h before ascent and while staying at 3100 m. Patients performed progressive cycling exercise to exhaustion at 760 m, before taking the study drug, and within 4 h after arrival at 3100 m. Primary outcome was the maximal power output (Wmax). ClinicalTrials.govNCT03177837.Results103 patients (32 women), mean ±sdage 57.2±8.1y, FEV1 66±11% predicted, were included in per protocol analyses. In 53 patients receiving acetazolamide, Wmax and oxygen uptake (V'O2max) at 760 m and 3100 m were 105±40 and 91±40watts, and 18.0±6.8 and 15.5±6.8 ml·min−1·kg−1(p&lt;0.001, both changes). Corresponding Wmax and V'O2max in 50 patients receiving placebo were 107±41 and 97±41watts, and 18.9±7.0 and 17.2±7.0 ml·min−1·kg−1(p&lt;0.001, both changes). Between-group differences (95%CI) in altitude-induced Wmax-changes were −3.0 watts (−8.7 to +2.7, p=0.305) and in V'O2max-changes were −0.8 ml·min−1·kg−1(−2.1 to +0.5, p=0.213). Acetazolamide mitigated the altitude-induced reduction of end-exercise PaO2by 0.7kPa (0.1 to 1.3, p=0.016). At 3100 m, maximal work rate with respiratory exchange ratio ≤1 was greater with acetazolamide than with placebo by 10.1 watts (4.0 to 16.2, p=0.022).ConclusionsIn lowlanders with COPD, preventive treatment with acetazolamide did not modify the altitude-induced reduction in maximal work rate. However, acetazolamide enhanced arterial oxygenation and submaximal, moderate-intensity work capacity compared to placebo.

Feasibility and efficacy of adding high-intensity interval training to a multidisciplinary lifestyle intervention in children with obesity-a randomized controlled trial.

Multidisciplinary lifestyle interventions for children with obesity in Denmark often include recommendations regarding physical activity, but no structured exercise program. We hypothesized that adding high-intensity interval training (HIIT) to a multidisciplinary lifestyle intervention would improve BMI z-score (primary outcome), waist circumference, blood pressure, and health-related quality of life (HRQOL). This randomized controlled trial included 173 children and adolescents with obesity. Participants were allocated to 12-months lifestyle intervention (N = 83), or 12-month lifestyle intervention accompanied by a 12-week HIIT program (N = 90). HIIT consisted of three weekly sessions and included activities eliciting intensities >85% of maximal heart rate. Attendance rate for the 3-months HIIT intervention was 68.0 ± 23.2%. Dropout was lower in HIIT compared to control at three months (7.8% vs. 20.5%) and 12 months (26.5% vs 48.2%). Changes in BMI z-score did not differ between HIIT and control at 3 months (Mean Difference (MD): 0.01, 95% confidence interval (CI): -0.09; 0.12, P = 0.82) or 12 months (MD: 0.06, CI: -0.07;0.19, P = 0.34). Across randomization, BMI z-score was reduced by 0.11 (CI: 0.17; 0.06, P < 0.01) at 3 months and 0.20 (CI: 0.26;0.14, P < 0.01) at 12 months. At 3 months, HIIT experienced a greater increase in HRQOL of 2.73 (CI: 0.01;5.44, P = 0.05) in PedsQL Child total-score and 3.85 (CI: 0.96; 6.74, P < 0.01) in psychosocial health-score compared to control. At 12 months, PedsQL Child physical-score was reduced by 6.89 (CI: 10.97; 2.83, P < 0.01) in HIIT compared to control. No group differences or changes over time were found for waist circumference or blood pressure. Adding a 12-week HIIT program did not further augment the positive effects of a 12-month lifestyle intervention on BMI z-score. Adding HIIT improved HRQOL after 3 months, but reduced HRQOL at 12 months. Implementation of HIIT in community-based settings was feasible and showed positive effects on adherence to the lifestyle intervention.

Non-additivity of the functional properties of individual P450 species and its manifestation in the effects of alcohol consumption on the metabolism of ketamine and amitriptyline

To explore functional interconnections between multiple P450 enzymes and their manifestation in alcohol-induced changes in drug metabolism, we implemented a high-throughput study of correlations between the composition of the P450 pool and the substrate saturation profiles (SSP) of amitriptyline and ketamine demethylation in a series of 23 individual human liver microsomes preparations from donors with a known history of alcohol consumption. The SSPs were approximated with linear combinations of three Michaelis-Menten equations with globally optimized KM (substrate affinity) values. This analysis revealed a strong correlation between the rate of ketamine metabolism and alcohol exposure. For both substrates, alcohol consumption caused a significant increase in the role of the low-affinity enzymes. The amplitudes of the kinetic components and the total rate were further analyzed for correlations with the abundance of 11 major P450 enzymes assessed by global proteomics. The maximal rate of metabolism of both substrates correlated with the abundance of CYP3A4, their predicted principal metabolizer. However, except for CYP2D6 and CYP2E1, responsible for the low-affinity metabolism of ketamine and amitriptyline, respectively, none of the other potent metabolizers of the drugs revealed a positive correlation. Instead, in the case of ketamine, we observed negative correlations with the abundances of CYP1A2, CYP2C9, and CYP3A5. For amitriptyline, the data suggest inhibitory effects of CYP1A2 and CYP2A6. Our results demonstrate the importance of functional interactions between multiple P450 species and their decisive role in the effects of alcohol exposure on drug metabolism.

