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Time for post-exercise phosphocreatine-recovery (PCr-R), deemed a robust index of mitochondrial function in vivo, was previously reported to be elevated (signifying impaired ATP production) in veterans with Gulf War illness (GWI). Here we sought to replicate the finding and assess the impact of contravening previous eligibility requirements. The replication sample comprised white males. Cases reported ≥ moderate muscle-weakness to match the organ assessed to an organ affected; controls lacked recent headache or multiple symptoms. The expansion sample added cases without muscle-weakness, controls with recent headache, females, nonwhites. PCr-R, following pedal-depression-exercise, was compared in veterans with GWI versus controls (sample N = 38). In the replication sample, PCr-R results closely matched the prior report: PCr-R veterans with GWI mean(SD) = 47.7(16.5); control mean(SD) = 30.3(9.2), p = 0.017. (Prior-study PCr-R veterans with GWI mean(SD) = 46.1(17.9), control mean(SD) = 29.0(8.7), p = 0.023. Combined replication + prior samples: p = 0.001.) No case-control difference was observed in the expansion sample. In cases, PCr-R related to muscle-weakness: PCr-R = 29.9(7.1), 38.2(8.9), 47.8(15.2) for muscle-weakness rated none/low, intermediate, and high respectively (p for trend = 0.02), validating desirability of matching tissue assessed to tissue affected. In controls, headache/multiple symptoms, sex, and ethnicity each mattered (affecting PCr-R significantly). This study affirms mitochondrial/bioenergetic impairment in veterans with GWI. The importance of careful case/control selection is underscored.

The cardioprotective drug cyclocreatine phosphate has been awarded Food and Drug Administration-orphan drug designation for the prevention of ischemic injury to enhance cardiac graft recovery and survival in heart transplantation. Cyclocreatine phosphate is the water-soluble derivative of cyclocreatine. Estimating the levels of Cyclocreatine phosphate, Adenosine triphosphate, Creatine Phosphate, Creatine and Cyclocreatine helps us in understanding the energy state as well as evaluating the heart cells' function. The quantification of endogenous compounds imposes a challenging task for analysts because of the absence of a true blank matrix, whose use is required according to international guidelines. Recently, the International Council for Harmonization issued a new guideline that contains guidance on the validation of methods used to quantify endogenous components, such as the background subtraction approach that was employed in our current study. Specifically, we developed and validated a sensitive, reliable and accurate liquid chromatography-tandem mass spectrometry assay to determine simultaneously the levels of mentioned endogenous compounds in rat heart tissue. Tissue samples were prepared by protein precipitation extraction using water: methanol (1:1). Using Ultra Performance Liquid Chromatography, Chromatographic separation was achieved with ZORBAX Eclipse Plus C18 4.6 × 100 mm,3.5 μm column and conditions as following: ammonium acetate (pH 8.5): acetonitrile, 70:30 mobile phase, 0.7 mL/min flow rate and 25 °C temperature. Electrospray ionization mass detector with Multiple reaction monitoring mode was then employed, using both positive and negative modes, Analysis was carried out using 5.00–2000.00 ng/mL linear concentration range within 2 min for each analyte. According to Food and Drug Administration guidelines for bioanalytical methods, validation was carried out. We investigated the matrix effect, recovery efficiency and process efficiency for the analyte in neat solvent, postextraction matrix and tissue. The results stated mean percentage recoveries higher than 99%, accuracy 93.32–111.99%, and Relative Standard Deviation (RSD) below 15% within the concentration range of our study which indicated that target analytes' stability in their real matrix is sufficient under the employed experimental conditions. Highlights: Development of a validated LC‒MS/MS method to quantify levels of CCrP, ATP, CrP, Crt, and CCr, simultaneously. LC‒MS/MS method is sensitive, simple and suitable for preclinical trials for CCrP quantitation in different biological fluids. Validated method with good selectivity, linearity, and stability for CCrP in the rat heart. Efficient CCrP quantitation to improve outcomes for heart transplant patients. [ABSTRACT FROM AUTHOR]

Aim of the study was to analyze the metabolic profile of badminton matches and training drills. Therefore, 11 male (23.2 ± 3.8 years, 182 ± 7 cm, 74.4 ± 8.4 kg) and five female (19.3 ± 1.5 years, 170 ± 6 cm, 62.6 ± 9.2 kg) elite badminton players participated in either a training match (TM; n = 7) and/or three protocols of multifeeding drills (T10, T30,T50;n = 13), that varied in interval and rest durations (10 s/10 s, 30 s/30 s, 50 s/50 s). Absolute and relative energetic costs (Wtot and Etot) and contribution to oxidative (WOxid), phosphagen (WPCr), and anaerobic glycolytic (WLa) metabolism were calculated by the three‐component PCr‐La‐O2‐method based on an indirect calorimetric approach from oxygen consumption during exercise, post exercise, and net blood lactate concentration. A novel intermittent approach was used to consider replenishment of phosphocreatine during each resting phase. Results show that during TM, Etot was 676 ± 98J·kg−1 min−1, while metabolic pathways contributed by 56.9 ± 8.6% (WOxid), 42.7 ± 8.7% (WPCr), and 0.4 ± 0.6% (WLa). In the multifeeding drills Etot was comparable between T10 (1020 ± 160J·kg−1 min−1) and T30 (985 ± 173 J·kg−1 min−1) but higher in T50 (1266 ± 194J·kg−1 min−1) (p < 0.001). Relative contribution of WOxid was lower in T10 (47.3 ± 7.7%) but similar in T30 (56.5 ± 6.2%) and T50 (57.3 ± 6.0%) (p < 0.001). WPCr was highest in T10 (51.1 ± 8.3%) followed by T30 (42.2 ± 6.9%) and lowest in T50 (31.2 ± 7.7%) (p < 0.001). WLa was similar between T10 (1.6 ± 1.0%) and T30 (2.1 ± 1.0%) but higher in T50 (11.6 ± 4.8%) (p < 0.001). Concludingly, metabolic costs in badminton are predominantly covered by oxidative and phosphagen energetic pathways. Metabolic profiles of the multifeeding drills differ depending on rally/interval duration, with increasing contribution of anaerobic glycolysis and decreasing phosphagen contribution in case of longer intervals. Plain Language Summary: Badminton stands out as a high‐paced and exceptionally demanding sport, necessitating a very complex interaction between the aerobic and anaerobic metabolic systems. Using an innovative approach of indirect caloric measurement, the main aim of the investigation was to determine the metabolic profiles of elite badminton match play and badminton‐specific training drills. Therefore, 16 elite players conducted either a training match and/or three different protocols of a multifeeding drill (with varying interval/rest durations). The study underscores a pivotal role of anaerobic alactic energy supply in badminton, highlighting the critical need for rapid phosphocreatine (PCr) replenishment to prevent performance decline attributed to increasing acidosis. While aerobic capacity remains vital for PCr replenishment, occasional reliance on lactic metabolism may be important in certain probable match deciding situations. The multifeeding drills exhibit variations in the metabolic profile depending on rally and rest durations. As the interval length increases, the dominance of aerobic and lactic metabolism rises, while the proportion of anaerobic alactic contribution decreases. Emphasizing that in on‐court drills different interval durations address different metabolic pathways, training content should be chosen wisely to accurately address individual training goals and to align with a long‐term training periodization perspective. Highlights: This is the first study using an intermittent approach of the three‐component PCr‐La‐O2‐method, to determine the metabolic profile of elite badminton match play and the impact of drill prescription on metabolic stress in badminton‐specific training drills.The present findings reveal that energy in badminton generally is predominantly derived from oxidative and phosphagen energetic pathways, with the anaerobic glycolytic system contributing only minimally.Multifeeding drills essentially mirror the metabolic demands of matches but exhibit variations depending on rally and rest periods. These findings underscore the need to select training protocols thoughtfully, tailor training according to individualized goals and to structure those goals within a long‐term training periodization. [ABSTRACT FROM AUTHOR]

In China, the processing of prickly ash (PA) produces a large number of by-products, including prickly ash seeds (PASs), which are rich in bioactive components such as flavonoids and phenolic compounds, and which may have an important influence on meat quality and muscle metabolites. Therefore, this study aimed to assess the impact of dietary PAS supplementation on the meat quality, antioxidant activity, and metabolite characteristics of lambs. Eighteen 3-month-old Hu lambs (25.66 ± 3.03 kg body weight) were randomly allotted to three different dietary treatment groups. In the three dietary treatments, 0% (basal diet, CON), 3% (CON with 3% PAS, low-dose PAS, and LPS), and 6% (CON with 6% PAS, high-dose PAS, and HPS) PASs were used. Results indicated significant improvements in the HPS group, including reduced cooking loss and increased fat content. The L* and b* 45 min values were significantly lower in the PAS groups than those in the CON group (p < 0.05). Additionally, dietary PAS supplementation increased in MUFA, PUFA, n-3 PUFA, PUFA/MUFA ratio, NEAA, and FFA compared to the CON group. Furthermore, PAS supplementation significantly improved serum and muscle antioxidant capacity. Metabolomic analyses revealed that increased metabolites, such as tryptophan, leucine, citric acid, adenosine 5′-triphosphate, creatine phosphate, inosine, and α-ketoglutaric acid, were primarily enriched in the biosynthesis of cofactors and nucleotide and purine metabolism pathways. Notably, supplementation with 6% of PASs exhibited the most prominent effect on lamb meat quality in this study. Therefore, the application of PASs as a feed component in lamb production can not only improve meat quality and muscle antioxidant capacity but also save feed costs. [ABSTRACT FROM AUTHOR]

