Expression and Purification of Active Monomeric MMP7.

MMP7 is the smallest member of the MMP family and plays multiple physiological and pathological roles through interaction with a variety of molecules. Purified MMP7 would be beneficial for studying its function and for the development of inhibitors, which could be potential therapeutics. Due to low levels of endogenously produced MMP7, its recombinant expression and purification using E.

Prevalence, Diagnostic Utility and Associated Characteristics of Bronchodilator Responsiveness.

The prevalence and diagnostic utility of bronchodilator responsiveness (BDR) in a real-life setting is unclear. To explore this uncertainty in patients aged ⩾12 years with physician-assigned diagnoses of asthma, asthma and chronic obstructive pulmonary disease (COPD), or COPD in NOVELTY, a prospective cohort study in primary and secondary care in 18 countries. The proportion of patients with a positive BDR test in each diagnostic category was calculated using 2005 (ΔFEV or ΔFVC ⩾12% and ⩾200 ml) and 2021 (ΔFEV or ΔFVC >10% predicted) European Respiratory Society/American Thoracic Society criteria.

Demographic, clinical and laboratory differences between paediatric acute COVID-19 and PIMS-TS-results from a single centre study in the UK.

Background: Paediatric symptomatic SARS-CoV-2 infections associate with two presentations, acute COVID-19 and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Phenotypic comparisons, and reports on predictive markers for disease courses are sparse and preliminary.

Methods: A chart review of COVID-19 and PIMS-TS patients (≤19 years) admitted to Alder Hey Children's NHS Foundation Trust, a tertiary centre in the North-West of England, was performed (02/2020-09/2022).

Adjunctive rosiglitazone treatment for severe pediatric malaria: A randomized placebo-controlled trial in Mozambican children.

Objectives: We tested the hypothesis that adjunctive rosiglitazone treatment would reduce levels of circulating angiopoietin-2 (Angpt-2) and improve outcomes of Mozambican children with severe malaria.

Methods: A randomized, double-blind, placebo-controlled trial of rosiglitazone vs placebo as adjunctive treatment to artesunate in children with severe malaria was conducted. A 0.

Core Palliative Care Research Competencies Framework for Palliative Care Clinicians.

Understanding the principles and practice of research by health care professionals helps to improve the evidence base for palliative care practice and service delivery. Research is a core competency in palliative care that enables the identification and addressing of problems for patients and their families, establishes best practice and improves ways to manage pain, other symptoms, and concerns. This work was undertaken in the research for all palliative care clinicians (RESPACC) Erasmus+ project.

Mesenchymal Stem Cells in the Pathogenesis and Therapy of Autoimmune and Autoinflammatory Diseases.

Mesenchymal stem cells (MSCs) modulate immune responses and maintain self-tolerance. Their trophic activities and regenerative properties make them potential immunosuppressants for treating autoimmune and autoinflammatory diseases. MSCs are drawn to sites of injury and inflammation where they can both reduce inflammation and contribute to tissue regeneration.

Small RNA Sequencing Reveals a Distinct MicroRNA Signature between Glucocorticoid Responder and Glucocorticoid Non-Responder Primary Human Trabecular Meshwork Cells after Dexamethasone Treatment.

Glucocorticoids (GCs) are known to regulate several physiological processes and are the mainstay in the management of inflammatory eye diseases. The long-term use of GC causes raised intraocular pressure (IOP) or ocular hypertension (OHT) in about 30-50% of the susceptible individuals depending on the route of administration, and can lead to steroid-induced secondary glaucoma. The present study aims to understand the role of microRNAs (miRNAs) in differential glucocorticoid (GC) responsiveness in human trabecular meshwork (HTM) cells using small RNA sequencing.

The independent and joint risks of alcohol consumption, smoking, and excess weight on morbidity and mortality: a systematic review and meta-analysis exploring synergistic associations.

Objective: Alcohol consumption, smoking, and excess weight independently increase the risk of morbidity/mortality. Less is known about how they interact. This research aims to quantify the independent and joint associations of these exposures across health outcomes and identify whether these associations are synergistic.

Multilayer analysis of dynamic network reconfiguration in pediatric posttraumatic stress disorder.

Neuroimage studies have reported functional connectome abnormalities in posttraumatic stress disorder (PTSD), especially in adults. However, these studies often treated the brain as a static network, and time-variance of connectome topology in pediatric posttraumatic stress disorder remain unclear. To explore case-control differences in dynamic connectome topology, resting-state functional magnetic resonance imaging data were acquired from 24 treatment-naïve non-comorbid pediatric posttraumatic stress disorder patients and 24 demographically matched trauma-exposed non-posttraumatic stress disorder controls.

Assessing and further developing age-appropriate information for young people about reporting suspected adverse drug reactions.

Aims: The Medicines and Healthcare products Regulatory Agency Yellow Card scheme (YCS) is the UK's system that collects spontaneous reports about suspected adverse drug reactions (ADRs). Reporting of suspected ADRs by young people (age <19 years) in the UK is extremely uncommon, driving efforts to improve awareness and reporting.

Methods: Quality improvement project, using an anonymous online survey about updated information for young people, distributed through school pupils (age 13-18 years) across the UK through the Alder Hey Research Ambassador programme.

Effects of PRRT2 mutation on brain gray matter networks in paroxysmal kinesigenic dyskinesia.

