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Key points: Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM).In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6‐month intensive supervised training intervention to assess the impact of disease and exercise on lipid metabolism dynamics.We provide evidence that muscle cells from IIM patients display altered dynamics of lipid metabolism and impaired adaptive response to saturated fatty acid load compared to healthy controls.A 6‐month intensive supervised exercise training intervention in patients with IIM mitigated disease effects in their cultured muscle cells, improving or normalizing their capacity to handle lipids.These findings highlight the putative role of intrinsic metabolic defects of skeletal muscle in the pathogenesis of IIM and the positive impact of exercise, maintained in vitro by yet unknown epigenetic mechanisms. Exercise improves skeletal muscle function, clinical state and quality of life in patients with idiopathic inflammatory myopathy (IIM). Our aim was to identify disease‐related metabolic perturbations and the impact of exercise in skeletal muscle cells of IIM patients. Patients underwent a 6‐month intensive supervised training intervention. Muscle function, anthropometric and metabolic parameters were examined and muscle cell cultures were established (m. vastus lateralis; Bergström needle biopsy) before and after training from patients and sedentary age/sex/body mass index‐matched controls. [14C]Palmitate was used to determine fat oxidation and lipid synthesis (thin layer chromatography). Cells were exposed to a chronic (3 days) and acute (3 h) metabolic challenge (the saturated fatty acid palmitate, 100 μm). Reduced oxidative (intermediate metabolites, −49%, P = 0.034) and non‐oxidative (diglycerides, −38%, P = 0.013) lipid metabolism was identified in palmitate‐treated muscle cells from IIM patients compared to controls. Three days of palmitate exposure elicited distinct regulation of oxidative phosphorylation (OxPHOS) complex IV and complex V/ATP synthase (P = 0.012/0.005) and adipose triglyceride lipase in patients compared to controls (P = 0.045) (immunoblotting). Importantly, 6 months of training in IIM patients improved lipid metabolism (CO2, P = 0.010; intermediate metabolites, P = 0.041) and activation of AMP kinase (P = 0.007), and nearly normalized palmitate‐induced changes in OxPHOS proteins in myotubes from IIM patients, in parallel with improvements of patients' clinical state. Myotubes from IIM patients displayed altered dynamics of lipid metabolism and impaired response to metabolic challenge with saturated fatty acid. Our observations suggest that metabolic defects intrinsic to skeletal muscle could represent non‐immune pathomechanisms, which can contribute to muscle weakness in IIM. A 6‐month training intervention mitigated disease effects in muscle cells in vitro, indicating the existence of epigenetic regulatory mechanisms. Key points: Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM).In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6‐month intensive supervised training intervention to assess the impact of disease and exercise on lipid metabolism dynamics.We provide evidence that muscle cells from IIM patients display altered dynamics of lipid metabolism and impaired adaptive response to saturated fatty acid load compared to healthy controls.A 6‐month intensive supervised exercise training intervention in patients with IIM mitigated disease effects in their cultured muscle cells, improving or normalizing their capacity to handle lipids.These findings highlight the putative role of intrinsic metabolic defects of skeletal muscle in the pathogenesis of IIM and the positive impact of exercise, maintained in vitro by yet unknown epigenetic mechanisms. [ABSTRACT FROM AUTHOR]

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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 1 H MR spectra and slab-localized 31 P MR spectra were acquired simultaneously in one interleaved exercise/recovery session. The time-resolved interleaved 1 H/ 31 P MRS acquisition yielded excellent data quality. A between-group difference in acetylcarnitine metabolism over time was detected. Significantly slower τ PCr recovery , τ PCr on-kinetics , and lower Q max in the overweight group, compared to the lean group was found. Linear relations between τ PCr on-kinetics , τ PCr recovery , VO 2max 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 1 H/ 31 P MRS at 7 T., (© 2024. The Author(s).)

Background: Thyroid hormones play an important role in energy metabolism and weight control, explained mostly by inducing thermogenesis and increasing basal metabolic rate. It has recently been shown that FT4 levels are associated with food preferences, which might also play a role in modulating body weight. The aim of this longitudinal follow-up study was to analyze the relationship of thyroid hormones levels (FT4, TSH) at baseline with weight/BMI-SDS changes in children and adolescents with obesity., Methods: Three hundred seventy-seven children and adolescents have been enrolled to this study and followed up without a systematic intervention program for 5.59 ± 1.85months. Children and adolescents were divided into three subgroups: 1) 144 adolescents with obesity (15-19 years), 2) 213 children with obesity (10-14.9 years), and 3) 20 lean adolescents (15-19 years). Thyroid hormones were measured at the baseline, and anthropometry was performed at the baseline and during the follow-up. For further analyses, participants were divided according to the BMI-SDS change into two groups: 1. with BMI-SDS decrease, and 2. with BMI-SDS increase., Results: Adolescents with obesity from the BMI-SDS decrease group had significantly lower baseline serum levels of TSH compared to the BMI-SDS increase group (2.4 ± 1.0 vs . 3.2 ± 2.0mIU/l; p=0.005). Similar difference was found for FT4 levels (14.7 ± 2.2 in the BMI-SDS decrease group vs . 15.5 ± 2.7pmol/l in the BMI-SDS increase group, p=0.048). Moreover, the BMI-SDS decrease was present in significantly higher percentage of adolescents with obesity with lower than median TSH level compared to those with higher than median TSH level at baseline (61.1% vs 38.6%, p=0.011). Likewise, the BMI-SDS decrease was present in significantly higher percentage of adolescent females with obesity and lower than median FT4 compared to those with higher than median FT4 level at baseline (70.6% vs . 23.5%, p<0.001). No associations of baseline thyroid hormones with the BMI-SDS change were observed in children with obesity or lean adolescents., Conclusion: Adolescents with obesity and increased BMI-SDS during the follow-up had significantly higher baseline levels of both TSH and FT4 compared to BMI-SDS decrease group. These results support the previous findings that higher FT4 in individuals with obesity may influence weight gain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Staníková, Krajčovičová, Lobotková, Vitariušová, Tichá, Pribilincová, Ukropcová, Ukropec and Staník.)