Background/Objective: Maintaining intracellular adenosine triphosphate (ATP) levels is essential for numerous cellular functions, including energy metabolism, muscle contraction, and nerve impulse transmission. ATP is primarily synthesized in mitochondria through oxidative phosphorylation. It is also generated in the cytosol under anaerobic conditions using phosphocreatine (PCr) as a phosphate donor to adenosine diphosphate. However, the intracellular delivery of exogenous PCr is challenging as it does not readily cross the plasma membrane. This complicates the use of PCr as a therapeutic agent to maintain energy homeostasis or to treat conditions like cerebral creatine deficiency syndrome (CDS), which results from defective creatine transporters. Methods: This study employs the use of fusogenic liposomes to deliver PCr directly into the cytosol, bypassing membrane impermeability issues. We engineered various 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based fusogenic liposomes, incorporating phospholipids such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in combination with phospholipid-aromatic dye components to facilitate membrane fusion and to enhance the delivery of the PCr cargo. Liposomal formulations were co-loaded with membrane-impermeable chromophores and PCr and studied on live cells using confocal microscopy. Conclusions: We demonstrated the successful intracellular delivery of these agents and observed a 23% increase in intracellular ATP levels in cells treated with PCr-loaded liposomes. This increase was not observed with free PCr, confirming the effectiveness of the liposome-based delivery system. Additionally, cell viability assays showed minimal toxicity from the liposomes. Our results indicate that fusogenic liposomes are a promising method for the delivery of PCr (and potentially other cell-impermeable therapeutic agents) to the cellular cytosol. The approach demonstrated here could be advantageous for treating energy-related disorders and improving cellular energy homeostasis. [ABSTRACT FROM AUTHOR]

The article explores the model for end-stage liver disease (MELD) score and its role in predicting mortality for patients awaiting liver transplantation. It discusses the limitations of the current MELD score due to changes in chronic liver disease and introduces a new scoring system called MELD 3.0. This updated system aims to better predict waitlist mortality and address healthcare disparities among underrepresented candidates. The article also addresses the disparity in waitlist mortality rates between men and women, highlighting factors such as kidney function underestimation and organ size limitations for women. It suggests that future iterations of the MELD system may address these issues and mentions the potential use of large language models and machine learning in improving waitlist mortality prediction and organ allocation. [Extracted from the article]

The present study aimed to verify the effect of acute nitrate supplementation on oxidative, phosphocreatine, and glycolytic energy contribution (COXI, CPCr, and CLAC, respectively) during a high-intensity intermittent exercise (HIIE). Fifteen physically active subjects were submitted to incremental running test on a treadmill and two random HIIE (10 × 1 min at maximal aerobic speed with 1 min of passive recovery) in the following conditions: sodium nitrate (SN) or Placebo (PL). Repeated measure ANOVA was used to compare COXI, and CPCr within the 10 efforts. Student t test was used to compare total COXI, CPCr, CLAC, as well oxidative and non-oxidative contribution. Considering the 10 efforts, COXI presented the main effect for condition (F = 16.7; p = .001; SN: 1.9 ± 0.1 L; PL: 1.6 ± 0.1 L), and no interaction effect (F = 0.9; p = .415), while CPCr presented effect for condition (F = 13.4; p = .003; SN: 1.2 ± 0.1; PL: 1.4 ± 0.8 L), and no interaction (F = 1.2; p = .317). Total oxidative contribution were higher (p < .001) after SN (19.1 ± 3.4 L) than Placebo (16.7 ± 3.1 L), while total CPCr were lower (p = .002) after SN (12.4 ± 2.5 L) than PL (14.1 ± 2.6 L). Total energy contribution were not different between trials. Acute dose of SN supplementation improved oxidative contribution during HIIE, and reduced CPCr. Higher COXI is likely related to increased oxygen kinetics, while the lower CPCr might be related to the improved energetic efficiency. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to ascertain the optimal test duration to elicit the highest maximal lactate formation rate ( V ˙ Lamax), whilst exploring the underpinning energetics, and identifying the optimal blood lactate sampling period. Methods: Fifteen trained to well-trained males (age 27 ± 6 years; peak power: 1134 ± 174 W) participated in a randomised cross-over design completing three all-out sprint cycling tests of differing test durations (10, 15, and 30 s). Peak and mean power output (W and W.kg−1), oxygen uptake, and blood lactate concentrations were measured. V ˙ Lamax and energetic contributions (phosphagen, glycolytic, and oxidative) were determined using these parameters. Results: The shortest test duration of 10 s elicited a significantly (p = 0.003; p < 0.001) higher V ˙ Lamax (0.86 ± 0.17 mmol.L−1.s−1; 95% CI 0.802–0.974) compared with both 15 s (0.68 ± 0.18 mmol.L−1.s−1; 95% CI 0.596–0.794) and 30 s (0.45 ± 0.07 mmol.L−1.s−1; 95% CI 0.410–0.487). Differences in V ˙ Lamax were associated with large effect sizes (d = 1.07, d = 3.15). We observed 81% of the PCr and 53% of the glycolytic work completed over the 30 s sprint duration was attained after 10 s. BLamaxpost were achieved at 5 ± 2 min (ttest 10 s), 6 ± 2 min (ttest 15 s), and 7 ± 2 min (ttest 30 s), respectively. Conclusion: Our findings demonstrated a 10 s test duration elicited the highest V ˙ Lamax. Furthermore, the 10 s test duration mitigated the influence of the oxidative metabolism during all-out cycling. The optimal sample time to determine peak blood lactate concentration following 10 s was 5 ± 2 min. [ABSTRACT FROM AUTHOR]

Background: Long-term adaptations and ongoing training seem to modify the energy system contribution in highly trained individuals. We aimed to compare the energy metabolism profile during sprint exercise in athletes of different specialties. Methods: Endurance (n = 17, 20.3 ± 6.0 yrs), speed-power (n = 14, 20.3 ± 2.5 yrs), and mixed (n = 19, 23.4 ± 4.8 yrs) athletes performed adapted 15-second all-out test before and after a general preparation training period. The contribution of phosphagen, glycolytic, and aerobic systems was calculated using the three-component PCr-LA-O2 method. Results: Between-group differences were observed in the contribution of energy systems in the first and second examinations. The proportions were 47:41:12 in endurance, 35:57:8 in team sports, and 45:48:7 in speed-power athletes. Endurance athletes differed in the phosphagen (p < 0.001) and glycolytic systems (p = 0.006) from team sports and in the aerobic system from speed-power athletes (p = 0.003). No substantial shifts were observed after the general preparatory phase, except a decrease in aerobic energy contribution in team sports athletes (p = 0.048). Conclusion: Sports specialization and metabolic profile influence energy system contribution during sprint exercise. Highly trained athletes show a stable energy profile during the general preparation phase, indicative of long-term adaptation, rather than immediate training effects. [ABSTRACT FROM AUTHOR]

The present study aimed to explore whether water flow velocity could affect the swimming ability and overall energy metabolism of wild Amur grayling (Thymallus grubii). Swimming performance was assessed by measuring critical swimming speed (Ucrit), burst speed (Uburst), and oxygen consumption rate (MO2) based on the stepped velocity test method. Our results showed that the absolute values of Ucrit and Uburst tended to increase with body length. In contrast, the relative values of Ucrit and Uburst tended to decrease and increase, respectively. MO2 in Amur grayling was elevated with increasing velocity, suggesting relatively high swimming efficiency. We also measured the biochemical indices related to energy metabolism. Lactate dehydrogenase, hexokinase, and pyruvate kinase activities significantly increased (p < 0.05). Hepatic glycogen, glucose, and muscle glycogen contents decreased with the increasing trend of velocity (p < 0.05), the lactic acid contents of the blood and muscles increased significantly with the increase in velocities (p < 0.05), and changes in creatine phosphate content showed no significant difference (p > 0.05). The results not only denote the relationship between body size and swimming speed but also show the effects of water flow velocity on energy metabolism in Amur grayling. The results provide basic data for the construction of fish passage. [ABSTRACT FROM AUTHOR]

