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The purpose of this study was to determine the validity of noninvasive anaerobic threshold (AT) estimation using %SpO2 (arterial oxyhemoglobin saturation) changes and respiratory gas exchanges. Fifteen active, healthy males performed 2 graded exercise tests on a motor-driven treadmill in 2 separated sessions. Respiratory gas exchanges and heart rate (HR), lactate concentration, and %SpO2 were measured continuously throughout the test. Anaerobic threshold was determined based on blood lactate concentration (lactate-AT), %SpO2 changes (%SpO2-AT), respiratory exchange ratio (RER-AT), V-slope method (V-slope-AT), and ventilatory equivalent for O2 (EqO2-AT). Blood lactate measuring was considered as gold standard assessment of AT and was applied to confirm the validity of other noninvasive methods. The mean O2 corresponding to lactate-AT, %SpO2-AT, RER-AT, V-slope -AT, and EqO2-AT were 2176.6 +/- 206.4, 1909.5 +/- 221.4, 2141.2 +/- 245.6, 1933.7 +/- 216.4, and 1975 +/- 232.4, respectively. Intraclass correlation coefficient (ICC) analysis indicates a significant correlation between 4 noninvasive methods and the criterion method. Blond-Altman plots showed the good agreement between O2 corresponding to AT in each method and lactate-AT (95% confidence interval (CI). Our results indicate that a noninvasive and easy procedure of monitoring the %SpO2 is a valid method for estimation of AT. Also, in the present study, the respiratory exchange ratio (RER) method seemed to be the best respiratory index for noninvasive estimation of anaerobic threshold, and the heart rate corresponding to AT predicted by this method can be used by coaches and athletes to define training zones. [ABSTRACT FROM AUTHOR]

Objective: Chronic venous disease is a common condition and has a significant impact on patients' health status. Validated patient-reported outcome measures (PROMs) used to assess health status are needed to measure health status. This state-of-the-art review summarizes the current validation evidence for disease-specific PROMs for chronic venous disease and provides a framework for their use in the clinical setting., Methods: A literature search in OVID Embase and Medline was conducted to identify relevant English-language studies of chronic venous disease that used disease-specific PROMs between January 1, 1993, and June 30, 2022. Abstracts and titles from identified studies were screened by four investigators, and full-text articles were subsequently screened for eligibility. Data on validation of disease-specific PROMs was abstracted from each included article. Classical test theory was used as a framework to examine a priori defined validation criteria for content validity, reliability (construct validity, internal reliability, and test-retest reliability), responsiveness, and expansion of the validation evidence base (use in randomized controlled trials and comparative effectiveness research, cultural or linguistic translations, predictive validity, or establishing the minimal clinically important difference threshold, defined as smallest amount an outcome or measure is perceived as a meaningful change to patients). The PROMs were categorized into three groups based on the manifestations of disease of the population for which they were developed. The overall validity of each PROM was assessed across three stages of validation including content validity (phase 1); construct validity, reliability, and responsiveness (phase 2); and expansion of the validation evidence base (phase 3)., Results: Of 2338 unique studies screened, 112 studies (4.8%) met inclusion criteria. The eight disease-specific PROMs identified were categorized into three groups: (1) overall chronic venous disease (C1 to C6); (2) C1 to C4 disease; and (3) C5 to C6 disease. Assessed by group, the Chronic Venous Insufficiency Questionnaire met criteria for validation at all three phases for patients with C1 to C4 disease, and the Charing Cross Venous Ulcer Questionnaire met criteria for validation at all three phases for patients with C5 to C6 disease. There were no PROMs that met all criteria for validation for use in overall chronic venous disease (C1 to C6)., Conclusions: Of the eight PROMs assessed in this review, only two met prespecified criteria at each phase for validation. The Chronic Venous Insufficiency Questionnaire and Charing Cross Venous Ulcer Questionnaire should be considered for use in patients with chronic venous disease without venous ulcers and with venous ulcers, respectively., Competing Interests: Disclosures C.M.-H. reports unrestricted research grants from Philips and Shockwave and is a consultant for Abbott Vascular, Cook, Medtronic, and Optum Labs. K.G.S. reports unrestricted research grants from Philips, Merck, Shockwave, and Johnson & Johnson; is a consultant for Optum Labs, Cook, Tegus, Twill Inc, and Abbott Vascular., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Impaired autophagy is a hallmark of diabetes. The current study proposed to investigate if high intensity interval training (HIIT) induced lactate accumulation could stimulate autophagy in type 2 diabetic male rats. 28 male Wistar rats were randomly assigned into four groups: Healthy Control (CO), Diabetes Control (T2D), Exercise (EX), and Diabetes + Exercise (T2D + EX). Diabetes was induced by feeding high-fat diet and administrating single dose of streptozotocin (35 mg/kg). After becoming diabetic, the animals in the exercise groups (EX and T2D + EX) performed an eight-week HIIT (4-10 interval, 80-100% Vmax, 5 days per week). Serum levels of lactate, glucose and insulin as well as the levels of lactate, pyruvate, lactate transporter monocarboxylate transporter 1 (MCT1), phosphorylated mitogen-activated protein kinases (p-MAP 1 and 2), phosphorylated extracellular signal-regulated protein kinases 1 and 2 (p-ERK 1 and 2), mammalian target of rapamycin (p-mTOR), ribosomal protein S6 kinase beta-1 (p-70S6k), p90 ribosomal S6 kinases (p-90RSK), autophagy related 7 (ATG7), Beclin-1, microtubule-associated protein 1A/1B, and 2A/2B -light chain 3 levels (LC3-I), (LC3- II), (LC3I/LC3II) in soleus muscle were measured. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and serum glucose was lower in T2D + EX compared to T2D group (P < 0.0001). While serum and soleus muscle levels of lactate was not different between T2D and T2D + Ex, the levels of Pyruvate (P < 0.01), MCT1, p-ERK1/2, p-mTOR, p70S6k, P-90RSK, ATG7, LC3-II, and LC3-II/LC3I ratios were higher in T2D + EX compared to T2D group (P < 0.0001). We concluded that eight weeks of high-intensity interval training could activated ERK/P90SRK while inhibiting mTOR/P70S6K signaling pathway in lactate dependent manner. It means increased autophagy which resulted in improve insulin resistance (IR) and reduce blood glucose., (© 2024. The Author(s).)