Purposes: Physical activity (PA) may mitigate late cardiometabolic toxicity of cisplatin-based chemotherapy in testicular germ cell tumor (TGCT) long-term survivors. In this cross-sectional study, we evaluated the effects of habitual PA on metabolic syndrome (MetS) prevalence, and on the markers of cardiometabolic health and chronic inflammation in a population of long-term TGCT survivors., Methods: MetS prevalence was evaluated, and habitual PA was assessed using Baecke's habitual PA questionnaire in TGCT survivors (n=195, age=41.1±8.1years, 11.7±5.2years post-therapy) and healthy male controls (n=41, age=38.2±8.8years). Participants were stratified into low- and high-PA groups based on median values. Differences were examined between low- and high-PA groups (in the entire sample, TGCT survivor sub-samples differing in disease stage, and healthy controls), and between TGCT survivors and controls. Next, TGCT survivors were stratified into age- and BMI-matched sub-groups based on post-treatment time (5-15/15/30years) and number of chemotherapy cycles (≤3/>3), allowing us to detect age- and BMI-independent effects of habitual PA on cardiometabolic health in the given TGCT survivor sub-populations. A correlation matrix of habitual PA and sport activity with cardiometabolic and pro-inflammatory markers was generated., Results: TGCT survivors had higher MetS prevalence than controls. Patients with high habitual PA had lower waist circumference and Systemic Inflammation Index. Habitual PA scores correlated positively with HDL-cholesterol and negatively with waist circumference and atherogenic risk. Furthermore, cardiometabolic benefits of habitual PA were more pronounced in patients with disease stages 1 and 2. Effects of habitual PA on patients sub-populations stratified by chemotherapy dose and post-treatment time clearly showed that higher levels of habitual PA were associated with lower numbers of MetS components, except for patients who received more than 3 chemotherapy cycles and were examined more than15 years post-therapy., Conclusions: Higher levels of habitual PA effectively mitigated cardiometabolic toxicity in TGCT survivors. Patients with higher cumulative doses of chemotherapy may need structured exercise interventions involving higher-intensity physical activity to achieve significant improvements in cardiometabolic health., (© 2023. The Author(s).)

Context: Type 2 diabetes mellitus (T2D) negatively affects muscle mass and function throughout life. Whether adult muscle stem cells contribute to the decrease in muscle health is not clear and insights into the stem cell niche are difficult to obtain., Objective: To establish the upstream signaling pathway of microRNA (miR)-501, a marker of activated myogenic progenitor cells, and interrogate this pathway in muscle biopsies from patients with T2D., Methods: Analysis of primary muscle cell cultures from mice and 4 normoglycemic humans and muscle biopsies from 7 patients with T2D and 7 normoglycemic controls using gene expression, information on histone methylation, peptide screening, and promoter assays., Results: miR-501 shares the promoter of its host gene, isoform 2 of chloride voltage-gated channel 5 (CLCN5-2), and miR-501 expression increases during muscle cell differentiation. We identify platelet-derived growth factor (PDGF) as an upstream regulator of CLCN5-2 and miR-501 via Janus kinase/signal transducer and activator of transcription. Skeletal muscle biopsies from patients with T2D revealed upregulation of PDGF (1.62-fold, P = .002), CLCN5-2 (2.85-fold, P = .03), and miR-501 (1.73-fold, P = .02) compared with normoglycemic controls. In addition, we observed a positive correlation of PDGF and miR-501 in human skeletal muscle (r = 0.542, P = .045, n = 14)., Conclusions: We conclude that paracrine signaling in the adult muscle stem cells niche is activated in T2D. Expression analysis of the PDGF-miR-501 signaling pathway could represent a powerful tool to classify patients in clinical trials that aim to improve muscle health and glucose homeostasis in patients with diabetes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: Strong evidence supports the benefits of exercise for healthy ageing, including reduced risk of neurodegenerative diseases. Recent studies suggested interorgan crosstalk as a key element of systemic adaptive response, however, the role of specific molecules in mediating exercise effects on the human brain are not fully understood. In the present study, we explored the exercise-related regulation of Growth Differentiation Factor 11 (GDF11) in cerebrospinal fluid (CSF) and blood., Methods: The samples of serum, plasma and CSF were obtained before and 60min after acute exercise (90min run) from twenty healthy young individuals. Additional serum and plasma samples were collected immediately after run. GDF11 protein content (immunoblotting), body composition (bioelectrical impedance), physical fitness (VO 2 max, cycle spiroergometry) and cognitive functions (standardized computerized tests, Cogstate) were evaluated., Results: Running decreased GDF11 protein content in CSF (-20.6%. p=0.046), while GDF11 in plasma and serum were not regulated. Two GDF11-specific antibodies of different origin were used to corroborate this result. Individuals with higher physical fitness displayed greater exercise-induced decrease of GDF11 in CSF than those with lower physical fitness (p=0.025). VO 2 max correlated positively with GDF11 in serum (r=0.63, p=0.020) as well as with the exercise-induced change in GDF11 levels in CSF (r=0.59, p=0.042). Indirect measure of blood-brain barrier permeability (i.e. CSF/serum albumin ratio) tended to positively correlate with CSF/serum GDF11 ratio (p=0.060). CSF levels of GDF11 correlated positively with cognitive functions, including working memory, both before and after run (p<0.05)., Conclusion: Running-induced down-regulation of the GDF11 protein in the cerebrospinal fluid of healthy young individuals indicates the potential role of GDF11 in the exercise-induced cross-talk between periphery and the brain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Schön, Marček Malenovská, Nemec, Alchus Laiferová, Straka, Košutzká, Matejička, Valkovič, Ukropec and Ukropcová.)

Background: Thyroid hormones profoundly affect energy metabolism but their interrelation with food preference, which might contribute to childhood obesity development, are much less understood. In this study, we investigated if thyroid hormone levels are associated with specific modulation of food preference and potentially linked to the level of obesity in children and adolescents., Methods: Interrelations between food preference and peripheral thyroid activity were examined in a population of 99 non-obese and 101 obese children and adolescents (12.8 ± 3.6 years of age, 111/89 F/M) randomly selected from the patients of the Obesity and Metabolic Disease Out-patient Research Unit at National Institute for Children's Diseases in Bratislava in a period between December 2017 and March 2020., Results: Children and adolescents with obesity had a lower preference for food rich in high sucrose and high-complex carbohydrates, while the preference for protein and fat-containing food and that for dietary fibers did not differ between obese and nonobese. In adolescents with obesity, free thyroxine (FT4) correlated positively with the preference for a high protein and high fat-rich diet, irrespective of the fatty acid unsaturation level. Moreover, FT4 correlated negatively with the preference for dietary fibers, which has been also exclusively found in obese adolescents. Individuals with obesity with higher FT4 levels had higher systemic levels of AST and ALT than the population with lower FT4. Multiple regression analysis with age, sex, BMI-SDS, and FT4 as covariates revealed that FT4 and male gender are the major predictors of variability in the preference for a diet high in protein, fat, and monounsaturated fatty acids. FT4 was the sole predictor of the preference for a diet containing saturated and polyunsaturated fatty acids as well as for a diet low in fiber., Conclusion: The link between free thyroxin levels and dietary preference for food rich in fat and protein is present exclusively in individuals with obesity. Higher serum FT4 was linked with elevated AST and ALT in children and adolescents with obesity, and FT4 was the best predictor for preference for food rich in fat and low in fiber. This may indicate that FT4 could contribute to the development of childhood obesity and its complications by modulating food preference., (Copyright © 2022 Staníková, Krajčovičová, Demková, Forišek-Paulová, Slobodová, Vitariušová, Tichá, Ukropcová, Staník and Ukropec.)

