NSW cannabis medicines advisory service retrospective enquiry analysis to inform clinical guidance resource development.

Background: An innovative New South Wales government funded statewide Cannabis Medicines Advisory Service (CMAS) operated between January 2018 and June 2022. The service provided comprehensive patient-specific and evidence-based information to support health professionals in prescribing and patient care decisions. This study aimed to describe real-world data collected by CMAS.

Monocyte NLRP3 inflammasome and interleukin-1β activation modulated by alpha-1 antitrypsin therapy in deficient individuals.

Introduction: Altered complement component 3 (C3) activation in patients with alpha-1 antitrypsin (AAT) deficiency (AATD) has been reported. To understand the potential impact on course of inflammation, the aim of this study was to investigate whether C3d, a cleavage-product of C3, triggers interleukin (IL)-1β secretion via activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. The objective was to explore the effect of AAT augmentation therapy in patients with AATD on the C3d/complement receptor 3 (CR3) signalling axis of monocytes and on circulating pro-inflammatory markers.

Tumor innervation is triggered by endoplasmic reticulum stress.

Nerve infiltration in the tumor microenvironment is emerging as a promoter of cancer progression that could be targeted in therapies, but the mechanisms initiating tumor innervation remain to be elucidated. Here we report that endoplasmic reticulum (ER) stress in cancer cells is transmitted to neuronal cells, resulting in neurite outgrowth and tumor innervation. In vitro, the induction of ER stress in various human cancer cells resulted in the synthesis and release of the precursor for brain-derived neurotrophic factor (proBDNF) through a mechanism dependent on the transcription factor X-box binding protein 1 (XBP1).

Over the counter low-dose cannabidiol: A viewpoint from the ACRE Capacity Building Group.

Amidst growing global acceptance of medicinal cannabinoids as a potential therapeutic interest in cannabidiol (CBD) is increasing. In Australia in 2020, a government inquiry examined the barriers that the public are experiencing in accessing medicinal cannabis. A number of recommendations to improve access were made.

Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid.

Background: Cannabidiol (CBD) confers therapeutic effects in some neurological disorders via modulation of inflammatory, oxidative and cell-signalling pathways. However, CBD is lipophilic and highly photooxidative with low oral bioavailability in plasma and brain. In this study, we aimed to design and test a CBD microencapsulation method as a drug delivery strategy to improve the absorption of CBD.

Pseudomonas aeruginosa associated with severity of non-cystic fibrosis bronchiectasis measured by the modified bronchiectasis severity score (BSI) and the FACED: The US bronchiectasis and NTM Research Registry (BRR) study.

Rationale: Non-cystic fibrosis bronchiectasis (NCFB) is characterized by dilated bronchi, poor mucus clearance and susceptibility to bacterial infection. Pseudomonas aeruginosa (PA) is one of the most frequently isolated pathogens in patients with NCFB. The purpose of this study was to evaluate the association between presence of PA and disease severity in patients within the US Bronchiectasis and Nontuberculous mycobacteria (NTM) Research Registry (BRR).

Nutrition and Markers of Disease Severity in Patients With Bronchiectasis.

Background: Increasing numbers of patients are being diagnosed with bronchiectasis, yet much remains to be elucidated about this heterogeneous patient population. We sought to determine the relationship between nutrition and health outcomes in non-cystic fibrosis (non-CF) bronchiectasis, using data from the U.S.

Airway Clearance Techniques in Bronchiectasis: Analysis From the United States Bronchiectasis and Non-TB Mycobacteria Research Registry.

Background: In patients with bronchiectasis, airway clearance techniques (ACTs) are important management strategies.

Research Question: What are the differences in patients with bronchiectasis and a productive cough who used ACTs and those who did not? What was the assessment of bronchiectasis exacerbation frequency and change in pulmonary function at 1-year follow up?

Study Design And Methods: Adult patients with bronchiectasis and a productive cough in the United States Bronchiectasis and NTM Research Registry were included in the analyses. ACTs included the use of instrumental devices and manual techniques.