Individuals with established cardiovascular disease or a high burden of cardiovascular risk factors may be particularly vulnerable to develop complications from coronavirus disease 2019 (COVID-19). We conducted a prospective cohort study at a tertiary care center to identify risk factors for in-hospital mortality and major adverse cardiovascular events (MACE; a composite of myocardial infarction, stroke, new acute decompensated heart failure, venous thromboembolism, ventricular or atrial arrhythmia, pericardial effusion, or aborted cardiac arrest) among consecutively hospitalized adults with COVID-19, using multivariable binary logistic regression analysis. The study population comprised 586 COVID-19 positive patients. Median age was 67 (IQR: 55 to 80) years, 47.4% were female, and 36.7% had cardiovascular disease. Considering risk factors, 60.2% had hypertension, 39.8% diabetes, and 38.6% hyperlipidemia. Eighty-two individuals (14.0%) died in-hospital, and 135 (23.0%) experienced MACE. In a model adjusted for demographic characteristics, clinical presentation, and laboratory findings, age (odds ratio [OR], 1.28 per 5 years; 95% confidence interval [CI], 1.13 to 1.45), previous ventricular arrhythmia (OR, 18.97; 95% CI, 3.68 to 97.88), use of P2Y 12 -inhibitors (OR, 7.91; 95% CI, 1.64 to 38.17), higher C-reactive protein (OR, 1.81: 95% CI, 1.18 to 2.78), lower albumin (OR, 0.64: 95% CI, 0.47 to 0.86), and higher troponin T (OR, 1.84; 95% CI, 1.39 to 2.46) were associated with mortality (p <0.05). After adjustment for demographics, presentation, and laboratory findings, predictors of MACE were higher respiratory rates, altered mental status, and laboratory abnormalities, including higher troponin T (p <0.05). In conclusion, poor prognostic markers among hospitalized patients with COVID-19 included older age, pre-existing cardiovascular disease, respiratory failure, altered mental status, and higher troponin T concentrations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The role of autophagy and lysosomal degradation pathway in the regulation of skeletal muscle metabolism was previously studied. However, underlying molecular mechanisms are poorly understood. L-lactate which is utilized as an energetic substrate by skeletal muscle can also augment genes expression related to metabolism and up-regulate those being responsive to reactive oxygen species (ROS). Since ROS is the most important regulator of autophagy in skeletal muscle, we tested if there is a link between cellular lactate metabolism and autophagy in differentiated C2C12 myotubes and the gastrocnemius muscle of male wistar rats. C2C12 mouse skeletal muscle was exposed to 2, 6, 10, and 20 mM lactate and evaluated for lactate autophagic effects. Lactate dose-dependently increased autophagy and augmented ROS generation in differentiated C2C12 myotubes. The autophagic effect of lactate deterred in N-acetylcysteine presence (NAC, a ROS scavenger) indicated lactate regulates autophagy with ROS participation. Lactate-induced up-regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) through ROS was required to regulate the autophagy by lactate. Further analysis about ERK1/2 up- and downstream indicated that lactate regulates autophagy through ROS-mediated the activation of ERK1/2/mTOR/p70S6K pathway in skeletal muscle. The in vitro effects of lactate on autophagy also occurred in the gastrocnemius muscle of male Wistar rats. In conclusion, we provided the lactate-associated regulation evidence of autophagy in skeletal muscle by activating ROS-mediated ERK1/2/mTOR/p70S6K pathway. Since the increase in cellular lactate concentration is a hallmark of energy deficiency, the results provide insight into a skeletal muscle mechanism to fulfill its enhanced energy requirement.