Hyperthyroidism is the most common feline endocrinopathy. In hyperthyroid humans, untargeted metabolomic analysis identified persistent metabolic derangements despite achieving a euthyroid state. Therefore, we sought to define the metabolome of hyperthyroid cats and identify ongoing metabolic changes after treatment. We prospectively compared privately-owned hyperthyroid cats (n = 7) admitted for radioactive iodine (I-131) treatment and euthyroid privately-owned control (CON) cats (n = 12). Serum samples were collected before (T0), 1-month (T1), and three months after (T3) I-131 therapy for untargeted metabolomic analysis by MS/MS. Hyperthyroid cats (T0) had a distinct metabolic signature with 277 significantly different metabolites than controls (70 increased, 207 decreased). After treatment, 66 (T1 vs. CON) and 64 (T3 vs. CON) metabolite differences persisted. Clustering and data reduction analysis revealed separate clustering of hyperthyroid (T0) and CON cats with intermediate phenotypes after treatment (T1 & T3). Mevalonate/mevalonolactone and creatine phosphate were candidate biomarkers with excellent discrimination between hyperthyroid and healthy cats. We found several metabolic derangements (e.g., decreased carnitine and α-tocopherol) do not entirely resolve after achieving a euthyroid state after treating hyperthyroid cats with I-131. Further investigation is warranted to determine diagnostic and therapeutic implications for candidate biomarkers and persistent metabolic abnormalities. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to unravel the clinical effect analysis of different doses of creatine phosphate sodium (CPS) combined with immunoglobulin in the treatment of pediatric viral myocarditis (VMC). One hundred and twenty children with VMC were recruited and randomized into three groups (40 patients each). Group I received 1.0 g of CPS dissolved in 100 mL of 5% glucose injection intravenously 1 time/day; group II received 1.25 g of CPS dissolved in 125 mL of 5% glucose injection intravenously 1 time/day; group III received 1.5 g of CPS dissolved in 150 mL of 5% glucose injection intravenously 1 time/day; then all three groups were treated with combined use of immunoglobulin (300–400 mg/day) intravenously once a day; and all three groups were treated for 14 days. The clinical efficacy, cardiac function, serum inflammatory factor levels, immune function, and the occurrence of drug toxicity and adverse effects of the children in the three groups were compared after 14 days of treatment. All three groups achieved better therapeutic effects after treatment, in which the effective rate of the Group II and Group III was notably higher versus the Group I. Lower levels of cTnI, CK-MB, LDH, AST, IL-18, IL-6, IFN-γ, and LVEDD and higher CD3+, CD4+, and CD4+/CD8+, FS, and LVEF values were noted in the Group II and Group III versus the Group I, and the results were more pronounced in the high-dose group. The liver and kidney functions of the children in the three groups before and after treatment did not show any significant changes and the incidence of adverse reactions during the treatment period was low in all three groups. Children with VMC can be treated with high-dose CPS in combination with immunoglobulin, which can improve their cardiac function and immune function and reduce the inflammatory response with good overall therapeutic efficacy and fewer adverse effects. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is linked to impaired mitochondrial function. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a gadolinium‐contrast‐free 1H method to assess mitochondrial function by measuring low‐concentration metabolites. A CEST MRI‐based technique may serve as a non‐invasive proxy for assessing mitochondrial health. Hypothesis: A 1H CEST MRI technique may detect significant differences in in vivo skeletal muscle phosphocreatine (SMPCr) kinetics between healthy volunteers and T2DM patients undergoing standardized isometric exercise. Study Type: Cross‐sectional study. Subjects: Seven subjects without T2DM (T2DM−) and seven age, sex, and BMI‐matched subjects with T2DM (T2DM+). Field Strength/Sequence: Single‐shot rapid acquisition with refocusing echoes (RARE) and single‐shot gradient‐echo sequences, 3 T. Assessment: Subjects underwent a rest‐exercise‐recovery imaging protocol to dynamically acquire SMPCr maps in calf musculature. Medial gastrocnemius (MG) and soleus SMPCr concentrations were plotted over time, and SMPCr recovery time, τ, was determined. Mitochondrial function index was calculated as the ratio of resting SMPCr to τ. Participants underwent a second exercise protocol for imaging of skeletal muscle blood flow (SMBF), and its association with SMPCr was assessed. Statistical Tests: Unpaired t‐tests and Pearson correlation coefficient. A P value <0.05 was considered statistically significant. Results: SMPCr concentrations in MG and soleus displayed expected declines during exercise and returns to baseline during recovery. τ was significantly longer in the T2DM+ cohort (MG 83.5 ± 25.8 vs. 54.0 ± 21.1, soleus 90.5 ± 18.9 vs. 51.2 ± 14.5). The mitochondrial function index in the soleus was significantly lower in the T2DM+ cohort (0.33 ± 0.08 vs. 0.66 ± 0.19). SMBF was moderately correlated with the SMPCr in T2DM−; this correlation was not significant in T2DM+ (r = −0.23, P = 0.269). Conclusion: The CEST MRI method is feasible for quantifying SMPCr in peripheral muscle tissue. T2DM+ individuals had significantly lower oxidative capacities than T2DM− individuals. In T2DM, skeletal muscle metabolism appeared to be decoupled from perfusion. Level of Evidence: 1 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

The study assessed vastus lateralis oxygen desaturation kinetics (SmO2) in 32 male cyclists (16 Seniors, 16 Juniors) during a 30 s sprint, examining effects of age and performance. An incremental test was used to determine ventilatory thresholds (VT1, VT2) and maximal oxygen uptake (VO2kg), followed by a sprint test to evaluate anaerobic performance. Cyclists' performance phenotype was determined as the ratio of power at VT2 to 5 s peak sprint power. Juniors exhibited sprinter-like traits, excelling in all functional tests except for lactate levels post-sprint. SmO2 data showed no age-related or bilateral differences across participants. The combined mean response time (MRT) revealed stronger bilateral goodness of fit (R2 = 0.64) than individual time delay (TD) and time constant (τ). Higher VO2kg at VT2, peak power, and maximal uptake were linked to longer TD, while shorter TD correlated with higher lactate production and increased fatigue. Bilaterally averaged SmO2 kinetics distinguished between sprint and endurance athletes, indicating the potential to reflect the alactic anaerobic system's capacity and depletion. Age did not affect desaturation rates, but younger cyclists showed greater response amplitude, attributed to a higher initial baseline rather than maximal desaturation at the end of the exercise. [ABSTRACT FROM AUTHOR]

Abstract Time for post-exercise phosphocreatine-recovery (PCr-R), deemed a robust index of mitochondrial function in vivo, was previously reported to be elevated (signifying impaired ATP production) in veterans with Gulf War illness (GWI). Here we sought to replicate the finding and assess the impact of contravening previous eligibility requirements. The replication sample comprised white males. Cases reported ≥ moderate muscle-weakness to match the organ assessed to an organ affected; controls lacked recent headache or multiple symptoms. The expansion sample added cases without muscle-weakness, controls with recent headache, females, nonwhites. PCr-R, following pedal-depression-exercise, was compared in veterans with GWI versus controls (sample N = 38). In the replication sample, PCr-R results closely matched the prior report: PCr-R veterans with GWI mean(SD) = 47.7(16.5); control mean(SD) = 30.3(9.2), p = 0.017. (Prior-study PCr-R veterans with GWI mean(SD) = 46.1(17.9), control mean(SD) = 29.0(8.7), p = 0.023. Combined replication + prior samples: p = 0.001.) No case–control difference was observed in the expansion sample. In cases, PCr-R related to muscle-weakness: PCr-R = 29.9(7.1), 38.2(8.9), 47.8(15.2) for muscle-weakness rated none/low, intermediate, and high respectively (p for trend = 0.02), validating desirability of matching tissue assessed to tissue affected. In controls, headache/multiple symptoms, sex, and ethnicity each mattered (affecting PCr-R significantly). This study affirms mitochondrial/bioenergetic impairment in veterans with GWI. The importance of careful case/control selection is underscored.

The aim of this study was to conduct a systematic review and meta-analysis of the effects of short-term creatine supplementation on repeated sprint ability. Fourteen studies met the inclusion criteria of adopting double-blind randomized placebo-controlled designs in which participants (age: 18–60 years) completed a repeated sprint test (number of sprints: 4 < n ≤ 20; sprint duration: ≤10 s; recovery duration: ≤90 s) before and after supplementing with creatine or placebo for 3–7 days in a dose of ∼20 g/day. No exclusion restrictions were placed on the mode of exercise. Meta-analyses were completed using random-effects models, with effects on measures of peak power output, mean power output, and fatigue (performance decline) during each repeated sprint test presented as standardized mean difference (δ), and with effects on body mass and posttest blood lactate concentration presented as raw mean difference (D). Relative to placebo, creatine resulted in a significant increase in body mass (D = 0.79 kg; p <.00001) and mean power output (δ = 0.61; p =.002). However, there was no effect of creatine on measures of peak power (δ = 0.41; p =.10), fatigue (δ = 0.08; p =.61), or posttest blood lactate concentration (D = 0.22 L/min; p =.60). In conclusion, creatine supplementation may increase mean power output during repeated sprint tests, although the absence of corresponding effects on peak power and fatigue means that more research, with measurements of intramuscular creatine content, is necessary to confirm. [ABSTRACT FROM AUTHOR]

Based on Mader's mathematical model, the rate of capillary blood lactate concentration (νLamax) following intense exercise is thought to reflect the maximal glycolytic rate. We aimed to investigate the reliability of important variables of Mader's model (i.e. power output, lactate accumulation, predominant phosphagen contribution time frames (tPCr)) and resulting νLamax values derived during and after a 15‐s cycling sprint. Fifty cyclists performed a 15‐s all‐out sprint test on a Cyclus2 ergometer three times. The first sprint test was considered a familiarization trial. Capillary blood was sampled before and every minute (for 8 min) after the sprint to determine νLamax. Test–retest analysis between T2 and T3 revealed excellent reliability for power output (Pmean and Ppeak; ICC = 0.99, 0.99), ∆La and νLamax with tPCr of 3.5 s (ICC = 0.91, 0.91). νLamax calculated with tPCr = tPpeak (ICC = 0.87) and tPCr = tPpeak–3.5% (ICC = 0.79) revealed good reliability. tPpeak and tPpeak–3.5% revealed only poor and moderate reliability (ICC = 0.41, 0.52). Power output and ∆La are reliable parameters in the context of this test. Depending on tPCr, reliability of νLamax varies considerably with tPCr of 3.5 s showing excellent reliability. We recommend standardization of this type of testing especially tPCr. [ABSTRACT FROM AUTHOR]