The Clinical Features of Bronchiectasis Associated with Alpha-1 Antitrypsin Deficiency, Common Variable Immunodeficiency and Primary Ciliary Dyskinesia--Results from the U.S. Bronchiectasis Research Registry.

Objective: This study compares and contrasts the clinical features of non-cystic fibrosis bronchiectasis with 3 uncommon disorders known to be associated with bronchiectasis but with distinctly different underlying defined pathophysiologic derangements, namely severe alpha-1 antitrypsin deficiency (AATD), common variable immunodeficiency (CVI) and primary ciliary dyskinesia (PCD).

Methods: The Bronchiectasis Research Registry provides a central database for studying patients with non-cystic fibrosis bronchiectasis. This report consists of information from 13 U.

Phospholipid transfer protein and alpha-1 antitrypsin regulate Hck kinase activity during neutrophil degranulation.

Excessive neutrophil degranulation is a common feature of many inflammatory disorders, including alpha-1 antitrypsin (AAT) deficiency. Our group has demonstrated that phospholipid transfer protein (PLTP) prevents neutrophil degranulation but serine proteases, which AAT inhibits, cleave PLTP in diseased airways. We propose to identify if airway PLTP activity can be restored by AAT augmentation therapy and how PLTP subdues degranulation of neutrophils in AAT deficient subjects.

The Prevalence and Significance of Staphylococcus aureus in Patients with Non-Cystic Fibrosis Bronchiectasis.

Rationale: Staphylococcus aureus is commonly cultured from the sputum of patients with bronchiectasis; however, little is known about the prevalence of the organism in these patients, the characteristics of patients who have grown the organism, or its implications.

Objectives: Determine the relationship between S. aureus and pulmonary function, frequency of exacerbations, and frequency of hospitalization in patients with bronchiectasis Methods: The Bronchiectasis Research Registry is a database of adults with non-cystic fibrosis bronchiectasis identified from 13 sites within the United States.

Understanding gas capacity, guest selectivity, and diffusion in porous liquids.

Porous liquids are a new class of material that could have applications in areas such as gas separation and homogeneous catalysis. Here we use a combination of measurement techniques, molecular simulations, and control experiments to advance the quantitative understanding of these liquids. In particular, we show that the cage cavities remain unoccupied in the absence of a suitable guest, and that the liquids can adsorb large quantities of gas, with gas occupancy in the cages as high as 72% and 74% for Xe and SF, respectively.

Pharmacotherapy for Non-Cystic Fibrosis Bronchiectasis: Results From an NTM Info & Research Patient Survey and the Bronchiectasis and NTM Research Registry.

Background: Non-cystic fibrosis bronchiectasis ("bronchiectasis") is a chronic inflammatory lung disease often associated with nontuberculous mycobacteria (NTM) infection. Very little data exist to guide bronchiectasis management decisions. We sought to describe patterns of inhaled corticosteroid (ICS) and antibiotic therapy in the United States.

Diaphragm Muscle Thinning in Subjects Receiving Mechanical Ventilation and Its Effect on Extubation.

Background: Diaphragm muscle weakness and atrophy are consequences of prolonged mechanical ventilation. Our purpose was to determine whether thickness of the diaphragm (TDI) changes over time after intubation and whether the degree of change affects clinical outcome.

Methods: For this prospective, longitudinal observational study, we identified subjects who required mechanical ventilation and measured their TDI by ultrasonography.

Improvement in Physical Activity in Persons With Obstructive Sleep Apnea Treated With Continuous Positive Airway Pressure.

Background: Exercise improves sleep quality, yet people with untreated obstructive sleep apnea (OSA) may engage in less physical activity (PA) due to fatigue and daytime sleepiness. We examined changes in PA and sleep quality before and after treatment with continuous positive airway pressure (CPAP) in OSA patients.