Background: The study aimed to synthesize participant retention-related data for longitudinal follow-up studies of survivors from trauma intensive care units (ICUs)., Methods: Within a published scoping review evaluating ICU patient outcomes after hospital discharge, two screeners independently searched for trauma ICU survivorship studies., Results: There were 11 trauma ICU follow-up studies, all of which were cohort studies. Twelve months (range: 1-60 months) was the most frequent follow-up time point for assessment (63% of studies). Retention rates ranged from 54% to 94% across time points and could not be calculated for two studies (18%). Pooled retention rates at 3, 6, and 12 months were 75%, 81%, and 81%, respectively. Mean patient age (OR 0.85 per 1-year increase, 95% CI 0.73 to 0.99, p=0.036), percent of men (OR 1.07, 95% CI 1.04 to 1.10, p=0.002), and publication year (OR 0.89 per 1-year increase, 95% CI 0.82 to 0.95, p=0.007) were associated with retention rates. Early (3-month) versus later (6-month, 12-month) follow-up time point was not associated with retention rates., Discussion: Pooled retention rates were >75%, at 3-month, 6-month, and 12-month time points, with wide variability across studies and time points. There was little consistency with reporting participant retention methodology and related data. More detailed reporting guidelines, with better author adherence, will help improve reporting of participant retention data. Utilization of existing research resources may help improve participant retention., Level of Evidence: Level III: meta-analyses (post-hoc analyses) of a prior scoping review., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: With an increasing number of follow-up studies of acute respiratory failure survivors, there is need for a better understanding of participant retention and its reporting in this field of research. Hence, our objective was to synthesize participant retention data and associated reporting for this field., Methods: Two screeners independently searched for acute respiratory failure survivorship studies within a published scoping review to evaluate subject outcomes after hospital discharge in critical illness survivors., Results: There were 21 acute respiratory failure studies ( n = 4,342 survivors) over 47 follow-up time points. Six-month follow-up (range: 2-60 months) was the most frequently reported time point, in 81% of studies. Only 1 study (5%) reported accounting for loss to follow-up in sample-size calculation. Retention rates could not be calculated for 5 (24%) studies. In 16 studies reporting on retention across all time points, retention ranged from 32% to 100%. Pooled retention rates at 3, 6, 12, and 24 months were 85%, 89%, 82%, and 88%, respectively. Retention rates did not significantly differ by publication year, participant mean age, or when comparing earlier (3 months) versus each later follow-up time point (6, 12, or 24 months)., Conclusions: Participant retention was generally high but varied greatly across individual studies and time points, with 24% of studies reporting inadequate data to calculate retention rate. High participant retention is possible, but resources for optimizing retention may help studies retain participants. Improved reporting guidelines with greater adherence would be beneficial., (Copyright © 2020 by Daedalus Enterprises.)