Monitoring the variation in phosphocreatine (PCr) levels following exercise provides valuable insights into muscle function. Chemical exchange saturation transfer (CEST) has emerged as a sensitive method with which to measure PCr levels in muscle, surpassing conventional MR spectroscopy. However, existing approaches for quantifying PCr CEST signals rely on time‐consuming fitting methods that require the acquisition of the entire or a section of the CEST Z‐spectrum. Additionally, traditional fitting methods often necessitate clear CEST peaks, which may be challenging to obtain at low magnetic fields. This paper evaluated the application of a new model‐free method using double saturation power (DSP), termed DSP‐CEST, to estimate the PCr CEST signal in muscle. The DSP‐CEST method requires the acquisition of only two or a few CEST signals at the PCr frequency offset with two different saturation powers, enabling rapid dynamic imaging. Additionally, the DSP‐CEST approach inherently eliminates confounding signals, offering enhanced robustness compared with fitting methods. Furthermore, DSP‐CEST does not demand clear CEST peaks, making it suitable for low‐field applications. We evaluated the capability of DSP‐CEST to enhance the specificity of PCr CEST imaging through simulations and experiments on muscle tissue phantoms at 4.7 T. Furthermore, we applied DSP‐CEST to animal leg muscle both before and after euthanasia and observed successful reduction of confounding signals. The DSP‐CEST signal still has contaminations from a residual magnetization transfer (MT) effect and an aromatic nuclear Overhauser enhancement effect, and thus only provides a PCr‐weighted imaging. The residual MT effect can be reduced by a subtraction of DSP‐CEST signals at 2.6 and 5 ppm. Results show that the residual MT‐corrected DSP‐CEST signal at 2.6 ppm has significant variation in postmortem tissues. By contrast, both the CEST signal at 2.6 ppm and a conventional Lorentzian difference analysis of CEST signal at 2.6 ppm demonstrate no significant variation in postmortem tissues. [ABSTRACT FROM AUTHOR]

Time for post-exercise phosphocreatine-recovery (PCr-R), deemed a robust index of mitochondrial function in vivo, was previously reported to be elevated (signifying impaired ATP production) in veterans with Gulf War illness (GWI). Here we sought to replicate the finding and assess the impact of contravening previous eligibility requirements. The replication sample comprised white males. Cases reported ≥ moderate muscle-weakness to match the organ assessed to an organ affected; controls lacked recent headache or multiple symptoms. The expansion sample added cases without muscle-weakness, controls with recent headache, females, nonwhites. PCr-R, following pedal-depression-exercise, was compared in veterans with GWI versus controls (sample N = 38). In the replication sample, PCr-R results closely matched the prior report: PCr-R veterans with GWI mean(SD) = 47.7(16.5); control mean(SD) = 30.3(9.2), p = 0.017. (Prior-study PCr-R veterans with GWI mean(SD) = 46.1(17.9), control mean(SD) = 29.0(8.7), p = 0.023. Combined replication + prior samples: p = 0.001.) No case–control difference was observed in the expansion sample. In cases, PCr-R related to muscle-weakness: PCr-R = 29.9(7.1), 38.2(8.9), 47.8(15.2) for muscle-weakness rated none/low, intermediate, and high respectively (p for trend = 0.02), validating desirability of matching tissue assessed to tissue affected. In controls, headache/multiple symptoms, sex, and ethnicity each mattered (affecting PCr-R significantly). This study affirms mitochondrial/bioenergetic impairment in veterans with GWI. The importance of careful case/control selection is underscored. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is characterised by asymmetric left ventricular hypertrophy, ventricular arrhythmias, and cardiomyocyte dysfunction that may cause sudden death. HCM is associated with mutations in sarcomeric proteins and is usually transmitted as an autosomal-dominant trait. The aim of this in silico study was to assess the mechanisms that underlie the altered electrophysiological activity, contractility, regulation of energy metabolism, and crossbridge cycling in HCM at the single-cell level. To investigate this, we developed a human ventricular cardiomyocyte model that incorporates electrophysiology, metabolism, and force generation. The model was validated by its ability to reproduce the experimentally observed kinetic properties of human HCM induced by (a) remodelling of several ion channels and Ca2+-handling proteins arising from altered Ca2+/calmodulin kinase II signalling pathways and (b) increased Ca2+ sensitivity of the myofilament proteins. Our simulation showed a decreased phosphocreatine-to-ATP ratio (-9%) suggesting a negative mismatch between energy expenditure and supply. Using a spatial myofilament half-sarcomere model, we also compared the fraction of detached, weakly bound, and strongly bound crossbridges in the control and HCM conditions. Our simulations showed that HCM has more crossbridges in force-producing states than in the control condition. In conclusion, our model reveals that impaired crossbridge kinetics is accompanied by a negative mismatch between the ATP supply and demand ratio. This suggests that improving this ratio may reduce the incidence of sudden death in HCM. [ABSTRACT FROM AUTHOR]

Performance in many racing sports depends on the ability of the athletes to produce and maintain the highest possible work i.e., the highest power for the duration of the race. To model this energy production in an individualized way, an adaptation and a reinterpretation (including a physiological meaning of parameters) of the three-component Margaria–Morton model were performed. The model is applied to the muscles involved in a given task. The introduction of physiological meanings was possible thanks to the measurement of physiological characteristics for a given athlete. A method for creating a digital twin was therefore proposed and applied for national-level cyclists. The twins thus created were validated by comparison with field performance, experimental observations, and literature data. Simulations of record times and 3-minute all-out tests were consistent with experimental data. Considering the literature, the model provided good estimates of the time course of muscle metabolite concentrations (e.g., lactate and phosphocreatine). It also simulated the behavior of oxygen kinetics at exercise onset and during recovery. This methodology has a wide range of applications, including prediction and optimization of the performance of individually modeled athletes. [ABSTRACT FROM AUTHOR]

Aim: We compared muscular metabolic stress during exercise performed at multiple intensities, from very low to moderate, with blood flow restriction (BFR) adjusted by the same work volume. Methods: Twenty‐five healthy young adults performed unilateral plantar flexion at 1 repetition/2 s in a magnetic resonance system. The BFR exercise protocols were as follows: (A) exercise with 10% of one repetition maximum (1‐RM) for 360 s, (B) 15% 1‐RM for 240 s, (C) 20% 1‐RM for 180 s, (D) 30% 1‐RM for 120 s, and (E) 40% 1‐RM for 90 s. All protocols had the same total work volume (load × repetitions = 1800). A high‐intensity protocol at 65% 1‐RM without BFR (60 s) was also performed for comparison. We used 31P‐magnetic resonance spectroscopy to evaluate the muscular metabolic stress in the subjects' calf muscle, defined as decreases in phosphocreatine and intramuscular pH. Results: The phosphocreatine depletion (A: 15.6 ± 0.7, B: 14.8 ± 0.8, C: 15.2 ± 0.6, D: 14.3 ± 0.6, E: 10.9 ± 0.5 mM; no significant difference [ns]) and the intramuscular pH decrease (A: 6.82 ± 0.02, B: 6.84 ± 0.01, C: 6.83 ± 0.02, D: 6.83 ± 0.02, E: 6.77 ± 0.02; ns) at the end of each exercise were similar and greater than those produced by the 65% 1‐RM without BFR. Conclusion: If the total work volumes are equal, the metabolic stress in exercising muscle may reach similar levels at the end of exercise with BFR and could provide similar successful training effects. [ABSTRACT FROM AUTHOR]

Purpose: To confirm that CrCEST in muscle exhibits a slow‐exchanging process, and to obtain high‐resolution amide, creatine (Cr), and phosphocreatine (PCr) maps of skeletal muscle using a POlynomial and Lorentzian Line‐shape Fitting (PLOF) CEST at 3T. Methods: We used dynamic changes in PCr/CrCEST of mouse hindlimb before and after euthanasia to assign the Cr and PCr CEST peaks in the Z‐spectrum at 3T and to obtain the optimum saturation parameters. Segmented 3D EPI was employed to obtain multi‐slice amide, PCr, and Cr CEST maps of human skeletal muscle. Subsequently, the PCrCEST maps were calibrated using the PCr concentrations determined by 31P MRS. Results: A comparison of the Z‐spectra in mouse hindlimb before and after euthanasia indicated that CrCEST is a slow‐exchanging process in muscle (<150.7 s−1). This allowed us to simultaneously extract PCr/CrCEST signals at 3T using the PLOF method. We determined optimal B1 values ranging from 0.3 to 0.6 μT for CrCEST in muscle and 0.3–1.2 μT for PCrCEST. For the study on human calf muscle, we determined an optimum saturation time of 2 s for both PCr/CrCEST (B1 = 0.6 μT). The PCr/CrCEST using 3D EPI were found to be comparable to those obtained using turbo spin echo (TSE). (3D EPI/TSE PCr: (2.6 ± 0.3) %/(2.3 ± 0.1) %; Cr: (1.3 ± 0.1) %/(1.4 ± 0.07) %). Conclusions: Our study showed that in vivo CrCEST is a slow‐exchanging process. Hence, amide, Cr, and PCr CEST in the skeletal muscle can be mapped simultaneously at 3T by PLOF CEST. [ABSTRACT FROM AUTHOR]

Cardiovascular disease remains one of the most common and influential causes of death worldwide, as the heart plays a key role in the human body. Energetic cardioprotective therapy of the myocardium is an important protective factor, regulating the synthesis and use of energy by myocardial cells, while having a little effect on heart rate, blood pressure, and blood supply. Phosphocreatine plays an important role in the intracellular energy buffering and transport system, ensuring energy transfer from the site of production to the site of use to meet the high and variable demands of the heart. Research shows that phosphocreatine can have a positive effect on patients with coronary heart disease, heart failure, and those who have undergone cardiac surgery. The accumulated information confirms the prospects of using phosphocreatine in clinical practice to improve treatment outcomes in patients with heart diseases.

