The relationships between distances covered above generic and relative speed thresholds by male soccer players in English Premier League matches across two competitive seasons. The effects of positional demands and possession.

The aims of this study were to: a) examine the relationships between high-intensity distances covered above generic and relative speed thresholds in English Premier League (EPL) matches across two consecutive seasons and b) analyze the effects of playing position and team possession. Sixteen elite male soccer players (seven defenders, six midfielders and three forwards) participated in this study (age 27.8 ± 3.

Azithromycin Prevents Subglottic Stenosis in Mice.

Objective: Pediatric subglottic stenosis (SGS) is characterized by subglottic narrowing which occurs when pathological fibroblasts deposit extracellular matrix that reduces airway patency. Recent clinical observations have suggested that azithromycin may have favorable impacts on SGS reduction while treating airway infections; furthermore, our recent work in mice demonstrated that the airway microbiome influences SGS. In this work, we characterize the protective effect of azithromycin as an immunomodulatory and antibacterial therapeutic against subglottic stenosis.

Physical match demands across different playing positions during transitional play and high-pressure activities in elite soccer.

This study explored physical match demands across different playing positions during transitional play, to inform the need for position-specific training interventions. Data was collected using 10 Hz GPS units from 10 competitive matches including 23 elite soccer players of the 1 Polish Division (Ekstraklasa) in season 2020-21. A total of 4249 positional observations were made; center backs (n = 884), full backs (n = 972), central defensive midfielders (n = 236), central attacking midfielders (n = 270), central midfielders (n = 578), wingers (n = 778), and attackers (n = 531).

An Analysis of Positional Generic and Individualized Speed Thresholds Within the Most Demanding Phases of Match Play in the English Premier League.

Objectives: To analyze the positional distances covered above generic and individualized speed thresholds within the most demanding phases of match play. Categorized by position, 17 English Premier League players' match data were analyzed over 2 consecutive seasons (2019-20 and 2020-21). The most demanding phases of play were determined using a rolling average across 4 periods of 1, 3, 5, and 10 minutes.

Amelioration of Subglottic Stenosis by Antimicrobial Peptide Eluting Endotracheal Tubes.

Introduction: Pediatric subglottic stenosis (SGS) results from prolonged intubation where scar tissue leads to airway narrowing that requires invasive surgery. We have recently discovered that modulating the laryngotracheal microbiome can prevent SGS. Herein, we show how our patent-pending antimicrobial peptide-eluting endotracheal tube (AMP-ET) effectively modulates the local airway microbiota resulting in reduced inflammation and stenosis resolution.

Brown Adipose Tissue and BMP3b Decrease Injury in Cardiac Ischemia-Reperfusion.

Background: Despite advances in treatment, myocardial infarction (MI) is a leading cause of heart failure and death worldwide, with both ischemia and reperfusion (I/R) causing cardiac injury. A previous study using a mouse model of nonreperfused MI showed activation of brown adipose tissue (BAT). Recent studies showed that molecules secreted by BAT target the heart.

RIP140 deficiency enhances cardiac fuel metabolism and protects mice from heart failure.

During the development of heart failure (HF), the capacity for cardiomyocyte (CM) fatty acid oxidation (FAO) and ATP production is progressively diminished, contributing to pathologic cardiac hypertrophy and contractile dysfunction. Receptor-interacting protein 140 (RIP140, encoded by Nrip1) has been shown to function as a transcriptional corepressor of oxidative metabolism. We found that mice with striated muscle deficiency of RIP140 (strNrip1-/-) exhibited increased expression of a broad array of genes involved in mitochondrial energy metabolism and contractile function in heart and skeletal muscle.

Extra-cardiac BCAA catabolism lowers blood pressure and protects from heart failure.

Pharmacologic activation of branched-chain amino acid (BCAA) catabolism is protective in models of heart failure (HF). How protection occurs remains unclear, although a causative block in cardiac BCAA oxidation is widely assumed. Here, we use in vivo isotope infusions to show that cardiac BCAA oxidation in fact increases, rather than decreases, in HF.

A Pilot Study to Examine If Dietary Habits Can Affect Symptomology in Mild Pre-Vaccination COVID-19 Cases.

The heterogeneity of the severity of symptoms of COVID-19 experienced by the young and healthy individuals is poorly understood. The present study was undertaken to mainly examine whether the respective diets and the type of symptoms experienced by patients are predictive of having long COVID-19. Disease severity was assessed with a symptomatology questionnaire and used to group 55 participants in asymptomatic (AS), mild symptoms (S) and long COVID (LC).

Genetic blockade of lymphangiogenesis does not impair cardiac function after myocardial infarction.

In recent decades, treatments for myocardial infarction (MI), such as stem and progenitor cell therapy, have attracted considerable scientific and clinical attention but failed to improve patient outcomes. These efforts indicate that more rigorous mechanistic and functional testing of potential MI therapies is required. Recent studies have suggested that augmenting post-MI lymphatic growth via VEGF-C administration improves cardiac function.

Ketone Ester Treatment Improves Cardiac Function and Reduces Pathologic Remodeling in Preclinical Models of Heart Failure.

Background: Accumulating evidence suggests that the failing heart reprograms fuel metabolism toward increased utilization of ketone bodies and that increasing cardiac ketone delivery ameliorates cardiac dysfunction. As an initial step toward development of ketone therapies, we investigated the effect of chronic oral ketone ester (KE) supplementation as a prevention or treatment strategy in rodent heart failure models.

