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Insulin deficiency in type 1 diabetes (T1D) leads to an impairment of glucose metabolism and mitochondrial function. Actovegin is a hemodialysate of calf blood, which has been shown to enhance glucose uptake and cell metabolism in healthy human skeletal muscle. The objectives of this study were to determine the effects of Actovegin on skeletal muscle mitochondrial respiration and functional aerobic capacity in a T1D mouse model. Effects on the expression of mitochondrial proteins, body mass, and food and water consumption were also investigated. Streptozotocin-induced T1D male C57B1/6 mice (aged 3–4 months) were randomized to an Actovegin group and a control group. Every third day, the Actovegin and control groups were injected intraperitoneally with (0.1 mL) Actovegin and (0.1 mL) physiological salt solution, respectively. Oxidative phosphorylation (OXPHOS) capacity of the vastus lateralis muscle was measured by high resolution respirometry in addition to the expression levels of the mitochondrial complexes as well as voltage-dependent anion channel. Functional aerobic capacity was measured using a rodent treadmill protocol. Body mass and food and water consumption were also measured. After 13 days, in comparison to the control group, the Actovegin group demonstrated a significantly higher skeletal muscle mitochondrial respiratory capacity in an ADP-restricted and ADP-stimulated environment. The Actovegin group displayed a significantly lesser decline in functional aerobic capacity and baseline body mass after 13 days. There were no significant differences in food or water consumption between groups. Actovegin could act as an effective agent for facilitating glucose metabolism and improving OXPHOS capacity and functional aerobic capacity in T1D. Further investigation is warranted to establish Actovegin's potential as an alternative therapeutic drug for T1D. [ABSTRACT FROM AUTHOR]

We assessed differences in mitochondrial function in gluteal (gSAT) and abdominal subcutaneous adipose tissue (aSAT) at baseline and in response to 12-weeks of exercise training; and examined depot-specific associations with body fat distribution and insulin sensitivity (SI). Obese, black South African women (n = 45) were randomized into exercise (n = 23) or control (n = 22) groups. Exercise group completed 12-weeks of aerobic and resistance training (n = 20), while the control group (n = 15) continued usual behaviours. Mitochondrial function (high-resolution respirometry and fluorometry) in gSAT and aSAT, SI (frequently sampled intravenous glucose tolerance test), body composition (dual-energy X-ray absorptiometry), and ectopic fat (MRI) were assessed pre- and post-intervention. At baseline, gSAT had higher mitochondrial respiratory capacity and hydrogen peroxide (H2O2) production than aSAT (p < 0.05). Higher gSAT respiration was associated with higher gynoid fat (p < 0.05). Higher gSAT H2O2 production and lower aSAT mitochondrial respiration were independently associated with lower SI (p < 0.05). In response to training, SI improved and gynoid fat decreased (p < 0.05), while H2O2 production reduced in both depots, and mtDNA decreased in gSAT (p < 0.05). Mitochondrial respiration increased in aSAT and correlated with a decrease in body fat and an increase in soleus and hepatic fat content (p < 0.05). This study highlights the importance of understanding the differences in mitochondrial function in multiple SAT depots when investigating the pathophysiology of insulin resistance and associated risk factors such as body fat distribution and ectopic lipid deposition. Furthermore, we highlight the benefits of exercise training in stimulating positive adaptations in mitochondrial function in gluteal and abdominal SAT depots. [ABSTRACT FROM AUTHOR]

Acetaminophen (APAP) is used worldwide and is regarded as safe in therapeutic concentrations but can cause acute liver failure in higher doses. High doses of APAP have been shown to inhibit complex I and II mitochondrial respiratory capacity in mouse hepatocytes, but human studies are lacking. Here, we studied mitochondrial respiratory capacity in human hepatic tissue ex vivo with increasing doses of APAP. Hepatic biopsies were obtained from 12 obese patients who underwent a Roux‐en‐Y gastric bypass (RYGB) or a sleeve gastrectomy surgery. Mitochondrial respiration was measured by high‐resolution respirometry. Therapeutic concentrations (≤0.13 mmol/L) of APAP did not inhibit state 3 complex I‐linked respiration. APAP concentrations of ≥2.0 mmol/L in the medium significantly reduced hepatic mitochondrial respiration in a dose‐dependent manner. Complex II‐linked mitochondrial respiration was not inhibited by APAP. We conclude that the mitochondrial respiratory capacity is affected by a hepato‐toxic effect of APAP, which involved complex I, but not complex II. [ABSTRACT FROM AUTHOR]

Sustaining a weight loss after a lifestyle intervention is challenging. The objective of the present study was to investigate if mitochondrial function is associated with the ability to maintain a weight loss. Sixty-eight former participants in an 11–12-week lifestyle intervention were recruited into 2 groups; weight loss maintenance (WLM; body mass index (BMI): 32 ± 1 kg/m2) and weight regain (WR; BMI: 43 ± 2 kg/m2) based on weight loss measured at a follow-up visit (WLM: 4.8 ± 0.4; WR: 7.6 ± 0.8 years after lifestyle intervention). Maximal oxygen consumption rate, physical activity level, and blood and muscle samples were obtained at the follow-up experiment. Mitochondrial respiratory capacity and reactive oxygen species (ROS) production were measured. Fasting blood samples were used to calculate glucose homeostasis index. WR had impaired glucose homeostasis and decreased maximal oxygen uptake and physical activity level compared with WLM. The decreased physical activity in WR was due to a lower activity level at vigorous and moderate intensities. Mitochondrial respiratory capacity and citrate synthase (CS) activity was higher in WLM, but intrinsic mitochondrial respiratory capacity (mitochondrial respiratory capacity corrected for mitochondrial content (CS activity)) was similar. ROS production was higher in WR compared with WLM, which was accompanied by a decreased content of antioxidant proteins in WR. Intrinsic mitochondrial respiratory capacity in skeletal muscle is not associated with the ability to maintain a long-term weight loss. WLM had a higher maximal oxygen uptake, physical activity level, mitochondrial respiratory capacity and CS activity compared with WR. The reduced glucose tolerance was concurrent with increased ROS production per mitochondria in WR, and could also be associated with the lower physical activity level in this group. [ABSTRACT FROM AUTHOR]

