Phosphoinositides regulate force-independent interactions between talin, vinculin, and actin

Focal adhesions (FA) are large macromolecular assemblies which help transmit mechanical forces and regulatory signals between the extracellular matrix and an interacting cell. Two key proteins talin and vinculin connecting integrin to actomyosin networks in the cell. Both proteins bind to F-actin and each other, providing a foundation for network formation within FAs. However, the underlying mechanisms regulating their engagement remain unclear. Here, we report on the results of in vitro reconstitution of talin-vinculin-actin assemblies using synthetic membrane systems. We find that neither talin nor vinculin alone recruit actin filaments to the membrane. In contrast, phosphoinositide-rich membranes recruit and activate talin, and the membrane-bound talin then activates vinculin. Together, the two proteins then link actin to the membrane. Encapsulation of these components within vesicles reorganized actin into higher-order networks. Notably, these observations were made in the absence of applied force, whereby we infer that the initial assembly stage of FAs is force independent. Our findings demonstrate that the local membrane composition plays a key role in controlling the stepwise recruitment, activation, and engagement of proteins within FAs

Detecting acromegaly: Screening for disease with a morphable model

Acromegaly is a rare disorder which affects about 50 of every million people. The disease typically causes swelling of the hands, feet, and face, and eventually permanent changes to areas such as the jaw, brow ridge, and cheek bones. The disease is often missed by physicians and progresses beyond where it might if it were identified and treated earlier. We consider a semi-automated approach to detecting acromegaly, using a novel combination of support vector machines (SVMs) and a morphable model. Our training set consists of 24 frontal photographs of acromegalic patients and 25 of disease-free subjects. We modelled each subject\u27s face in an analysis-by-synthesis loop using the three-dimensional morphable face model of Blanz and Vetter. The model parameters capture many features of the 3D shape of the subject\u27s head from just a single photograph, and are used directly for classification. We report encouraging results of a classifier built from the training set of real human subjects

POstLAparoscopic Reduction of pain By combining intraperitoneal normal salinE And the pulmonary Recruitment maneuver (POLAR BEAR trial). RCT to estimate reduction in pain after laparoscopic surgery when using a combination therapy of intraperitoneal normal saline and the pulmonary recruitment maneuver

Abstract Background Shoulder pain and pain in the upper abdomen are common complaints after laparoscopy, sometimes surpassing the pain at incision sites. The incidence of shoulder pain ranges from 35 to 80%. Post-laparoscopic pain is caused by retention of carbon dioxide in the abdomen, which irritates the phrenic nerve and diaphragm, causing referred pain in the shoulder and in the upper abdomen. A promising strategy to reduce this post-laparoscopic pain is the pulmonary recruitment maneuver, which indirectly increases intraperitoneal pressure and thereby facilitates removal of residual carbon dioxide. An alternative strategy is the infusion of intraperitoneal normal saline. With normal saline infusion, carbon dioxide rises and escapes through the port sites. In addition, normal saline offers a physiologic buffer system to dissolve excess carbon dioxide. Methods/Design This multicenter randomized controlled trial is conducted in two teaching hospitals in the Netherlands. Women between 18 and 65 years of age, with an ASA classification of I-II who are scheduled to undergo an elective laparoscopic procedure with benign gynecologic indication can participate. Following informed consent, participants are randomly allocated into two groups at the end of the surgical procedure. In the intervention group, the upper abdomen is filled with normal saline infusion with the patient in the Trendelenburg position. Then the anesthesiologist performs a standardized pulmonary recruitment maneuver with a pressure of 40 cm H2O. The trocar sleeve valves will be left open, so carbon dioxide can escape the abdominal cavity. With the patient in a neutral position the instruments are removed from the abdomen. In the control group, carbon dioxide is removed from the abdominal cavity at the end of surgery, with gentle abdominal pressure and passive exsufflation through the port sites, with open sleeve valves. The primary outcomes are the incidence and intensity of post-laparoscopic pain in the shoulder, upper abdomen and at the operation sites, at 8, 24 and 48 h after surgery. Secondary outcomes are postoperative use of analgesics, nausea, vomiting and pulmonary complications. Discussion This study may reduce post-laparoscopic pain in women undergoing laparoscopy. Trial registration Dutch trial register, number NTR4812

