Mapping disease-specific vascular cell populations responsible for obliterative arterial remodeling during development of pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) is a lethal pulmonary vascular disease characterized by arteriolar pruning and occlusive vascular remodeling leading to increased pulmonary vascular resistance and eventually right heart failure. While endothelial cell (EC) injury and apoptosis are known triggers for this disease, the mechanisms by which they lead to complex arterial remodeling remain obscure.

Aims: We employed multiplexed single-cell RNA sequencing at multiple timepoints during the onset and progression of disease in a model of severe PAH to identify mechanisms involved in the development of occlusive arterial lesions.

Comparative Analysis of a Rapid Quantitative Immunoassay to the Reference Methodology for the Measurement of Blood Vitamin D Levels.

Vitamin D is the only vitamin that is conditionally essential, as it is synthesized from precursors after UV light exposure, whilst also being obtained from the diet. It has numerous health benefits, with deficiency becoming a major concern globally, such that dietary supplementation has more recently achieved vital importance to maintain satisfactory levels. In recent years, measurements made from blood have, therefore, become critical to determine the status of vitamin D levels in individuals and the larger population.

Comparative Evaluation of Lipopolysaccharide Administration Methods to Induce Acute Lung Injury in Murine Models: Efficacy, Consistency, and Technical Considerations.

Context: Direct preclinical lipopolysaccharide acute lung injury (ALI) models are commonly used to study acute respiratory distress syndrome. Differences in lipopolysaccharide delivery methods may impact lung injury severity and reproducibility.

Hypothesis: We hypothesized that the severity and variability of ALI outcomes in mice would differ depending on the technique of lipopolysaccharide administration.

Study of angiogenic cell therapy for progressive pulmonary arterial hypertension: intervention with repeat dosing of eNOS-enhanced EPCs: the SAPPHIRE trial.

Pulmonary arterial hypertension (PAH) is characterized by widespread pruning of the distal pulmonary arterial bed, leading to increased pulmonary vascular resistance, right heart failure, and death. PAH patients receiving background therapy were randomized to receive a course of 4 monthly infusions of placebo or angiogenic endothelial progenitor cells (EPCs) transfected with endothelial NO synthase (eNOS) over the first 6-month period for a cumulative dose of 80 M cells. Due to the COVID-19 pandemic, the trial was stopped after 12 of the planned 45 patients were enrolled (five placebo, seven eNOS-EPCs).

Single-cell microencapsulation improves lung retention of endothelial colony-forming cells after intravascular delivery and unmasks therapeutic benefit in severe pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is triggered by pulmonary vascular endothelial cell apoptosis and microvascular loss. Therefore, therapies that can regenerate lost vasculature may offer therapeutic benefit. Endothelial colony-forming cells (ECFCs) can directly repair damaged blood vessels and may have therapeutic potential for the treatment of PAH.

Barriers and leverage points for seeing alcohol differently in integrated care systems in England: a senior stakeholder interview study.

Introduction: Integrated care systems (ICSs) are the latest major innovation aiming to develop localised, integrated health and social care services to improve population health in England. Nationally, alcohol has received limited attention in National Health Service (NHS) strategic decision-making relative to its burden of harm, which varies considerably in localities. We examined decision-making and progress on alcohol in two contrasting ICSs, identifying systemic barriers to dealing with alcohol harm and potential leverage points, particularly in primary care.

Sexual dimorphism in right ventricular adaptation to pressure overload involves differential angiogenic response.

This study investigated the sexual dimorphism in right ventricle (RV) remodeling in right heart failure susceptible Fischer CDF rats using the pulmonary artery banding (PAB) model. Echocardiography and hemodynamic measurements were performed in adult male and female Fischer CDF rats at 1- or 2-wk post-PAB. RV systolic pressure and RV hypertrophy were significantly elevated in PAB rats compared with sham control at 1- and 2-wk post-PAB; however, no differences were observed between male and female rats.

Improving access to pulmonary rehabilitation for patients with COPD treated for substance misuse in the London Borough of Islington.

Chronic obstructive pulmonary disease (COPD) is a collection of conditions that cause permanent damage to the lungs. Among a range of treatment options, patients can benefit from pulmonary rehabilitation (PR) programmes involving physical exercises and education.The risk of developing COPD is higher for substance misusers than the general population.

Outcomes of Single Anastomosis Duodeno-Ileal Bypass With Sleeve Gastrectomy (SADI-S): A Single Bariatric Center Experience.

Introduction Bariatric surgery is increasingly employed to address the global burden of morbid obesity, with Roux-en-Y gastric bypass (RYGB) representing the predominant procedure. However, some patients, particularly those with extreme obesity (BMI >50 kg/m²), may experience unsatisfactory weight-related outcomes following RYGB. While biliopancreatic diversion with duodenal switch (BPD-DS) offers superior weight reduction for this population, its complexity and associated risks limit its widespread use.

Single-Cell RNA Sequencing to Guide Autologous Preterm Cord Mesenchymal Stromal Cell Therapy.

The chronic lung disease bronchopulmonary dysplasia (BPD) remains the most common complication of extreme prematurity (<28 wk of gestation). Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) represent an opportunity for autologous cell therapy, as UC-MSCs have been shown to improve lung function and structure in experimental BPD. However, characterization and repair capacity of UC-MSCs derived from donors with pregnancy-related complications associated with prematurity remain unexplored.

Cellular senescence in the pathogenesis of pulmonary arterial hypertension: the good, the bad and the uncertain.

Senescence refers to a cellular state marked by irreversible cell cycle arrest and the secretion of pro-inflammatory and tissue-remodeling factors. The senescence associated secretory phenotype (SASP) impacts the tissue microenvironment and provides cues for the immune system to eliminate senescent cells (SCs). Cellular senescence has a dual nature; it can be beneficial during embryonic development, tissue repair, and tumor suppression, but it can also be detrimental in the context of chronic stress, persistent tissue injury, together with an impairment in SC clearance.

Key quality parameter comparison of mesenchymal stem cell product cryopreserved in different cryopreservation solutions for clinical applications.

Introduction: Cryopreservation is a critical process of cell products for achieving a commercial viability through wide scale adoption. By preserving cells in a lower temperature, cryopreservation enables a product to be off-the-shelf and ready for infusion. An optimized cryopreservation strategy can maintain the viability, phenotype, and potency of thawed mesenchymal stromal/stem cells (MSCs) while being regulatory compliant.

Targeting extracellular vesicle delivery to the lungs by microgel encapsulation.

Extracellular vesicles (EVs) secreted by stem and progenitor cells have significant potential as cell-free 'cellular' therapeutics. Yet, small EVs (<200 nm) are rapidly cleared after systemic administration, mainly by the liver, presenting challenges targeting EVs to a specific organ or tissue. Microencapsulation using natural nano-porous hydrogels (microgels) has been shown to enhance engraftment and increase the survival of transplanted cells.

Brief interventions 2.0: a new agenda for alcohol policy, practice and research.

Background: Alcohol problems are increasing across the world and becoming more complex. Limitations to international evidence and practice mean that the screening and brief intervention paradigm forged in the 1980s is no longer fit for the purpose of informing how conversations about alcohol should take place in healthcare and other services. A new paradigm for brief interventions has been called for.

Atrial Fibrosis and Inflammation in Postoperative Atrial Fibrillation: Comparative Effects of Amiodarone, Colchicine, or Exosomes.

Background: Extracellular vesicles (EVs) isolated from human heart-derived cells have shown promise in suppressing inflammation and fibroblast proliferation. However, their precise benefits in atrial fibrillation (AF) prevention and the role of their antifibrotic/anti-inflammatory properties remain unclear.

Objectives: The purpose of this study was to conduct a head-to-head comparison of antiarrhythmic strategies to prevent postoperative AF using a rat model of sterile pericarditis.

Single-Cell RNA Sequencing Reveals Repair Features of Human Umbilical Cord Mesenchymal Stromal Cells.

The chronic lung disease bronchopulmonary dysplasia (BPD) is the most severe complication of extreme prematurity. BPD results in impaired lung alveolar and vascular development and long-term respiratory morbidity, for which only supportive therapies exist. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) improve lung structure and function in experimental BPD.

'Really putting a different slant on my use of a glass of wine': patient perspectives on integrating alcohol into Structured Medication Reviews in general practice.

Background: Alcohol is often overlooked in primary care even though it has wide-ranging impacts. The Structured Medication Review (SMR) in England is a new 'holistic' service designed to tackle problematic polypharmacy, delivered by clinical pharmacists in a general practice setting. Implementation has been protracted owing to the COVID-19 pandemic.

Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cell Therapy in Preclinical Models of Sepsis: A Systematic Review and Meta-analysis.

Background: In preclinical studies, mesenchymal stromal cells (MSCs), including umbilical cord-derived MSCs (UC-MSCs), demonstrate the ability to modulate numerous pathophysiological processes related to sepsis; however, a systematic synthesis of the literature is needed to assess the efficacy of UC-MSCs for treating sepsis.

Objective: To examine the effects of UC-MSCs on overall mortality (primary outcome) as well as on organ dysfunction, coagulopathy, endothelial permeability, pathogen clearance, and systemic inflammation (secondary outcomes) at prespecified time intervals in preclinical models of sepsis.

Methods: A systematic search was conducted on Embase, Ovid MEDLINE, and Web of Science up to June 20, 2023.

A preclinical systematic review and meta-analysis assessing the effect of biological sex in lipopolysaccharide-induced acute lung injury.

It is unclear what effect biological sex has on outcomes of acute lung injury (ALI). Clinical studies are confounded by their observational design. We addressed this knowledge gap with a preclinical systematic review of ALI animal studies.

Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study.

Sepsis is the result of an uncontrolled host inflammatory response to infection that may lead to septic shock with multiorgan failure and a high mortality rate. There is an urgent need to improve early diagnosis and to find markers identifying those who will develop septic shock and certainly a need to develop targeted treatments to prevent septic shock and its high mortality. Herein, we explore metabolic alterations due to mesenchymal stromal cell (MSC) treatment of septic shock.