Abstract: Bed rest leads to impaired glucose tolerance. Whether this is linked to maladaptation's in skeletal muscle mitochondrial function and in particular to the level of reactive oxygen species (ROS) is at present unknown. The aim of this longitudinal study was to quantify skeletal muscle mitochondrial function (respiratory capacity and ROS production) together with glucose tolerance after 4 days of strict bed rest in healthy young male subjects (n = 14). Mitochondrial function was determined in permeabilized muscle fibers using high‐resolution respirometry and fluorometry, mitochondrial content (citrate synthase [CS] activity) and antioxidant protein expression levels were assessed in parallel to this. Glucose tolerance was determined by means of oral glucose tolerance tests. Intrinsic mitochondrial respiratory capacity was augmented after the bed rest period (CI + IIP: 0.43 ± 0.12 vs. 0.55 ± 0.14 [pmol/sec/mg]/CS activity), due to a decreased CS activity (158 ± 39 vs. 129 ± 25 mU/mg dw.). No differences were observed in ROS production (per mg of tissue or when normalized to CS activity). Furthermore, the protein content for catalase was increased while superoxide dismutase and glutathione peroxidase remained unaffected. These findings were accompanied by an impaired glucose tolerance after the bed rest period (Matsuda index: 12 ± 6 vs. 9 ± 5). The change in intrinsic mitochondrial respiratory capacity could be an early indication in the development of impaired glucose tolerance. The increased catalase protein content might explain that no change was seen in ROS production after 4 days of bed rest. Whether these findings can be extrapolated to lifestyle‐dependent decrements in physical activity and the development of type‐2‐diabetes remains unknown. [ABSTRACT FROM AUTHOR]

Background. A prevalent side-effect of simvastatin is attenuated glucose homeostasis. The underlying mechanism is unknown, but impaired lipid metabolism may provide the link. The aim of this study was to investigate whether simvastatin-treated patients had a lower capacity to oxidize lipids and reduced expression of the major proteins regulating lipid uptake, synthesis, lipolysis, and storage in skeletal muscle than matched controls. Materials and Methods. Ten men were treated with simvastatin (HbA1c: 5.7 ± 0.1%), and 10 healthy men (HbA1c: 5.2 ± 0.1%) underwent an oral glucose tolerance test and a muscle biopsy was obtained. Fat oxidation rates were measured at rest and during exercise. Western blotting was used to assess protein content. Results. Patients treated with simvastatin had impaired glucose tolerance compared with control subjects, but fat oxidation at rest and during exercise was compatible. Skeletal muscle protein content of CD36, lipoprotein lipase (LPL), and diacylglycerol acyltransferase (DGAT) 1 were lower, and DGAT 2 tended to be lower in patients treated with simvastatin. Conclusions. Patients treated with simvastatin had a reduced capacity to synthesize FA and diacylglycerol (DAG) into triacylglycerol in skeletal muscle compared to matched controls. Decreased lipid synthesis capacity may lead to accumulation of lipotoxic intermediates (FA and DAG) and hence impair glucose tolerance. [ABSTRACT FROM AUTHOR]

This review provides an overview of the evidence regarding mtDNA and valid biomarkers for assessing mitochondrial adaptions. Mitochondria are small organelles that exist in almost all cells throughout the human body. As the only organelle, mitochondria contain their own DNA, mitochondrial DNA (mtDNA). mtDNA-encoded polypeptides are subunits of the enzyme complexes in the electron transport chain (ETC) that are responsible for production of ATP to the cells. mtDNA is frequently used as a biomarker for mitochondrial content, since changes in mitochondrial volume are thought to induce similar changes in mtDNA. However, some exercise studies have challenged this "gene-dosage theory", and have indicated that changes in mitochondrial content can adapt without changes in mtDNA. Thus, the aim of this scoping review was to summarize the studies that used mtDNA as a biomarker for mitochondrial adaptions and address the question as to whether changes in mitochondrial content, induce changes in mtDNA in response to aerobic exercise in the healthy skeletal muscle. The literature was searched in PubMed and Embase. Eligibility criteria included: interventional study design, aerobic exercise, mtDNA measurements reported pre- and postintervention for the healthy skeletal muscle and English language. Overall, 1585 studies were identified. Nine studies were included for analysis. Eight out of the nine studies showed proof of increased oxidative capacity, six found improvements in mitochondrial volume, content and/or improved mitochondrial enzyme activity and seven studies did not find evidence of change in mtDNA copy number. In conclusion, the findings imply that mitochondrial adaptions, as a response to aerobic exercise, can occur without a change in mtDNA copy number. [ABSTRACT FROM AUTHOR]

Abstract: It has been suggested that human mitochondrial variants influence maximal oxygen uptake (VO2max). Whether mitochondrial respiratory capacity per mitochondrion (intrinsic activity) in human skeletal muscle is affected by differences in mitochondrial variants is not known. We recruited 54 males and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present. [Copyright &y& Elsevier]

Abstract: The number of studies on mitochondrial function is growing as a result of the recognition of the pivotal role of an intact mitochondrial function in numerous diseases. Measurements of oxygen consumption by the mitochondria in human skeletal muscle are used in many studies. There are several advantages of studying mitochondrial respiration in permeabilized fibers (Pfi), but the method requires a manual procedure of mechanical separation of the fiber bundles in the biopsy and chemical permeabilization of the cell membrane. This is time-consuming and subject to interpersonal variability. An alternative is to use a semiautomatic tool for preparation of a homogenate of the muscle biopsy. We investigated whether the PBI shredder is useful in preparing a muscle homogenate for measurements of mitochondrial respiratory capacity. The homogenate is compared with the Pfi preparation. Maximal respiratory capacity was significantly reduced in the homogenate compared with the Pfi from human skeletal muscle. A marked cytochrome c response was observed in the homogenate, which was not the case with the Pfi, indicating that the outer mitochondrial membrane was not intact. The mitochondria in the homogenate were more uncoupled compared with the Pfi. Manual permeabilization is an advantageous technique for preparing human skeletal muscle biopsies for respirometry. [Copyright &y& Elsevier]

Chronic ischemic heart disease is associated with myocardial hypoperfusion. The resulting hypoxia potentially inflicts damage upon the mitochondria, leading to a compromised energetic state. Furthermore, ischemic damage may cause excessive production of reactive oxygen species (ROS), producing mitochondrial damage, hereby reinforcing a vicious circle. Ischemic preconditioning has been proven protective in acute ischemia, but the subject of chronic ischemic preconditioning has not been explored in humans. We hypothesized that mitochondrial respiratory capacity would be diminished in chronic ischemic regions of human myocardium but that these mitochondria would be more resistant to ex vivo ischemia and, second, that ROS generation would be higher in ischemic myocardium. The aim of this study was to test mitochondrial respiratory capacity during hyperoxia and hypoxia, to investigate ROS production, and finally to assess myocardial antioxidant levels. Mitochondrial respiration in biopsies from ischemic and nonischemic regions from the left ventricle of the same heart was compared in nine human subjects. Maximal oxidative phosphorylation capacity in fresh muscle fibers was lower in ischemic compared with nonischemic myocardium (P < 0.05), but the degree of coupling (respiratory control ratio) did not differ (P > 0.05). The presence of ex vivo hypoxia did not reveal any chronic ischemic preconditioning of the ischemic myocardial regions (P > 0.05). ROS production was higher in ischemic myocardium (P < 0.05), and the levels of antioxidant protein expression was lower. Diminished mitochondrial respiration capacity and excessive ROS production demonstrate an impaired mitochondrial function in ischemic human heart muscle. No chronic ischemic preconditioning effect was found. [ABSTRACT FROM AUTHOR]

