Improving shared decision-making in bronchiectasis.

Bronchiectasis is a heterogeneous lung disease. There is an increasing focus on personalised medicine in bronchiectasis, with targeted pharmacological interventions for inflammation, immunology and infection. Airway clearance techniques (ACTs) are non-pharmacological treatments used to manage bronchiectasis.

Promoting functional independence and reducing the risk of hospital-associated deconditioning for acutely hospitalised older adults: a group concept mapping service evaluation.

Purpose: To identify and prioritise key activities to promote functional independence and reduce the risk of hospital-associated deconditioning for older adults admitted to our acute care wards.

Materials And Methods: A local, stand-alone evaluation and planning project using group concept mapping methodology. Multidisciplinary healthcare workers took part in a statement generation activity, individually sorted these statements into themes, and rated each statement for perceived importance and current success.

Delineating the Metabolic Phenotype of Biopsy-Derived Kidney Cells.

Kidney transplantation is the optimal treatment for end-stage kidney disease; however, transplanted kidneys are often lost prematurely, with up to 50% graft loss at 10 years post-transplant. One of the major causes of premature graft loss is the injury sustained by the graft at the time of transplantation, known as ischemia-reperfusion injury (IRI). Delayed graft function (DGF), defined as the need for dialysis in the first week post-transplant, is a manifestation of severe IRI that shows functional and histologic features of acute kidney injury (AKI).

Health and economic benefits of energy, urban planning, and food interventions that lower greenhouse gas emissions.

Public health can be immediately and substantially improved by policies that also mitigate climate change over the longer term. However, implementation of these policies has been slowed at least in part by doubts and lack of awareness of these health co-benefits. To address this barrier to progress, we demonstrate how an illustrative set of interventions led to environmental, health, and economic benefits, in addition to mitigating climate change.

The neurorepellent SLIT2 inhibits LPS-induced proinflammatory signaling in macrophages.

Macrophages are important mediators of immune responses with critical roles in the recognition and clearance of pathogens, as well as in the resolution of inflammation and wound healing. The neuronal guidance cue SLIT2 has been widely studied for its effects on immune cell functions, most notably directional cell migration. Recently, SLIT2 has been shown to directly enhance bacterial killing by macrophages, but the effects of SLIT2 on inflammatory activation of macrophages are less known.

Normothermic ex vivo kidney perfusion preserves mitochondrial and graft function after warm ischemia and is further enhanced by AP39.

We previously reported that normothermic ex vivo kidney  perfusion (NEVKP) is superior in terms of organ protection compared to static cold storage (SCS), which is still the standard method of organ preservation, but the mechanisms are incompletely understood. We used a large animal kidney autotransplant model to evaluate mitochondrial function during organ preservation and after kidney transplantation, utilizing live cells extracted from fresh kidney tissue. Male porcine kidneys stored under normothermic perfusion showed preserved mitochondrial function and higher ATP levels compared to kidneys stored at 4 °C (SCS).

Molecular Regulation of Bone Turnover in Juvenile Idiopathic Arthritis: Animal Models, Cellular Features and TNFα.

We review the abnormal bone turnover that is the basis of idiopathic inflammatory or rheumatoid arthritis and bone loss, with emphasis on Tumor Necrosis Factor-alpha (TNFα)-related mechanisms. We review selected data on idiopathic arthritis in juvenile human disease, and discuss mouse models focusing on induction of bone resorbing cells by TNFα and Receptor Activator of Nuclear Factor kappa B Ligand (RANKL). In both humans and animal models, macrophage-derived cells in the joint, particularly in the synovium and periosteum, degrade bone and cartilage.

Preclinical evaluation of ELP-004 in mice.

This study provides a detailed understanding of the preclinical pharmacokinetics and metabolism of ELP-004, an osteoclast inhibitor in development for the treatment of bone erosion. Current treatments for arthritis, including biological disease-modifying antirheumatic drugs, are not well-tolerated in a substantial subset of arthritis patients and are expensive; therefore, new treatments are needed. Pharmacokinetic parameters of ELP-004 were tested with intravenous, oral, and subcutaneous administration and found to be rapidly absorbed and distributed.

Bridging the gap between in vitro and in vivo models: a way forward to clinical translation of mitochondrial transplantation in acute disease states.

Mitochondrial transplantation and transfer are being explored as therapeutic options in acute and chronic diseases to restore cellular function in injured tissues. To limit potential immune responses and rejection of donor mitochondria, current clinical applications have focused on delivery of autologous mitochondria. We recently convened a Mitochondrial Transplant Convergent Working Group (CWG), to explore three key issues that limit clinical translation: (1) storage of mitochondria, (2) biomaterials to enhance mitochondrial uptake, and (3) dynamic models to mimic the complex recipient tissue environment.

Exploring the content and delivery of feedback facilitation co-interventions: a systematic review.

Background: Policymakers and researchers recommend supporting the capabilities of feedback recipients to increase the quality of care. There are different ways to support capabilities. We aimed to describe the content and delivery of feedback facilitation interventions delivered alongside audit and feedback within randomised controlled trials.

Adopting electric school buses in the United States: Health and climate benefits.

Electric school buses have been proposed as an alternative to reduce the health and climate impacts of the current U.S. school bus fleet, of which a substantial share are highly polluting old diesel vehicles.

