Task failure from inspiratory resistive loaded breathing: a role for inspiratory muscle fatigue?

The use of non-invasive resistive breathing to task failure to assess inspiratory muscle performance remains a matter of debate. CO2 retention rather than diaphragmatic fatigue was suggested to limit endurance during inspiratory resistive breathing. Cervical magnetic stimulation (CMS) allows discrimination between diaphragmatic and rib cage muscle fatigue. We tested a new protocol with respect to the extent and the partitioning of inspiratory muscle fatigue at task failure. Nine healthy subjects performed two runs of inspiratory resistive breathing at 67 (12)% of their maximal inspiratory mouth pressure, respiratory rate ( f R), paced at 18min-1, with a 15-min pause between runs. Diaphragm and rib cage muscle contractility were assessed from CMS-induced esophageal (P es,tw), gastric (P ga,tw), and transdiaphragmatic (P di,tw) twitch pressures. Average endurance times of the first and second runs were similar [9.1 (6.7)and 8.4 (3.5)min]. P di,tw significantly decreased from 33.1 to 25.9cmH2O in the first run, partially recovered (27.6cmH2O), and decreased further in the second run (23.4cmH2O). P es,tw also decreased significantly (-5.1 and -2.4cmH2O), while P ga,tw did not change significantly (-2.0 and -1.9cmH2O), indicating more pronounced rib cage rather than diaphragmatic fatigue. End-tidal partial pressure of CO2 (P ETCO2) rose from 37.2 to 44.0 and 45.3mmHg, and arterial oxygen saturation (S aO2) decreased in both runs from 98% to 94%. Thus, task failure in mouth-pressure-targeted, inspiratory resistive breathing is associated with both diaphragmatic and rib cage muscle fatigue. Similar endurance times despite different degrees of muscle fatigue at the start of the runs indicate that other factors, e.g. increases in P ETCO2, and/or decreases in S aO2, probably contributed to task-failur

Locomotor and diaphragm muscle fatigue in endurance athletes performing time-trials of different durations

Purpose: Fatigue in leg muscles might differ between running and cycling due to inherent differences in muscle activation patterns. Moreover, postural demand placed upon the diaphragm during running could augment the development of diaphragm fatigue. Methods: We investigated quadriceps and diaphragm fatigue in 11 runners and 11 cyclists (age: 29±5years; $$\dot{V}$$ V ˙ O2,peak: 66.9±5.5mlmin−1kg−1) by assessing quadriceps twitch force (Q tw) and transdiaphragmatic twitch pressure (P di,tw) before and after 15- and 30-min time-trials (15TT, 30TT). Inspiratory muscle fatigue was also obtained after volitional normocapnic hyperpnoea (NH) where postural demand is negligible. We hypothesized that running and cycling would induce different patterns of fatigue and that runners would develop less respiratory muscle fatigue when performing NH. Results: The reduction in Q tw was greater in cyclists (32±6%) compared to runners (13±8%, p0.05). Conclusion: Different levels of leg muscle fatigue in runners and cyclists could in part be related to the specific muscle activation patterns including concentric contractions in both modalities but eccentric contractions in runners only. Diaphragm fatigue likely resulted from the large ventilatory load which is characteristic for both exercise modalities and which was higher in 15TTs than in 30TTs (+27%, p<0.01) while postural demand appears to be of less importance

Effects of Dance Interventions on Aspects of the Participants' Self: A Systematic Review