Methods: In this prospective longitudinal study, persons with a primary diagnosis of OSA were enrolled at a community-based hospital in New York City.

Adult Patients With Bronchiectasis: A First Look at the US Bronchiectasis Research Registry.

Objectives: We sought to describe the characteristics of adult patients with bronchiectasis enrolled in the US Bronchiectasis Research Registry (BRR).

Methods: The BRR is a database of patients with non-cystic-fibrosis bronchiectasis (NCFB) enrolled at 13 sites in the United States. Baseline demographic, spirometric, imaging, microbiological, and therapeutic data were entered into a central Internet-based database.

Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner.

Background: The use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established. Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades. To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells.

TLR9 expression is required for the development of cigarette smoke-induced emphysema in mice.

The expression of Toll-like receptor (TLR)-9, a pathogen recognition receptor that recognizes unmethylated CpG sequences in microbial DNA molecules, is linked to the pathogenesis of several lung diseases. TLR9 expression and signaling was investigated in animal and cell models of chronic obstructive pulmonary disease (COPD). We observed enhanced TLR9 expression in mouse lungs following exposure to cigarette smoke.

Spatially resolved multicomponent gels.

Multicomponent supramolecular systems could be used to prepare exciting new functional materials, but it is often challenging to control the assembly across multiple length scales. Here we report a simple approach to forming patterned, spatially resolved multicomponent supramolecular hydrogels. A multicomponent gel is first formed from two low-molecular-weight gelators and consists of two types of fibre, each formed by only one gelator.

Matrix Metalloproteinase 9 Exerts Antiviral Activity against Respiratory Syncytial Virus.

Increased lung levels of matrix metalloproteinase 9 (MMP9) are frequently observed during respiratory syncytial virus (RSV) infection and elevated MMP9 concentrations are associated with severe disease. However little is known of the functional role of MMP9 during lung infection with RSV. To determine whether MMP9 exerted direct antiviral potential, active MMP9 was incubated with RSV, which showed that MMP9 directly prevented RSV infectivity to airway epithelial cells.

Desmosine and Isodesmosine as a Novel Biomarker for Pulmonary Arterial Hypertension: A Pilot Study.

Delayed diagnosis is common in patients with pulmonary arterial hypertension (PAH). Right-sided heart catheterization, the gold standard for diagnosis, is invasive and cannot be applied for routine screening. Some biomarkers have been looked into; however, due to the lack of a clear pathological mechanism linking the marker to PAH, the search for an ideal one is still ongoing.

α1-Antitrypsin activates protein phosphatase 2A to counter lung inflammatory responses.

Rationale: α1-Antitrypsin (A1AT) was identified as a plasma protease inhibitor; however, it is now recognized as a multifunctional protein that modulates immunity, inflammation, proteostasis, apoptosis, and cellular senescence. Like A1AT, protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, regulates similar biologic processes and plays a key role in chronic obstructive pulmonary disease.

Objectives: Given their common effects, this study investigated whether A1AT acts via PP2A to alter tumor necrosis factor (TNF) signaling, inflammation, and proteolytic responses in this disease.

The effect of self-sorting and co-assembly on the mechanical properties of low molecular weight hydrogels.

Self-sorting in low molecular weight hydrogels can be achieved using a pH triggered approach. We show here that this method can be used to prepare gels with different types of mechanical properties. Cooperative, disruptive or orthogonal assembled systems can be produced.

Cathepsin G degradation of phospholipid transfer protein (PLTP) augments pulmonary inflammation.

Phospholipid transfer protein (PLTP) regulates phospholipid transport in the circulation and is highly expressed within the lung epithelium, where it is secreted into the alveolar space. Since PLTP expression is increased in chronic obstructive pulmonary disease (COPD), this study aimed to determine how PLTP affects lung signaling and inflammation. Despite its increased expression, PLTP activity decreased by 80% in COPD bronchoalveolar lavage fluid (BALF) due to serine protease cleavage, primarily by cathepsin G.