The higher the fraction of maximal oxygen uptake is during interval training, the greater is the cycling performance gain.

It has been suggested that time at a high fraction (%) of maximal oxygen uptake (VO2max) plays a decisive role for adaptations to interval training. Yet, no study has, to date, measured the % of VO2max during all interval sessions throughout a prolonged training intervention and subsequently related it to the magnitude of training adaptations. Thus, the present study aimed to investigate the relationship between % of VO2max achieved during an interval training intervention and changes in endurance performance and its physiological determinants in well-trained cyclists. Twenty-two cyclists (VO2max 67.1 (6.4) mL·min-1·kg-1; males, n=19; females, n=3) underwent a 9-week interval training intervention, consisting 21 sessions of 5×8-min intervals conducted at their 40-min highest sustainable mean power output (PO). Oxygen uptake was measured during all interval sessions, and the relationship between % of VO2max during work intervals and training adaptations were investigated using linear regression. A performance index was calculated from several performance measures. With higher % of VO2max during work intervals, greater improvements were observed for maximal PO during the VO2max test (R2 adjusted=0.44, p=0.009), PO at 4mmol·L-1 [blood lactate] (R2 adjusted=0.25, p=0.035), the performance index (R2 adjusted=0.36, p=0.013), and VO2max (R2 adjusted=0.54, p=0.029). Other measures, such as % of maximal heart rate, were related to fewer outcome variables and exhibited poorer session-to-session repeatability compared to % of VO2max. In conclusion, improvements in endurance measures were positively related to the % of VO2max achieved during interval training. Percentage of VO2max was the measure that best reflected the magnitude of training adaptations.

Microcrystalline and nanocrystalline structure of diamond films grown by MPCVD with nitrogen additions: Study of transitional synthesis conditions

This research explores the complex influence of nitrogen concentration and substrate temperature on the resultant properties of polycrystalline diamond (PCD) films grown by microwave plasma chemical vapor deposition (CVD). In particular, we investigated the growth parameters to find the exact conditions for changing the morphology of the resulting film from microcrystalline (MCD) to nanocrystalline (NCD). A series of 2 µm-thick polycrystalline diamond films was grown on Si substrates in methane-hydrogen–nitrogen gas mixtures with varied: (i) nitrogen concentration (0–2 %) and (ii) substrate temperature (700–1050 °C). Comprehensive characterization techniques, including scanning electron microscopy (SEM), micro-Raman spectroscopy, and X-ray diffraction, were employed to assess the morphological, structural, and spectroscopic properties of the films. The study reveals that even minor additions of nitrogen significantly modulate secondary nucleation, impacting both film morphology and phase composition. Furthermore, substrate temperature emerges as another critical parameter, influencing the growth kinetics and crystallite size. The comparison of the characteristics of grown PCD films allowed us to find conditions for the formation of NCD films with minimal surface roughness and maximal growth rate: nitrogen concentration [N2] ≈ 0.2–0.5 % and temperature T ≈ 850–900 °C. These findings can be used to optimize the CVD synthesis parameters of PCD films for applications as protective or friction-reducing layers, as well as for superhard cutting tools and optical devices.