Background: Theoretical and empirical studies indicate that dance can strengthen the participants' self. The aim of the systematic review is to give an overview of studies investigating the effects of dance interventions on aspects of the self (e.g., self-concept/-esteem). Research questions are: (a) What is the evidence of the reported effects on different aspects of the self in children/adolescents and in adults? (b) Which study approaches and designs are used and what characterizes the interventions? (c) What are the qualitative facets of the implemented studies and what are issues for future research?Methods: We searched online databases for English and German journal articles with the following main inclusion criteria: (i) Intervention study (qualitative and quantitative approaches) (ii) Investigation of aspects of the self (iii) Dance as intervention content. Two reviewers independently screened studies for eligibility using the PRISMA guidelines and assessed the methodological quality of the included studies.Results: Out of 24 included studies, 11 investigate a sample of children/adolescents and 13 an adult sample. The review showed that dance interventions can have positive effects on aspects of the participants' self. The review of studies with qualitative methodologies suggests: children/adolescents benefit in body-related perceptions, self-trust, self-esteem, self-expression and perception of dance-abilities; adults benefit in self-expression, self-efficacy, self-/body-awareness, self-development and self-confidence. Studies with quantitative methodologies report improvement especially for body-related perceptions in both populations. Contradictory results exist concerning self-esteem/-efficacy. The evaluated studies show a heterogeneous nature of populations, intervention contents, timeframes, outcomes, research methods and study quality. Evidence for each of the aspects is still poor due to the small number of studies on each construct, inconsistent findings or methodological shortcomings.Conclusions: This review indicates that dance may be a valuable approach to strengthen aspects of the self. However, as evidence for the different aspects of the self is still poor, further studies with high quality are required (e.g., large samples, active control group). Research considering the complexity and specificity of dance interventions in the design and reporting (e.g., choice of outcomes, presentation of intervention details) seem to be particularly suitable to capture the effects of dance considering its holistic nature

Altered skeletal muscle (mitochondrial) properties in patients with mitochondrial DNA single deletion myopathy

BACKGROUND: Mitochondrial myopathy severely affects skeletal muscle structure and function resulting in defective oxidative phosphorylation. However, the major pathomechanisms and therewith effective treatment approaches remain elusive. Therefore, the aim of the present study was to investigate disease-related impairments in skeletal muscle properties in patients with mitochondrial myopathy. Accordingly, skeletal muscle biopsies were obtained from six patients with moleculargenetically diagnosed mitochondrial myopathy (one male and five females, 53 ± 9 years) and eight age- and gender-matched healthy controls (two males and six females, 58 ± 14 years) to determine mitochondrial respiratory capacity of complex I-V, mitochondrial volume density and fiber type distribution. RESULTS: Mitochondrial volume density (4.0 ± 0.5 vs. 5.1 ± 0.8 %) as well as respiratory capacity of complex I-V were lower (P < 0.05) in mitochondrial myopathy and associated with a higher (P < 0.001) proportion of type II fibers (65.2 ± 3.6 vs. 44.3 ± 5.9 %). Additionally, mitochondrial volume density and maximal oxidative phosphorylation capacity correlated positively (P < 0.05) to peak oxygen uptake. CONCLUSION: Mitochondrial myopathy leads to impaired mitochondrial quantity and quality and a shift towards a more glycolytic skeletal muscle phenotype

Changes of hemodynamic and cerebral oxygenation after exercise in normobaric and hypobaric hypoxia: associations with acute mountain sickness

Objective: Normobaric (NH) and hypobaric hypoxia (HH) are associated with acute mountain sickness (AMS) and cognitive dysfunction. Only few variables, like heart-rate-variability, are correlated with AMS. However, prediction of AMS remains difficult. We therefore designed an expedition-study with healthy volunteers in NH/HH to investigate additional non-invasive hemodynamic variables associated with AMS.Methods: Eleven healthy subjects were examined in NH (FiO(2) 13.1%;equivalent of 3.883m a.s.l;duration 4h) and HH (3.883ma.s.l.;duration 24h) before and after an exercise of 120min. Changes in parameters of electrical cardiometry (cardiac index (CI), left-ventricular ejection time (LVET), stroke volume (SV), index of contractility (ICON)), near-infrared spectroscopy (cerebral oxygenation, rScO(2)), Lake-Louise-Score (LLS) and cognitive function tests were assessed. One-Way-ANOVA, Wilcoxon matched-pairs test, Spearman's-correlation-analysis and Student's t-test were performed.Results: HH increased heart rate (HR), mean arterial pressure (MAP) and CI and decreased LVET, SV and ICON, whereas NH increased HR and decreased LVET. In both NH and HH cerebral oxygenation decreased and LLS increased significantly. After 24h in HH, 6 of 11 subjects (54.6%) developed AMS. LLS remained increased until 24h in HH, whereas cognitive function remained unaltered. In HH, HR and LLS were inversely correlated (r=-0.692;p<0.05). More importantly, the rScO2-decrease after exercise in NH significantly correlated with LLS after 24h in HH (r=-0.971;p<0.01) and rScO2 correlated significantly with HR (r=0.802;p<0.01), CI (r=0.682;p<0.05) and SV (r=0.709;p<0.05) after exercise in HH.Conclusion: sBoth acute NH and HH altered hemodynamic and cerebral oxygenation and induced AMS. Subjects, who adapted their CI had higher rScO2 and lower LLS. Furthermore, rScO2 after exercise under normobaric conditions was associated with AMS at high altitudes

