Cortical brain activity is influenced by cadence in cyclists

The importance of the central nervous system in endurance exercise has not yet been exhaustively investigated because of difficulties in measuring cortical parameters in sport science. During exercise there are a lot of artifacts and perturbations which can affect signal quality of cortical brain activity. The technical developments of surface electroencephalography (EEG) minimize such influences during standardized test conditions on a bicycle ergometer. The aim of this study was to investigate how movement frequency affects cortical brain activity and established physiological parameters during exercise. In cycling peak performance is affected by cadence. The analysis of brain cortical activity might lead to new insights in the relation of power and cadence. In a laboratory study sixteen male, endurance-trained cyclists completed a 60 min endurance exercise on a high-performance bicycle ergometer. Cadence was changed every 10 min (90-120-60-120-60-90 rpm). EEG was used to analyze changes in cortical brain activity. Furthermore, heart rate, blood lactate and rate of perceived exertion (RPE) were measured after each cadence change. The results indicate that heart rate, blood lactate and RPE were higher at 120 rpm compared to 60 rpm. The spectral EEG power increased statistically significantly in the alpha-2 and beta-2 frequency range by changing cadence from 60 to 120 rpm. By lowering the cadence from 120 to 60 rpm the spectral power dropped statistically significantly in all analyzed EEG frequency bands. The data also showed a statistically significant decrease of spectral EEG power in all frequency ranges over time. In conclusion, the analyzed EEG data indicate that cadence should be considered as an independent exercise normative in the training process, because it directly influences metabolic, cardiac and cortical parameters

"The non-ischemic repair" as a safe alternative method for repair of anterior post-infarction VSD

Patient's myocardium with post-infarction ventricular septum defect (VSD) is characterized by severe dysfunction. The "additive ischemia" caused by the operating process of cross-clamp ischemia and reperfusion injury, has a significant aggravation to the myocardium and overall negative impact to patient's outcome. We present a useful, safe and advantageous methodology in order to abolish "the toxic phase" of ischemia-reperfusion which is adopted by most as the "classic repair method" of myocardial protection. This abolition is in our opinion, particularly beneficial in order to reverse postoperatively the Low Cardiac Output Syndrome (LOS) and achieve better short and long term results. By using this method we avoid the aortic occlusion, the use of systematic hypothermia and any cardioplegic arrest. Furthermore, the total cardio-pulmonary bypass (CPB) time is significantly reduced, tissue debridement and stitching is much easier and safer. We think the method is applicable for every anterior and apical case of post-infarction septum rupture. After application of method in 3 patients with anterior post-myocardial infarction VSD, we are convinced that the patient will have a better postoperative haemodynamic condition and therefore a better outcome

Direct and cross-scheme effects in a research and development subsidy program

This study investigates the effects of an R&D subsidy scheme on participating firms’ net R&D investment. Making use of a specific policy design in Belgium that explicitly distinguishes between research and development grants, we estimate direct and cross-scheme effects on research versus development intensities in recipients firms. We find positive direct effects from research (development) subsidies on net research (development) spending. This direct effect is larger for research grants than for development grants. We also find cross-scheme effects that may arise due to complementarity between research and development activities. Finally, we find that the magnitude of the treatment effects depends on firm size and age and that there is a minimum effective grant size, especially for research projects. The results support the view that public subsidies induce higher additional investment particularly in research where market failures are larger, even when the subsidies are targeting development

Macroeconomic impact of stranded fossil-fuel assets

Several major economies rely heavily on fossil-fuel production and exports, yet current low-carbon technology diffusion, energy efficiency and climate policy may be substantially reducing global demand for fossil fuels.1-4 This trend is inconsistent with observed investment in new fossil-fuel ventures1,2, which could become stranded as a result. Here we use an integrated global economy environment simulation model to study the macroeconomic impact of stranded fossil-fuel assets (SFFA). Our analysis suggests that part of the SFFA would occur as a result of an already ongoing technological trajectory, irrespective of whether new climate policies are adopted or not; the loss would be amplified if new climate policies to reach the 2°C target are adopted and/or if low-cost producers (some OPEC countries) maintain their level of production (‘sell-out’) despite declining demand; the magnitude of the loss from SFFA may amount to a discounted global wealth loss of $1-4tn; and there are clear distributional impacts, with winners (e.g. net importers such as China or the EU) and losers (e.g. Russia, the US or Canada, which could see their fossil-fuel industries nearly shut down), although the two effects would largely offset each other at the level of aggregate global GDP.The authors acknowledge C-EERNG and Cambridge Econometrics for support, and funding from EPSRC (JFM, fellowship no. EP/ K007254/1); the Newton Fund (JFM, PS, JV, EPSRC grant no EP/N002504/1 and ESRC grant no ES/N013174/1), NERC (NRE, PH, HP, grant no NE/P015093/1), CONICYT (PS), the Philomathia Foundation (JV), the Cambridge Humanities Research Grants Scheme (JV), and Horizon 2020 (HP, JFM; Sim4Nexus project)