Metabolomics has emerged as a powerful new tool in precision medicine. No studies have yet been published on the metabolomic changes in cerebrospinal fluid (CSF) produced by acute endurance exercise. CSF and plasma were collected from 19 young active adults (13 males and 6 females) before and 60 min after a 90-min monitored outdoor run. The median age, BMI, and VO 2 max of subjects was 25 years (IQR 22-31), 23.2 kg/m 2 (IQR 21.7-24.5), and 47 ml/kg/min (IQR 38-51), respectively. Targeted, broad-spectrum metabolomics was performed by liquid chromatography, tandem mass spectrometry (LC-MS/MS). In the CSF, purines and pyrimidines accounted for 32% of the metabolic impact after acute endurance exercise. Branch chain amino acids, amino acid neurotransmitters, fatty acid oxidation, phospholipids, and Krebs cycle metabolites traceable to mitochondrial function accounted for another 52% of the changes. A narrow but important channel of metabolic communication was identified between the brain and body by correlation network analysis. By comparing these results to previous work in experimental animal models, we found that over 80% of the changes in the CSF correlated with a cascade of mitochondrial and metabolic changes produced by ATP signaling. ATP is released as a co-neurotransmitter and neuromodulator at every synapse studied to date. By regulating brain mitochondrial function, ATP release was identified as an early step in the kinetic cascade of layered benefits produced by endurance exercise., (© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Objectives: Idiopathic inflammatory myopathies/IIM are associated with changes in muscle-specific microRNA/miR. Exercise improves muscle function and metabolism in parallel with changes in miR expression. We investigated the effects of disease and exercise on miRs in differentiated muscle cells/myotubes from IIM patients and controls., Methods: Samples of m. vastus lateralis were obtained by needle biopsy from IIM patients before/after 6-month training and from matched sedentary healthy controls. Muscle cell cultures were established and exposed to saturated fatty acid during differentiation. MiR-133a,-133b,-206,-1 and their target genes (qPCR), fat oxidation (FOx), lipids (chromatography) and mitochondrial oxidative phosphorylation (OxPHOS) complexes (immunoblotting) were measured. Interrelations between in vitro miRs and metabolism of myotubes as well as clinical parameters and disease activity/MITAX were explored., Results: Levels of miRs were higher in myotubes derived from IIM patients compared to healthy controls (up to 3.5-fold, p<0.05). Neither 6-month training (IIM patients) nor in vitro palmitate treatment modulated myomiRs in myotubes. However, miR-133a,-133b, and miR-1 correlated negatively with FOx (p<0.01), triacylglycerols (p<0.05) and OxPHOS complex-V (p<0.05) and positively with OxPHOS complex-I (p<0.05) in myotubes. MiR-133a and miR-133b in myotubes were related to disease activity and fasting glycaemia in vivo (both p<0.05)., Conclusions: Upregulation of microRNAs involved in myogenesis and regeneration in muscle cells derived from IIM patients indicates activation of compensatory epigenetic mechanisms, potentially aimed to counteract disease progression. Relationships of microRNAs with in vitro metabolic profile of muscle cells as well as with clinical parameters support the role of muscle-specific microRNAs in modulating muscle metabolism and clinical state of patients.

Background/aims: Walking speed (WS) is an objective measure of physical capacity and a modifiable risk factor of morbidity and mortality in the elderly. In this study, we (i) determined effects of 3-month supervised aerobic-strength training on WS, muscle strength, and habitual physical activity; (ii) evaluated capacity of long-term (21 months) training to sustain higher WS; and (iii) identified determinants of WS in the elderly., Methods: Volunteers (F 48/M 14, 68.4 ± 7.1 years) completed either 3-month aerobic-strength (3 × 1 h/week, n = 48) or stretching (active control, n = 14) intervention (study A). Thirty-one individuals (F 24/M 7) from study A continued in supervised aerobic-strength training (2 × 1 h/week, 21 months) and 6 (F 5/M 1) became nonexercising controls., Results: Three-month aerobic-strength training increased preferred and maximal WS (10-m walk test, p < 0.01), muscle strength (p < 0.01) and torque (p < 0.01) at knee extension, and 24-h habitual physical activity (p < 0.001), while stretching increased only preferred WS (p < 0.03). Effect of training on maximal WS was most prominent in individuals with baseline WS between 1.85 and 2.30 m·s-1. Maximal WS measured before intervention correlated negatively with age (r = -0.339, p = 0.007), but this correlation was weakened by the intervention (r = -0.238, p = 0.06). WS progressively increased within the first 9 months of aerobic-strength training (p < 0.001) and remained elevated during 21-month intervention (p < 0.01). Cerebellar gray matter volume (MRI) was positively associated with maximal (r = 0.54; p < 0.0001) but not preferred WS and explained >26% of its variability, while age had only minor effect., Conclusions: Supervised aerobic-strength training increased WS, strength, and dynamics of voluntary knee extension as well as habitual physical activity in older individuals. Favorable changes in WS were sustainable over the 21-month period by a lower dose of aerobic-strength training. Training effects on WS were not limited by age, and cerebellar cortex volume was the key determinant of WS., (© 2021 S. Karger AG, Basel.)

Background: Testicular germ cell tumors (TGCTs) represent ∼95% of testicular malignancies and are the most common type of malignancy in young male adults. While the incidence of TGCTs has increased during the last decades, the advances in treatment, namely introducing cisplatin into the chemotherapy regimen, have made TGCTs highly curable with the 10-year survival rate exceeding 95%. However, in parallel with increased cure rates, survivors may experience acute and late adverse effects of treatment, which increase morbidity, reduce the quality of life, and can be potentially life-threatening. Chemotherapy-related toxicities include cardiovascular and metabolic diseases, secondary cancer, avascular necrosis, cognitive impairment, cancer-related fatigue, poor mental health-related quality of life, nephrotoxicity, hypogonadism, neurotoxicity, pulmonary toxicity, anxiety, and depression. These treatment-related adverse effects have emerged as important survivorship dilemmas in TGCT cancer survivors. Recently, regular physical exercise has increasingly attracted research and clinical attention as an adjunct therapy for cancer patients., Purpose: Herein, we review the most common chemotherapy-related adverse effects in TGCT survivors and clinical relevance of exercise and increased cardio-respiratory fitness in modulating chemotherapy-related toxicity and quality of life in this population., Results and Conclusion: Exercise has positive effects on a spectrum of physical and psychosocial outcomes during and after cancer treatment, and current guidelines on exercise prescription in chronic diseases define the recommended dose (volume and intensity) of regular exercise for cancer survivors, highlighting regular, sufficiently intensive physical activity as an essential part of patients' care., (© 2021 American Society of Andrology and European Academy of Andrology.)