POstLAparoscopic Reduction of pain By combining intraperitoneal normal salinE And the pulmonary Recruitment maneuver (POLAR BEAR trial). RCT to estimate reduction in pain after laparoscopic surgery when using a combination therapy of intraperitoneal normal saline and the pulmonary recruitment maneuver

Abstract Background Shoulder pain and pain in the upper abdomen are common complaints after laparoscopy, sometimes surpassing the pain at incision sites. The incidence of shoulder pain ranges from 35 to 80%. Post-laparoscopic pain is caused by retention of carbon dioxide in the abdomen, which irritates the phrenic nerve and diaphragm, causing referred pain in the shoulder and in the upper abdomen. A promising strategy to reduce this post-laparoscopic pain is the pulmonary recruitment maneuver, which indirectly increases intraperitoneal pressure and thereby facilitates removal of residual carbon dioxide. An alternative strategy is the infusion of intraperitoneal normal saline. With normal saline infusion, carbon dioxide rises and escapes through the port sites. In addition, normal saline offers a physiologic buffer system to dissolve excess carbon dioxide. Methods/Design This multicenter randomized controlled trial is conducted in two teaching hospitals in the Netherlands. Women between 18 and 65 years of age, with an ASA classification of I-II who are scheduled to undergo an elective laparoscopic procedure with benign gynecologic indication can participate. Following informed consent, participants are randomly allocated into two groups at the end of the surgical procedure. In the intervention group, the upper abdomen is filled with normal saline infusion with the patient in the Trendelenburg position. Then the anesthesiologist performs a standardized pulmonary recruitment maneuver with a pressure of 40 cm H2O. The trocar sleeve valves will be left open, so carbon dioxide can escape the abdominal cavity. With the patient in a neutral position the instruments are removed from the abdomen. In the control group, carbon dioxide is removed from the abdominal cavity at the end of surgery, with gentle abdominal pressure and passive exsufflation through the port sites, with open sleeve valves. The primary outcomes are the incidence and intensity of post-laparoscopic pain in the shoulder, upper abdomen and at the operation sites, at 8, 24 and 48 h after surgery. Secondary outcomes are postoperative use of analgesics, nausea, vomiting and pulmonary complications. Discussion This study may reduce post-laparoscopic pain in women undergoing laparoscopy. Trial registration Dutch trial register, number NTR4812

Randomised controlled trial to estimate reduction in pain after laparoscopic surgery when using a combination therapy of intraperitoneal normal saline and the pulmonary recruitment manoeuvre

ObjectiveTo evaluate the effect of two manoeuvres at the end of gynaecological laparoscopy on postoperative pain. DesignRandomised controlled trial. SettingOne teaching and one university hospital in the Netherlands. SampleWomen aged between 18 and 65 years, with American Society of Anaesthesiologists (ASA) classification I-II, scheduled for an elective laparoscopic procedure for a benign gynaecological indication. MethodsWomen were randomly allocated to two groups. In the intervention group, carbon dioxide was removed from the abdomen by a combination treatment of intraperitoneal warm saline and performing a pulmonary recruitment manoeuvre. In the control group, carbon dioxide was removed with gentle abdominal pressure. Main outcome measuresFrequency and intensity of post-laparoscopic shoulder pain and pain in the upper abdomen at 8, 24, and 48 hours after surgery. ResultsA total of 200 women participated, with 100 in each group. No difference was observed in the occurrence of post-laparoscopic shoulder pain during the first 48 hours after surgery between the intervention group (46%) and the control group (55%). The incidence of abdominal pain was not significantly different between the two groups. The mean visual analogue scale (VAS) scores of participants who reported shoulder pain were not statistically different between the groups. The mean VAS score for abdominal pain at 8 hours after surgery was significantly lower in the intervention group compared with the control group (3.2 versus 4.2, P = 0.02). No difference in pain medication between the groups was observed, nor was there any difference in nausea or vomiting. ConclusionsCombined intervention of intraperitoneal saline and the pulmonary recruitment manoeuvre does not lower post-laparoscopic shoulder pain. FundingThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Tweetable abstractPRM with intraperitoneal saline does not influence the incidence and intensity of post-laparoscopic shoulder pain. Tweetable abstract PRM with intraperitoneal saline does not influence the incidence and intensity of post-laparoscopic shoulder pain