Development of an adaptation framework to implement a new professional pharmacy service (PPS) to a new environment.

The effective provision of professional pharmacy services is critical to support the delivery of primary health care. Structured frameworks and theoretical strategies are required to facilitate successful service implementation processes, outcomes and sustainability. This commentary discusses the considerations of what framework (adoption versus adaptation) would be suitable when implementing a new professional pharmacy service to a new environment.

RAGE and its ligand amyloid beta promote retinal ganglion cell loss following ischemia-reperfusion injury.

Introduction: Glaucoma is a progressive neurodegenerative disease associated with age. Accumulation of amyloid-beta (Aß) proteins in the ganglion cell layer (GCL) and subsequent retinal ganglion cell (RGC) loss is an established pathological hallmark of the disease. The mechanism through which Aß provokes RGC loss remains unclear.

Macrophage migration inhibitory factor promotes glucocorticoid resistance of neutrophilic inflammation in a murine model of severe asthma.

Background: Severe neutrophilic asthma is resistant to treatment with glucocorticoids. The immunomodulatory protein macrophage migration inhibitory factor (MIF) promotes neutrophil recruitment to the lung and antagonises responses to glucocorticoids. We hypothesised that MIF promotes glucocorticoid resistance of neutrophilic inflammation in severe asthma.

LL-37 and HMGB1 induce alveolar damage and reduce lung tissue regeneration via RAGE.

The receptor for advanced glycation end-products (RAGE) has been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). However, it is still unknown whether RAGE directly contributes to alveolar epithelial damage and abnormal repair responses. We hypothesize that RAGE activation not only induces lung tissue damage but also hampers alveolar epithelial repair responses.

Establishing consensus for the education, training and assessment requirements of community pharmacy staff to deliver minor ailments services: A modified Delphi study.

Introduction: Minor ailments services (MASs) are pharmacy-based and support individuals to manage minor conditions. MASs are delivered by community pharmacists and non-pharmacist staff. Limited information exists regarding education, training, assessment requirements, and suitability of existing processes to support MAS delivery.

Exploration of health professional stakeholders' views and experiences regarding minor ailments services' education, training and assessment.

Background Minor ailments services are structured pharmacy-based primary health care services that manage minor conditions. Limited training, education and assessment exists to promote the delivery of minor ailments services by pharmacy staff and it is unclear if the existing training and education processes meet professional requirements. Objective To explore the views and experiences of health professional stakeholders such as community pharmacists, intern pharmacists, medicines counter assistants and general medical practitioners with regards to minor ailments services education, training and assessment practices and preferences.

RAGE and TLR4 differentially regulate airway hyperresponsiveness: Implications for COPD.

Background: The receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4) is implicated in COPD. Although these receptors share common ligands and signalling pathways, it is not known whether they act in concert to drive pathological processes in COPD. We examined the impact of RAGE and/or TLR4 gene deficiency in a mouse model of COPD and also determined whether expression of these receptors correlates with airway neutrophilia and airway hyperresponsiveness (AHR) in COPD patients.

Educational needs of community pharmacy staff in minor ailment service delivery: A systematic scoping review.

Background: Minor ailment services (MASs) are structured, protocol driven pharmacy services established locally or nationally. Community pharmacy staff may benefit from education and training to deliver MASs. Our objective was to examine the evidence regarding training, education, and assessment requirements associated with the delivery of MASs by community pharmacists and other community pharmacy staff.

HMGB1 amplifies ILC2-induced type-2 inflammation and airway smooth muscle remodelling.

Type-2 immunity elicits tissue repair and homeostasis, however dysregulated type-2 responses cause aberrant tissue remodelling, as observed in asthma. Severe respiratory viral infections in infancy predispose to later asthma, however, the processes that mediate tissue damage-induced type-2 inflammation and the origins of airway remodelling remain ill-defined. Here, using a preclinical mouse model of viral bronchiolitis, we find that increased epithelial and mesenchymal high-mobility group box 1 (HMGB1) expression is associated with increased numbers of IL-13-producing type-2 innate lymphoid cell (ILC2s) and the expansion of the airway smooth muscle (ASM) layer.

Investigating MIF in Mouse Models of Severe Corticosteroid-Resistant Neutrophilic Asthma.

Experimental mouse models of asthma are widely used to investigate the underlying mechanisms of this complex and heterogeneous disease. Using mouse models of ovalbumin-induced asthma, previous investigators have established a crucial role for MIF in the development of type 2-mediated eosinophilic asthma. Surprisingly, however, the role of MIF in other phenotypes of asthma has received little attention.

Proteomic Analysis of Extracellular HMGB1 Identifies Binding Partners and Exposes Its Potential Role in Airway Epithelial Cell Homeostasis.