A wealth of evidence has shown that a single bout of aerobic exercise can facilitate executive function. However, none of current studies on this topic have addressed whether the magnitude of the acute-exercise benefit on executive function and oculomotor performance is influenced by different aerobic exercise modes. The present study was thus aimed toward an investigation of the acute effects of high-intensity interval exercise (HIIE) vs. moderate-intensity continuous exercise (MICE) on executive-related oculomotor performance in healthy late middle-aged and older adults. Using a within-subject design, twenty-two participants completed a single bout of 30 min of HIIE, MICE, or a non-exercise-intervention (REST) session in a counterbalanced order. The behavioral [e.g., reaction times (RTs), coefficient of variation (CV) of the RT], and oculomotor (e.g., saccade amplitude, saccade latency, and saccadic peak velocity) indices were measured when participants performed antisaccade and prosaccade tasks prior to and after an intervention mode. The results showed that a 30-min single-bout of HIIE and MICE interventions shortened the RTs in the antisaccade task, with the null effect on the CV of the RT in the late middle-aged and older adults. In terms of oculomotor metrics, although the two exercise modes could not modify the performance in terms of saccade amplitudes and saccade latencies, the participants' saccadic peak velocities while performing the oculomotor paradigm were significantly altered only following an acute HIIE intervention. The present findings suggested that a 30-min single-bout of HIIE and MICE interventions modulated post-exercise antisaccade control on behavioral performance (e.g., RTs). Nevertheless, the HIIE relative MICE mode appears to be a more effective aerobic exercise in terms of oculomotor control (e.g., saccadic peak velocities) in late middle-aged and older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tsai, Chang, Pan, Wang, Ukropec and Ukropcová.)

Cold exposure results in activation of metabolic processes required for fueling thermogenesis, potentially promoting improved metabolic health. However, the metabolic complexity underlying this process is not completely understood. We aimed to analyze changes in plasma metabolites related to acute cold exposure and their relationship to cold-acclimatization level and metabolic health in cold-acclimatized humans. Blood samples were obtained before and acutely after 10-15 min of ice-water swimming (<5 °C) from 14 ice-water swimmers. Using mass spectrometry, 973 plasma metabolites were measured. Ice-water swimming induced acute changes in 70 metabolites. Pathways related to amino acid metabolism were the most cold-affected and cold-induced changes in several amino acids correlated with cold-acclimatization level and/or metabolic health markers, including atherogenic lipid profile or insulin resistance. Metabolites correlating with cold-acclimatization level were enriched in the linoleic/α-linolenic acid metabolic pathway. N-lactoyl-tryptophan correlated with both cold-acclimatization level and cold-induced changes in thyroid and parathyroid hormones. Acute cold stress in cold-acclimatized humans induces changes in plasma metabolome that involve amino acids metabolism, while the linoleic and α-linolenic acid metabolism pathway seems to be affected by regular cold exposure. Metabolites related to metabolic health, thermogenic hormonal regulators and acclimatization level might represent prospective molecular factors important in metabolic adaptations to regular cold exposure.

Objectives: The aim of this cross-sectional study was to explore the circulating and skeletal muscle expression of clusterin (CLU) in inflammatory myopathies (IIM) and its potential implication in pathogenetic mechanisms of the disease., Methods: A total of 85 IIM patients and 86 healthy controls (HC) were recruited. In addition, 20 IIM patients and 21 HC underwent a muscle biopsy. Circulating CLU was measured by ELISA. Serum cytokine profile of patients and HC was assessed by Cytokine 27-plex Assay. Immunohistochemical localisation of CLU was assessed in 10 IIM and 4 control muscle tissue specimens. The expression of CLU and myositis related cytokines in muscle was determined by qPCR., Results: Serum levels of CLU were significantly increased in IIM patients compared to controls (86.2 (71.6-99.0) vs. 59.6 (52.6-68.4) μg/mL, p<0.0001) and positively correlated with myositis disease activity assessment (MYOACT) (r=0.337, p=0.008), myositis intention-to-treat activity index (MITAX) (r=0.357, p=0.004) and global disease assessment evaluated by physician (r=0.309, p=0.015). Moreover, serum CLU correlated with cytokines and chemokines involved in IIM and their combined effect on disease activity was revealed by multivariate redundancy analysis. In muscle tissue, CLU mRNA was increased in IIM patients compared to controls (p=0.032) and CLU accumulated in the cytoplasm of regenerating myofibres., Conclusions: We suggest that the up-regulation of clusterin in circulation and skeletal muscle of IIM patients may be an inflammation and atrophy induced response of the organism intended to limit the environment, favouring further muscle damage.