Aims Heart failure (HF) with left ventricular systolic dysfunction (LVSD) is associated with a shift in substrate utilization and a compromised energetic state. Whether these changes are connected with mitochondrial dysfunction is not known. We hypothesized that the cardiac phenotype in LVSD could be caused by reduced mitochondrial oxidative phosphorylation (OXPHOS) capacity and reduced mitochondrial creatine kinase (miCK) capacity. The study aim was to test mitochondrial OXPHOS capacity in LVSD myocardium compared with OXPHOS capacity in a comparable patient group without LVSD. Methods and results Myocardial biopsies were obtained from the left ventricle during cardiac valve or left ventricular assist device (LVAD) surgery. Patients were stratified according to left ventricular ejection fraction (LVEF) into LVSD (LVEF <45%, n = 14) or CONTROL (LVEF >45%, n = 15). Mitochondrial respiration was measured in muscle fibres with addition of non-fatty acid substrates or octanoyl-l-carnitine, a medium chain fatty acid (MCFA). The in situ enzyme capacity of miCK was determined from APD titrations in the presence or absence of creatine. Maximal OXPHOS capacity with non-fatty acid substrates was lower in the LVSD group compared with the CONTROL group (P ≤ 0.05). ADP sensitivity always increased significantly (P ≤ 0.05) with the addition of creatine, after which the sensitivity was highest (P ≤ 0.05) in LVSD compared with CONTROL. The stimulation of OXPHOS from octanoyl-l-carnitine titrations elicited ∼40% lower respiration in LVSD compared with CONTROL (P ≤ 0.05). Conclusion Human LVSD is associated with markedly diminished OXPHOS capacity, particularly in MCFA oxidation. This offers a candidate mechanism for a compromised energetic state and decreased reliance on fatty acid utilization in HF. [ABSTRACT FROM PUBLISHER]

Objectives: Glucose tolerance and skeletal muscle coenzyme Q10 (Q10) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9). Background: A prevalent side effect of statin therapy is muscle pain, and yet the basic mechanism behind it remains unknown. We hypothesize that a statin-induced reduction in muscle Q10 may attenuate mitochondrial OXPHOS capacity, which may be an underlying mechanism. Methods: Plasma glucose and insulin concentrations were measured during an oral glucose tolerance test. Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers by high-resolution respirometry in a cross-sectional design. Mitochondrial content (estimated by citrate synthase [CS] activity, cardiolipin content, and voltage-dependent anion channel [VDAC] content) as well as Q10 content was determined. Results: Simvastatin-treated patients had an impaired glucose tolerance and displayed a decreased insulin sensitivity index. Regarding mitochondrial studies, Q10 content was reduced (p = 0.05), whereas mitochondrial content was similar between the groups. OXPHOS capacity was comparable between groups when complex I– and complex II–linked substrates were used alone, but when complex I + II–linked substrates were used (eliciting convergent electron input into the Q intersection [maximal ex vivo OXPHOS capacity]), a decreased (p < 0.01) capacity was observed in the patients compared with the control subjects. Conclusions: These simvastatin-treated patients were glucose intolerant. A decreased Q10 content was accompanied by a decreased maximal OXPHOS capacity in the simvastatin-treated patients. It is plausible that this finding partly explains the muscle pain and exercise intolerance that many patients experience with their statin treatment. [Copyright &y& Elsevier]

Metformin is used as an anti-diabetic drug. Metformin ameliorates insulin resistance by improving insulin sensitivity in liver and skeletal muscle. Reduced mitochondrial content has been reported in type 2 diabetic muscles and it may contribute to decreased insulin sensitivity characteristic for diabetic muscles. The molecular mechanism behind the effect of metformin is not fully clarified but inhibition of complex I in the mitochondria and also activation of the 5'AMP activated protein kinase (AMPK) has been reported in muscle. Furthermore, both AMPK activation and metformin treatment have been associated with stimulation of mitochondrial function and biogenesis. However, a causal relationship in skeletal muscle has not been investigated. We hypothesized that potential effects of in vivo metformin treatment on mitochondrial function and protein expressions in skeletal muscle are dependent upon AMPK signaling. We investigated this by two weeks of oral metformin treatment of muscle specific kinase dead α2 (KD) AMPK mice and wild type (WT) littermates. We measured mitochondrial respiration and protein activity and expressions of key enzymes involved in mitochondrial carbohydrate and fat metabolism and oxidative phosphorylation. Mitochondrial respiration, HAD and CS activity, PDH and complex I-V and cytochrome c protein expression were all reduced in AMPK KD compared to WT tibialis anterior muscles. Surprisingly, metformin treatment only enhanced respiration in AMPK KD mice and thereby rescued the respiration defect compared to the WT mice. Metformin did not influence protein activities or expressions in either WT or AMPK KD mice. We conclude that two weeks of in vivo metformin treatment enhances mitochondrial respiration in the mitochondrial deficient AMPK KD but not WT mice. The improvement seems to be unrelated to AMPK, and does not involve changes in key mitochondrial proteins. [ABSTRACT FROM AUTHOR]

Key points Several biochemical measures of mitochondrial components are used as biomarkers of mitochondrial content and muscle oxidative capacity. However, no studies have validated these surrogates against a morphological measure of mitochondrial content in human subjects., The most commonly used markers (citrate synthase activity, cardiolipin content, mitochondrial DNA content (mtDNA), complex I-V protein, and complex I-IV activity) were correlated with a measure of mitochondrial content (transmission electron microscopy) and muscle oxidative capacity (respiration in permeabilized fibres)., Cardiolipin content followed by citrate synthase activity and complex I activity were the biomarkers showing the strongest association with mitochondrial content., mtDNA was found to be a poor biomarker of mitochondrial content., Complex IV activity was closely associated with mitochondrial oxidative phosphorylation capacity., Abstract Skeletal muscle mitochondrial content varies extensively between human subjects. Biochemical measures of mitochondrial proteins, enzyme activities and lipids are often used as markers of mitochondrial content and muscle oxidative capacity (OXPHOS). The purpose of this study was to determine how closely associated these commonly used biochemical measures are to muscle mitochondrial content and OXPHOS. Sixteen young healthy male subjects were recruited for this study. Subjects completed a graded exercise test to determine maximal oxygen uptake () and muscle biopsies were obtained from the vastus lateralis. Mitochondrial content was determined using transmission electron microscopy imaging and OXPHOS was determined as the maximal coupled respiration in permeabilized fibres. Biomarkers of interest were citrate synthase (CS) activity, cardiolipin content, mitochondrial DNA content (mtDNA), complex I-V protein content, and complex I-IV activity. Spearman correlation coefficient tests and Lin's concordance tests were applied to assess the absolute and relative association between the markers and mitochondrial content or OXPHOS. Subjects had a large range of (range 29.9-71.6 ml min−1 kg−1) and mitochondrial content (4-15% of cell volume). Cardiolipin content showed the strongest association with mitochondrial content followed by CS and complex I activities. mtDNA was not related to mitochondrial content. Complex IV activity showed the strongest association with muscle oxidative capacity followed by complex II activity. We conclude that cardiolipin content, and CS and complex I activities are the biomarkers that exhibit the strongest association with mitochondrial content, while complex IV activity is strongly associated with OXPHOS capacity in human skeletal muscle. [ABSTRACT FROM AUTHOR]