A group concept mapping and ethnographic study of intensive care rehabilitation culture.

Background: Early physical activity and physical rehabilitation are advocated in the critical care unit for patients recovering from critical illness. Despite this, there are still many factors associated with implementation of early physical rehabilitation into routine critical care and practice. One such factor that has been consistently identified is unit culture, yet there is little understanding of how or why the culture of a critical care unit impacts on implementation of early rehabilitation.

The effect of lower limb strengthening exercise on orthostatic blood pressure and the skeletal muscle pump in older people with orthostatic hypotension.

Introduction: Activation of muscles during standing is recommended to activate the skeletal muscle pump, increasing venous return and increasing blood pressure (BP) in people with orthostatic hypotension (OH).

Aim: The aim of this study is to determine if increasing the strength of the lower limb muscles can improve the effectiveness of the venous pump and postural BP in older people with OH.

Methods: Ten older people with OH underwent an 8-week lower limb strengthening intervention.

Management and Outcomes of Type I and Type II Myocardial Infarction in Cardiogenic Shock.

Background: Type I myocardial infarction (T1MI) or type II myocardial infarction (T2MI) have different underlying mechanisms; however, in the setting of cardiogenic shock (CS), it is not understood if patients experience resultantly different outcomes. The objective of this study was to determine clinical features, biomarker patterns, and outcomes in these subgroups.

Methods: Patients from the CAPITAL-DOREMI trial presenting with acute myocardial infarction-associated CS (n = 103) were classified as T1MI (n = 61) or T2MI (n = 42).

The chemorepellent, SLIT2, bolsters innate immunity against .

Neutrophils are essential for host defense against (). The neuro-repellent, SLIT2, potently inhibits neutrophil chemotaxis, and might, therefore, be expected to impair antibacterial responses. We report here that, unexpectedly, neutrophils exposed to the N-terminal SLIT2 (N-SLIT2) fragment kill extracellular more efficiently.

Combining Oxygenated Cold Perfusion With Normothermic Ex Vivo Perfusion Improves the Outcome of Donation After Circulatory Death Porcine Kidney Transplantation.

Background: Ex vivo machine perfusion is a novel preservation technique for storing and assessing marginal kidney grafts. All ex vivo perfusion techniques have advantages and shortcomings. The current study analyzed whether a combination of oxygenated hypothermic machine perfusion (oxHMP) followed by a short period of normothermic ex vivo kidney perfusion (NEVKP) could combine the advantages of both techniques.

SLIT2/ROBO1 signaling suppresses mTORC1 for organelle control and bacterial killing.

SLIT/ROBO signaling impacts many aspects of tissue development and homeostasis, in part, through the regulation of cell growth and proliferation. Recent studies have also linked SLIT/ROBO signaling to the regulation of diverse phagocyte functions. However, the mechanisms by which SLIT/ROBO signaling acts at the nexus of cellular growth control and innate immunity remain enigmatic.

The calcium channel Orai1 is required for osteoblast development: Studies in a chimeric mouse with variable in vivo Runx-cre deletion of Orai-1.

The calcium-selective ion channel Orai1 has a complex role in bone homeostasis, with defects in both bone production and resorption detected in Orai1 germline knock-out mice. To determine whether Orai1 has a direct, cell-intrinsic role in osteoblast differentiation and function, we bred Orai1 flox/flox (Orai1fl/fl) mice with Runx2-cre mice to eliminate its expression in osteoprogenitor cells. Interestingly, Orai1 was expressed in a mosaic pattern in Orai1fl/fl-Runx2-cre bone.

Inotrope versus placebo therapy in cardiogenic shock: Rationale and study design of the CAPITAL DOREMI2 trial.

Background: Cardiogenic shock (CS) is a state of end-organ hypoperfusion related to cardiac dysfunction. Current guidelines recommend consideration of inotrope therapy in patients with CS, however no robust data support their use. The purpose of the CAPITAL DOREMI2 trial is to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of patients with CS.

The loss of glycocalyx integrity impairs complement factor H binding and contributes to cyclosporine-induced endothelial cell injury.

Background: Calcineurin inhibitors (CNIs) are associated with nephrotoxicity, endothelial cell dysfunction, and thrombotic microangiopathy (TMA). Evolving evidence suggests an important role for complement dysregulation in the pathogenesis of CNI-induced TMA. However, the exact mechanism(s) of CNI-induced TMA remain(s) unknown.

Identifying and prioritising the key components of a Quality Improvement Network for allied health professionals and psychological therapists: a group concept mapping project.

Introduction: Despite growing enthusiasm for quality improvement (QI), the complexities of modern healthcare continue to create gaps in our ability to consistently deliver the most effective and efficient care for patients, and improvement activities often fail to achieve widespread uptake even when there is robust evidence of their benefits.

Methods: We undertook a novel, mixed methods evaluation and planning project using group concept mapping (GCM) methodology to identify and prioritise the ways in which our recently established Quality Improvement Network (QIN) could support allied health professionals, psychological therapists and administrative staff in their daily work to improve patient outcomes and experience. Mid-level leaders across our therapy services department contributed towards a statement generation activity and individually sorted these statements into themes.