Objectives: The aim of this study was to investigate the systemic and skeletal muscle levels of atrophy-associated myokines in patients with idiopathic inflammatory myopathies (IIM) and their association with clinical characteristics of myositis., Methods: A total of 94 IIM patients and 162 healthy controls were recruited. Of those, 20 IIM patients and 28 healthy controls underwent a muscle biopsy. Circulating concentrations of myostatin, follistatin, activin A and TGF-β1 were assessed by ELISA. The expression of myokines and associated genes involved in the myostatin signalling pathway in muscle tissue was determined by real-time PCR., Results: We report decreased levels of circulating myostatin (median 1817 vs 2659 pg/ml; P = 0.003) and increased follistatin (1319 vs 1055 pg/ml; P = 0.028) in IIM compared with healthy controls. Activin A levels were also higher in IIM (414 vs 309 pg/ml; P = 0.0005) compared with controls. Myostatin was negatively correlated to muscle disease activity assessed by physician on visual analogue scale (MDA) (r = -0.289, P = 0.015) and positively to manual muscle testing of eight muscles (r = 0.366, P = 0.002). On the other hand, follistatin correlated positively with MDA (r = 0.235, P = 0.047). Gene expression analysis showed higher follistatin (P = 0.003) and myostatin inhibitor follistatin-like 3 protein (FSTL3) (P = 0.008) and lower expression of activin receptor type 1B (ALK4) (P = 0.034), signal transducer SMAD3 (P = 0.023) and atrophy marker atrogin-1 (P = 0.0009) in IIM muscle tissue compared with controls., Conclusion: This study shows lower myostatin and higher follistatin levels in circulation and attenuated expression of myostatin pathway signalling components in skeletal muscle of patients with myositis, a newly emerging pattern of the activin A-myostatin-follistatin system in muscle wasting diseases., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cold-induced activation of thermogenesis modulates energy metabolism, but the role of humoral mediators is not completely understood. We aimed to investigate the role of parathyroid and thyroid hormones in acute and adaptive response to cold in humans. Examinations were performed before/after 15 minutes of ice-water swimming (n = 15) or 120 to 150 minutes of cold-induced nonshivering thermogenesis (NST) applied to cold-acclimatized (n = 6) or non-acclimatized (n = 11) individuals. Deep-neck brown adipose tissue (BAT) was collected from non-acclimatized patients undergoing elective neck surgery (n = 36). Seasonal variations in metabolic/hormonal parameters of ice-water swimmers were evaluated. We found that in ice-water swimmers, PTH and TSH increased and free T3, T4 decreased after a 15-minute winter swim, whereas NST-inducing cold exposure failed to regulate PTH and free T4 and lowered TSH and free T3. Ice-water swimming-induced increase in PTH correlated negatively with systemic calcium and positively with phosphorus. In non-acclimatized men, NST-inducing cold decreased PTH and TSH. Positive correlation between systemic levels of PTH and whole-body metabolic preference for lipids as well as BAT volume was found across the 2 populations. Moreover, NST-cooling protocol-induced changes in metabolic preference for lipids correlated positively with changes in PTH. Finally, variability in circulating PTH correlated positively with UCP1/UCP1, PPARGC1A, and DIO2 in BAT from neck surgery patients. Our data suggest that regulation of PTH and thyroid hormones during cold exposure in humans varies by cold acclimatization level and/or cold stimulus intensity. Possible role of PTH in NST is indicated by its positive relationships with whole-body metabolic preference for lipids, BAT volume, and UCP1 content., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Aging is associated with changes in muscle energy metabolism. Proton ( 1 H) and phosphorous ( 31 P) magnetic resonance spectroscopy (MRS) has been successfully applied for non-invasive investigation of skeletal muscle metabolism. The aim of this study was to detect differences in adenosine triphosphate (ATP) production in the aging muscle by 31 P-MRS and to identify potential changes associated with buffer capacity of muscle carnosine by 1 H-MRS. Methods: Fifteen young and nineteen elderly volunteers were examined. 1 H and 31 P-MRS spectra were acquired at high field (7T). The investigation included carnosine quantification using 1 H-MRS and resting and dynamic 31 P-MRS, both including saturation transfer measurements of phosphocreatine (PCr), and inorganic phosphate (Pi)-to-ATP metabolic fluxes. Results: Elderly volunteers had higher time constant of PCr recovery (τ PCr ) in comparison to the young volunteers. Exercise was connected with significant decrease in PCr-to-ATP flux in both groups. Moreover, PCr-to-ATP flux was significantly higher in young compared to elderly both at rest and during exercise. Similarly, an increment of Pi-to-ATP flux with exercise was found in both groups but the intergroup difference was only observed during exercise. Elderly had lower muscle carnosine concentration and lower postexercise pH. A strong increase in phosphomonoester (PME) concentration was observed with exercise in elderly, and a faster Pi:PCr kinetics was found in young volunteers compared to elderly during the recovery period. Conclusion: Observations of a massive increment of PME concentration together with high Pi-to-ATP flux during exercise in seniors refer to decreased ability of the muscle to meet the metabolic requirements of exercise and thus a limited ability of seniors to effectively support the exercise load., (Copyright © 2020 Krumpolec, Klepochová, Just, Tušek Jelenc, Frollo, Ukropec, Ukropcová, Trattnig, Krššák and Valkovič.)

The study compared the effect of 12-week multimodal training programme performed twice a week at the regular exercise facility (REF) with the 12-week multimodal training programme performed three times per week as a part of the research programme (EX). Additionally, the study analysed how the experimental training programme affect the physical performance of cognitive healthy and mild cognitive impaired elderly (MCI). The REF training group included 19 elderly (65.00±3.62 years). The experimental training programme combined cognitively healthy (EXH: n=16; 66.3±6.42 years) and age-matched individuals with MCI (EXMCI: n=14; 66.00±4.79 years). 10m maximal walking speed (10mMWS), Five Times Sit-to-Stand Test (FTSS), maximal and relative voluntary contraction (MVC & rel. MVC) were analysed. The REF group improved in 10mMWS (t=2.431, p=.026), the MVC (t=-3.528, p=.002) and relative MVC (t=3.553, p=.002). The EXH group improved in FTSS (t=5.210, P=.000), MVC (t=2.771, p=.018) and relative MVC (t=-3.793, p=.004). EXMCI improved in FTSS (t=2.936, p=.012) and MVC (t=-2.276, p=.040). According to results, both training programmes sufficiently improved walking speed and muscle strength in cognitively healthy elderly. Moreover, the experimental training programme improved muscle strength in MCI elderly., Competing Interests: Conflict of interest The authors have no conflicts to disclose.We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Introduction: The objective of the study was to examine the relationship between the values of selected parameters of physical function, body composition, body mass index (BMI) and biochemical markers of metabolic health with the total testosterone (TT) levels in adult males. We aimed to analyse the correlation between these values and variations in the TT levels., Methods: A total of 17 subjects (age = 50.2 ± 8.1 years, TT = 11.4 ± 3.8nmol/l) were included in the study. Subjects were tested on physical function (1RM on leg press, bench-press, handgrip, VO2max), body composition (DXA), biochemical parameters (morning fasting blood samples)., Results: TT was inversely correlated with abdominal circumference (AC) (p.

