Mechanistic insights into the selective targeting of P2X3 receptor by camlipixant antagonist.

ATP-activated P2X3 receptors play a pivotal role in chronic cough, affecting more than 10% of the population. Despite the challenges posed by the highly conserved structure of P2X receptors, efforts to develop selective drugs targeting P2X3 have led to the development of camlipixant, a potent, selective P2X3 antagonist. However, the mechanisms of receptor desensitization, ion permeation, and structural basis of camlipixant binding to P2X3 remain unclear.

Practices of assessment of pain, sedation, iatrogenic withdrawal syndrome, and delirium in European paediatric intensive care units: A secondary analysis of the European Prevalence of Acute Rehab for Kids in the paediatric intensive care unit study.

Background: Analgosedation is standard practice to ensure comfort and safety of critically ill children in paediatric intensive care units (PICUs). However, a significant number of children develop iatrogenic withdrawal syndrome or delirium with these drugs. The European Society of Paediatric and Neonatal Intensive Care published a position statement in 2016, but how successfully its recommendations have been implemented is unknown.

Extended Synaptotagmins 1 and 2 Are Required for Store-Operated Calcium Entry, Cell Migration and Viability in Breast Cancer Cells.

Extended synaptotagmins (E-Syts) are endoplasmic reticulum (ER)-associated proteins that facilitate the tethering of the ER to the plasma membrane (PM), participating in lipid transfer between the membranes and supporting the Orai1-STIM1 interaction at ER-PM junctions. Orai1 and STIM1 are the core proteins of store-operated Ca entry (SOCE), a major mechanism for Ca influx that regulates a variety of cellular functions. Aberrant modulation of SOCE in cells from different types of cancer has been reported to underlie the development of several tumoral features.