Brain health in Norwegian female former top-level football players: a protocol for a longitudinal cohort study.

Introduction: Repetitive head impacts (RHI) in sports may represent a risk factor for long-term cognitive and neurological sequelae. Recent studies have identified an association between playing football at the top level and an elevated risk of cognitive impairment and neurodegenerative disease. However, these were conducted on men, and there is a knowledge gap regarding these risks in female athletes.

Germline deletion of Rgs2 and/or Rgs5 in male mice does not exacerbate left ventricular remodeling induced by subchronic isoproterenol infusion.

Sympathoexcitation is a hallmark of heart failure, with sustained β-adrenergic receptor (βAR)-G protein signaling activation. βAR signaling is modulated by regulator of G protein signaling (RGS) proteins. Previously, we reported that Gα regulation by RGS2 or RGS5 is key to ventricular rhythm regulation, while the dual loss of both RGS proteins results in left ventricular (LV) dilatation and dysfunction.

Clinical importance of patient-reported outcome measures in severe asthma: results from U-BIOPRED.

Rationale: Knowledge about the clinical importance of patient-reported outcome measures (PROMs) in severe asthma is limited.

Objectives: To assess whether and to what extent asthma exacerbations affect changes in PROMS over time and asthma-specific PROMs can predict exacerbations in adult patients with severe asthma in usual care.

Methods: Data of 421 patients with severe asthma (62% female; mean age 51.

Development of an asthma health-care burden score as a measure of severity and predictor of remission in SARP III and U-BIOPRED: results from two major longitudinal asthma cohorts.

Background: Current asthma guidelines, including those of the European Respiratory Society (ERS) and American Thoracic Society (ATS), suboptimally predict asthma remission, disease severity, and health-care utilisation. We aimed to establish a novel approach to assess asthma severity based on asthma health-care burden data.

Methods: We analysed prospectively collected data from the Severe Asthma Research Program III (SARP III; USA) and the European Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED; 11 European countries) to calculate a composite burden score based on asthma exacerbations and health-care utilisation, which was modified to include the use of short-acting beta agonists (SABAs) to reflect asthma symptom burden.

Targeting of the IL-5 pathway in severe asthma reduces mast cell progenitors.

Background: Therapies targeting IL-5 or its receptor (IL-5Rα) are currently used to treat patients with severe eosinophilic asthma.

Objective: We sought to investigate the impact of anti-IL-5 and anti-IL-5Rα biological therapies on mast cells (MCs) and their progenitors.

Methods: Surface IL-5Rα expression was investigated on MCs and their progenitors in mouse lungs and bone marrow and in human lungs and blood.

Radiomultiomics: quantitative CT clusters of severe asthma associated with multiomics.

Background: Lung quantitative computed tomography (qCT) severe asthma clusters have been reported, but their replication and underlying disease mechanisms are unknown. We identified and replicated qCT clusters of severe asthma in two independent asthma cohorts and determined their association with molecular pathways, using radiomultiomics, integrating qCT, multiomics and machine learning/artificial intelligence.

Methods: We used consensus clustering on qCT measurements of airway and lung CT scans, performed in 105 severe asthmatic adults from the U-BIOPRED cohort.

Host-microbial interactions differ with age of asthma onset.

https://bit.ly/3xSa4Fe

Endotypes of severe neutrophilic and eosinophilic asthma from multi-omics integration of U-BIOPRED sputum samples.

Background: Clustering approaches using single omics platforms are increasingly used to characterise molecular phenotypes of eosinophilic and neutrophilic asthma. Effective integration of multi-omics platforms should lead towards greater refinement of asthma endotypes across molecular dimensions and indicate key targets for intervention or biomarker development.

Objectives: To determine whether multi-omics integration of sputum leads to improved granularity of the molecular classification of severe asthma.

Fulfilling the Promise of Breathomics: Considerations for the Discovery and Validation of Exhaled Volatile Biomarkers.

The exhaled breath represents an ideal matrix for noninvasive biomarker discovery, and exhaled metabolomics have the potential to be clinically useful in the era of precision medicine. In this concise translational review, we specifically address volatile organic compounds in the breath, with a view toward fulfilling the promise of these as actionable biomarkers, in particular, for lung diseases. We review the literature paying attention to seminal work linked to key milestones in breath research; discuss potential applications for breath biomarkers across disease areas and healthcare systems, including the perspectives of industry; and outline critical aspects of study design that will need to be considered for any pivotal research going forward if breath analysis is to provide robust validated biomarkers that meet the requirements for future clinical implementation.

Heading in football: a systematic review of descriptors, definitions, and reporting methods used in heading incidence studies.