Although proline-rich transmembrane protein 2 is the primary causative gene of paroxysmal kinesigenic dyskinesia, its effects on the brain structure of paroxysmal kinesigenic dyskinesia patients are not yet clear. Here, we explored the influence of proline-rich transmembrane protein 2 mutations on similarity-based gray matter morphological networks in individuals with paroxysmal kinesigenic dyskinesia. A total of 51 paroxysmal kinesigenic dyskinesia patients possessing proline-rich transmembrane protein 2 mutations, 55 paroxysmal kinesigenic dyskinesia patients possessing proline-rich transmembrane protein 2 non-mutation, and 80 healthy controls participated in the study.

Implantation in the lower half of the uterine cavity and decreased trophoblastic thickness can predict subsequent miscarriage: a prospective cohort study.

Abstract: Embryo implantation is vital for successful conception but remains to be fully understood. Trophoblast invasion is key for implantation, with anchorage and depth of placentation determined by its extent. There is a dearth of synchronous information regarding IVF, implantation site, and trophoblastic thickness (TT).

scDiffCom: a tool for differential analysis of cell-cell interactions provides a mouse atlas of aging changes in intercellular communication.

Dysregulation of intercellular communication is a hallmark of aging. To better quantify and explore changes in intercellular communication, we present scDiffCom and scAgeCom. scDiffCom is an R package, relying on approximately 5,000 curated ligand-receptor interactions, that performs differential intercellular communication analysis between two conditions from single-cell transcriptomics data.

Atrial fibrillation and stroke: State-of-the-art and future directions.

Atrial fibrillation (AF) and stroke remain a major cause of morbidity and mortality. The two conditions shared common co-morbidities and risk factors. AF-related strokes are associated with worse clinical outcomes and higher mortality compared to non-AF-related.

Modifying gastruloids to dissect mechanisms of tissue-specific induction.

How functional organisms arise from a single cell is a fundamental question in biology with direct relevance to understanding developmental defects and diseases. Dissecting developmental processes provides the basic, critical framework for understanding disease progression and treatment. Bottom-up approaches to recapitulate formation of various components of the embryo have been effective to probe symmetry-breaking, self-organisation, tissue patterning and morphogenesis.

Cryo-Electrospinning Generates Highly Porous Fiber Scaffolds Which Improves Trabecular Meshwork Cell Infiltration.

Human trabecular meshwork is a sieve-like tissue with large pores, which plays a vital role in aqueous humor outflow. Dysfunction of this tissue can occur, which leads to glaucoma and permanent vision loss. Replacement of trabecular meshwork with a tissue-engineered device is the ultimate objective.

Mesothelial Cells Exhibit Characteristics of Perivascular Cells in an In Vitro Angiogenesis Assay.

Mesothelial cells have been shown to have remarkable plasticity towards mesenchymal cell types during development and in disease situations. Here, we have characterized the potential of mesothelial cells to undergo changes toward perivascular cells using an in vitro angiogenesis assay. We demonstrate that GFP-labeled mesothelial cells (GFP-MCs) aligned closely and specifically with endothelial networks formed when human dermal microvascular endothelial cells (HDMECs) were cultured in the presence of VEGF-A on normal human dermal fibroblasts (NHDFs) for a 7-day period.

The Functional and Anatomical Impacts of Healthy Muscle Ageing.

Even "healthy" muscle ageing is often associated with substantial changes in muscle form and function and can lead to increased injury risks and significant negative impacts on quality of life. However, the impacts of healthy muscle ageing on the fibre architecture and microstructure of different muscles and muscle groups throughout the lower limb, and how these are related to their functional capabilities, are not fully understood. Here, a previously established framework of magnetic resonance and diffusion tensor imaging was used to measure the muscle volumes, intramuscular fat, fibre lengths and physiological cross-sectional areas of 12 lower limb muscles in a cohort of healthily aged individuals, which were compared to the same data from a young population.

Transcriptomic analysis reveals a tissue-specific loss of identity during ageing and cancer.

Introduction: Understanding changes in cell identity in cancer and ageing is of great importance. In this work, we analyzed how gene expression changes in human tissues are associated with tissue specificity during cancer and ageing using transcriptome data from TCGA and GTEx.

Results: We found significant downregulation of tissue-specific genes during ageing in 40% of the tissues analyzed, which suggests loss of tissue identity with age.

Management of ischaemic stroke survivors in primary care setting: the road to holistic care.

The management of ischaemic stroke survivors is multidisciplinary, necessitating the collaboration of numerous medical professionals and rehabilitation specialists. However, due to the lack of comprehensive and holistic follow-up, their post-discharge management may be suboptimal. Achieving this holistic, patient-centred follow-up requires coordination and interaction of subspecialties, which general practitioners can provide as the first point of contact in healthcare systems.

Multimorbidity in rheumatoid arthritis: common mechanistic links and impact and challenges in routine clinical practice.

Early identification and management of multimorbidity in patients with rheumatic and musculoskeletal diseases (RMDs), such as RA, is an integral, but often neglected, aspect of care. The prevalence and incidence of conditions such as osteoporosis, cardiovascular disease, pulmonary disease and malignancies, often co-existing with RA, continues to have significant implications for the management of this patient group. Multimorbidity in RMDs can be associated with inflammatory disease activity and target organ damage.