The TGF-β1-Smad pathway is a well-known negative regulator of muscle growth; however, its potential role in resistance training-induced muscle hypertrophy is not clear. The present study proposed to determine whether and how this pathway may be involved in resistance training-induced muscle hypertrophy. Skeletal muscle samples were collected from the control, trained (RT), control + SB431542 (CI TGF ), and trained + SB431542 (RTI TGF ) animals following 3, 5, and 8 weeks of resistance training. Inhibition of the TGF-β1-Smad pathway by SB431542 augmented muscle satellite cells activation, upregulated Akt/mTOR/S6K1 pathway, and attenuated FOXO1 and FOXO3a expression in the CI TGF group (all p < .01), thereby causing significant muscle hypertrophy in animals from the CI TGF . Resistance training significantly decreased muscle TGF-β1 expression and Smad3 (P-Smad3 S423/425 ) phosphorylation at COOH-terminal residues, augmented Smad2 (P-Smad2-L S245/250/255 ) and Smad3 (P-Smad3-L Ser208 ) phosphorylation levels at linker sites (all p < .01), and led to a muscle hypertrophy which was unaffected by SB431542, suggesting that the TGF-β1-Smad signaling pathway is involved in resistance training-induced muscle hypertrophy. The effects of inhibiting the TGF-β1-Smad signaling pathway were not additive to the resistance training effects on FOXO1 and FOXO3a expression, muscle satellite cells activation, and the Akt/mTOR/S6K1 pathway. Resistance training effect of satellite cell differentiation was independent of the TGF-β1-Smad signaling pathway. These results suggested that the effect of the TGF-β1-Smad signaling pathway on resistance training-induced muscle hypertrophy can be attributed mainly to its diminished inhibitory effects on satellite cell activation and protein synthesis. Suppressed P-Smad3 S423/425 and enhanced P-Smad2-L S245/250/255 and P-Smad3-L Ser208 are the molecular mechanisms that link the TGF-β1-Smad signaling pathway to resistance training-induced muscle hypertrophy., (© 2020 Wiley Periodicals, Inc.)

Background: HIV-infected patients with poor antiretroviral therapy (ART) adherence are prone to depression, and depression can exacerbate the disease condition. This study was conducted to determine ART Adherence based on Information, Motivation, and Behavioral Skills (IMB) Model and its association with depression among HIV-positive patients., Materials and Methods: This descriptive-correlational study was carried out on people over the age of 18 years with HIV/AIDS, who referred to the Behavioral Diseases Counseling Center in Kerman City, Iran, in 2017. In this regard, 119 patients were selected using the table of random numbers. To collect the data, we used the Beck's depressioninventory-II and the IMB researcher made questionnaire to evaluate the ART adherence., Results: The results of the study reveal that a significant association was observed between the total adherence and all constructs of the IMB model ( P < 0.001). Risk perception and self-efficacy had the highest mean scores regarding the ART adherence. The prevalence of depression was 71.5% among patients. Information, personal motivation, and total adherence had a significant association with depression., Conclusions: IMB model was an appropriate and practical strategy with regard to the ART adherence among people living with HIV who are prone to depression and drug consumption is crucial for them to achieve the 90-90-90 target. This article created a questionnaire to assist policy-makers and health professionals designing interventions to improve adherence and health outcomes of ART., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Education and Health Promotion.)

Background: Delirium is common in hospitalized patients and is associated with worse outcomes. Antipsychotics are commonly used; however, the associated benefits and harms are unclear., Purpose: To conduct a systematic review evaluating the benefits and harms of antipsychotics to treat delirium in adults., Data Sources: PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception to July 2019 without language restrictions., Study Selection: Randomized controlled trials (RCTs) of antipsychotic versus placebo or another antipsychotic, and prospective observational studies reporting harms., Data Extraction: One reviewer extracted data and assessed strength of evidence (SOE) for critical outcomes, with confirmation by another reviewer. Risk of bias was assessed independently by 2 reviewers., Data Synthesis: Across 16 RCTs and 10 observational studies of hospitalized adults, there was no difference in sedation status (low and moderate SOE), delirium duration, hospital length of stay (moderate SOE), or mortality between haloperidol and second-generation antipsychotics versus placebo. There was no difference in delirium severity (moderate SOE) and cognitive functioning (low SOE) for haloperidol versus second-generation antipsychotics, with insufficient or no evidence for antipsychotics versus placebo. For direct comparisons of different second-generation antipsychotics, there was no difference in mortality and insufficient or no evidence for multiple other outcomes. There was little evidence demonstrating neurologic harms associated with short-term use of antipsychotics for treating delirium in adult inpatients, but potentially harmful cardiac effects tended to occur more frequently., Limitations: Heterogeneity was present in terms of dose and administration route of antipsychotics, outcomes, and measurement instruments. There was insufficient or no evidence regarding multiple clinically important outcomes., Conclusion: Current evidence does not support routine use of haloperidol or second-generation antipsychotics to treat delirium in adult inpatients., Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