Brain-derived neurotrophic factor (BDNF) participates in orchestrating the adaptive response to exercise. However, the importance of transient changes in circulating BDNF for eliciting whole-body and skeletal muscle exercise benefits in humans remains relatively unexplored. Here, we investigated effects of acute aerobic exercise and 3-month aerobic-strength training on serum, plasma and skeletal muscle BDNF in twenty-two sedentary older individuals (69.0 ± 8.0 yrs., 9 M/13F). BDNF response to acute exercise was additionally evaluated in young trained individuals (25.1 ± 2.1 yrs., 3 M/5F). Acute aerobic exercise transiently increased serum BDNF in sedentary (16%, p = .007) but not in trained elderly or young individuals. Resting serum or plasma BDNF was not regulated by exercise training in the elderly. However, subtle training-related changes of serum BDNF positively correlated with improvements in walking speed (R = 0.59, p = .005), muscle mass (R = 0.43, p = .04) and cognitive performance (R = 0.41, p = .05) and negatively with changes in body fat (R = -0.43, p = .04) and triglyceridemia (R = -0.53, p = .01). Individuals who increased muscle BDNF protein in response to 3-month training (responders) displayed stronger acute exercise-induced increase in serum BDNF than non-responders (p = .006). In addition, muscle BDNF protein content positively correlated with type II-to-type I muscle fiber ratio (R = 0.587, p = .008) and with the rate of post-exercise muscle ATP re-synthesis (R = 0.703, p = .005). Contrary to serum, acute aerobic exercise resulted in a decline of plasma BDNF 1 h post-exercise in both elderly-trained (-34%, p = .002) and young-trained individuals (-48%, p = .034). Acute circulating BDNF regulation by exercise was dependent on the level of physical fitness and correlated with training-induced improvements in metabolic and cognitive functions. Our observations provide an indirect evidence that distinct exercise-induced changes in serum and plasma BDNF as well as training-related increase in muscle BDNF protein, paralleled by improvements in muscle and whole-body clinical phenotypes, are involved in the coordinated adaptive response to exercise in humans., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Omega-3 (n-3) fatty acids (FA) play and important role in neural development and other metabolic diseases such as obesity and diabetes. The knowledge about the in vivo content and distribution of n-3 FA in human body tissues is not well established and the standard quantification of FA is invasive and costly., Purpose: To detect omega-3 (n-3 CH 3 ) and non-omega-3 (CH 3 ) methyl group resonance lines with echo times up to 1200 msec, in oils, for the assessment of n-3 FA content, and the n-3 FA fraction in adipose tissue in vivo., Study Type: Prospective technical development., Population: Three oils with different n-3 FA content and 24 healthy subjects., Field Strength/sequence: Single-voxel MR spectroscopy (SVS) with a point-resolved spectroscopy (PRESS) sequence with an echo time (TE) of 1000 msec at 7 T., Assessment: Knowledge about the J-coupling evolution of both CH 3 resonances was used for the optimal detection of the n-3 CH 3 resonance line at a TE of 1000 msec. The accuracy of the method in oils and in vivo was validated from a biopsy sample with gas chromatography analysis., Statistical Tests: SVS data were compared to gas chromatography with the Pearson correlation coefficient., Results: T 2 relaxation times in oils were assessed as follows: CH 2 , 65 ± 22 msec; CH 3 , 325 ± 7 msec; and n-3 CH 3 , 628 ± 34 msec. The n-3 FA fractions from oil phantom experiments (n = 3) were in agreement with chromatography analysis and the comparison of in vivo obtained data with the results of chromatography analysis (n = 5) yielded a significant correlation (P = 0.029)., Data Conclusion: PRESS with ultralong-TE can detect and quantify the n-3 CH 3 signal in vivo at 7 T., Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:71-82., (© 2018 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Neurological, neurodegenerative, and psychiatric disorders represent a serious burden because of their increasing prevalence, risk of disability, and the lack of effective causal/disease-modifying treatments. There is a growing body of evidence indicating potentially favourable effects of carnosine, which is an over-the-counter food supplement, in peripheral tissues. Although most studies to date have focused on the role of carnosine in metabolic and cardiovascular disorders, the physiological presence of this di-peptide and its analogues in the brain together with their ability to cross the blood-brain barrier as well as evidence from in vitro, animal, and human studies suggest carnosine as a promising therapeutic target in brain disorders. In this review, we aim to provide a comprehensive overview of the role of carnosine in neurological, neurodevelopmental, neurodegenerative, and psychiatric disorders, summarizing current evidence from cell, animal, and human cross-sectional, longitudinal studies, and randomized controlled trials., Competing Interests: The authors declare no conflict of interest.

Background: Decreased levels of the neuroprotective growth factors, low-grade inflammation, and reduced neurocognitive functions during aging are associated with neurodegenerative diseases, such as Alzheimer's disease. Physical exercise modifies these disadvantageous phenomena while a sedentary lifestyle promotes them., Purpose: The purposes of the present study included investigating whether both aerobic and resistance exercise produce divergent effects on the neuroprotective growth factors, inflammatory cytokines, and neurocognitive performance, and further exploring whether changes in the levels of these molecular biomarkers are associated with alterations in neurocognitive performance., Methods: Fifty-five older adults with amnestic MCI (aMCI) were recruited and randomly assigned to an aerobic exercise (AE) group, a resistance exercise (RE) group, or a control group. The assessment included neurocognitive measures [e.g., behavior and event-related potential (ERP)] during a task-switching paradigm, as well as circulating neuroprotective growth factors (e.g., BDNF, IGF-1, VEGF, and FGF-2) and inflammatory cytokine (e.g., TNF-α, IL-1β, IL-6, IL-8, and IL-15) levels at baseline and after either a 16-week aerobic or resistance exercise intervention program or a control period., Results: Aerobic and resistance exercise could effectively partially facilitate neurocognitive performance [e.g., accuracy rates (ARs), reaction times during the heterogeneous condition, global switching cost, and ERP P3 amplitude] when the participants performed the task switching paradigm although the ERP P2 components and P3 latency could not be changed. In terms of the circulating molecular biomarkers, the 16-week exercise interventions did not change some parameters (e.g., leptin, VEGF, FGF-2, IL-1β, IL-6, and IL-8). However, the peripheral serum BDNF level was significantly increased, and the levels of insulin, TNF-α, and IL-15 levels were significantly decreased in the AE group, whereas the RE group showed significantly increased IGF-1 levels and decreased IL-15 levels. The relationships between the changes in neurocognitive performance (AR and P3 amplitudes) and the changes in the levels of neurotrophins (BDNF and IGF-1)/inflammatory cytokines (TNF-α) only approached significance., Conclusion: These findings suggested that in older adults with aMCI, not only aerobic but also resistance exercise is effective with regard to increasing neurotrophins, reducing some inflammatory cytokines, and facilitating neurocognitive performance. However, the aerobic and resistance exercise modes likely employed divergent molecular mechanisms on neurocognitive facilitation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study evaluates the effect of 3 months resistance and aerobic training on muscle strength and power in 17 male overweight and obese men. Subjects underwent either a resistance or aerobic training for a period of 3 months (three sessions per week). Peak isometric force, rate of force development, peak power and height of countermovement and squat jumps, reactive strength index, and mean power in the concentric phase of bench presses were all assessed prior to and after completing the training program. Results identified a significant increase of mean power during both countermovement bench presses at 30 kg (18.6%, p = .021), 40 kg (14.6%, p = .033), and 50 kg (13.1%, p = .042) and concentric-only bench presses at 30 kg (19.6%, p = .017) and 40 kg (13.9%, p = .037) after the resistance training. There was also a significant increase in the height of the jump (12.8%, p = .013), peak power (10.1%, p = .026), and peak velocity (9.7%, p = .037) during the countermovement jump and height of the jump (11.8%, p = .019), peak power (9.6%, p = .032), and peak velocity (9.5%, p = .040) during the squat jump. There were no significant changes in the reactive strength index, peak force, and the rate of force development after the resistance training. The aerobic group failed to show any significant improvements in these parameters. It may be concluded that 3 months of resistance training without caloric restriction enhances upper and lower body muscle power in overweight and obese men.