The Influence of Recovery and Training Phases on Body Composition, Peripheral Vascular Function and Immune System of Professional Soccer Players

Professional soccer players have a lengthy playing season, throughout which high levels of physical stress are maintained. The following recuperation period, before starting the next pre-season training phase, is generally considered short but sufficient to allow a decrease in these stress levels and therefore a reduction in the propensity for injury or musculoskeletal tissue damage. We hypothesised that these physical extremes influence the body composition, blood flow, and endothelial/immune function, but that the recuperation may be insufficient to allow a reduction of tissue stress damage. Ten professional football players were examined at the end of the playing season, at the end of the season intermission, and after the next pre-season endurance training. Peripheral blood flow and body composition were assessed using venous occlusion plethysmography and DEXA scanning respectively. In addition, selected inflammatory and immune parameters were analysed from blood samples. Following the recuperation period a significant decrease of lean body mass from 74.4±4.2 kg to 72.2±3.9 kg was observed, but an increase of fat mass from 10.3±5.6 kg to 11.1±5.4 kg, almost completely reversed the changes seen in the pre-season training phase. Remarkably, both resting and post-ischemic blood flow (7.3±3.4 and 26.0±6.3 ml/100 ml/min) respectively, were strongly reduced during the playing and training stress phases, but both parameters increased to normal levels (9.0±2.7 and 33.9±7.6 ml/100 ml/min) during the season intermission. Recovery was also characterized by rising levels of serum creatinine, granulocytes count, total IL-8, serum nitrate, ferritin, and bilirubin. These data suggest a compensated hypo-perfusion of muscle during the playing season, followed by an intramuscular ischemia/reperfusion syndrome during the recovery phase that is associated with muscle protein turnover and inflammatory endothelial reaction, as demonstrated by iNOS and HO-1 activation, as well as IL-8 release. The data provided from this study suggest that the immune system is not able to function fully during periods of high physical stress. The implications of this study are that recuperation should be carefully monitored in athletes who undergo intensive training over extended periods, but that these parameters may also prove useful for determining an individual's risk of tissue stress and possibly their susceptibility to progressive tissue damage or injury

Multifaceted SlyD from Helicobacter pylori: implication in [NiFe] hydrogenase maturation

SlyD belongs to the FK506-binding protein (FKBP) family with both peptidylprolyl isomerase (PPIase) and chaperone activities, and is considered to be a ubiquitous cytosolic protein-folding facilitator in bacteria. It possesses a histidine- and cysteine-rich C-terminus binding to selected divalent metal ions (e.g., Ni2+, Zn2+), which is important for its involvement in the maturation processes of metalloenzymes. We have determined the solution structure of C-terminus-truncated SlyD from Helicobacter pylori (HpSlyDΔC). HpSlyDΔC folds into two well-separated, orientation-independent domains: the PPIase-active FKBP domain and the chaperone-active insert-in-flap (IF) domain. The FKBP domain consists of a four-stranded antiparallel β-sheet with an α-helix on one side, whereas the IF domain folds into a four-stranded antiparallel β-sheet accompanied by a short α-helix. Intact H. pylori SlyD binds both Ni2+ and Zn2+, with dissociation constants of 2.74 and 3.79 μM respectively. Intriguingly, binding of Ni2+ instead of Zn2+ induces protein conformational changes around the active sites of the FKBP domain, implicating a regulatory role of nickel. The twin-arginine translocation (Tat) signal peptide from the small subunit of [NiFe] hydrogenase (HydA) binds the protein at the IF domain. Nickel binding and the recognition of the Tat signal peptide by the protein suggest that SlyD participates in [NiFe] hydrogenase maturation processes

N-Octanoyl-Dopamine inhibits cytokine production in activated T-cells and diminishes MHC-class-II expression as well as adhesion molecules in IFN gamma-stimulated endothelial cells