Background: Delirium is an acute disorder marked by impairments in attention and cognition, caused by an underlying medical problem. Antipsychotics are used to prevent delirium, but their benefits and harms are unclear., Purpose: To conduct a systematic review evaluating the benefits and harms of antipsychotics for prevention of delirium in adults., Data Sources: PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception through July 2019, without restrictions based on study setting, language of publication, or length of follow-up., Study Selection: Randomized, controlled trials (RCTs) that compared an antipsychotic with placebo or another antipsychotic, and prospective observational studies with a comparison group., Data Extraction: One reviewer extracted data and graded the strength of the evidence, and a second reviewer confirmed the data. Two reviewers independently assessed the risk of bias., Data Synthesis: A total of 14 RCTs were included. There were no differences in delirium incidence or duration, hospital length of stay (high strength of evidence [SOE]), and mortality between haloperidol and placebo used for delirium prevention. Little to no evidence was found to determine the effect of haloperidol on cognitive function, delirium severity (insufficient SOE), inappropriate continuation, and sedation (insufficient SOE). There is limited evidence that second-generation antipsychotics may lower delirium incidence in the postoperative setting. There is little evidence that short-term use of antipsychotics was associated with neurologic harms. In some of the trials, potentially harmful cardiac effects occurred more frequently with antipsychotic use., Limitations: There was significant heterogeneity in antipsychotic dosing, route of antipsychotic administration, assessment of outcomes, and adverse events. There were insufficient or no data available to draw conclusions for many of the outcomes., Conclusion: Current evidence does not support routine use of haloperidol or second-generation antipsychotics for prevention of delirium. There is limited evidence that second-generation antipsychotics may lower the incidence of delirium in postoperative patients, but more research is needed. Future trials should use standardized outcome measures., Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

Background: The aim of this study was to investigate the adherence to medication and Physical Activity (PA) among People Living with HIV (PLHIV)., Materials and Methods: In the present cross-sectional study, 122 PLHIV were selected. The research tools included the Baecke questionnaire and the AIDS Clinical Trials Group questionnaire. Data were analyzed by independent t test and multiple logistic regression., Results: The results of 7- and 30-day recalls showed that 76.21 and 82.23% of patients had proper medication adherence. The mean score of PA in patients was less than the recommended average score in the questionnaire. Furthermore, there was no significant difference observed between the medication adherence and PA., Conclusions: Although the adherence to medication was appropriate, nurses and health care providers should increase the level of PA for PLHIV by dealing with the related barriers to live an active life., Competing Interests: Nothing to declare.

Objectives: This descriptive-correlational study was conducted on 122 Iranian people living with HIV (PWHIV), who referred to a behavioral diseases counseling center in 2018. The AIDS Clinical Trial Group (ACTG) questionnaire was used to collect the required data. The study aimed to determine the level of medication adherence and its determinants in PWHIV., Results: About 75.4% (confidence interval 67.2%-82.8%) of the samples had a good combined antiretroviral therapy (cART) adherence and 74.6% (n = 91) of them were sure about the positive effects of medications on their health. Patients reported that most important reasons for medication non-adherence included forgetfulness, high drug dosage, lack of knowledge about ART value, and transportation problems.

Context: Goal-concordant care has been identified as an important outcome of advance care planning and shared decision-making initiatives. However, validated methods for measuring goal concordance are needed., Objectives: To estimate the inter-rater reliability of senior critical care fellows rating the goal concordance of preference-sensitive interventions performed in intensive care units (ICUs) while considering patient-specific circumstances as described in a previously proposed methodology., Methods: We identified ICU patients receiving preference-sensitive interventions in three adult ICUs at Johns Hopkins Hospital. A simulated cohort was created by randomly assigning each patient one of 10 sets of goals and preferences about limiting life support. Critical care fellows then independently reviewed patient charts and answered two questions: 1) Is this patient's goal achievable? and 2) Will performing this intervention help achieve the patient's goal? When the answer to both questions was yes, the intervention was rated as goal concordant. Inter-rater agreement was summarized by estimating intraclass correlation coefficient using mixed-effects models., Results: Six raters reviewed the charts of 201 patients. Interventions were rated as goal concordant 22%-92% of the time depending on the patient's goal-limitation combination. Percent agreement between pairs of raters ranged from 59% to 86%. The intraclass correlation coefficient for ratings of goal concordance was 0.50 (95% CI 0.31-0.69) and was robust to patient age, gender, ICU, severity of illness, and lengths of stay., Conclusion: Inter-rater agreement between intensivists using a standardized methodology to evaluate the goal concordance of preference-sensitive ICU interventions was moderate. Further testing is needed before this methodology can be recommended as a clinical research outcome., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Fitness profile and the physiological determinants of wrestling success in Greco-Roman wrestlers were investigated., Methods: The wrestlers from the Iranian National Greco-Roman Team (14 junior wrestlers and 12 senior wrestlers) participated in this study. The junior and senior wrestlers were divided into two groups of successful and less successful athletes based on their performance during the previous wrestling season. The wrestlers were evaluated for anthropometric measurements, flexibility, muscular endurance, explosive power, peak and mean power of upper and lower limbs, cardiovascular endurance, running speed, agility, and muscular strength., Results: In senior wrestler, significant differences in favor of the successful wrestlers were found for relative grip strength (P<0.01), pull-ups (P<0.01), peak and mean anaerobic power of upper limbs (P<0.05), and oxygen consumption (O2) corresponding to ventilatory threshold (VT). The results of discriminant analysis revealed that the relative grip strength, pull-ups, and mean anaerobic power were the most important variables separating the groups. In junior wrestlers, the successful wrestlers had significantly more relative grip strength (P<0.01), pull-ups (P<0.01), peak and mean anaerobic power of upper limbs (P<0.05), and peak anaerobic power of lower limbs (P<0.05). However, the results of discriminant analysis showed that the model could not successfully determine group membership., Conclusions: In summary, muscular strength, muscular endurance, and anaerobic capacity are the most important variables in Greco-Roman wrestling and athletes must pay particular attention to improving these variables to be a successful wrestler.