Although exercise is an effective way to decrease the risk of developing Alzheimer's disease, the biological basis for such benefits from the different exercise modes remains elusive. The present study thus aimed (i) to investigate the effects of acute aerobic or resistance exercise on neurocognitive performances and molecular markers when performing a cognitive task involving executive functioning in older adults with amnestic mild cognitive impairment (aMCI), and (ii) to explore relationships of acute exercise-induced neurocognitive changes with changes in circulating levels of neuroprotective growth factors (e.g., BDNF, IGF-1, VEGF, and FGF-2, collectively termed 'exerkines'), elicited by different acute exercise modes. Sixty-six older adults with aMCI were recruited and randomly assigned to an aerobic exercise (AE) group, a resistance exercise (RE) group, or a non-exercise-intervention (control) group. The behavioral [i.e., accuracy rate (AR) and reaction time (RT)] and electrophysiological [i.e., event-related potential (ERP) P3 latency and amplitude collected from the Fz, Cz, and Pz electrodes] indices were simultaneously measured when participants performed a Flanker task at baseline and after either an acute bout of 30 min of moderate-intensity AE, RE or a control period. Blood samples were taken at three time points, one at baseline (T1) and two after an acute exercise intervention (T2 and T3: before and after cognitive task test, respectively). The results showed that the acute AE and RE not only improved behavioral (i.e., RTs) performance but also increased the ERP P3 amplitudes in the older adults with aMCI. Serum FGF-2 levels did not change with acute aerobic or resistance exercise. However, an acute bout of aerobic exercise significantly increased serum levels of BDNF and IGF-1 and tended to increase serum levels of VEGF in elderly aMCI individuals. Acute resistance exercise increased only serum IGF-1 levels. However, the exercise-induced elevated levels of these molecular markers returned almost to baseline levels in T3 (about 20 min after acute exercise). In addition, changes in the levels of neurotrophic and angiogenic factors were not correlated with changes in RTs and P3 amplitudes. The present findings of changes in neuroprotective growth factors and neurocognitive performances through acute AE or RE suggest that molecular and neural prerequisites for exercise-dependent plasticity are preserved in elderly aMCI individuals. However, the distinct pattern of changes in circulating molecular biomarkers induced by two different exercise modes in aMCI elderly individuals and the potentially interactive mechanisms of the effects of BDNF, IGF-1, and VEGF on amyloid-β provide a basis for future long-term exercise intervention to investigate whether AE relative to RE might be more effective in prevention/treatment of an early stage neurodegenerative disease.

The authors evaluated the effect of 3 months of resistance and aerobic training (3 sessions/week) on body balance in a group of 25 overweight and obese individuals. Prior to and after the training, they performed static and task-oriented balance tests under various conditions. Mean center of pressure (CoP) velocity and mean trace length of the CoP in the y-axis registered during a one-legged stance significantly decreased after the resistance training (19.1%, p = .024; 29.3%, p = .009). Mean trace length of the CoP in the y-axis decreased significantly also during a bipedal stance on a foam surface with eyes open and closed (10.9%, p = .040; 18.2%, p = .027). In addition, mean CoP distance and mean squared CoP distance in the anteroposterior direction during a visually guided center of mass (CoM) tracking task significantly improved (14.7%, p = .033; 28.2%, p = .016). However, only mean trace length of the CoP in the y-axis during a bipedal stance on a foam surface with eyes open and closed significantly decreased after the aerobic training (10.3%, p = .047; 16.5%, p = .029). It may be concluded that resistance training is more efficient for the improvement of the anteroposterior unilateral stability and the accuracy of the regulation of the CoM anteroposterior position than aerobic training in overweight and obese individuals.

Background: This study evaluates the effect on power produced during a modified lifting task in the overweight and obese after three months of either resistance or aerobic training., Methods: Seventeen male subjects divided randomly into two groups performed deadlift and deadlift high pull, both with increasing weights up to maximal power, prior to and after the training programs (three sessions per week)., Results: Their mean power increased significantly during the deadlift at 20 kg (14.3%, p = 0.026), 30 kg (17.7%, p = 0.008), 40 kg (16.5%, p = 0.011), 50 kg (14.5%, p = 0.020), and 60 kg (14.3%, p = 0.021) and during the deadlift high pull at 30 kg (9.9%, p = 0.037), 40 kg (10.1%, p = 0.035), and 50 kg (8.2%, p = 0.044) after the resistance training. However, the group that participated in the aerobic training failed to show any significant changes in power performance during either the deadlift or deadlift high pull., Conclusion: Three months of resistance training enhances power outputs during a lifting task with weights from 30 to 50 kg (~40%⁻60% of 1-repetition maximum) in the overweight and obese. Because this test was sensitive in revealing pre-post training changes in lifting performance, it should be implemented in the functional diagnostics for overweight and obese individuals and also complement existing testing methods., Competing Interests: The authors declare no conflict of interest.

Background: Contrary to static and dynamic balance, there is a lack of scientific evidence on the training induced changes in reactive balance control in response to unexpected perturbations in overweight and obese individuals., Objective: This study evaluates the effect of 3 months of resistance and aerobic training programs on postural responses to unexpected perturbations under stable and unstable conditions in the overweight and obese., Methods: A group of 17 overweight and obese subjects, divided into two groups, underwent either resistance or aerobic training for a period of 3 months (3 sessions per week). Prior to and after completing the training, they performed the load release balance test while standing on either a stable or unstable surface, with eyes open and closed., Results: Peak posterior center of pressure (CoP) displacement, and the time to peak posterior CoP displacement during a bipedal stance on a foam surface with eyes open (17.3%, p = 0.019 and 15.4%, p = 0.029) and eyes closed (15.0%, p = 0.027 and 13.2%, p = 0.034), decreased significantly. In addition, the total anterior to posterior CoP displacement, and the time from peak anterior to peak posterior CoP displacement, both with eyes open (18.1%, p = 0.017 and 12.2%, p = 0.040) and eyes closed (16.3%, p = 0.023 and 11.7%, p = 0.044), also significantly decreased. However, after completing the resistance training, the parameters registered while standing on a stable platform, both with eyes open and closed, did not change significantly. The group that underwent an aerobic training also failed to show any significant changes in parameters of the load release balance test., Conclusion: Three months of resistance training in overweight and obese subjects improves reactive balance control in response to unexpected perturbations under unstable conditions, both with and without visual cues. Due to the fact that this unstable load release balance test was found to be sensitive in revealing post-training changes, it would be suitable for implementing in the functional diagnostic for this group, in addition to complementing existing testing methods.

Although elderly people with amnestic mild cognitive impairment (aMCI) have been found to show impaired behavioral performance in task switching, no research has yet explored the electrophysiological mechanisms and the potential correlation between physical fitness and neurocognitive (i.e., behavioral and electrophysiological) performance in aMCI. The present study was thus aimed to examine whether there are differences in electrophysiological (i.e., event-related potential) performance between aMCI participants and controls when performing a task-switching paradigm, and to investigate the role of physical fitness in the relationship between neurocognitive performance and aMCI. Sixty participants were classified into aMCI (n = 30) and control (n = 30) groups, and performed a task-switching paradigm with concomitant electrophysiological recording, as well as underwent senior functional physical fitness tests. The aMCI group showed comparable scores on most parts of the physical fitness tests, but reduced lower body flexibility and VO2max as compared to the control group. When performing the task-switching paradigm, the aMCI group showed slower reaction times in the heterogeneous condition and larger global switching costs, although no significant difference was observed in accuracy rates between the two groups. In addition, the aMCI group showed significantly prolonged P3 latencies in the homogeneous and heterogeneous conditions, and a smaller P3 amplitude only in the heterogeneous condition. The level of cardiorespiratory fitness was significantly correlated with P3 amplitude in the aMCI group, particularly in the heterogeneous condition of the task-switching paradigm. These results show that the aMCI group exhibited abnormalities in their neurocognitive performance when performing the task-switching paradigm and such a deficit was likely associated with reduced cardiorespiratory fitness, which was shown to be the important predictor of neurocognitive performance.