Adoption of the 10GbE Ethernet standard as a high performance interconnect has been impeded by two important performance-oriented considerations: (1) processing requirements of common protocol stacks and (2) end-to-end latency. The overheads of typical software based protocol stacks on CPU utilization and throughput have been well evaluated in several recent studies. We focus on end-to-end latency and present a detailed characterization across typical server system hardware and software stack components. We demonstrate that application level end-to-end one-way latency with a 10GbE connection can be as low as 10 μs for a single isolated request in a standard Linux network stack. The paper analyzes the components of the latency and discusses possible significant variations to the components under realistic conditions. We found that methods that optimize for throughput can significantly compromise Ethernet based latencies. Methods to pursue reducing the minimum latency and controlling the variations are presented. [ABSTRACT FROM AUTHOR]

Presents a report on the library visits in Germany conducted by the members of the Liber Architecture Group Seminars. Library visit at Universit ä tsbibliothek Leipzig; Universit ä ts-und Forschungsbibliothek Erfurt; Library visit at Deutsche B ü cherei in Leipzig.

Thirty years after fleeing from Poland to Denmark, 20 immigrants were enlisted in a study of bilingual autobiographical memory. Ten "early immigrators" averaged 24 years old at the time of immigration, and ten "late immigrators" averaged 34 years old at immigration. Although all 20 had spent 30 years in Denmark, early immigrators reported more current inner speech behaviours in Danish, whereas late immigrators showed more use of Polish. Both groups displayed proportionally more numerous autobiographical retrievals that were reported as coming to them internally in Polish (vs Danish) for the decades prior to immigration and more in Danish (vs Polish) after immigration. We propose a culture- and language-specific shaping of semantic and conceptual stores that underpins autobiographical and world knowledge. [ABSTRACT FROM AUTHOR]

Highlights the debate on the national library's main obligations. Dual strategy of preserving digital and traditional documents; Elements of the strategy for digital works and for traditional media; Ways of safeguarding the national library.

Presents an article about novel activities at the Royal Library of Copenhagen that could become a part of a modern library concept. Background on the Black Diamond building of the Royal Library; Functional parts; Concepts adopted in consideration of the region's culture.

High-resolution respirometry in human permeabilized muscle fibers is extensively used for analysis of mitochondrial adaptions to nutrition and exercise interventions, and is linked to athletic performance. However, the lack of standardization of experimental conditions limits quantitative inter- and intra-laboratory comparisons. In our study, an international team of investigators measured mitochondrial respiration of permeabilized muscle fibers obtained from three biopsies (vastus lateralis) from the same healthy volunteer to avoid inter-individual variability. High-resolution respirometry assays were performed together at the same laboratory to assess whether the heterogenity in published results are due to the effects of respiration media (MiR05 versus Z) with or without the myosin inhibitor blebbistatin at low- and high-oxygen regimes. Our findings reveal significant differences between respiration media for OXPHOS and ETcapacities supported by NADH&succinate-linked substrates at different oxygen concentrations. Respiratory capacities were approximately 1.5-fold higher in MiR05 at high-oxygen regimes compared to medium Z near air saturation. The presence or absence of blebbistatin in human permeabilized muscle fiber preparations was without effect on oxygen flux. Our study constitutes a basis to harmonize and establish optimum experimental conditions for respirometric studies of permeabilized human skeletal muscle fibers to improve reproducibility. [Display omitted] • Understanding muscle energetics' link to athletic performance is crucial. • Harmonizing mitochondrial bioenergetics protocols is critical for inter-study data analysis. • Medium composition and oxygen concentration influence muscle mitochondria respiratory capacity in permeabilized fibers. • Optimizing experimental protocols is pivotal for precise athletic performance evaluation. [ABSTRACT FROM AUTHOR]

In this study, theories of discourse processing are applied to mass communicated news reports. Subjects' free recall and prior knowledge of an ordinary 5-min. radio news bulletin was examined. The bulletin comprised four different news items and was broadcast immediately prior to the experiment. Two predictions from the text processing theory of Kintsch & Ran Dijk (1978) were confirmed. Thus, propositions selected by the buffer memory mechanism of the theory, and propositions included in the macrostructure derived according to the theory, both had increased recall probabilities. The two factors interacted, however, suggesting that the derivation of macrostructure dominated the subjects' processing strategy. Propositions denoting facts that were previously known by most subjects had increased probability of recall too. Among unfamiliar propositions, chronologically new information tended to be recalled more frequently than unfamiliar background information. The latter result suggests that subjects attempted to use the news for updating their previous knowledge, although only to a limited extent compared to the effects of text structure processing and familiarity. [ABSTRACT FROM AUTHOR]

Investigates mechanisms affecting memory for the dates of events selected and recorded by subjects in diaries. Comparison of retention time for personal and public events; Day-of-the-week (DOW) accuracy; High DOW accuracy for events with personal context; Memory reconstruction based on a reference to a temporal week schema based on personal experiences.

Freud used archaeological excavation as a metaphor for the remembering of previous experiences in therapy. This metaphor for memory has recently come under attack on the grounds that modern psychology of memory has cast doubt on whether memories preserve "historical truths." In particular, it seems that information about later events-including verbalizations and narrativizations of the original event-are integrated with and thus change the memory. This contrasts with the solid, immutable objects that are supposedly uncovered by archaeologists. However, it is now recognized that the nature of archaeological evidence does not fit this naive view. Not only do objects change over time, but the process of excavation inevitably disturbs and destroys contextual evidence decisive for interpretation. It is argued here that with this richer contemporary understanding of archaeology, Freud's metaphor of memory is still quite appropriate. Some epistemological implications are discussed as examples of interesting issues suggested by the revised archaeology metaphor. [ABSTRACT FROM AUTHOR]

Reported events are distinguished from personally experienced (autobiographical) events by being known from reports provided from some person or agency--far example, news reports. Memory for reported events has usually been ignored theoretically, or classified as 'semantic', though it is clearly concerned with specific, dated episodes. We discuss a number of differences between the information available to specify experienced and reported events, and the possible implications of such differences for remembering the events. A study of retrieval of the two types of events, prompted by cue words, showed that reported events take much longer time to retrieve but are dated as being equally old as experienced events. Effects of using emotion words as cues were similar for the two event types. These results suggest that reported events are forgotten (or become inaccessible) at the same rate as experienced events, but that memories are organized in such a way that reported events often have to be accessed indirectly through memories of associated autobiographical events. [ABSTRACT FROM AUTHOR]

