Squaramides enhance NLRP3 inflammasome activation by lowering intracellular potassium.

The NLRP3 inflammasome is a component of the inflammatory response to infection and injury, orchestrating the maturation and release of the pro-inflammatory cytokines interleukin-1β (IL-1β), IL-18, and triggering pyroptotic cell death. Appropriate levels of NLRP3 activation are needed to avoid excessive tissue damage while ensuring host protection. Here we report a role for symmetrical diarylsquaramides as selective K efflux-dependent NLRP3 inflammasome enhancers.

Anal sac mast cell tumor in a dog.

An 11-year-old castrated mixed-breed dog was diagnosed with a unilateral anal sac mass. Anal sacculectomy was performed without complication. Histopathology of the mass was consistent with a well-differentiated mast cell tumor.

Selective inhibition of the K efflux sensitive NLRP3 pathway by Cl channel modulation.

The NLRP3 inflammasome regulates production of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, and contributes to inflammation exacerbating disease. Fenamate non-steroidal anti-inflammatory drugs (NSAIDs) were recently described as NLRP3 inflammasome inhibitors chloride channel inhibition. Fenamate NSAIDs inhibit cyclooxygenase (COX) enzymes, limiting their potential as therapeutics for NLRP3-associated diseases due to established side effects.

Responsible Practice or Restricted Practice? an Empirical Study of the Use of Clinical Guidelines in Medical Negligence Litigation.

In medical negligence litigation, the standard for breach of duty is measured against the Bolam test which reflects accepted practice. Despite protracted debate and common law development, the Bolam standard remains the touchstone for litigation in this area. Clinical guidelines (CGs) are statements based upon best available medical evidence and are designed to facilitate clinical decision-making to optimise outcomes thereby reflecting expected practice.

LRRC8A is essential for hypotonicity-, but not for DAMP-induced NLRP3 inflammasome activation.

The NLRP3 inflammasome is a multi-molecular protein complex that converts inactive cytokine precursors into active forms of IL-1β and IL-18. The NLRP3 inflammasome is frequently associated with the damaging inflammation of non-communicable disease states and is considered an attractive therapeutic target. However, there is much regarding the mechanism of NLRP3 activation that remains unknown.