The purpose of this study was to determine the validity of anaerobic threshold (AnT)-equivalent to the second turn point for lactate (LTP2)-estimation using the O2 pulse changes in highly trained endurance cyclists who do not show heart rate deflection point (HRDP) during incremental testing. Sixteen endurance cyclists (age, 24.8 ± 4.7 years) and fifteen active men (age, 24.8 ± 3.7 years) performed an incremental cycling test to exhaustion. Pulmonary oxygen uptake (V[Combining Dot Above]O2) and other hemodynamic variables, heart rate, and blood lactate concentration were measured continuously throughout the test. O2 pulse anaerobic threshold (O2 pulse-AnT) was defined as the second turn point in O2 pulse-workload curve. LTP2 was considered as gold standard assessment of AnT and was applied to confirm the validity of O2 pulse-AnT. Intraclass correlation coefficients and the Bland-Altman method were used to determine the relationship and agreement between the O2 corresponding to LTP2 and O2 pulse-AnT, respectively. The active men and 68.7% of the endurance cyclists showed HRDP, whereas all subjects showed O2 pulse-AnT during incremental testing. In both groups, the values for V[Combining Dot Above]O2 corresponding to LTP2 were not significantly different from the V[Combining Dot Above]O2 at O2 pulse-AnT. The V[Combining Dot Above]O2 at LTP2 and O2 pulse-AnT were highly correlated (endurance cyclists: R = 0.68; standard error of estimate [SEE] = 3.74 ml·kg·min and active men: R = 0.58; SEE = 2.91 ml·kg·min) and Bland-Altman plot revealed the limit of agreement of O2 at LTP2 and O2 pulse-AnT differences between 5.1 and 8.6 ml·kg·min (95% CI). In summary, results of this study showed that the second turn point in the O2 pulse-workload curve occurs around LTP2. Therefore, using O2 pulse-AnT is recommended for the noninvasive determination of AnT in highly trained endurance cyclists who do not show HRDP during incremental exercise.

