Reinforced POSE: the 18-Plication Solution.

BACKGROUND: Obesity is one of the main challenges in the first world nowadays. New alternatives are needed and endoscopic endoluminal approaches are gaining importance against the risky surgery and the non-efficient pharmacological treatments. Nevertheless, these techniques seem to be inefficient in obese III patients. The aim of the study is to demonstrate the safety and efficiency of the new reinforced POSE 18-plication protocol. METHODS: Mean body mass index (BMI) ≈ 47 kg/m2 obese type III patients were treated in different Spanish centers with the new POSE method consisting of 18 plications in the stomach body. On the other hand, 15 lower body mass patients BMI ≈ 40 kg/m2 were treated with the standard POSE method previously described. RESULTS: Three months follow-up shows an overall % total weight loss (TWL) and % excess weight loss (EWL) of 15% and 41% respectively for standard POSE and 17% and 36% for the new reinforced POSE18. Both are equally safe and the endpoint weight loss objectives are reached. Endoluminal procedures have been demonstrated to be useful in overweight and obese type I/II. However, bariatric surgery is recommended for higher BMI > 40 kg/m2. We successfully applied a non-standard POSE protocol and the patients reached 17%TWL in 3 months. CONCLUSIONS: Our study shows that reinforced POSE 18 can be successfully applied in obese type III; it is safer than bariatric surgery and there are no associated risks when compared with standard endoscopic surgery.

Structural basis for interdomain communication in SHIP2 providing high phosphatase activity.

SH2-containing-inositol-5-phosphatases (SHIPs) dephosphorylate the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) and play important roles in regulating the PI3K/Akt pathway in physiology and disease. Aiming to uncover interdomain regulatory mechanisms in SHIP2, we determined crystal structures containing the 5-phosphatase and a proximal region adopting a C2 fold. This reveals an extensive interface between the two domains, which results in significant structural changes in the phosphatase domain. Both the phosphatase and C2 domains bind phosphatidylserine lipids, which likely helps to position the active site towards its substrate. Although located distant to the active site, the C2 domain greatly enhances catalytic turnover. Employing molecular dynamics, mutagenesis and cell biology, we identify two distinct allosteric signaling pathways, emanating from hydrophobic or polar interdomain interactions, differentially affecting lipid chain or headgroup moieties of PI(3,4,5)P3. Together, this study reveals details of multilayered C2-mediated effects important for SHIP2 activity and points towards interesting new possibilities for therapeutic interventions.