Estimation of Energy Expenditure in Wheelchair-Bound Spinal Cord Injured Individuals Using Inertial Measurement Units

A healthy lifestyle reduces the risk of cardio-vascular disease. As wheelchair-bound individuals with spinal cord injury (SCI) are challenged in their activities, promoting and coaching an active lifestyle is especially relevant. Although there are many commercial activity trackers available for the able-bodied population, including those providing feedback about energy expenditure (EE), activity trackers for the SCI population are largely lacking, or are limited to a small set of activities performed in controlled settings. The aims of the present study were to develop and validate an algorithm based on inertial measurement unit (IMU) data to continuously monitor EE in wheelchair-bound individuals with a SCI, and to establish reference activity values for a healthy lifestyle in this population. For this purpose, EE was measured in 30 subjects each wearing four IMUs during 12 different physical activities, randomly selected from a list of 24 activities of daily living. The proposed algorithm consists of three parts: resting EE estimation based on multi-linear regression, an activity classification using a k-nearest-neighbors algorithm, and EE estimation based on artificial neural networks (ANNs). The mean absolute estimation error for the ANN-based algorithm was 14.4% compared to indirect calorimeter measurements. Based on reference values from the literature and the data collected within this study, we recommend wheeling 3 km per day for a healthy lifestyle in wheelchair-bound SCI individuals. Combining the proposed algorithm with a recommendation for physical activity provides a powerful tool for the promotion of an active lifestyle in the SCI population, thereby reducing the risk for secondary diseases

Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response

MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

Pre-exercise hyperpnea attenuates exercise-induced bronchoconstriction without affecting performance

Whole-body warm-up exercises were shown to attenuate exercise-induced bronchoconstriction (EIB). Whether intense pre-exercise hyperpnea offers similar protection and whether this might negatively affect exercise performance is unknown. Nine subjects with EIB (25±5 yrs; forced expiratory volume in 1s [FEV1], 104±15% predicted) performed an exercise challenge (ECh) followed-after 30min-by a constant-load cycling test to exhaustion. The ECh was preceded by one of four conditions: by i) control warm-up (CON) or by 10min of normocapnic hyperpnea with partial rebreathing at either ii) 50% (WU50) or iii) variable intensity (8x 30s-80%/45s-30%; WU80/30), or at iv) 70% (WU70) of maximal voluntary ventilation. FEV1 was measured at baseline and in 5-min intervals until 15min after CON/warm-up and 30min after ECh. None of the warm-up conditions induced EIB. The maximal post-ECh decrease in FEV1 was -13.8±3.1% after CON, -9.3±5.0% after WU50 (p = 0.081 vs. CON), -8.6±7.5% after WU80/30 (p = 0.081 vs. CON) and -7.2±5.0% after WU70 (p = 0.006 vs. CON), and perception of respiratory exertion was significantly attenuated (all p≤0.048), with no difference between warm-up conditions. Only after CON, FEV1 remained significantly reduced up to the start of the cycling endurance test (-8.0±4.3%, p = 0.004). Cycling performance did not differ significantly between test days (CON: 13±7min; WU50: 14±9min; WU80/30: 13±9min; WU70: 14±7min; p = 0.582). These data indicate that intense hyperpnea warm-up is effective in attenuating EIB severity and accelerating lung function recovery while none of the warm-up condition do compromise cycling performance