The mechanism regulating the utilization of intramuscular triacylglycerol (IMTG) during high-intensity interval training (HIIT) and post-exercise recovery period remains elusive. In this study, the acute and long-term effects of HIIT on transforming growth factor beta 1 (TGF-β1) abundance in rat skeletal muscle and role of lactate and TGF-β1 in IMTG lipolysis during post-exercise recovery period were examined. TGF-β1 and Adipose triacylglycerol lipase (ATGL) abundance as well as total lipase activity in the gastrocnemius muscle significantly increased to a maximum value 10 h after acute bout of HIIT. Inhibition of TGF-β1 signaling by intramuscular injection of SB431542 30 min prior to the acute exercise attenuated ATGL abundance and total lipase activity in the gastrocnemius muscle in response to acute exercise. Intramuscular acute injection of lactate increased TGF-β1 and ATGL abundance in the gastrocnemius muscle and there were a significant increase in Muscle TGF-β1 and ATGL abundance after 5 weeks of HIIT/lactate treatment. These results indicate that exercise-induced lactate accumulation regulates intramuscular triglyceride metabolism via transforming growth factor-β1 mediated pathways during post-exercise recovery from strenuous exercise., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Key Points: Monocarboxylate transporters (MCTs) and lactate dehydrogenase A (LDH-A) play important roles in sustaining the glycolytic phenotype seen in cancer. Endurance training improves aerobic capacity; however, whether endurance training alters the metabolic phenotype of a solid tumour, from the perspective of lactate metabolism, is yet to be proven. This study showed that endurance training decreases expression of the MCT1 basigin (CD147) and LDH-A , and also increases LDH-B expression in solid tumours and attenuates tumour lactate metabolism. Similar results for MCT1 and LDH-B were found with inhibition of the oestrogen-related receptor alpha (ERRα). The training effects were not additive to the ERRα effects on MCT1 and LDH-B expression in the tumour, which indicated that exercise-induced alterations in MCT1 and LDH-B expression were modulated by ERRα. These results suggest that endurance training could be a useful tool in cancer therapy, especially in basal-like and luminal-like breast carcinomas., Abstract: Several factors, including overexpression of lactate dehydrogenase (LDH) and monocarboxylate transporters (MCTs), promote an aerobic lactate production that allows some cancer cells to sustain higher proliferation rates in hostile environments outside the cell. To elucidate the effect of endurance training on the metabolic phenotype of solid tumours, we focused on the tumour expression of LDH-A, LDH-B, MCT1, MCT4, oestrogen-related receptor alpha (ERRα) and LDH isozymes in control (C), trained (T), control+XCT790 (CX) and trained+XCT790 (TX) mice. First, we found that the metabolically altered tumours from the trained animals exhibited lower values for lactate concentration than the control group. The decreased lactate concentration was associated with a shift in the tumour LDH isozyme profile towards LDH-1. These exercise-induced changes were also associated with decreases in the expression of the tumour MCT1, ERRα and CD147 in the trained animals. Secondly, the inhibition of ERRα by treatment of MC4-L2 human breast cancer cells with XCT790 (inverse agonist ligand of ERRα) before injection into the animals not only increased LDH-B expression in the tumour, but also decreased MCT1 expression in the CX group in comparison to the C group. The effects of ERRα inhibition were not additive to the training effects on the expressions of MCT1 and LDH-B in the solid tumours. In conclusion, our results suggest that exercise-induced suppression of ERRα expression modulates alterations in solid tumour expression of LDH-B and MCT1 and contributes towards the prevention of tumour development., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

This study predicted aerobic and anaerobic capacities using relative changes of arterial blood lactate during the isocapnic buffering phase (relative [La]ISBP). Fourteen male professional cyclists (sprint-trained [n = 6] and endurance [n = 8]) performed 2 exercise sessions to exhaustion on a cycle ergometer; 1 incremental standard test to determine the isocapnic buffering phase, buffering capacities, and relative [La]ISBP and 1 supramaximal exercise test to determine maximal accumulated oxygen deficit (MAOD). The time between Lactate threshold (LT) and respiratory compensatory threshold (RCT) was considered to be the isocapnic buffering phase. Total buffering capacity was calculated as Δ[La]·ΔpH. Bicarbonate buffering was calculated as Δ[HCO3]·ΔpH, and the difference between -Δ[La]·ΔpH and Δ[HCO3]·ΔpH was considered as nonbicarbonate buffering. The lactate concentration for LT (p ≤ 0.05) and RCT (p ≤ 0.05), and relative [La]ISBP (p < 0.01) were significantly lower for endurance cyclists than for sprint-trained cyclists. A significant difference was found for bicarbonate buffering capacity between groups (p < 0.01). A significant correlation was found between relative [La]ISBP with (Equation is included in full-text article.)(r = -0.71, p ≤ 0.05) and MAOD (r = 0.73, p < 0.01). Relative [La]ISBP was useful for predicting aerobic power (R = 51%) and anaerobic capacity (R = 53%). These results demonstrated that relative [La]ISBP is an important variable in intermediary metabolism and in addition to (Equation is included in full-text article.)and LT is recommended for better evaluation of performance of athletes who show nearly equal contributions from the aerobic and anaerobic energy systems during exercise.