Appreciation of literature (understanding beyond literal comprehension and inference) is hypothesized to depend on readers' application of knowledge derived from personal experiences, a cognitive process called personal resonance. The influence of cultural difference, in personal experience on appreciating a literary work was studied through retrospective reports about remindings that occurred while reading. A Hungarian short story in which geographical and temporal location were left open was read by Danish (culturally distant) and Hungarian (culturally proximate) subjects. Cultural proximity was found to influence considerably readers' location and overall evaluation of the story as well as the nature of remindings during the reading process. The culturally proximate Hungarian readers exhibited a higher level of personal resonance: they had more vivid remindings and were reminded of more complete events (as opposed to decontextualized event elements), particularly more personally experienced events. The personal relevance, pleasantness, and aggressiveness of the evoked memories were important determinants of readers' overall evaluation of the story, but with very different patterns in the two cultural groups. [ABSTRACT FROM AUTHOR]

The three studies described by Abul'khanova-Slavskaia are concerned with different aspects of people's organization of their activities, ranging from current tasks to life-span planning. A rich framework of concepts is outlined to capture the complexities of this vast territory, including phenomena of both objective and subjective time; cognition, values, and motives; external constraints and demands; self-generated goals and ideals; and so forth. The general approach to tying these diverse aspects together is to search for typologies that characterize the temporal organization of groups of individuals. [ABSTRACT FROM AUTHOR]

Introduction: Liver fat (LF) and visceral adipose tissue (VAT) content decreases with training, however, this has mainly been investigated in sedentary obese or healthy participants. The aim of this study was to investigate the effects of repeated prolonged exercise on LF and VAT content in well‐trained older men and to compare baseline LF and VAT content to recreationally active older men. Method: A group of five well‐trained older men were tested before and after cycling a total distance of 2558 km in 16 consecutive days. VAT content and body composition was measured using DXA before a bicycle ergometer test was performed to determine maximal fat oxidation (MFO), maximal oxygen consumption (VO2max$$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$), and the relative intensity at which MFO occurred (Fatmax). LF content was measured on a separate day using MRI. For comparison of baseline values, a control group of eight healthy age‐ and BMI‐matched recreationally active men were recruited. Results: The well‐trained older men had lower VAT (p = 0.02), and a tendency toward lower LF content (p = 0.06) compared with the control group. The intervention resulted in decreased LF content (p = 0.02), but VAT, fat mass, and lean mass remained unchanged. VO2max$$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$, MFO, and Fatmax were not affected by the intervention. Conclusion: The study found that repeated prolonged exercise reduced LF content, but VAT and VO2max$$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$ remained unchanged. Aerobic capacity was aligned with lower LF and VAT in older active men. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular senescence may be a causal factor in the development and progression of non-alcoholic steatohepatitis (NASH). The most effective currently available treatment for NASH is lifestyle intervention, including dietary modification. This study aimed to evaluate the effects of dietary intervention on hallmarks of NASH and molecular signatures of hepatocellular senescence in the Gubra-Amylin NASH (GAN) diet-induced obese (DIO) and biopsy-confirmed mouse model of NASH. Methods: GAN DIO-NASH mice with liver biopsy-confirmed NASH and fibrosis received dietary intervention by switching to chow feeding (chow reversal) for 8, 16 or 24 weeks. Untreated GAN DIO-NASH mice and chow-fed C57BL/6J mice served as controls. Pre-to-post liver biopsy histology was performed for within-subject evaluation of NAFLD Activity Score and fibrosis stage. Terminal endpoints included blood/liver biochemistry, quantitative liver histology, mitochondrial respiration and RNA sequencing. Results: Chow-reversal promoted substantial benefits on metabolic outcomes and liver histology, as demonstrated by robust weight loss, complete resolution of hepatomegaly, hypercholesterolemia, elevated transaminase levels and hepatic steatosis in addition to attenuation of inflammatory markers. Notably, all DIO-NASH mice demonstrated ≥ 2 point significant improvement in NAFLD Activity Score following dietary intervention. While not improving fibrosis stage, chow-reversal reduced quantitative fibrosis markers (PSR, collagen 1a1, α-SMA), concurrent with improved liver mitochondrial respiration, complete reversal of p21 overexpression, lowered γ-H2AX levels and widespread suppression of gene expression markers of hepatocellular senescence. Conclusions: Dietary intervention (chow reversal) substantially improves metabolic, biochemical and histological hallmarks of NASH and fibrosis in GAN DIO-NASH mice. These benefits were reflected by progressive clearance of senescent hepatocellular cells, making the model suitable for profiling potential senotherapeutics in preclinical drug discovery for NASH. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular senescence may be a causal factor in the development and progression of non-alcoholic steatohepatitis (NASH). The most effective currently available treatment for NASH is lifestyle intervention, including dietary modification. This study aimed to evaluate the effects of dietary intervention on hallmarks of NASH and molecular signatures of hepatocellular senescence in the Gubra-Amylin NASH (GAN) diet-induced obese (DIO) and biopsy-confirmed mouse model of NASH. Methods: GAN DIO-NASH mice with liver biopsy-confirmed NASH and fibrosis received dietary intervention by switching to chow feeding (chow reversal) for 8, 16 or 24 weeks. Untreated GAN DIO-NASH mice and chow-fed C57BL/6J mice served as controls. Pre-to-post liver biopsy histology was performed for within-subject evaluation of NAFLD Activity Score and fibrosis stage. Terminal endpoints included blood/liver biochemistry, quantitative liver histology, mitochondrial respiration and RNA sequencing. Results: Chow-reversal promoted substantial benefits on metabolic outcomes and liver histology, as demonstrated by robust weight loss, complete resolution of hepatomegaly, hypercholesterolemia, elevated transaminase levels and hepatic steatosis in addition to attenuation of inflammatory markers. Notably, all DIO-NASH mice demonstrated ≥ 2 point significant improvement in NAFLD Activity Score following dietary intervention. While not improving fibrosis stage, chow-reversal reduced quantitative fibrosis markers (PSR, collagen 1a1, α-SMA), concurrent with improved liver mitochondrial respiration, complete reversal of p21 overexpression, lowered γ-H2AX levels and widespread suppression of gene expression markers of hepatocellular senescence. Conclusions: Dietary intervention (chow reversal) substantially improves metabolic, biochemical and histological hallmarks of NASH and fibrosis in GAN DIO-NASH mice. These benefits were reflected by progressive clearance of senescent hepatocellular cells, making the model suitable for profiling potential senotherapeutics in preclinical drug discovery for NASH. [ABSTRACT FROM AUTHOR]