Background/Objective: Maintaining intracellular adenosine triphosphate (ATP) levels is essential for numerous cellular functions, including energy metabolism, muscle contraction, and nerve impulse transmission. ATP is primarily synthesized in mitochondria through oxidative phosphorylation. It is also generated in the cytosol under anaerobic conditions using phosphocreatine (PCr) as a phosphate donor to adenosine diphosphate. However, the intracellular delivery of exogenous PCr is challenging as it does not readily cross the plasma membrane. This complicates the use of PCr as a therapeutic agent to maintain energy homeostasis or to treat conditions like cerebral creatine deficiency syndrome (CDS), which results from defective creatine transporters. Methods: This study employs the use of fusogenic liposomes to deliver PCr directly into the cytosol, bypassing membrane impermeability issues. We engineered various 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based fusogenic liposomes, incorporating phospholipids such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in combination with phospholipid-aromatic dye components to facilitate membrane fusion and to enhance the delivery of the PCr cargo. Liposomal formulations were co-loaded with membrane-impermeable chromophores and PCr and studied on live cells using confocal microscopy. Conclusions: We demonstrated the successful intracellular delivery of these agents and observed a 23% increase in intracellular ATP levels in cells treated with PCr-loaded liposomes. This increase was not observed with free PCr, confirming the effectiveness of the liposome-based delivery system. Additionally, cell viability assays showed minimal toxicity from the liposomes. Our results indicate that fusogenic liposomes are a promising method for the delivery of PCr (and potentially other cell-impermeable therapeutic agents) to the cellular cytosol. The approach demonstrated here could be advantageous for treating energy-related disorders and improving cellular energy homeostasis.

Acetylcarnitine is an essential metabolite for maintaining metabolic flexibility and glucose homeostasis. The in vivo behavior of muscle acetylcarnitine content during exercise has not been shown with magnetic resonance spectroscopy. Therefore, this study aimed to explore the behavior of skeletal muscle acetylcarnitine during rest, plantar flexion exercise, and recovery in the human gastrocnemius muscle under aerobic conditions. Ten lean volunteers and nine overweight volunteers participated in the study. A 7 T whole-body MR system with a double-tuned surface coil was used to acquire spectra from the gastrocnemius medialis. An MR-compatible ergometer was used for the plantar flexion exercise. Semi-LASER-localized 1H MR spectra and slab-localized 31P MR spectra were acquired simultaneously in one interleaved exercise/recovery session. The time-resolved interleaved 1H/31P MRS acquisition yielded excellent data quality. A between-group difference in acetylcarnitine metabolism over time was detected. Significantly slower τPCr recovery, τPCr on-kinetics, and lower Qmax in the overweight group, compared to the lean group was found. Linear relations between τPCr on-kinetics, τPCr recovery, VO2max and acetylcarnitine content were identified. In conclusion, we are the first to show in vivo changes of skeletal muscle acetylcarnitine during acute exercise and immediate exercise recovery with a submaximal aerobic workload using interleaved 1H/31P MRS at 7 T. [ABSTRACT FROM AUTHOR]

Purpose: Often, the glycolytic contribution in a bout of heavy or severe intensity exercise is estimated by multiplying the increase in blood lactate concentration above resting levels that is engendered by the exercise (in mM) by 3.3 (or 3) mL⋅kg-1 per mM. Our purpose was to verify the value of this conversion factor, using methods that were completely different from those of the original studies. Methods: Six women (mean ± SD), age, 23 ± 1 year; VO2max, 46±4mL⋅kg-1⋅min-1) and three men (23 ± 0 years; 54 ± 8 mL⋅kg-1⋅min-1) completed 6 min of heavy intensity exercise in conditions of normoxia and hypoxia (FIO2, ~12%). VO2 was measured throughout the exercise and 7 min of recovery. The increase in glycolytic contribution was estimated as the reduction in aerobic contribution in hypoxia, after correction for the effects of hypoxia on the oxygen demand and on the contribution from phosphocreatine. The peak post-exercise blood lactate concentration was measured in fingerstick blood samples. Results: The ratio between the increase in estimated glycolytic contribution (in mL⋅kg-1) in hypoxia and the increase in peak blood lactate concentration (in mM) yielded an oxygen equivalent of 3.4 ± 0.4 mL⋅kg-1 per mM (range, 2.6 mL⋅kg-1 per mM to 4.0 mL⋅kg-1 per mM) for cycle ergometer exercise. Conclusion: These results generally support the use of a common conversion factor to calculate the glycolytic contribution from post-exercise blood lactate concentrations. However, there is some inter-individual variability in the conversion factor. [ABSTRACT FROM AUTHOR]

Adenosine triphosphate (ATP) is the main energy currency of all cells, while creatine phosphate (CrP) is considered as a buffer of high energy-bond phosphate that facilitates rapid regeneration of ATP from adenosine diphosphate (ADP). Astrocyte-rich primary cultures contain ATP, ADP and adenosine monophosphate (AMP) in average specific contents of 36.0 ± 6.4 nmol/mg, 2.9 ± 2.1 nmol/mg and 1.7 ± 2.1 nmol/mg, respectively, which establish an adenylate energy charge of 0.92 ± 0.04. The average specific cellular CrP level was found to be 25.9 ± 10.8 nmol/mg and the CrP/ATP ratio was 0.74 ± 0.28. The specific cellular CrP content, but not the ATP content, declined with the age of the culture. Absence of fetal calf serum for 24 h caused a partial loss in the cellular contents of both CrP and ATP, while application of creatine for 24 h doubled the cellular CrP content and the CrP/ATP ratio, but did not affect ATP levels. In glucose-deprived astrocytes, the high cellular ATP and CrP contents were rapidly depleted within minutes after application of the glycolysis inhibitor 2-deoxyglucose and the respiratory chain inhibitor antimycin A. For those conditions, the decline in CrP levels always preceded that of ATP contents. In contrast, incubation of glucose-fed astrocytes for up to 30 min with antimycin A had little effect on the high cellular ATP content, while the CrP level was significantly lowered. These data demonstrate the importance of cellular CrP for maintaining a high cellular ATP content in astrocytes during episodes of impaired ATP regeneration. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effectiveness of sodium creatine phosphate (SCP) in pediatric viral myocarditis, and cellular immune functions. Methods: Clinical data of 83 children with viral myocarditis admitted to Dezhou Traditional Chinese Medicine Hospital, China between May 2019 and June 2021 were collected and randomly assigned to control (n = 41) and study groups (n = 42). Control group (CNG) received conventional treatment for 14 days, including intravenous drip of sodium fructose diphosphate, vitamin C, and ribavirin, with the addition of prednisone if necessary. Study group (SG) received SCP in addition to conventional treatment for 14 days. Clinical efficacy, cardiac function, inflammatory and immune markers, myocardial injury, and adverse effects at the end of treatment were determined. Results: Results indicated a significantly higher total effective rate in study group (95.24 %) compared to control group (78.05 %) (p < 0.05). Study group demonstrated significantly lower heart rates and improved cardiac output, stroke volume, and left ventricular ejection fraction after 14 days of treatment compared to control group (p < 0.05). Furthermore, study group exhibited significant reduction in levels of inflammatory markers (p < 0.05), enhanced cellular immune markers (p < 0.05), and reduced myocardial injury and remodeling markers (p < 0.05). Both groups showed similar incidence of adverse reactions. Conclusion: Sodium creatine phosphate (SCP) is effective in treating pediatric viral myocarditis, enhances cardiac function, restores cellular immune function, reduces inflammation, and minimizes myocardial damage and remodeling. There will be need to evaluate the long-term efficacy and prognosis of SCP in treating pediatric viral myocarditis in the future. [ABSTRACT FROM AUTHOR]