Objective: The aim of this study was to investigate the effect of type 2 diabetes induced by high-fat diet and streptozotocin, and the effect of endurance training on basal circulating levels of calcitonin gene-related peptide (CGRP) and lactate., Methods: Male Wistar rats were randomly divided into 4 groups: 1) control (n=8); 2) trained (n=8); 3) diabetic (n=8) and 4) trained diabetic (n=8). At the age of 7 weeks, diabetes was induced by feeding the animals a high-fat diet and injecting them with a low dose of streptozotocin (35 mg/kg). The animals at 10 weeks of age underwent an endurance training protocol on a treadmill for 7 weeks. Plasma lactate concentrations were measured by a lactate assay kit, and an enzyme immunoassay kit was used to measure CGRP., Results: The diabetic rats showed significant increases in plasma CGRP (3.0±1 ng/mL vs. 0.5±0.3 ng/mL, p<0.001) and plasma lactate levels (3.6±0.5 mmol/L vs. 1.3±0.5 mmol/L, p<0.001). Further, significant decrease in basal plasma lactate (2.6±0.5 mmol/L vs. 3.6±0.5 mmol/L, p<0.025) but not plasma CGRP levels (2.5±1.2 ng/mL vs. 3.0±1.3 ng/mL) were found in the diabetic subjects after the endurance training., Conclusions: The results showed that endurance training could modify the basal circulating levels of lactate but not CGRP, which were elevated in this model of type 2 diabetic rats, indicating the lack of correspondence between the endurance training-induced changes of lactate and CGRP in this model of diabetes., (Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Aims/introduction: The present study was designed to investigate from which tissues the decrease in retinol-binding protein 4 (RBP4) expression could contribute to the improvement of serum RBP4 and insulin resistance (IR) after endurance training., Materials and Methods: Male 7-week-old Wistar rats were randomly assigned into four groups including control (C), trained (T), diabetic control (DC) and trained diabetic (TD). At 8 weeks-of-age, diabetes was induced by a high-fat diet and intraperitoneal injection of low-dose streptozotocin (STZ; 35 mg/kg). Rats in the T and TD groups carried out a 7-week exercise program on a motorized treadmill (15-20 m/min for 20 min/day for 5 weeks), whereas the C and DC remained sedentary in their cages. Tissues gene expression and protein levels of RBP4 were assessed by using real-time polymerase chain reaction and western blot, respectively, while serum RBP4 was measured using an enzyme-linked immunosorbent assay kit., Results: Exercise significantly improved IR and reduced serum concentration of RBP4 in the TD group. This reduction of serum RBP4 was accompanied by decreased RBP4 protein expression in visceral fat tissue. In contrast, exercise had no significant effect on RBP4 expression in liver and subcutaneous fat tissue in the TD group. Exercise also significantly decreased RBP4 gene expression in visceral fat tissue and muscle, whereas the effect of exercise on liver RBP4 messenger ribonucleic acid expression was not significant., Conclusions: The present study showed that the mechanism for RBP4 reducing the effect of endurance training could involve decreased RBP4 messenger ribonucleic acid expression and its protein level in adipose tissue in STZ-induced diabetic rats.

The capacity of the brain to metabolize non-glucose substrates under hypoglycemic state maintains its energy requirements. We hypothesized that exercise-induced increase in capacity for brain utilization of lactate by up regulation of the monocarboxylate transporters (MCTs) may contribute metabolic substrates during hypoglycemia in diabetic rats induced by streptozotocin. The induced diabetes increased MCT1 and MCT2 expression in the cortex and the hippocampus in the sedentary diabetic animals. There were exercise-induced increases in MCT1 in the cortex and the hippocampus and MCT2 expression in the cortex in trained diabetic animals; whereas, no changes were found in the healthy trained animals. Both diabetic and healthy trained animals showed higher values for brain lactate uptake during insulin-induced hypoglycemia when animals were intraperitoneally injected by L(+)-lactic acid. However, the response of counterregulatory hormones during hypoglycemia were blunted in the diabetic trained animals which indicates to carefully monitoring of glycemic targets both during and following prolonged exercise., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

We hypothesized that a part of therapeutic effects of endurance training on insulin resistance is mediated by increase in cardiac and skeletal muscle mitochondrial lactate transporter, monocarboxylate transporter 1 (MCT1). Therefore, we examined the effect of 7 weeks endurance training on the mRNA and protein expression of MCT1 and MCT4 and their chaperon, CD147, on both sarcolemmal and mitochondrial membrane, separately, in healthy and type 2 diabetic rats. Diabetes was induced by injection of low dose of streptozotocin and feeding with high-fat diet. Insulin resistance was confirmed by homeostasis model assessment-estimated insulin resistance index and accuracy of two membranes separation was confirmed by negative control markers (glucose transporter 1 and cytochrome c oxidase. Real-time PCR and western blotting were used for mRNA and protein expression, respectively. Diabetes dramatically reduced MCT1 and MCT4 mRNA and their expression on sarcolemmal membrane whereas the reduction in MCT1 expression was less in mitochondrial membrane. Training increased the MCT1 mRNA and protein expression in both membranes and decreased insulin resistance as an adaptive consequence. In both tissues increase in CD147 mRNA was only parallel to MCT1 expression. The response of MCT1 on sarcolemmal and mitochondrial membranes was different between cardiac and skeletal muscles which indicate that intracellular lactate kinetic is tissue specific that allows a tissue to coordinate whole organism metabolism.