Ageing, a sedentary lifestyle, and obesity are associated with increased oxidative stress, while regular exercise is associated with an increased antioxidant capacity in trained skeletal muscles. Whether a higher aerobic fitness is associated with increased expression of antioxidant enzymes and their regulatory factors in skeletal muscle remains unknown. Although oestrogens could promote a higher antioxidant capacity in females, it remains unknown whether a sex dimorphism exists in humans regarding the antioxidant capacity of skeletal muscle. Thus, the aim was to determine the protein expression levels of the antioxidant enzymes SOD1, SOD2, catalase and glutathione reductase (GR) and their regulatory factors Nrf2 and Keap1 in 189 volunteers (120 males and 69 females) to establish whether sex differences exist and how age, VO 2 max and adiposity influence these. For this purpose, vastus lateralis muscle biopsies were obtained in all participants under resting and unstressed conditions. No significant sex differences in Nrf2, Keap1, SOD1, SOD2, catalase and GR protein expression levels were observed after accounting for VO 2 max, age and adiposity differences. Multiple regression analysis indicates that the VO 2 max in mL.kg LLM−1.min−1can be predicted from the levels of SOD2, Total Nrf2 and Keap1 (R = 0.58, P < 0.001), with SOD2 being the main predictor explaining 28 % of variance in VO 2 max, while Nrf2 and Keap1 explained each around 3 % of the variance. SOD1 protein expression increased with ageing in the whole group after accounting for differences in VO 2 max and body fat percentage. Overweight and obesity were associated with increased pSer40-Nrf2, pSer40-Nrf2/Total Nrf2 ratio and SOD1 protein expression levels after accounting for differences in age and VO 2 max. Overall, at the population level, higher aerobic fitness is associated with increased basal expression of muscle antioxidant enzymes, which may explain some of the benefits of regular exercise. [Display omitted] • It remains unknown how aerobic fitness, adiposity, age and sex may influence antioxidant enzymes in human skeletal muscle. • Here we show that SOD2 is the main antioxidant enzyme associated with VO 2 max. • In young and middle-aged humans, there is no sex-dimorphism in antioxidant enzymes expression in skeletal muscle or their regulatory factors. • SOD1 protein expression is increased with ageing after accounting for differences in VO2max and body fat percentage. • Overweight and obesity are associated with increased pSer40-Nrf2, pSer40-Nrf2/Total Nrf2 ratio and SOD1 protein expression levels. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate if peak fat oxidation rate (PFO) is related to Ironman performance in female athletes. Thirty-six female Ironman athletes (age: 34 ± 1 yrs, [21--45 yrs.] SEM [Range]) with a BMI of 22.1 ± 2.0 kg/m2 [18.8-- 28.4 kg/m2], a body fat percentage of 24.8 ± 1.0 % [9.0--37.0 %] and a VO2peak of 53.0 ± 1.3 ml/min/kg [36.5--70.5 ml/min/kg] were tested in the laboratory prior to the Ironman Copenhagen 2017. Race time ranged from 9:17:07 to 15:23:48 with mean race time being 11:57:26 h:min:s (717 min). By simple linear regression analyses we found associations between race time and P FO (r² = 0.22, p < 0.005), VO2peak (r2 = 0.65, p < 0.0001) and the relative exercise intensity eliciting PFO (Fatmax) (r² = 0.35, p = 0.0001). Furthermore, associations were found between race time and body fat percentage (r² = 0.44, p < 0.0001) and age (r² = 0.16, p < 0.05). By means of multiple regression analysis, VO2peak was the only statistically signifi- cant variable explaining 64 % of the variation in race time (adj. r² = 0.64, p < 0.005). In conclusion, these results demonstrate that PFO is not independently related to Ironman performance in a heterogeneous group of female athletes. Interestingly, VO2 peak alone was able to predict 64 % of the variation in Ironman race times. [ABSTRACT FROM AUTHOR]

Objectives: Traditional jumping–dance rituals performed by Maasai men involve prolonged physical exertion that may contribute significantly to overall physical activity level. We aimed to objectively quantify the metabolic intensity of jumping–dance activity and assess associations with habitual physical activity and cardiorespiratory fitness (CRF). Methods: Twenty Maasai men (18–37 years) from rural Tanzania volunteered to participate in the study. Habitual physical activity was monitored using combined heart rate (HR) and movement sensing over 3 days, and jumping–dance engagement was self‐reported. A 1‐h jumping–dance session resembling a traditional ritual was organized, during which participants' vertical acceleration and HR were monitored. An incremental, submaximal 8‐min step test was performed to calibrate HR to physical activity energy expenditure (PAEE) and assess CRF. Results: Mean (range) habitual PAEE was 60 (37–116) kJ day−1 kg−1, and CRF was 43 (32–54) mL O2 min−1 kg−1. The jumping–dance activity was performed at an absolute HR of 122 (83–169) beats·min−1, and PAEE of 283 (84–484) J min−1 kg−1 or 42 (18–75)% when expressed relative to CRF. The total PAEE for the session was 17 (range 5–29) kJ kg−1, ~28% of the daily total. Self‐reported engagement in habitual jumping–dance frequency was 3.8 (1–7) sessions/week, with a total duration of 2.1 (0.5–6.0) h/session. Conclusions: Intensity during traditional jumping–dance activity was moderate, but on average sevenfold higher than habitual physical activity. These rituals are common, and can make a substantial contribution to overall physical activity in Maasai men, and thus be promoted as a culture‐specific activity to increase energy expenditure and maintain good health in this population. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemo‐ and radiotherapy cause cellular damage to tumorous and healthy dividing cells. Chemotherapy has been shown to cause mitochondrial respiratory dysfunction in non‐tumorous tissues, but the effects on human peripheral blood mononuclear cells (PBMCs) remain unknown. Aim: We aimed to investigate mitochondrial respiration of PBMCs before and after adjuvant chemo‐ and radiotherapy in postmenopausal patients with early breast cancer (EBC) and relate these to metabolic parameters of the patients. Methods: Twenty‐three postmenopausal women diagnosed with EBC were examined before and shortly after chemotherapy with (n = 18) or without (n = 5) radiotherapy. Respiration (O2 flux per million PBMCs) was assessed by high‐resolution respirometry of intact and permeabilized PBMCs. Clinical metabolic characteristics and mitochondrial DNA (mtDNA) content of PBMCs (mtDN relative to nuclear DNA) were furthermore assessed. Results: Respiration of intact and permeabilized PBMCs from EBC patients significantly increased with adjuvant chemo‐ and radiotherapy (p = 6 × 10−5 and p = 1 × 10−7, respectively). The oxygen flux attributed to specific mitochondrial complexes and respiratory states increased by 17–43% compared to before therapy initiation. Similarly, PBMC mtDNA content increased by 40% (p = 0.002). Leukocytes (p = 0.0001), hemoglobin (p = 0.0003), and HDL cholesterol (p = 0.003) concentrations decreased whereas triglyceride (p = 0.01) and LDL (p = 0.02) concentrations increased after treatment suggesting a worsened metabolic state. None of the metabolic parameters or the mtDNA content of PBMCs correlated significantly with PBMC respiration. Conclusion: This study shows that mitochondrial respiration and mtDNA content in circulating PBMCs increase after adjuvant chemo‐ and radiotherapy in postmenopausal patients with EBC. Besides the increased mtDNA content, a shift in PBMC subpopulation proportions towards cells relying on oxidative phosphorylation, who may be less sensitive to chemotherapy, might influence the increased mitochondrial respiration observed iafter chemotherapy. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is a progressive neurodegenerative disorder for which there is no existing therapeutic approach to delay or stop progression. Genetic, biochemical and pre-clinical studies have provided evidence that leucine-rich-repeat-kinase-2 (LRRK2) kinase is involved in the pathogenesis of PD, and small molecule LRRK2 inhibitors represent a novel potential therapeutic approach. However, potentially adverse target-related effects have been discovered in the lung and kidneys of LRRK2 knock-out (ko) mice and rats. It is unclear if the LRRK2 ko effect in the kidneys and lung is also induced by pharmacological inhibition of the LRRK2 kinase. Here, we show that treatment with the LRRK2 inhibitor PFE-360 in rats induces a morphological kidney phenotype resembling that of the LRRK2 ko rats, whereas no effects were observed in the lung. The PFE-360 treatment induced morphological changes characterised by darkened kidneys and progressive accumulation of hyaline droplets in the renal proximal tubular epithelium. However, no histopathological evidence of renal tubular injury or changes in the blood and urine parameters that would be indicative of kidney toxicity or impaired kidney function were observed after up to 12 weeks of treatment. Morphological changes were detected in the kidney after 2 weeks of treatment and were partially reversible within a 30 day treatment-free period. Our findings suggest that pharmacological LRRK2 inhibition may not have adverse consequences for kidney function. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the relationship between maximal fat oxidation rate (MFO) measured during a progressive exercise test on a cycle ergometer and ultra-endurance performance. 61 male ironman athletes (age: 35 ± 1 yrs. [23-47 yrs.], with a BMI of 23.6 ± 0.3 kg/m² [20.0-30.1 kg/ m²], a body fat percentage of 16.7 ± 0.7 % [8.4-30.7 %] and a VO2peak of 58.7 ± 0.7 ml/min/kg [43.9-72.5 ml/m in/kg] SEM [Range]) were tested in the laboratory between 25 and 4 days prior to the ultra-endurance event, 2016 Ironman Copenhagen. Simple bivariate analyses revealed significant negative correlations between race time and MFO (r² = 0.12, p < 0.005) and VO2peak (r² = 0.45, p < 0.0001) and a positive correlation between race time and body fat percentage (r² = 0.27, p < 0.0001). MFO and VO2peak were not correlated. When the significant variables from the bivariate regression analyses were entered into the multiple regression models, VO2peak and MFO together explained 50 % of the variation observed in race time among the 61 Ironman athletes (adj R² = 0.50, p < 0.001). These results suggests that maximal fat oxidation rate exert an independent influence on ultra-endurance performance (> 9 h). Furthermore, we demonstrate that 50 % of the variation in Ironman triathlon race time can be explained by peak oxygen uptake and maximal fat oxidation. [ABSTRACT FROM AUTHOR]