The release of damage-associated molecular patterns (DAMPs) by airway epithelial cells is believed to play a crucial role in the initiation and development of chronic airway conditions such as asthma and chronic obstructive pulmonary disease (COPD). Intriguingly, the classic DAMP high-mobility group box-1 (HMGB1) is detected in the culture supernatant of airway epithelial cells under basal conditions, indicating a role for HMGB1 in the regulation of epithelial cellular and immune homeostasis. To gain contextual insight into the potential role of HMGB1 in airway epithelial cell homeostasis, we used the orthogonal and complementary methods of high-resolution clear native electrophoresis, immunoprecipitation, and pull-downs coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile HMGB1 and its binding partners in the culture supernatant of unstimulated airway epithelial cells.

Development of a Soluplus budesonide freeze-dried powder for nasal drug delivery.

Objective: The aim of this work was to develop an amorphous solid dispersions/solutions (ASD) of a poorly soluble drug, budesonide (BUD) with a novel polymer Soluplus (BASF, Germany) using a freeze-drying technique, in order to improve dissolution and absorption through the nasal route.

Significance: The small volume of fluid present in the nasal cavity limits the absorption of a poorly soluble drug. Budesonide is a corticosteroid, practically insoluble and normally administered as a suspension-based nasal spray.

Autophagy and inflammasomes.

Autophagy is a ubiquitous cellular mechanism for the targeted lysosomal degradation of various cytosolic constituents, from proteins to organelles. As an essential homeostatic mechanism, autophagy is upregulated in response to numerous environmental and pharmacological stimuli, including starvation, where it facilitates the recycling of essential amino acids. In addition, autophagy plays specific roles within the immune system; it serves as a source of peptides for antigen presentation, a mechanism for the engulfment and degradation of intracellular pathogens and as a key regulator of inflammatory cytokines.

RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma.

Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown.

The nasal delivery of nanoencapsulated statins - an approach for brain delivery.

Purpose: Along with their cholesterol-lowering effect, statins have shown a wide range of pleiotropic effects potentially beneficial to neurodegenerative diseases. However, such effects are extremely elusive via the conventional oral administration. The purpose of the present study was to prepare and characterize the physicochemical properties and the in vivo biodistribution of simvastatin-loaded lecithin/chitosan nanoparticles (SVT-LCNs) suitable for nasal administration in view of an improved delivery of the statins to the brain.

The SPARC protein: an overview of its role in lung cancer and pulmonary fibrosis and its potential role in chronic airways disease.

The SPARC (secreted protein acidic and rich in cysteine) protein is matricellular molecule regulating interactions between cells and their surrounding extracellular matrix (ECM). This protein thus governs fundamental cellular functions such as cell adhesion, proliferation and differentiation. SPARC also regulates the expression and activity of numerous growth factors and matrix metalloproteinases essential for ECM degradation and turnover.

Application of RPMI 2650 nasal cell model to a 3D printed apparatus for the testing of drug deposition and permeation of nasal products.

The aim of this study was to incorporate an optimized RPMI2650 nasal cell model into a 3D printed model of the nose to test deposition and permeation of drugs intended for use in the nose. The nasal cell model was optimized for barrier properties in terms of permeation marker and mucus production. RT-qPCR was used to determine the xenobiotic transporter gene expression of RPMI 2650 cells in comparison with primary nasal cells.

Allergen-induced IL-6 trans-signaling activates γδ T cells to promote type 2 and type 17 airway inflammation.

Background: A variant in the IL-6 receptor (IL-6R) gene increases asthma risk and is predicted to decrease IL-6 classic signaling and increase IL-6 trans-signaling. This suggests that inhibition of IL-6 trans-signaling, but not classic signaling, might suppress allergic airway inflammation.

Objectives: We sought to determine whether IL-6 signaling contributes to (1) acute experimental asthma induced by clinically relevant allergens and (2) variation in asthma clinical phenotypes in asthmatic patients.

Receptor for advanced glycation end products and its ligand high-mobility group box-1 mediate allergic airway sensitization and airway inflammation.

Background: The receptor for advanced glycation end products (RAGE) shares common ligands and signaling pathways with TLR4, a key mediator of house dust mite (Dermatophagoides pteronyssinus) (HDM) sensitization. We hypothesized that RAGE and its ligand high-mobility group box-1 (HMGB1) cooperate with TLR4 to mediate HDM sensitization.

Objectives: To determine the requirement for HMGB1 and RAGE, and their relationship with TLR4, in airway sensitization.

RAGE and TLRs: relatives, friends or neighbours?

The innate immune system forms the first line of protection against infectious and non-infectious tissue injury. Cells of the innate immune system detect pathogen-associated molecular patterns or endogenous molecules released as a result of tissue injury or inflammation through various innate immune receptors, collectively termed pattern-recognition receptors. Members of the Toll-like receptor (TLR) family of pattern-recognition receptors have well established roles in the host immune response to infection, while the receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor predominantly involved in the recognition of endogenous molecules released in the context of infection, physiological stress or chronic inflammation.

RAGE: a new frontier in chronic airways disease.

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern-recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern-recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically.