Clustering analysis across different speeds reveals two distinct running techniques with no differences in running economy

Establishing the links between running technique and economy remains elusive due to high inter-individual variability. Clustering runners by technique may enable tailored training recommendations, yet it is unclear if different techniques are equally economical and whether clusters are speed-dependent. This study aimed to identify clusters of runners based on technique and to compare cluster kinematics and running economy. Additionally, we examined the agreement of clustering partitions of the same runners at different speeds. Trunk and lower-body kinematics were captured from 84 trained runners at different speeds on a treadmill. We used Principal Component Analysis for dimensionality reduction and agglomerative hierarchical clustering to identify groups of runners with a similar technique, and we evaluated cluster agreement across speeds. Clustering runners at different speeds independently produced different partitions, suggesting single speed clustering can fail to capture the full speed profile of a runner. The two clusters identified using data from the whole range of speeds showed differences in pelvis tilt and duty factor. In agreement with self-optimisation theories, there were no differences in running economy, and no differences in participants characteristics between clusters. Considering inter-individual technique variability may enhance the efficacy of training designs as opposed to “one size fits all” approaches

Clustering analysis across different speeds reveals two distinct running techniques with no differences in running economy

Establishing the links between running technique and economy remains elusive due to high inter-individual variability. Clustering runners by technique may enable tailored training recommendations, yet it is unclear if different techniques are equally economical and whether clusters are speed-dependent. This study aimed to identify clusters of runners based on technique and to compare cluster kinematics and running economy. Additionally, we examined the agreement of clustering partitions of the same runners at different speeds. Trunk and lower-body kinematics were captured from 84 trained runners at different speeds on a treadmill. We used Principal Component Analysis for dimensionality reduction and agglomerative hierarchical clustering to identify groups of runners with a similar technique, and we evaluated cluster agreement across speeds. Clustering runners at different speeds independently produced different partitions, suggesting single speed clustering can fail to capture the full speed profile of a runner. The two clusters identified using data from the whole range of speeds showed differences in pelvis tilt and duty factor. In agreement with self-optimisation theories, there were no differences in running economy, and no differences in participants characteristics between clusters. Considering inter-individual technique variability may enhance the efficacy of training designs as opposed to “one size fits all” approaches

CLUSTERING LONG-DISTANCE RUNNERS BASED ON THEIR TECHNIQUE AT ONE SINGLE SPEED DOES NOT GENERALISE TO MULTIPLE SPEEDS

The aim of this study was to assess whether clustering runners based on their technique resulted in consistent group allocations across multiple speeds. Eighty-four runners (34 females) completed four 4-minute running stages at 10, 11, 12 and 13 km/h. For each stage, running technique was characterised using a set of continuous variables in the sagittal plane and discrete stride-based variables. An autoencoder neural network was used for dimensionality reduction and agglomerative hierarchical clustering was applied to identify groups of runners with a similar technique. Two clusters for each speed were selected and the clustering partitions at different incremental speeds were compared. Our results showed that partitions were inconsistent across speeds, and therefore clustering results at one single speed do not generalise to the range of speeds an athlete typically runs at. Single speed clustering may be limited to drive the design of cluster-specific running training interventions and different clustering approaches are needed to better capture runners’ technique at their typical speeds

Red blood cell precursor mass as an independent determinant of serum erythropoietin level.

Serum erythropoietin (sEpo) concentration is primarily related to the rate of renal production and, under the stimulus of hypoxia, increases exponentially as hemoglobin (Hb) decreases. Additional factors, however, appear to influence sEpo, and in this work, we performed studies to evaluate the role of the red blood cell precursor mass. We first compared the relationship of sEpo with Hb in patients with low versus high erythroid activity. The first group included 27 patients with erythroid aplasia or hypoplasia having serum transferrin receptor (sTfR) levels 10 mg/L (erythroid activity > 2 times normal). There was no difference between the two groups with respect to Hb (8.3 +/- 1.6 v 8.0 +/- 1.3 g/dL, P > .05), but sEpo levels were notably higher in patients with low erythroid activity (1,601 +/- 1,542 v 235 +/- 143 mU/mL, P < . 001). In fact, multivariate analysis of variance (ANOVA) showed that, at any given Hb level, sEpo was higher in patients with low erythroid activity (P < .0001). Twenty patients undergoing allogeneic or autologous bone marrow transplantation (BMT) were then investigated. A marked increase in sEpo was seen in all cases at the time of marrow aplasia, disproportionately high when compared with the small decrease in Hb level. Sequential studies were also performed in five patients with iron deficiency anemia undergoing intravenous (IV) iron therapy. Within 24 to 72 hours after starting iron treatment, marked decreases in sEpo (up to one log magnitude) were found before any change in Hb level. Similar observations were made in patients with megaloblastic anemia and in a case of pure red blood cell aplasia. These findings point to an inverse relationship between red blood cell precursor mass and sEpo: at any given Hb level, the higher the number of red blood cell precursors, the lower the sEpo concentration. The most likely explanation for this is that sEpo levels are regulated not only by the rate of renal production, but also by the rate of utilization by erythroid cells

Concentration-Dependent Effects of N-3 Long-Chain Fatty Acids on Na,K-ATPase Activity in Human Endothelial Cells

N-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to prevent endothelial dysfunction, a crucial step in atherogenesis, by modulating the levels of vasoactive molecules and by influencing Na,K-ATPase activity of vascular myocytes. The activity of endothelial Na,K-ATPase controls the ionic homeostasis of the neighboring cells, as well as cell function. However, controversy exists with respect to the vascular protective effect of EPA and DHA. We argue that this dispute might be due to the use of different concentrations of EPA and DHA in different studies. Therefore, this study was designed to define an optimal concentration of EPA and DHA to investigate endothelial function. For this purpose, human endothelial cells were exposed for 24 h to different concentrations of DHA or EPA (0\u201320 \u3bcM) to study membrane fluidity, peroxidation potential and Na,K-ATPase activity. EPA and DHA were linearly incorporated and this incorporation was mirrored by the linear increase of unsaturation index, membrane fluidity, and peroxidation potential. Na,K-ATPase activity peaked at 3.75 \u3bcM of EPA and DHA and then gradually decreased. It is noteworthy that DHA effects were always more pronounced than EPA. Concluding, low concentrations of EPA and DHA minimize peroxidation sensitivity and optimize Na,K-ATPase activity

Severe Asthma and Biological Therapy: When, Which, and for Whom

Asthma is a heterogeneous chronic inflammatory disease of the airways that affects approximately 300 million people worldwide. About 5–10% of all asthmatics suffer from severe or uncontrolled asthma, associated with increased mortality and hospitalization, reduced quality of life, and increased health care costs. In recent years, new treatments have become available, and different asthma phenotypes characterized by specific biomarkers have been identified. Biological drugs are currently indicated for patients with severe asthma that is not controlled with recommended treatments. They are mostly directed against inflammatory molecules of the type 2 inflammatory pathway and are effective at reducing exacerbations, maintaining control over asthma symptoms, and reducing systemic steroid use, which is associated with well-known adverse events. Although biological drugs for severe asthma have had a major impact on the management of the disease, there is still a need for head-to-head comparison studies of biologics and to identify new biomarkers for asthma diagnosis, prognosis, and response to treatment.&nbsp;Identifying novel biomarkers could facilitate the development of therapeutic strategies that are precisely tailored to each patient’s requirements

Induced sputum as a tool for early detection of airway inflammation in connective diseases-related lung involvement.

Induced sputum (IS) sampling is a safe and validated approach to study bronchial inflammation in chronic obstructive lung diseases. Although promising results have also been reported in various diffuse interstitial lung disorders, the potential use of IS in the assessment of connective tissue diseases (CTD)-related lung involvement has not yet been investigated. Aim of the study: To evaluate the clinical usefulness of IS in the early management of patients suffering from rheumatoid arthritis (RA) and systemic sclerosis (SSc) at the onset of respiratory symptoms. Patients and methods: The study population included 19 patients (RA ¼ 12; SSc ¼ 7) and 14 age- and sex-matched healthy volunteers. Lung function testing, high resolution computed tomography (HRCT) of the thorax and IS collection were performed in all cases. Broncho-alveolar lavage (BAL) was obtained in selected patients. Results: IS samples from patients contained a significantly higher percentage of neutrophils and a lower percentage of macrophages compared to healthy subjects (p ¼ 0.002 and 0.001, respectively), while the total cell number showed no differences. In addition, sputa yielded both higher cell counts and higher neutrophils than BAL samples (p ¼ 0.02 in all instances). No correlations were found between IS findings and lung function parameters, HRCT and BAL findings

A long-term clinical trial on the efficacy and safety profile of doxofylline in Asthma: The LESDA study.