Opinion. Identifies the correspondence view of memory as an essential feature of the archaeology metaphor. Discussion of memory metaphors and metatheoretical assumptions initiated by Asher Koriat and Morris Goldsmith; Major points of the archaeology metaphor; Prism of the archaeology metaphor.

It has recently been established that myosin, the molecular motor protein, is able to exist in two conformations in relaxed skeletal muscle. These conformations are known as the super-relaxed (SRX) and disordered-relaxed (DRX) states and are finely balanced to optimize ATP consumption and skeletal muscle metabolism. Indeed, SRX myosins are thought to have a 5- to 10-fold reduction in ATP turnover compared with DRX myosins. Here, we investigated whether chronic physical activity in humans would be associated with changes in the proportions of SRX and DRX skeletal myosins. For that, we isolated muscle fibers from young men of various physical activity levels (sedentary, moderately physically active, endurance-trained, and strength-trained athletes) and ran a loaded Mant-ATP chase protocol. We observed that in moderately physically active individuals, the amount of myosin molecules in the SRX state in type II muscle fibers was significantly greater than in age-matched sedentary individuals. In parallel, we did not find any difference in the proportions of SRX and DRX myosins in myofibers between highly endurance- and strength-trained athletes. We did however observe changes in their ATP turnover time. Altogether, these results indicate that physical activity level and training type can influence the resting skeletal muscle myosin dynamics. Our findings also emphasize that environmental stimuli such as exercise have the potential to rewire the molecular metabolism of human skeletal muscle through myosin. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine if the expression of the mitochondrial biogenesis-regulating proteins SIRT1, SIRT3 and PGC-1alpha in human skeletal muscle is influenced by adiposity.Method: Twenty-nine male subjects were recruited into three groups: control (n = 10), obese (n = 10) and post-obese (n = 9). Intentionally, groups were matched by age, aerobic capacity and in addition the control and post-obese groups also by BMI. Muscle biopsies were obtained from the m. deltoid and vastus lateralis. PGC-1alpha, SIRT1 and SIRT3 protein expression was analyzed by Western blot.Result: PGC-1alpha, SIRT1 and SIRT3 protein expression was similar regardless of the level of adiposity. Only a main effect of group on SIRT1 protein showed a trend toward higher expression in post-obese than control and obese (P = 0.09). Despite similar muscle fiber-type composition (previously reported), PGC-1alpha, SIRT1 and SIRT3 protein expression was higher in leg compared to arm muscle in all groups (P < 0.05).Conclusion: This study shows that PGC-1alpha, SIRT1 and SIRT3 protein expression in basal conditions was not altered in humans with different levels of adiposity but similar aerobic capacity. The expression of PGC-1alpha, SIRT1 and SIRT3 was higher in vastus lateralis than in deltoid muscle, indicating that local rather than systemic factors prevail in regulating the level of expression of these proteins. [ABSTRACT FROM AUTHOR]

Aim & Methods: Extreme endurance exercise provides a valuable research model for understanding the adaptive metabolic response of older and younger individuals to intense physical activity. Here, we compare a wide range of metabolic and physiologic parameters in two cohorts of seven trained men, age 30 ± 5 years or age 65 ± 6 years, before and after the participants travelled ≈3000 km by bicycle over 15 days. Results: Over the 15‐day exercise intervention, participants lost 2–3 kg fat mass with no significant change in body weight. V̇O2max did not change in younger cyclists, but decreased (p = 0.06) in the older cohort. The resting plasma FFA concentration decreased markedly in both groups, and plasma glucose increased in the younger group. In the older cohort, plasma LDL‐cholesterol and plasma triglyceride decreased. In skeletal muscle, fat transporters CD36 and FABPm remained unchanged. The glucose handling proteins GLUT4 and SNAP23 increased in both groups. Mitochondrial ROS production decreased in both groups, and ADP sensitivity increased in skeletal muscle in the older but not in the younger cohort. Conclusion: In summary, these data suggest that older but not younger individuals experience a negative adaptive response affecting cardiovascular function in response to extreme endurance exercise, while a positive response to the same exercise intervention is observed in peripheral tissues in younger and older men. The results also suggest that the adaptive thresholds differ in younger and old men, and this difference primarily affects central cardiovascular functions in older men after extreme endurance exercise. [ABSTRACT FROM AUTHOR]