12255 Brain GFRAL Signaling Mediates Chemotherapy-Induced Fatigue And Cognitive Impairment In Mice

Abstract Disclosure: R. Dantzer: None. Brain GFRAL Signaling Mediates Chemotherapy-Induced Fatigue and Cognitive Impairment in Mice Brandon Chelette, PhD, Anand Singh, PhD, Robert Dantzer, DVM, PhDDept. of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA Fatigue and cognitive impairments are commonly reported by cancer patients undergoing chemotherapy. The mechanisms of these neurotoxicities are still obscure. We hypothesize that they are mediated by mitokines that are released by cells undergoing mitochondrial stress in response to chemotherapy. For the present study, we have focused on growth differentiation factor 15 (GDF15) which acts in the brain by activating its receptor, GDNF family receptor alpha-like (GFRAL). Chemotherapy-induced fatigue was assessed by reduced voluntary wheel running. Cognitive impairment was assessed by altered performance in the Puzzle Box Test that measures executive function. We first checked whether commonly used chemotherapeutic drugs can induce GDF15. Mice were injected with cisplatin, paclitaxel, or bortezomib, and their effects on plasma levels of GDF15 were measured 24 h after (ELISA). Cisplatin was used in the following experiments in the form of one or two cycles of daily injections for five days with a rest of five days between cycles. To determine whether GFRAL mediates the effects of cisplatin on wheel running and performance in the puzzle box, mice were injected with a neutralizing antibody targeted to GFRAL (GFRALna) during or after cisplatin treatment. All studies were carried out in male and female C57BL/6 J mice using a 2 (+ chemotherapy) x 2 (+ GFRALna) factorial design with a minimum of 6 mice/group. Mitochondrial dysfunction was measured via Seahorse XF Analyzer Mito Stress Test. To determine whether activation of the GDF15/GFRAL axis recruits a central GDF15 compartment, Gdf15 mRNA was measured by qRT-PCR in the brain parenchyma, meninges, and choroid plexus. All the chemotherapeutic agents we tested induced statistically significant increases in circulating GDF15. GFRALna administered during cisplatin treatment (prevention) or after completion of cisplatin treatment (cure) abrogated cisplatin-induced decrease in wheel running and the deficit displayed by cisplatin-treated mice in the first hard trial run in the puzzle box. GFRALna also blocked the decrease in maximal oxygen consumption rate of mitochondrial in synaptosomes from cisplatin-treated mice. Cisplatin did not induce Gdf15 mRNA in the brain parenchyma but increased its expression in the meninges and choroid plexus. Although the role of this GDF15 brain compartment in the neurotoxicity of cisplatin remains to be determined, the present findings can be interpreted to suggest that GDF15-GFRAL signaling represents a new target for the treatment of chemotherapy-induced fatigue and cognitive impairment. Count: 2,246 characters Presentation: 6/1/2024

Respiratory Muscle Strength as a Predictor of VO2max and Aerobic Endurance in Competitive Athletes

This study explores the association of respiratory muscle strength with aerobic endurance kinetics among athletes, with a specific focus on maximal oxygen consumption (VO2max). Previous research has elucidated the complex interactions between respiratory and skeletal muscles during exercise, highlighting the critical role of efficient respiration in maximizing athletic performance. The interplay between active skeletal muscles and respiratory muscles, especially the influence of respiratory muscle fatigue on exercise capacity, is well-documented. High-intensity exercise has been shown to activate the respiratory muscle metaboreflex, which can restrict blood flow to working muscles, thereby impacting the energy required for respiration. A total of 41 athletes, drawn from the disciplines of biathlon, judo, and cross-country, participated in this study. Respiratory function tests (RFTs) were administered to assess various respiratory parameters, including changes in chest circumference. Additionally, maximal oxygen consumption (VO2max) and heart rate were measured during a treadmill test. To explore the associations between VO2max and ventilatory parameters—namely, ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2)—as well as respiratory metrics, linear regression analysis was employed. Based on the standardized regression coefficients (β), it was found that maximum expiratory pressure (MEP) (mean ± SD: 130.95 ± 42.82) and inspiratory diaphragmatic circumference values were significantly associated with VE, VO2, and VCO2. Conversely, the other predictor variables did not exhibit a significant effect on VE (mean ± SD: 134.80 ± 36.69), VO2 (mean ± SD: 3877.52 ± 868.47 mL), and VCO2 (mean ± SD: 4301.27 ± 1001.07 mL). Similarly, measurements of chest circumference (mean ± SD: 91.40 ± 10.72 cm), MEP, and diaphragmatic circumference during inspiration (mean ± SD: 95.20 ± 10.21 cm) were significantly associated with VO2max (mean ± SD: 58.52 ± 10.74 mL/kg/min), while the remaining predictor variables did not demonstrate a significant effect on VO2max. Additionally, a multiple linear regression analysis was conducted to examine the combined effects of respiratory muscle strength and ventilatory factors on VO2max. The model, which included interaction terms, explained 89.9% of the variance in VO2max (R2 = 0.899, adjusted R2 = 0.859). Significant interactions were found between MIP and VE (B = −0.084, p = 0.006), as well as MEP and VE (B = 0.072, p = 0.012). These findings suggest that respiratory muscle strength plays a more substantial role in determining VO2max in individuals with higher ventilatory efficiency, highlighting the importance of both respiratory strength and breathing efficiency in aerobic performance. Our findings underscore the importance of considering respiratory muscle strength in assessing and enhancing athletes’ aerobic performance. Integrating objective measurements such as maximal inspiratory and expiratory pressure assessments into routine performance evaluations allows coaches and sports scientists to monitor changes in respiratory function over time and adjust training protocols accordingly.