Defects in skeletal muscle energy metabolism are indicative of systemic disorders such as obesity or type 2 diabetes. Phosphorus magnetic resonance spectroscopy ((31)P-MRS), in particularly dynamic (31)P-MRS, provides a powerful tool for the non-invasive investigation of muscular oxidative metabolism. The increase in spectral and temporal resolution of (31)P-MRS at ultra high fields (i.e., 7T) uncovers new potential for previously implemented techniques, e.g., saturation transfer (ST) or highly resolved static spectra. In this study, we aimed to investigate the differences in muscle metabolism between overweight-to-obese sedentary (Ob/Sed) and lean active (L/Ac) individuals through dynamic, static, and ST (31)P-MRS at 7T. In addition, as the dynamic (31)P-MRS requires a complex setup and patient exercise, our aim was to identify an alternative technique that might provide a biomarker of oxidative metabolism. The Ob/Sed group exhibited lower mitochondrial capacity, and, in addition, static (31)P-MRS also revealed differences in the Pi-to-ATP exchange flux, the alkaline Pi-pool, and glycero-phosphocholine concentrations between the groups. In addition to these differences, we have identified correlations between dynamically measured oxidative flux and static concentrations of the alkaline Pi-pool and glycero-phosphocholine, suggesting the possibility of using high spectral resolution (31)P-MRS data, acquired at rest, as a marker of oxidative metabolism.

The aims of this study were to observe the behavior of carnosine peaks in human soleus (SOL) and gastrocnemius (GM) muscles following acute exercise, to determine the relaxation times and to assess the repeatability of carnosine quantification by (1) H MRS at 7 T. Relaxation constants in GM and SOL were measured by a stimulated echo acquisition mode (STEAM) localization sequence. For T1 measurement, an inversion recovery sequence was used. The repeatability of the measurement and the absolute quantification of carnosine were determined in both muscles in five healthy volunteers. For absolute quantification, an internal water reference signal was used. The effect of acute exercise on carnosine levels and resonance lines was tested in eight recreational runners/cyclists. The defined carnosine measurement protocol was applied three times - before and twice after (approximately 20 and 40 min) a 1-h submaximal street run and additional toe-hopping. The measured T1 relaxation times for the C2-H carnosine peak at 7 T were 2002 ± 94 and 1997 ± 259 ms for GM and SOL, respectively, and the T2 times were 95.8 ± 9.4 and 81.0 ± 21.8 ms for GM and SOL, respectively. The coefficient of variation of the carnosine quantification measurement was 9.1% for GM and 6.3% for SOL, showing high repeatability, and the intraclass correlation coefficients (ICCs) of 0.93 for GM and 0.98 for SOL indicate the high reliability of the measurement. Acute exercise did not change the concentration of carnosine in the muscle, but affected the shape of the resonance lines, in terms of the shifting and splitting into doublets. Carnosine measurement by (1) H MRS at 7 T in skeletal muscle exhibits high repeatability and reliability. The observed effects of acute exercise were more prominent in GM, probably as a result of the larger portion of glycolytic fibers in this muscle and the more pronounced exercise-induced change in pH. Our results support the application of the MRS-based assessment of carnosine for pH measurement in muscle compartments., (© 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Dynamic (31) P-MRS with sufficiently high temporal resolution enables the non-invasive evaluation of oxidative muscle metabolism through the measurement of phosphocreatine (PCr) recovery after exercise. Recently, single-voxel localized (31) P-MRS was compared with surface coil localization in a dynamic fashion, and was shown to provide higher anatomical and physiological specificity. However, the relatively long TE needed for the single-voxel localization scheme with adiabatic pulses limits the quantification of J-coupled spin systems [e.g. adenosine triphosphate (ATP)]. Therefore, the aim of this study was to evaluate depth-resolved surface coil MRS (DRESS) as an alternative localization method capable of free induction decay (FID) acquisition for dynamic (31) P-MRS at 7 T. The localization performance of the DRESS sequence was tested in a phantom. Subsequently, two dynamic examinations of plantar flexions at 25% of maximum voluntary contraction were conducted in 10 volunteers, one examination with and one without spatial localization. The DRESS slab was positioned obliquely over the gastrocnemius medialis muscle, avoiding other calf muscles. Under the same load, significant differences in PCr signal drop (31.2 ± 16.0% versus 43.3 ± 23.4%), end exercise pH (7.06 ± 0.02 versus 6.96 ± 0.11), initial recovery rate (0.24 ± 0.13 mm/s versus 0.35 ± 0.18 mm/s) and maximum oxidative flux (0.41 ± 0.14 mm/s versus 0.54 ± 0.16 mm/s) were found between the non-localized and DRESS-localized data, respectively. Splitting of the inorganic phosphate (Pi) signal was observed in several non-localized datasets, but in none of the DRESS-localized datasets. Our results suggest that the application of the DRESS localization scheme yielded good spatial selection, and provided muscle-specific insight into oxidative metabolism, even at a relatively low exercise load. In addition, the non-echo-based FID acquisition allowed for reliable detection of ATP resonances, and therefore calculation of the specific maximum oxidative flux, in the gastrocnemius medialis using standard assumptions about resting ATP concentration in skeletal muscle., (Copyright © 2014 John Wiley & Sons, Ltd.)

Phosphorus magnetic resonance spectroscopy ((31)P-MRS) enables the non-invasive evaluation of muscle metabolism. Resting Pi-to-ATP flux can be assessed through magnetization transfer (MT) techniques, and maximal oxidative flux (Q(max)) can be calculated by monitoring of phosphocreatine (PCr) recovery after exercise. In this study, the muscle metabolism parameters of 13 overweight-to-obese sedentary individuals were measured with both MT and dynamic PCr recovery measurements, and the interrelation between these measurements was investigated. In the dynamic experiments, knee extensions were performed at a workload of 30% of maximal voluntary capacity, and the consecutive PCr recovery was measured in a quadriceps muscle with a time resolution of 2 s with non-localized (31)P-MRS at 3 T. Resting skeletal muscle metabolism was assessed through MT measurements of the same muscle group at 7 T. Significant linear correlations between the Q(max) and the MT parameters k(ATP) (r = 0.77, P = 0.002) and F(ATP) (r = 0.62, P = 0.023) were found in the study population. This would imply that the MT technique can possibly be used as an alternative method to assess muscle metabolism when necessary (e.g. in individuals after stroke or in uncooperative patients)., (Copyright © 2013 John Wiley & Sons, Ltd.)