The natural variation in estrogen secretion throughout the female menstrual cycle impacts various organs, including estrogen receptor (ER)-expressed skeletal muscle. Many women commonly experience increased fatigue or reduced energy levels in the days leading up to and during menstruation, when blood estrogen levels decline. Yet, it remains unclear whether endogenous 17β-estradiol, a major estrogen component, directly affects the energy metabolism in skeletal muscle due to the intricate and fluctuating nature of female hormones. In this study, we employed 2D 31P FID-MRSI at 7T to investigate phosphoryl metabolites in the soleus muscle of a cohort of young females (average age: 28 ± 6 years, n = 7) during the early follicular (EF) and peri-ovulation (PO) phases, when their blood 17β-estradiol levels differ significantly (EF: 28 ± 18 pg/mL vs. PO: 71 ± 30 pg/mL, p < 0.05), while the levels of other potentially interfering hormones remain relatively invariant. Our findings reveal a reduction in ATP-referenced phosphocreatine (PCr) levels in the EF phase compared to the PO phase for all participants (5.4 ± 4.3%). Furthermore, we observe a linear correlation between muscle PCr levels and blood 17β-estradiol concentrations (r = 0.64, p = 0.014). Conversely, inorganic phosphate Pi and phospholipid metabolite GPC levels remain independent of 17β-estradiol but display a high correlation between the EF and PO phases (p = 0.015 for Pi and p = 0.0008 for GPC). The robust association we have identified between ATP-referenced PCr and 17β-estradiol suggests that 17β-estradiol plays a modulatory role in the energy metabolism of skeletal muscle. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is a hallmark of cellular senescence and many age-related neurodegenerative diseases. We therefore investigated the relationship between mitochondrial function in peripheral blood cells and cerebral energy metabolites in young and older sex-matched, physically and mentally healthy volunteers. Cross-sectional observational study involving 65 young (26.0 ± 0.49 years) and 65 older (71.7 ± 0.71 years) women and men recruited. Cognitive health was evaluated using established psychometric methods (MMSE, CERAD). Blood samples were collected and analyzed, and fresh peripheral blood mononuclear cells (PBMCs) were isolated. Mitochondrial respiratory complex activity was measured using a Clarke electrode. Adenosine triphosphate (ATP) and citrate synthase activity (CS) were determined by bioluminescence and photometrically. N-aspartyl-aspartate (tNAA), ATP, creatine (Cr), and phosphocreatine (PCr) were quantified in brains using 1H- and 31P-magnetic resonance spectroscopic imaging (MRSI). Levels of insulin-like growth factor 1 (IGF-1) were determined using a radio-immune assay (RIA). Complex IV activity (CIV) (− 15%) and ATP levels (− 11%) were reduced in PBMCs isolated from older participants. Serum levels of IGF-1 were significantly reduced (− 34%) in older participants. Genes involved in mitochondrial activity, antioxidant mechanisms, and autophagy were unaffected by age. tNAA levels were reduced (− 5%), Cr (+ 11%), and PCr (+ 14%) levels were increased, and ATP levels were unchanged in the brains of older participants. Markers of energy metabolism in blood cells did not significantly correlate with energy metabolites in the brain. Age-related bioenergetic changes were detected in peripheral blood cells and the brains of healthy older people. However, mitochondrial function in peripheral blood cells does not reflect energy related metabolites in the brain. While ATP levels in PBMCs may be be a valid marker for age-related mitochondrial dysfunction in humans, cerebral ATP remained constant. [ABSTRACT FROM AUTHOR]

Our purpose was to characterize the oxygen uptake kinetics (VO2), energy systems contributions and total energy expenditure during a CrossFit® benchmark workout performed in the extreme intensity domain. Fourteen highly trained male CrossFitters, aged 28.3 ± 5.4 years, with height 177.8 ± 9.4 cm, body mass 87.9 ± 10.5 kg and 5.6 ± 1.8 years of training experience, performed the Isabel workout at maximal exertion. Cardiorespiratory variables were measured at baseline, during exercise and the recovery period, with blood lactate and glucose concentrations, including the ratings of perceived exertion, measured pre- and post-workout. The Isabel workout was 117 ± 10 s in duration and the VO2 peak was 47.2 ± 4.7 mL·kg−1·min−1, the primary component amplitude was 42.0 ± 6.0 mL·kg−1·min−1, the time delay was 4.3 ± 2.2 s and the time constant was 14.2 ± 6.0 s. The accumulated VO2 (0.6 ± 0.1 vs. 4.8 ± 1.0 L·min−1) value post-workout increased substantially when compared to baseline. Oxidative phosphorylation (40%), glycolytic (45%) and phosphagen (15%) pathways contributed to the 245 ± 25 kJ total energy expenditure. Despite the short ~2 min duration of the Isabel workout, the oxygen-dependent and oxygen-independent metabolism energy contributions to the total metabolic energy release were similar. The CrossFit® Isabel requires maximal effort and the pattern of physiological demands identifies this as a highly intensive and effective workout for developing fitness and conditioning for sports. [ABSTRACT FROM AUTHOR]

Maximal accumulated oxygen deficit (MAOD) is a gold standard measure of anaerobic capacity. The purpose of this study was to evaluate an alternative measure that avoids the contentious assumptions and the time-consuming procedures of the MAOD method. Twenty-seven women (mean ± SD, age, 22 ± 1 y, height 165 ± 7 cm, weight 63.4 ± 9.7 kg) and 25 men (22 ± 1 y, 179 ± 6 cm, 80.8 ± 14.8 kg) performed running and cycling tests that resulted in exhaustion after ∼5 min. In each test, anaerobic capacity was determined as MAOD and as the sum of the phosphocreatine (PCr) and glycolytic contributions, which were determined from the post-exercise oxygen uptake curve and blood lactate concentration, respectively. The sum, " PCr + glycolysis ", was compared to MAOD using analysis of variance. There was no difference (P = 0.64) between MAOD and PCr + glycolysis (no main effect of method in the analysis of variance). Values were 78 ± 7 mL·kg−1 and 75 ± 8 mL·kg−1 in running (effect size for paired means = 0.8) and 59 ± 6 mL·kg−1 and 61 ± 8 mL·kg−1 in cycling (effect size for paired means = –0.7). Values were greater (P < 0.01) in running (significant effect of mode) with effect sizes of 4.6 for MAOD and 2.9 for PCr + glycolysis. There was no interaction effect involving sex. It is concluded that PCr + glycolysis provides a valid measure of anaerobic capacity that avoids difficulties associated with the MAOD method and is suitable for running as well as for cycling exercise and for recreationally-active, moderately fit men as well as for women. [ABSTRACT FROM AUTHOR]

Abstract Background This study was conducted to test the hypothesis that phosphocreatine (PCr), administered intravenously and as cardioplegia adjuvant in patients undergoing cardiac surgery with prolonged aortic cross clamping and cardiopulmonary bypass (CPB) time, would decrease troponin I concentration after surgery. Methods In this randomized, double-blind, placebo-controlled pilot study we included 120 patients undergoing double/triple valve repair/replacement under cardiopulmonary bypass in the cardiac surgery department of a tertiary hospital. The treatment group received: intravenous administration of 2 g of PCr after anesthesia induction; 2.5 g of PCr in every 1 L of cardioplegic solution (concentration = 10 mmol/L); intravenous administration of 2 g of PCr immediately after heart recovery following aorta declamping; 4 g of PCr at intensive care unit admission. The control group received an equivolume dose of normosaline. Results The primary endpoint was peak concentration of troponin I after surgery. Secondary endpoints included peak concentration of serum creatinine, need for, and dosage of inotropic support, number of defibrillations after aortic declamping, incidence of arrhythmias, duration of Intensive Care Unit (ICU) stay, length of hospitalization. There was no difference in peak troponin I concentration after surgery (PCr, 10,508 pg/ml [IQR 6,838–19,034]; placebo, 11,328 pg/ml [IQR 7.660–22.894]; p = 0.24). There were also no differences in median peak serum creatinine (PCr, 100 µmol/L [IQR 85.0–117.0]; placebo, 99.5 µmol/L [IQR 90.0–117.0]; p = 0.87), the number of patients on vasopressor/inotropic agents (PCr, 49 [88%]; placebo, 57 [91%]; p = 0.60), the inotropic score on postoperative day 1 (PCr, 4.0 (0–7); placebo, 4.0 (0–10); p = 0.47), mean SOFA score on postoperative day 1 (PCr, 5.25 ± 2.33; placebo, 5,45 ± 2,65; p = 0.83), need for defibrillation after declamping of aorta (PCr, 22 [39%]; placebo, 25 [40%]; p = 0.9),, duration of ICU stay and length of hospitalization as well as 30-day mortality (PCr, 0 (0%); placebo,1 (4.3%); p = 0.4). Conclusion PCr administration to patients undergoing double/triple valve surgery under cardiopulmonary bypass is safe but is not associated with a decrease in troponin I concentration. Phosphocreatine had no beneficial effect on clinical outcomes after surgery. Trial registration The study is registered at ClinicalTrials.gov with the Identifier: NCT02757443. First posted (published): 02/05/2016.

The study assessed vastus lateralis oxygen desaturation kinetics (SmO2) in 32 male cyclists (16 Seniors, 16 Juniors) during a 30 s sprint, examining effects of age and performance. An incremental test was used to determine ventilatory thresholds (VT1, VT2) and maximal oxygen uptake (VO2kg), followed by a sprint test to evaluate anaerobic performance. Cyclists’ performance phenotype was determined as the ratio of power at VT2 to 5 s peak sprint power. Juniors exhibited sprinter-like traits, excelling in all functional tests except for lactate levels post-sprint. SmO2 data showed no age-related or bilateral differences across participants. The combined mean response time (MRT) revealed stronger bilateral goodness of fit (R2 = 0.64) than individual time delay (TD) and time constant (τ). Higher VO2kg at VT2, peak power, and maximal uptake were linked to longer TD, while shorter TD correlated with higher lactate production and increased fatigue. Bilaterally averaged SmO2 kinetics distinguished between sprint and endurance athletes, indicating the potential to reflect the alactic anaerobic system’s capacity and depletion. Age did not affect desaturation rates, but younger cyclists showed greater response amplitude, attributed to a higher initial baseline rather than maximal desaturation at the end of the exercise.