IFN gamma enhances allograft immunogenicity and facilitates T-cell mediated rejection. This may cause interstitial fibrosis and tubular atrophy (IFTA), contributing to chronic allograft loss. We assessed if inhibition of T-cell activation by N-octanoyl dopamine (NOD) impairs adherence of activated T-cells to endothelial cells and the ability of activated T-cells to produce IFN gamma. We also assessed if NOD affects IFN gamma mediated gene expression in endothelial cells. The presence of NOD during T-cell activation significantly blunted their adhesion to unstimulated and cytokine stimulated HUVEC. Supernatants of these T-cells displayed significantly lower concentrations of TNF alpha and IFN gamma and were less capable to facilitate T-cell adhesion. In the presence of NOD VLA-4 (CD49d/CD29) and LFA-1 (CD11a/CD18) expression on T-cells was reduced. NOD treatment of IFN gamma stimulated HUVEC reduced the expression of MHC class II transactivator (CIITA), of MHC class II and its associated invariant chain CD74. Since IFTA is associated with T-cell mediated rejection and IFN gamma to a large extent regulates immunogenicity of allografts, our current data suggest a potential clinical use of NOD in the treatment of transplant recipients. Further in vivo studies are warranted to confirm these in vitro findings and to assess the benefit of NOD on IFTA in clinically relevant models

Biomarkers of Multiple Sclerosis

The search for an ideal multiple sclerosis biomarker with good diagnostic value, prognostic reference and an impact on clinical outcome has yet to be realized and is still ongoing. The aim of this review is to establish an overview of the frequent biomarkers for multiple sclerosis that exist to date. The review summarizes the results obtained from electronic databases, as well as thorough manual searches. In this review the sources and methods of biomarkers extraction are described; in addition to the description of each biomarker, determination of the prognostic, diagnostic, disease monitoring and treatment response values besides clinical impact they might possess. We divided the biomarkers into three categories according to the achievement method: laboratory markers, genetic-immunogenetic markers and imaging markers. We have found two biomarkers at the time being considered the gold standard for MS diagnostics. Unfortunately, there does not exist a single solitary marker being able to present reliable diagnostic value, prognostic value, high sensitivity and specificity as well as clinical impact. We need more studies to find the best biomarker for MS.publishersversionPeer reviewe

Commentaries on viewpoint : physiology and fast marathons

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Potential of FX06 to prevent disease progression in hospitalized non-intubated COVID-19 patients — the randomized, EU-wide, placebo-controlled, phase II study design of IXION

Background: More than 2.7 million hospitalizations of COVID-19-infected patients have occurred in Europe alone since the outbreak of the coronavirus in 2020. Interventions against SARS-CoV-2 are still in high need to prevent admissions to ICUs worldwide. FX06, a naturally occurring peptide in humans and other mammals, has the potential to reduce capillary leak by improving endothelial dysfunction and thus preventing the deterioration of patients. With IXION, we want to investigate the potential of FX06 to prevent disease progression in hospitalized, non-intubated COVID-19 patients. Methods: IXION is an EU-wide, multicentre, placebo-controlled, double-blinded, parallel, randomized (2:1) phase II clinical study. Patient recruitment will start in September 2022 (to Q2/2023) in Germany, Italy, Lithuania, Spain, Romania, Portugal, and France. A total of 306 hospitalized patients (>= 18 years and < 75 years) with a positive SARS-CoV-2 PCR test and a COVID-19 severity of 4-6 according to the WHO scale will be enrolled. After randomization to FX06 or placebo, patients will be assessed until day 28 (and followed up until day 60). FX06 (2 x 200 mg per day) or placebo will be administered intravenously for 5 consecutive days. The primary endpoint is to demonstrate a difference in the proportion of patients with progressed/worsened disease state in patients receiving FX06 compared to patients receiving placebo. Secondary endpoints are lung function, oxygen saturation and breathing rate, systemic inflammation, survival, capillary refill time, duration of hospital stay, and drug accountability. Discussion: With IXION, the multidisciplinary consortium aims to deliver a new therapy in addition to standard care against SARS-CoV-2 for the clinical management of COVID-19 during mild and moderate stages. Potential limitations might refer to a lack of recruiting and drop-out due to various possible protocol violations. While we controlled for drop-outs in the same size estimation, recruitment problems may be subject to external problems difficult to control for