Doxofylline, an oral methylxanthine with bronchodilator and anti-inflammatory activities, offers a promising alternative to theophylline due to its superior efficacy/safety profile. No long-term studies on the efficacy and safety of doxofylline are currently available in asthma. The aim of the Long-term clinical trial on the Efficacy and Safety profile of Doxofylline in Asthma (LESDA) study was to investigate the safety and efficacy profile of doxofylline administered for one year in asthmatic patients. LESDA was a multicenter, open-label, Phase III, clinical trial in which adult asthmatic patients received the same treatment (oral doxofylline 400 mg t.i.d.) for one year. Efficacy was assessed through periodic pulmonary function tests and by having the subjects keep monthly records of asthma events rates and use of salbutamol as rescue medication. The rate of adverse events (AEs) was recorded during the study. Three-hundred nine patients were screened and allocated in the study. Doxofylline significantly improved the change from baseline in forced expiratory volume in 1 s (FEV1) (+16.90 ± 1.81%, P < 0.001 vs. baseline). Doxofylline also significantly improved the rate of asthma events (events/day: -0.57 ± 0.18, P < 0.05 vs. baseline) and the use of salbutamol as rescue medication (puffs/day: -1.48 ± 0.25, P < 0.01 vs. baseline). The most common AEs were nausea (14.56%), headache (14.24%), insomnia (10.68%), and dyspepsia (10.03%). There were neither serious AEs nor deaths during or shortly after the study. Concluding, doxofylline is effective and well tolerated when administered chronically in asthmatic patients

Impact of doxofylline compared to theophylline in asthma: A pooled analysis of functional and clinical outcomes from two multicentre, double-blind, randomized studies (DOROTHEO 1 and DOROTHEO 2)

Abstract This pooled analysis of double-blind, randomized, placebo-controlled trials aimed to investigate the impact of DOxofylline compaRed tO THEOphylline (DOROTHEO 1 and DOROTHEO 2 studies) on functional and clinical outcomes in asthma. Asthmatic patients ≥16 years of age with forced expiratory volume in 1 s (FEV1) ≥50% and  0.05) increase the risk of AEs compared to placebo, conversely in patients treated with theophylline 250 mg the risk of AEs was significantly (

A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron.

Background Hepcidin plays a key role in body iron metabolism by preventing the release of iron from macrophages and intestinal cells. Defective hepcidin synthesis causes iron loading, while overproduction results in defective reticuloendothelial iron release and iron absorption. Design and Methods We studied a Sardinian family in which microcytic anemia due to defective iron absorption and utilization is inherited as a recessive character. Five members showed iron deficiency anemia that was not responsive to oral iron and only partially responsive to parenteral iron administration. To investigate the involvement of known genes implicated in iron metabolism we carried out linkage analysis with microsatellite markers mapping close to these genes. Afterwards, a genome-wide search was performed. Results No linkage was found between the phenotype of the patients and several known human genes involved in iron metabolism ( DMT1, TF, TFRC, ZIRTL, HAMP, HJV ). Genome-wide scanning by microsatellites and single nucleotide polymorphisms showed a multipoint LOD score of 5.6 on chromosome 22q12.3–13.1, where the matriptase-2 (also known as transmembrane protease, serine 6 or TMPRSS6 ) gene is located. Its murine counterpart ( Tmprss6 ) has recently been found to be an essential component of a pathway that detects iron deficiency and suppresses hepcidin production. Sequencing analysis of TMPRSS6 revealed a homozygous causal mutation, predicting a splicing error and a truncated TMPRSS6 protein in affected members. Homozygous subjects had inappropriately elevated levels of serum and urinary hepcidin. Conclusions The findings of this study suggest that the observed TMPRSS6 mutation leads to overproduction of hepcidin and, in turn, to defective iron absorption and utilization. More generally, they confirm in humans the inhibitory effect of matriptase-2 on hepcidin synthesis already demonstrated in mice