Background: This study was conducted to test the hypothesis that phosphocreatine (PCr), administered intravenously and as cardioplegia adjuvant in patients undergoing cardiac surgery with prolonged aortic cross clamping and cardiopulmonary bypass (CPB) time, would decrease troponin I concentration after surgery. Methods: In this randomized, double-blind, placebo-controlled pilot study we included 120 patients undergoing double/triple valve repair/replacement under cardiopulmonary bypass in the cardiac surgery department of a tertiary hospital. The treatment group received: intravenous administration of 2 g of PCr after anesthesia induction; 2.5 g of PCr in every 1 L of cardioplegic solution (concentration = 10 mmol/L); intravenous administration of 2 g of PCr immediately after heart recovery following aorta declamping; 4 g of PCr at intensive care unit admission. The control group received an equivolume dose of normosaline. Results: The primary endpoint was peak concentration of troponin I after surgery. Secondary endpoints included peak concentration of serum creatinine, need for, and dosage of inotropic support, number of defibrillations after aortic declamping, incidence of arrhythmias, duration of Intensive Care Unit (ICU) stay, length of hospitalization. There was no difference in peak troponin I concentration after surgery (PCr, 10,508 pg/ml [IQR 6,838–19,034]; placebo, 11,328 pg/ml [IQR 7.660–22.894]; p = 0.24). There were also no differences in median peak serum creatinine (PCr, 100 µmol/L [IQR 85.0–117.0]; placebo, 99.5 µmol/L [IQR 90.0–117.0]; p = 0.87), the number of patients on vasopressor/inotropic agents (PCr, 49 [88%]; placebo, 57 [91%]; p = 0.60), the inotropic score on postoperative day 1 (PCr, 4.0 (0–7); placebo, 4.0 (0–10); p = 0.47), mean SOFA score on postoperative day 1 (PCr, 5.25 ± 2.33; placebo, 5,45 ± 2,65; p = 0.83), need for defibrillation after declamping of aorta (PCr, 22 [39%]; placebo, 25 [40%]; p = 0.9),, duration of ICU stay and length of hospitalization as well as 30-day mortality (PCr, 0 (0%); placebo,1 (4.3%); p = 0.4). Conclusion: PCr administration to patients undergoing double/triple valve surgery under cardiopulmonary bypass is safe but is not associated with a decrease in troponin I concentration. Phosphocreatine had no beneficial effect on clinical outcomes after surgery. Trial registration: The study is registered at ClinicalTrials.gov with the Identifier: NCT02757443. First posted (published): 02/05/2016. [ABSTRACT FROM AUTHOR]

Acid phosphatases (ACPs) perform a fundamental role in the digestion of egg proteins (vitellins), ensuring the survival of ticks by providing nutrients necessary for their oogenesis. Here, acid phosphatase activity is detected during embryogenesis of the camel tick Hyalomma dromedarii and reached its highest activity level in the larval stage. The tick larvae acid phosphatase which was named TLACP is homogeneously purified using CM cellulose cation exchange chromatography followed by gel filtration on Sephacryl S-300 column. TLACP is purified to 11 times purification folds and 51.3% yield with a specific activity of 12.9 U mg-1 protein. The molecular weight of TLACP was derived from both the gel filtration column and SDS-PAGE as monomer protein of 40 kDa. The Km of TLACP for p-nitrophenyl phosphate (p-NPP) was 1.25 mM and Vmax was 6.4 Umg-1. TLACP exhibited its optimum enzymatic activity at pH 4.8. TLACP was found highly specific to p-NPP followed by ATP, ADP, glucose-6-phosphate, naphthyl phosphate, phospho-enol-pyruvate, creatine phosphate, AMP, and GMP. The ions of Ca2+, Co2+, Mg2+, Ni2+, and Zn2+ motivated TLACP activity while Mn2+, Cu2+, and Fe2+ suppressed it. TLACP is noncompetitively inhibited with sodium fluoride with Ki value 0.15 mM. Thus, the presence of TLACP in tick embryonic and larval cells classifies this enzyme as an important molecular target for evolving potential vaccines in further studies aiming to find new strategies to control ticks. [ABSTRACT FROM AUTHOR]

Mitochondria are specialized organelles, which serve as the "Power House" to generate energy for maintaining heart function. These organelles contain various enzymes for the oxidation of different substrates as well as the electron transport chain in the form of Complexes I to V for producing ATP through the process of oxidative phosphorylation (OXPHOS). Several studies have shown depressed OXPHOS activity due to defects in one or more components of the substrate oxidation and electron transport systems which leads to the depletion of myocardial high-energy phosphates (both creatine phosphate and ATP). Such changes in the mitochondria appear to be due to the development of oxidative stress, inflammation, and Ca2+-handling abnormalities in the failing heart. Although some investigations have failed to detect any changes in the OXPHOS activity in the failing heart, such results appear to be due to a loss of Ca2+ during the mitochondrial isolation procedure. There is ample evidence to suggest that mitochondrial Ca2+-overload occurs, which is associated with impaired mitochondrial OXPHOS activity in the failing heart. The depression in mitochondrial OXPHOS activity may also be due to the increased level of reactive oxygen species, which are formed as a consequence of defects in the electron transport complexes in the failing heart. Various metabolic interventions which promote the generation of ATP have been reported to be beneficial for the therapy of heart failure. Accordingly, it is suggested that depression in mitochondrial OXPHOS activity plays an important role in the development of heart failure. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis examined the effects of creatine supplementation on recovery from exercise-induced muscle damage, and is reported according to the PRISMA guidelines. MEDLINE and SPORTDiscus were searched for articles from inception until April 2020. Inclusion criteria were adult participants (≥18 years); creatine provided before and/or after exercise versus a noncreatine comparator; measurement of muscle function recovery, muscle soreness, inflammation, myocellular protein efflux, oxidative stress; range of motion; randomized controlled trials in humans. Thirteen studies (totaling 278 participants; 235 males and 43 females; age range 20–60 years) were deemed eligible for analysis. Data extraction was performed independently by both authors. The Cochrane Collaboration Risk of Bias Tool was used to critically appraise the studies; forest plots were generated with random-effects model and standardized mean differences. Creatine supplementation did not alter muscle strength, muscle soreness, range of motion, or inflammation at each of the five follow-up times after exercise (<30 min, 24, 48, 72, and 96 hr; p >.05). Creatine attenuated creatine kinase activity at 48-hr postexercise (standardized mean difference: −1.06; 95% confidence interval [−1.97, −0.14]; p =.02) but at no other time points. High (I2; >75%) and significant (Chi2; p <.01) heterogeneity was identified for all outcome measures at various follow-up times. In conclusion, creatine supplementation does not accelerate recovery following exercise-induced muscle damage; however, well-controlled studies with higher sample sizes are warranted to verify these conclusions. Systematic review registration (PROSPERO CRD42020178735). [ABSTRACT FROM AUTHOR]

Impaired bioenergetics have been reported in veterans with Gulf War illness (VGWIs), including prolonged post-exercise recovery of phosphocreatine (PCr-R) assessed with 31Phosphorus magnetic resonance spectroscopy. The citric acid cycle (CAC) is considered the most important metabolic pathway for supplying energy, with relationships among CAC markers reported to shift in some but not all impaired bioenergetic settings. We sought to assess relations of CAC markers to one another and to PCr-R. Participants were 33 VGWIs and 33 healthy controls 1:1 matched on age-sex-ethnicity. We assessed seven CAC intermediates, and evaluated PCr-R in a subset of matched case-control pairs (N = 14). CAC markers did not significantly differ between cases and controls. Relationships of alpha-ketoglutarate to malate, isocitrate, and succinate were strongly significant in cases with materially weaker relationships in controls, suggesting possible shifts in these markers in concert in VGWIs. PCr-R correlated strongly with five of seven CAC markers in controls (succinate, malate, fumarate, citrate, isocitrate, range r = -0.74 to -0.88), but bore no relationship in VGWIs. In summary, PCr-R related significantly to CAC markers in healthy controls, but not VGWIs. In contrast, relations of CAC markers to one another appeared to shift (often strengthen) in VGWIs.

