National Trends in the Surgical Management of Adolescent Idiopathic Scoliosis: Analysis of a National Estimate of 60,108 Children From the National Inpatient Sample Over a 13-Year Time Period in the United States.

Study Design: Analysis of Nationwide Inpatient Sample (NIS).

Objective: Evaluate evolution of operative treatment of adolescent idiopathic scoliosis (AIS).

Summary Of Background Data: Spinal surgery is one of the most rapidly evolving branches of surgery.

Pannexin 1, an ATP release channel, is activated by caspase cleavage of its pore-associated C-terminal autoinhibitory region.

Pannexin 1 (PANX1) channels mediate release of ATP, a "find-me" signal that recruits macrophages to apoptotic cells; PANX1 activation during apoptosis requires caspase-mediated cleavage of PANX1 at its C terminus, but how the C terminus inhibits basal channel activity is not understood. Here, we provide evidence suggesting that the C terminus interacts with the human PANX1 (hPANX1) pore and that cleavage-mediated channel activation requires disruption of this inhibitory interaction. Basally silent hPANX1 channels localized on the cell membrane could be activated directly by protease-mediated C-terminal cleavage, without additional apoptotic effectors.

Pannexin1 regulates α1-adrenergic receptor- mediated vasoconstriction.

Rationale: The coordination of vascular smooth muscle cell constriction plays an important role in vascular function, such as regulation of blood pressure; however, the mechanism responsible for vascular smooth muscle cell communication is not clear in the resistance vasculature. Pannexins (Panx) are purine-releasing channels permeable to the vasoconstrictor ATP and thus may play a role in the coordination of vascular smooth muscle cell constriction.

Objective: We investigated the role of pannexins in phenylephrine- and KCl-mediated constriction of resistance arteries.

Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis.

Apoptotic cells release 'find-me' signals at the earliest stages of death to recruit phagocytes. The nucleotides ATP and UTP represent one class of find-me signals, but their mechanism of release is not known. Here, we identify the plasma membrane channel pannexin 1 (PANX1) as a mediator of find-me signal/nucleotide release from apoptotic cells.

The role of nucleotides in apoptotic cell clearance: implications for disease pathogenesis.

Apoptosis occurs in many tissues, during both normal and pathogenic processes. Normally, apoptotic cells are rapidly cleared, either by neighboring or recruited phagocytes. The prompt clearance of apoptotic cells requires that the apoptotic cells announce their presence through the release of chemotactic factors, known as "find-me" signals, to recruit phagocytes to the site of death, and through the exposure of so-called "eat-me" signals, which are ligands for phagocytic uptake.

Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance.

Phagocytic removal of apoptotic cells occurs efficiently in vivo such that even in tissues with significant apoptosis, very few apoptotic cells are detectable. This is thought to be due to the release of 'find-me' signals by apoptotic cells that recruit motile phagocytes such as monocytes, macrophages and dendritic cells, leading to the prompt clearance of the dying cells. However, the identity and in vivo relevance of such find-me signals are not well understood.