Methods: Two independent rodent heart failure models were used for the studies: transverse aortic constriction/myocardial infarction (MI) in mice and post-MI remodeling in rats.

Author Correction: Targeting cardiac fibrosis with engineered T cells.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Targeting cardiac fibrosis with engineered T cells.

Fibrosis is observed in nearly every form of myocardial disease. Upon injury, cardiac fibroblasts in the heart begin to remodel the myocardium by depositing excess extracellular matrix, resulting in increased stiffness and reduced compliance of the tissue. Excessive cardiac fibrosis is an important factor in the progression of various forms of cardiac disease and heart failure.

Author Correction: Variabilities in retinal function and structure in a canine model of cone-rod dystrophy associated with RPGRIP1 support multigenic etiology.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Variabilities in retinal function and structure in a canine model of cone-rod dystrophy associated with RPGRIP1 support multigenic etiology.

Defects in the cilia gene RPGRIP1 cause Leber congenital amaurosis and cone-rod dystrophy in humans. A form of canine cone-rod dystrophy (cord1) was originally associated with a homozygous insertion in RPGRIP1 (RPGRIP1 ) as the primary disease locus while a homozygous deletion in MAP9 (MAP9 ) was later identified as a modifier associated with the early onset form. However, we find further variability in cone electroretinograms (ERGs) ranging from normal to absent in an extended RPGRIP1 canine colony, irrespective of the MAP9 genotype.

Collagen cross-linking treatment increases adhesion in mock corneal grafts.

Purpose: We tested the hypothesis that collagen cross-linking (CXL) could be used to promote adhesion in mock corneal grafts.

Methods: Donated human corneal tissue underwent epithelial debridement and was cut into sections measuring 4mm×3mm. Paired sections were sutured together with 10-0 vicryl, forming mock corneal grafts.

CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma.

CXCR2 has been suggested to have both tumor-promoting and tumor-suppressive properties. Here we show that CXCR2 signaling is upregulated in human pancreatic cancer, predominantly in neutrophil/myeloid-derived suppressor cells, but rarely in tumor cells. Genetic ablation or inhibition of CXCR2 abrogated metastasis, but only inhibition slowed tumorigenesis.

Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease.

Inherited retinal degenerations cause progressive loss of photoreceptor neurons with eventual blindness. Corrective or neuroprotective gene therapies under development could be delivered at a predegeneration stage to prevent the onset of disease, as well as at intermediate-degeneration stages to slow the rate of progression. Most preclinical gene therapy successes to date have been as predegeneration interventions.

Framework for ethical decision-making based on mission, vision and values of the institution.

The authors led the development of a framework for ethical decision-making for an Academic Health Sciences Centre. They understood the existing mission, vision, and values statement (MVVs) of the centre as a foundational assertion that embodies an ethical commitment of the institution. Reflecting the Patient and Family Centred Model of Care the institution is living, the MVVs is a suitable base on which to construct an ethics framework.

Barriers to keeping warm in later life.

Aim: To identify factors influencing older people's ability to keep warm and well in winter.

Method: This qualitative study used in-depth individual interviews with older people (n=50) and health and social care staff,(n=25), alongside six focus groups with 43 participants and a consultation event. Temperatures were measured in the homes of the older people interviewed.

Tumor stromal architecture can define the intrinsic tumor response to VEGF-targeted therapy.

Purpose: The aim of the study was to investigate the vascular and stromal architecture of preclinical tumor models and patient tumor specimens from malignancies with known clinical outcomes to VEGFi treatment, to gain insight into potential determinants of intrinsic sensitivity and resistance.

Experimental Design: The tumor stroma architecture of preclinical and clinical tumor samples were analyzed by staining for CD31 and α-smooth muscle actin (α-SMA). Tumor models representative of each phenotype were then tested for sensitivity to the VEGFR2-blocking antibody DC101.

A human monoclonal antibody 264RAD targeting αvβ6 integrin reduces tumour growth and metastasis, and modulates key biomarkers in vivo.

αvβ6 integrin expression is upregulated on a wide range of epithelial tumours, and is thought to play a role in modulating tumour growth. Here we describe a human therapeutic antibody 264RAD, which binds and inhibits αvβ6 integrin function. 264RAD cross-reacts with human, mouse and cynomolgus monkey αvβ6, and inhibits binding to all ligands including the latency-associated peptide of TGF-β.

Exclusion of RPGRIP1 ins44 from primary causal association with early-onset cone-rod dystrophy in dogs.

Purpose: Canine cone-rod dystrophy 1 (cord1) has been previously mapped to CFA15, and a homozygous 44-bp insertion in exon 2 (Ins44) of canine RPGRIP1 (cRPGRIP1(Ins/Ins)) has been associated with the disease. However, from the recent identification of a significant discordance in genotype-phenotype association, we have reexamined the role of cRPGRIP1 in cord1.

Methods: Retinal structure and function was assessed by clinical retinal examination, noninvasive imaging, electroretinography, and histopathology/immunohistochemistry.

Understanding factors influencing vulnerable older people keeping warm and well in winter: a qualitative study using social marketing techniques.

Objectives: To understand the influences and decisions of vulnerable older people in relation to keeping warm in winter.

Design: A qualitative study incorporating in-depth, semi-structured individual and group interviews, framework analysis and social marketing segmentation techniques.

Setting: Rotherham, South Yorkshire, UK.