Purpose: To analyze the energetic profiles of the Yo-Yo Intermittent Recovery Tests 1 and 2 (YYIR1 and YYIR2). Methods: Intermittent running distance (IR1D and IR2D), time to exhaustion (IR1T and IR2T), and total recovery time between shuttles (IR1R and IR2R) were measured in 10 well-trained male athletes (age 24.4 [2.0] y, height 182 [1] cm, weight 75.8 [7.9] kg). Respiratory gases and blood lactate (BLC) were obtained preexercise, during exercise, and until 15 min postexercise. Metabolic energy, average metabolic power , and energy share (percentage of aerobic [WAER], anaerobic lactic [WBLC], and anaerobic alactic energy system [WPCr]) were calculated using the PCr-La-O2 method. Results: Peak oxygen consumption was possibly higher in YYIR2 (60.3 [5.1] mL·kg−1·min−1) than in YYIR1 (P =.116, 57.7 [4.5] mL·kg−1·min−1, d = −0.58). IR1D, IR1T, and IR1R were very likely higher than IR2D, IR2T, and IR2R, respectively (P <.001, 1876 [391] vs 672 [132] m, d = −2.83; P <.001, 916 [175] vs 304 [57] s, d = −3.03; and P <.001, 460 [100] vs 150 [40] s, d = −2.83). Metabolic energy was most likely lower in YYIR2 than in YYIR1 (P <.001, 493.5 [118.1] vs 984.8 [171.7] kJ, d = 3.24). Average metabolic power was most likely higher in YYIR2 than in YYIR1 (P <.001, 21.5 [1.7] vs 14.5 [2.2] W·kg−1, d = 3.54). When considering aerobic phosphocreatine restoration during breaks between shuttles, WAER (P =.693, 49% [10%] vs 48% [5%], d = −0.16) was similar, WPCr (P =.165, 47% [11%] vs 42% [6%], d = −0.54) possibly higher, and WBLC (P <.001, 4% [1%] vs 10% [3%], d = 1.95) almost certainly lower in YYIR1 than in YYIR2. Conclusions:WAER and WPCr are predominant in YYIR1 and YYIR2 with almost identical WAER. Higher IR1D and IR1T in YYIR1 result in higher metabolic energy but lower average metabolic power and slightly lower peak oxygen consumption. Higher IR1R allows for higher reliance on WPCr in YYIR1, while YYIR2 requires a higher fraction of WBLC. [ABSTRACT FROM AUTHOR]

This article, published in the journal Circulation, explores the relationship between myocardial energy metabolism and left ventricular ejection fraction (LVEF) recovery in patients with heart failure with reduced ejection fraction (HFrEF). The study found that patients with higher myocardial creatine kinase (CK) energy reserve, as detected by noninvasive 31P magnetic resonance spectroscopy (MRS), were more likely to recover LVEF and exhibit left ventricular reverse remodeling. These findings suggest that interventions targeting the restoration of CK flux and other energy-generating metabolic reactions may lead to myocardial recovery in patients with HFrEF. Further research is needed to confirm these results in a larger population. [Extracted from the article]

The aim of this study was to investigate the effects of traditional, rest redistribution, and velocity-based repeated sprint training methods on repeated sprint performance, perceived effort, heart rate, and changes in force-velocity-power (FVP) profiles in male semiprofessional athletes. In a randomized crossover design, a traditional (2 sets of 6 repetitions [TRAD]), 2 different rest redistribution (4 sets of 3 repetitions [RR4] and 12 sets of 1 repetition [RR12]), and a 5% velocity loss (VL5%) (12 repetitions, with sets terminated when a 5% reduction in mean velocity had occurred) condition were completed. Mean and peak velocity, mean heart rate, and differential ratings of perceived exertion (dRPE) were measured throughout each session, while horizontal FVP profiles were assessed presession and postsession. The RR4 and RR12 conditions allowed the greatest maintenance of velocity, while the RR4, RR12, and VL5% had a moderate, significantly greater mean heart rate than the traditional condition. Trivial, nonsignificant differences between all conditions were observed in dRPE of the legs and breathlessness and FVP profiles. These findings indicate that rest redistribution can allow for greater maintenance of sprint velocity and heart rate, without altering perceived effort during repeated sprint training. In addition, velocity-loss thresholds may be a feasible method of prescription if athletes have diverse physical qualities and reductions in sprint performance during repeated sprint training are undesirable. Practitioners should consider these outcomes when designing repeated sprint training sessions because the strategic use of these methods can alter sprint performance and internal load without changing perceptions of intensity. [ABSTRACT FROM AUTHOR]

Boar sperm are less resistant to drastic changes in the external environment during cryopreservation, mainly because their plasma membranes are rich in unsaturated fatty acids but lack cholesterol and are thus susceptible to lipid peroxidation caused by the attack of reactive oxygen species. This study evaluated the effect of adding phosphocreatine to cryopreservation extenders on boar sperm quality and antioxidant capacity. Different concentrations (0, 5.0, 7.5, 10.0 and 12.5 mmol/L) of phosphocreatine were added to the cryopreservation extender. After thawing, sperm were analysed for morphological parameters, kinetic parameters, acrosome integrity, membrane integrity, mitochondrial activity, DNA integrity and antioxidant enzyme activity. The results showed that 10.0 mmol/L phosphocreatine samples enhanced the boar sperm motility, viability, average path velocity, straight‐line velocity, curvilinear velocity and beat cross frequency after cryopreservation and reduced the malformation rate compared to the control group (p <.05). The acrosome integrity, membrane integrity, mitochondrial activity and DNA integrity of boar sperm were higher than those of the control group after adding 10.0 mmol/L phosphocreatine to the cryopreservation extender (p <.05). Extenders containing 10.0 mmol/L phosphocreatine maintained high total antioxidant capacity; elevated the activities of catalase, glutathione peroxidase and superoxide dismutase; reduced malondialdehyde and H2O2 content (p <.05). Therefore, adding phosphocreatine to the extender is potentially beneficial for boar sperm cryopreservation at an optimal 10.0 mmol/L concentration. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the exchange rate of creatine (Cr) CEST and to evaluate the pH sensitivity of guanidinium (Guan) CEST in the mouse brain. Methods: Polynomial and Lorentzian line‐shape fitting (PLOF) were implemented to extract the amine, amide, and Guan CEST signals from the brain Z‐spectrum at 11.7T. Wild‐type (WT) and knockout mice with the guanidinoacetate N‐methyltransferase deficiency (GAMT−/−) that have low Cr and phosphocreatine (PCr) concentrations in the brain were used to extract the CrCEST signal. To quantify the CrCEST exchange rate, a two‐step Bloch‐McConnell (BM) fitting was used to fit the CrCEST line‐shape, B1‐dependent CrCEST, and the pH response with different B1 values. The pH in the brain cells was altered by hypercapnia to measure the pH sensitivity of GuanCEST. Results: Comparison between the Z‐spectra of WT and GAMT−/− mice suggest that the CrCEST is between 20% and 25% of the GuanCEST in the Z‐spectrum at 1.95 ppm between B1 = 0.8 and 2 μT. The CrCEST exchange rate was found to be around 240–480 s−1 in the mouse brain, which is significantly lower than that in solutions (∼1000 s−1). The hypercapnia study on the mouse brain revealed that CrCEST at B1 = 2 μT and amineCEST at B1 = 0.8 μT are highly sensitive to pH change in the WT mouse brain. Conclusions: The in vivo CrCEST exchange rate is slow, and the acquisition parameters for the CrCEST should be adjusted accordingly. CrCEST is the major contribution to the opposite pH‐dependence of GuanCEST signal under different conditions of B1 in the brain. [ABSTRACT FROM AUTHOR]

Cell-free protein synthesis (CFPS) system is an ideal platform for fast and convenient protein research and has been used for macromolecular assembly, unnatural amino acid embedding, glycoprotein production, and more. To realize the construction of an efficient eukaryotic CFPS platform with the advantages of low cost and short time, a CFPS system based on the yeast Pichia pastoris was built in this study. The internal ribosomal entry site (IRES) can independently initiate translation and thus promote protein synthesis. The Kozak sequences can facilitate translation initiation. Therefore, the screening of IRES and its combination with Kozak was performed, in which cricket paralysis virus (CRPV) exhibited as the best translation initiation element from 14 different IRESs. Furthermore, the system components and reaction environment were explored. The protein yield was nearly doubled by the addition of RNase inhibitor. The cell extract amount, energy regeneration system (phosphocreatine and phosphocreatine kinase), and metal ions (K+ and Mg2+) were optimized to achieve the best protein synthesis yield. This P. pastoris CFPS system can extend the eukaryotic CFPS platform, providing an enabling technology for fast prototyping design and functional protein synthesis. [ABSTRACT FROM AUTHOR]

Chemical exchange saturation transfer (CEST) MRI has become a promising technique to assay target proteins and metabolites through their exchangeable protons, noninvasively. The ubiquity of creatine (Cr) and phosphocreatine (PCr) due to their pivotal roles in energy homeostasis through the creatine phosphate pathway has made them prime targets for CEST in the diagnosis and monitoring of disease pathologies, particularly in tissues heavily dependent on the maintenance of rich energy reserves. Guanidinium CEST from protein arginine residues (i.e. arginine CEST) can also provide information about the protein profile in tissue. However, numerous obfuscating factors stand as obstacles to the specificity of arginine, Cr, and PCr imaging through CEST, such as semisolid magnetization transfer, fast chemical exchanges such as primary amines, and the effects of nuclear Overhauser enhancement from aromatic and amide protons. In this review, the specific exchange properties of protein arginine residues, Cr, and PCr, along with their validation, are discussed, including the considerations necessary to target and tune their signal effects through CEST imaging. Additionally, strategies that have been employed to enhance the specificity of these exchanges in CEST imaging are described, along with how they have opened up possible applications of protein arginine residues, Cr and PCr CEST imaging in the study and diagnosis of pathology. A clear understanding of the capabilities and caveats of using CEST to image these vital metabolites and mitigation strategies is crucial to expanding the possibilities of this promising technology. [ABSTRACT FROM AUTHOR]