RG7774 (Vicasinabin), an orally bioavailable cannabinoid receptor 2 (CB2R) agonist, decreases retinal vascular permeability, leukocyte adhesion, and ocular inflammation in animal models.

Introduction: Preclinical studies suggest that cannabinoid receptor type 2 (CB2R) activation has a therapeutic effect in animal models on chronic inflammation and vascular permeability, which are key pathological features of diabetic retinopathy (DR). A novel CB2R agonist, triazolopyrimidine RG7774, was generated through lead optimization of a high-throughput screening hit. The aim of this study was to characterize the pharmacology, absorption, distribution, metabolism, elimination, and toxicity (ADMET) profile of RG7774, and to explore its potential for managing the key pathological features associated with retinal disease in rodents.

Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study.

Background: We hypothesised that zanubrutinib, a highly selective next-generation Bruton tyrosine kinase (BTK) inhibitor, would be a safe and active treatment for patients intolerant of ibrutinib, acalabrutinib, or both. We aimed to assess whether zanubrutinib would prolong treatment duration by minimising treatment-related toxicities and discontinuations in patients with previously treated B-cell malignancies.

Methods: This ongoing, phase 2, multicentre, open-label, single-arm study was done in 20 centres in the USA.

Selective Cannabinoid 2 Receptor Agonists as Potential Therapeutic Drugs for the Treatment of Endotoxin-Induced Uveitis.

(1) Background: The cannabinoid 2 receptor (CBR) is a promising anti-inflammatory drug target and development of selective CBR ligands may be useful for treating sight-threatening ocular inflammation. (2) Methods: This study examined the pharmacology of three novel chemically-diverse selective CBR ligands: CBR agonists, RO6871304, and RO6871085, as well as a CBR inverse agonist, RO6851228. In silico molecular modelling and cell-based receptor assays were used to verify CBR interactions, binding, cell signaling (ß-arrestin and cAMP) and early absorption, distribution, metabolism, excretion, and toxicology (ADMET) profiling of these receptor ligands.

A Phase II Study of Pemetrexed in Patients with Recurrent Thymoma and Thymic Carcinoma.

Introduction: Thymoma and thymic carcinoma (TC) are neoplastic diseases with reported chemosensitivity to a broad range of agents. However, because of the rarity of these diseases, few prospective trials have been conducted in patients with advanced thymic malignancies. We conducted a prospective phase II trial to evaluate the clinical activity of pemetrexed, a multitargeted antifolate agent, in previously treated patients with thymoma and TC.

Cannabinoid 2 receptor is a novel anti-inflammatory target in experimental proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) can develop after ocular trauma or inflammation and is a common complication of surgery to correct retinal detachment. Currently, there are no pharmacological treatments for PVR. Cannabinoids acting at cannabinoid 2 receptor (CB2R) can decrease inflammation and fibrosis.

A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas.

Background: Thymomas are one of the most rarely diagnosed malignancies. To better understand its biology and to identify therapeutic targets, we performed next-generation RNA sequencing.

Methods: The RNA was sequenced from 13 thymic malignancies and 3 normal thymus glands.

Seeing over the horizon - targeting the endocannabinoid system for the treatment of ocular disease.

The observation that marijuana reduces intraocular pressure was made by Hepler and Frank in the 1970s. Since then, there has been a significant body of work investigating cannabinoids for their potential use as therapeutics. To date, no endocannabinoid system (ECS)-modulating drug has been approved for clinical use in the eye; however, recent advances in our understanding of the ECS, as well as new pharmacological tools, has renewed interest in the development of ocular ECS-based therapeutics.

Fragmented esophageal smooth muscle contraction segments on high resolution manometry: a marker of esophageal hypomotility.

Background: Esophageal peristalsis consists of a chain of contracting striated and smooth muscle segments on high resolution manometry (HRM). We compared smooth muscle contraction segments in symptomatic subjects with reflux disease to healthy controls.

Methods: High resolution manometry Clouse plots were analyzed in 110 subjects with reflux disease (50 ± 1.

Analysis of intersegmental trough and proximal latency of smooth muscle contraction using high-resolution esophageal manometry.

Background And Aims: Intersegmental troughs (ISTs) between striated and smooth muscle contraction segments on high-resolution manometry (HRM) have been linked to hypomotility disorders. We investigated the relationship between ISTs, latency of initiation of smooth muscle contraction, and motor patterns in symptomatic patients and normal controls.

Methods: HRM Clouse plots were analyzed in 199 participants (47.

Botulinum toxin injection in dysphagia syndromes with preserved esophageal peristalsis and incomplete lower esophageal sphincter relaxation.

Background: Botulinum toxin injection into the lower esophageal sphincter (LES) treats dysphagia syndromes with preserved peristalsis and incomplete LES relaxation (LESR). We evaluated clinical and esophageal motor characteristics predicting response, and compared duration of efficacy to similarly treated achalasia patients.

Methods: Thirty-six subjects (59 ± 2.

The performance of warning systems in avoiding controlled-flight-into-terrain (CFIT) accidents.

This paper examines the performance of two systems to prevent controlled-flight-into-terrain (CFIT) accidents, including their development and preimplementation issues and attitudes. The airborne version, the Ground Proximity Warning System (GPWS), was required for certain large turbine-powered airplanes. The ground-base system, the Minimum Safe Altitude Warning (MSAW) is a feature of the ARTS-3 system.