The primary objective of this systematic review was to describe the number and type of heading descriptors used in all published studies which report on heading incidence in football. The secondary objective was to detail the data collection and reporting methods used in the included studies to present heading incidence data. Eligible studies were identified through searches of five electronic databases: Ovid MEDLINE, CINAHL, EMBASE, SPORTDiscus, and Web of Science, using a combination of free-text keywords (inception to 12th September 2023).

Discovery and Validation of a Volatile Signature of Eosinophilic Airway Inflammation in Asthma.

Volatile organic compounds (VOCs) in asthmatic breath may be associated with sputum eosinophilia. We developed a volatile biomarker signature to predict sputum eosinophilia in asthma. VOCs emitted into the space above sputum samples (headspace) from patients with severe asthma ( = 36) were collected onto sorbent tubes and analyzed using thermal desorption gas chromatography-mass spectrometry (GC-MS).

Evaluation of the SCAT 5 tool in the assessment of concussion in Para athletes: a Delphi study.

Objectives: To investigate if the sport concussion assessment tool version 5 (SCAT5) could be suitable for application to Para athletes with a visual impairment, a spinal cord injury, or a limb deficiency.

Methods: A 16-member expert panel performed a Delphi technique protocol. The first round encompassed an open-ended questionnaire, with round 2 onwards being composed of a series of closed-ended statements requiring each expert's opinion using a five-point Likert scale.

Biomarker Predictors of Clinical Efficacy of the Anti-IgE Biologic Omalizumab in Severe Asthma in Adults: Results of the SoMOSA Study.

The anti-IgE monoclonal antibody omalizumab is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during 1 year of omalizumab treatment. One-year open-label Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA) involving 216 patients with severe (Global Initiative for Asthma step 4/5) uncontrolled atopic asthma (at least two severe exacerbations in the previous year) taking high-dose inhaled corticosteroids and long-acting β-agonists with or without maintenance oral corticosteroids.

Airway hyperresponsiveness in asthma: The role of the epithelium.

Airway hyperresponsiveness (AHR) is a key clinical feature of asthma. The presence of AHR in people with asthma provides the substrate for bronchoconstriction in response to numerous diverse stimuli, contributing to airflow limitation and symptoms including breathlessness, wheeze, and chest tightness. Dysfunctional airway smooth muscle significantly contributes to AHR and is displayed as increased sensitivity to direct pharmacologic bronchoconstrictor stimuli, such as inhaled histamine and methacholine (direct AHR), or to endogenous mediators released by activated airway cells such as mast cells (indirect AHR).

Milestone Papers on Signal Transduction Mechanisms of Hypertension and Its Complications.

To celebrate 100 years of American Heart Association-supported cardiovascular disease research, this review article highlights milestone papers that have significantly contributed to the current understanding of the signaling mechanisms driving hypertension and associated cardiovascular disorders. This article also includes a few of the future research directions arising from these critical findings. To accomplish this important mission, 4 principal investigators gathered their efforts to cover distinct yet intricately related areas of signaling mechanisms pertaining to the pathogenesis of hypertension.

Proteomic signatures of eosinophilic and neutrophilic asthma from serum and sputum.

Background: Eosinophilic and neutrophilic asthma defined by high levels of blood and sputum eosinophils and neutrophils exemplifies the inflammatory heterogeneity of asthma, particularly severe asthma. We analysed the serum and sputum proteome to identify biomarkers jointly associated with these different phenotypes.

Methods: Proteomic profiles (N = 1129 proteins) were assayed in sputum (n = 182) and serum (n = 574) from two cohorts (U-BIOPRED and ADEPT) of mild-moderate and severe asthma by SOMAscan.

Study protocol for a single-blind, parallel-group, randomised, controlled non-inferiority trial of 4-day intensive versus standard cognitive behavioural therapy for adults with obsessive-compulsive disorder.

Introduction: Individual cognitive behavioural therapy (CBT) with exposure and response prevention is an effective treatment for obsessive-compulsive disorder (OCD). However, individual CBT is costly and time-consuming, requiring weekly therapy sessions for 3-4 months. A 4-day intensive version of CBT for OCD delivered in group format has been recently developed in Norway (Bergen 4-day treatment, B4DT).

A single extraction 96-well method for LC-MS/MS quantification of urinary eicosanoids, steroids and drugs.

Urinary eicosanoid concentrations reflect inflammatory processes in multiple diseases and have been used as biomarkers of disease as well as suggested for patient stratification in precision medicine. However, implementation of urinary eicosanoid profiling in large-scale analyses is restricted due to sample preparation limits. Here we demonstrate a single solid-phase extraction of 300 µL urine in 96-well-format for prostaglandins, thromboxanes, isoprostanes, cysteinyl-leukotriene E and the linoleic acid-derived dihydroxy-octadecenoic acids (9,10- and 12,13-DiHOME).

Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids.

Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.