• There is great potential for high-resolution respirometry (HRR) of blood cells, but no defined standards. • This study shows how MiR05, PBS, RPMI and Plasmax affect the count, size and HRR of intact blood cells (PBMCs). • MiR05 causes higher cell counts, smaller cell size and increased aggregation than the other media, when resuspending PBMCs. • Higher cell counts in MiR05 cause O 2 flux underestimation during HRR. • We propose use of Plasmax, PBS or RPMI for HRR of intact PBMCs and provide new oxygen solubility factors. High-resolution respirometry (HRR) can assess peripheral blood mononuclear cell (PBMC) bioenergetics, but no standardized medium for PBMC preparation and HRR analysis exist. Here, we study the effect of four different media (MiR05, PBS, RPMI, Plasmax) on the count, size, and HRR (Oxygraph-O2k) of intact PBMCs. Remarkably, the cell count was 21 % higher when PBMCs were resuspended in MiR05 than in PBS or Plasmax, causing O 2 flux underestimation during HRR due to inherent adjustments. Moreover, smaller cell size and cell aggregation was observed in MiR05. Based on our findings, we propose that Plasmax, PBS or RPMI is more suitable than MiR05 for HRR of intact PBMCs. We provide oxygen solubility factors for Plasmax and PBS and encourage further optimization of a standardized HRR protocol for intact PBMCs. [ABSTRACT FROM AUTHOR]

Objectives: The agro‐pastoralist Maasai of East Africa are highly physically active, but their aerobic fitness has so far only been estimated using heart rate (HR) response to submaximal exercise and not directly measured. Thus, we aimed to measure aerobic fitness directly using respiratory gas analysis in a group of Maasai, and habitual physical activity energy expenditure (PAEE) as explanatory variable. Methods: In total, 21 (10 rural, 11 semi‐urban) of 30 volunteering Tanzanian Maasai men were eligible to participate. Respiratory gas exchange was measured during a graded exercise test until exhaustion on a stationary bicycle to determine aerobic fitness. Maximal effort criteria were at least two of the following (1) leveling off, (2) respiratory exchange ratio (RER) >1.10, and (3) maximum HR within 10 bpm of age‐estimated maximum HR. Habitual PAEE was estimated using combined accelerometry and HR monitoring. Anthropometry, biochemistry, blood pressure, resting HR, and dietary intake information were collected for background information. Results: Mean age was 43.2 (range 26–60) years, and hemoglobin was higher in the rural versus semi‐urban Maasai (16.9 vs. 15.4 g/dl, p =.02). Mean aerobic fitness (34.4 vs. 33.3 mlO2/min/kg, p =.79), and mean PAEE (58.5 vs. 52.9 kJ/day/kg, p =.64) were similar in rural and semi‐urban Maasai, respectively. Conclusions: Aerobic fitness was low to moderate in male rural and semi‐urban Maasai. This may be explained by relatively low PAEE in comparison to previous objectively measured activity levels in Maasai, which indicates recent lifestyle changes. [ABSTRACT FROM AUTHOR]

Introduction: Decreased fasting and oral glucose-stimulated incretin hormone concentrations following moderate-intensity continuous endurance training interventions have been reported in glucose-tolerant people, however results are conflicting. The effect of more time-efficient, very low-volume, high-intensity interval training (HIT) on circulating incretin hormone levels has never been studied. Materials and methods: Ten sedentary and overweight-to-obese participants (4 women and 6 men; age 43 ± 6 years (mean ± SD); BMI 30.2 ± 3.2 kg∙m−2; HbA1c 35 ± 5.1 mmol∙mol−1 (5.3 ± 0.3%); VO2max 30 ± 5 ml∙min−1∙kg−1) from the Copenhagen cohort of the METAPREDICT trial underwent 6 weeks of supervised low-volume HIT (3 sessions per week: 7 × 1 min at ∼100% VO2max separated by 1 min of active recovery). We measured glucose, insulin, C-peptide, glucagon, GLP-1 and GIP concentrations during a frequently sampled 75 g oral glucose tolerance test as well as VO2max and body composition before and after the intervention. Results: Training compliance was 100%. Relative VO2max improved after the intervention (median 2.69 ml∙min−1∙kg−1, IQR [0.43; 3.14], p = 0.037) while there were no significant effects on body weight and composition. No significant effects on oral glucose-stimulated glucose and hormone responses or estimates of insulin sensitivity and β-cell function were observed. Conclusion: Low-volume HIT improved aerobic fitness, but neither affected glucose tolerance nor oral glucose-stimulated incretin hormone responses in sedentary and overweight-to-obese people. Highlights Ten sedentary, overweight-to-obese, glucose-tolerant participants underwent 6 weeks of supervised, very low-volume HIT. Aerobic fitness improved. Fasting and oral glucose-stimulated incretin hormone concentrations were not affected. [ABSTRACT FROM AUTHOR]

Statins are prescribed for the treatment of elevated cholesterol, but they may negatively affect metabolism, muscle performance, and the response to training. Coenzyme Q10 (CoQ10) supplementation may alleviate these effects. Combined simvastatin and CoQ10 treatment during physical training has never been tested. We studied the response to 8 weeks training (maximal oxygen uptake (V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$), fat oxidation (MFO), the workload at which MFO occurred, and muscle strength) in statin naive dyslipidaemic patients who received simvastatin (40 mg/day) with (S + Q, n = 9) or without (S + Pl, n = 10) CoQ10 supplementation (2 × 200 mg/day) or placebo (Pl + Pl, n = 7) in a randomized, double‐blind placebo‐controlled study. V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ and maximal workload increased with training (main effect of time, P < 0.05). MFO increased from 0.29 ± 0.10, 0.26 ± 0.10, and 0.38 ± 0.09 to 0.42 ± 0.09, 0.38 ± 0.10 and 0.48 ± 0.16 g/min in S + Q, S + Pl, and Pl + Pl, respectively (main effect of time, P = 0.0013). The workload at MFO increased from 75 ± 25, 56 ± 23, and 72 ± 17 to 106 ± 25, 84 ± 13 and 102 ± 31 W in S + Q, S + Pl, and Pl + Pl, respectively (main effect of time, P < 0.0001). Maximal voluntary contraction and rate of force development were unchanged. Exercise improved aerobic physical capacity and simvastatin with or without CoQ10 supplementation did not inhibit this adaptation. The similar increases in MFO and in the workload at which MFO occurred in response to training shows that the ability to adapt substrate selection and oxidation rates is preserved with simvastatin treatment, despite the potential negative impact of simvastatin at the mitochondrial level. CoQ10 supplementation does not augment this adaptation. Key points: Simvastatins are prescribed for treatment of elevated cholesterol, but they may negatively affect metabolism, muscle performance and the response to training.Coenzyme Q10 (CoQ10) supplementation may alleviate some of these effects.We found that simvastatin treatment does not negatively affect training‐induced adaptations of substrate oxidation during exercise.Likewise, maximal oxygen uptake increases with physical training also in patients in treatment with simvastatin.CoQ10 supplementation in simvastatin‐treated patients presents no advantage in the adaptations to physical trainingSimvastatin treatment decreases plasma concentrations of total CoQ10, but this can be alleviated by simultaneous supplementation with CoQ10 [ABSTRACT FROM AUTHOR]