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Membrane curvature is essential for many cellular structures and processes, and factors such as leaflet asymmetry, lipid composition, and proteins all play important roles. Cardiolipin is the signature lipid of mitochondrial membranes and is essential for maintaining the highly curved shapes of the inner mitochondrial membrane (IMM) and the spatial arrangement of membrane proteins. In this study, we investigate the partitioning behavior of various lipids present in the IMM using coarse-grained molecular dynamics simulations. This study explores curved bilayer systems containing phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CDL) in binary and ternary component mixtures. Curvature properties such as mean and Gaussian curvatures, as well as the distribution of lipids into the various curved regions of the cristae models, are quantified. Overall, this work represents an advance beyond previous studies on lipid curvature sensing by simulating these systems in a geometry that has the morphological features and scales of curvature consistent with regions of the IMM. We find that CDL has a stronger preference for accumulating in regions of negative curvature than PE lipids, in agreement with previous results. Furthermore, we find lipid partitioning propensity is dominated by sensitivity to mean curvature, while there is a weaker correlation with Gaussian curvature.
Assuntos
Cardiolipinas , Membranas Mitocondriais , Proteínas de Membrana , Simulação de Dinâmica Molecular , Distribuição NormalRESUMO
Introduction: Adnexal torsion is an emergent surgical condition. Transabdominal pelvic ultrasound (US) with ovarian Doppler is used to diagnose adnexal torsion and requires a sufficient bladder volume. Reduce the turnaround time for US by 25% in girls 8-18 years of age who present to the emergency department (ED) for 24 months. Methods: Our baseline period was from January 2020 to June 2021, and the intervention period was from July 2021 to June 2023. Patients 8-18 years old who required an US in the ED were included. There are two key drivers: early identification of US readiness and expeditious bladder filling. Interventions were (1) bladder volume screening; (2) utilization of bladder volume nomogram to identify US readiness; (3) epic order panels; and (4) rapid intravenous fluid method. The primary outcome was US turnaround time. Secondary outcomes were percentage of patients requiring invasive interventions to fill the bladder and patients with an US study duration of ≤45 minutes. The percent of patients screened by bladder scan was used as a process measure. Balancing measures used episodes of fluid overload and ED length of stay. Results: Turnaround time for USs improved from 112.4 to 101.6 minutes. The percentage of patients who had successful USs without invasive bladder filling improved from 32.1% to 42.6%. Bladder volume screening using a bladder scan increased from 40.3% to 82.9%. The successful first-pass US completion rate improved from 77% to 90% consistently. Conclusions: Through quality improvement methodology, we have identified pelvic US readiness earlier, eliminated some invasive bladder-filling measures, and implemented a rapid fluid protocol. We have sustained these successful results for 2 years. This study can be generalized to any ED with similar patients.
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Introduction: Testicular torsion (TT) is a urologic emergency that requires timely diagnosis and surgery. We noted variation in the door-to-detorsion times for patients with TT at our institution and our orchiectomy rate was 25.8%. We aimed to decrease the mean door-to-detorsion time from 124.6 to 114.6 minutes or less over 12 months. Methods: A multidisciplinary team of pediatric emergency medicine, radiology, urology physicians, and nurses, was formed. Our key drivers were use of Testicular Workup for Ischemia and Suspected Torsion (TWIST) score, prompt urology consultation, and efficient transfer from emergency department (ED) to operating room. Our process measures were TWIST score documentation rate and early urology consultation rate, outcome measures were door-to-detorsion time and orchiectomy rate, and balancing measure was ultrasound utilization rate. Early urology consultation occurred when the ED provider documented telephone communication with urology, immediately after placing a testicular doppler ultrasound (TDUS) order and before TDUS result. Results: Over 2 years, 45 cases of TT were diagnosed. TWIST score documentation was implemented and was sustained at 78%. This improved early urology consultations from 40% to 60%. The mean door-to-detorsion time improved from 124.6 to 114.2 minutes. There was no reduction in the orchiectomy rate or TDUS utilization rate. Conclusions: A quality improvement project to improve the timeliness of care for children with TT resulted in expedited ED care but did not impact the orchiectomy rate.