Putnammonaghan3578

Human GLUT2 and GLUT3, members of the GLUT/SLC2 gene family, facilitate glucose transport in specific tissues. Their malfunction or misregulation is associated with serious diseases, including diabetes, metabolic syndrome, and cancer. Despite being promising drug targets, GLUTs have only a few specific inhibitors. To identify and characterize potential GLUT2 and GLUT3 ligands, we developed a whole-cell system based on a yeast strain deficient in hexose uptake, whose growth defect on glucose can be rescued by the functional expression of human transporters. The simplicity of handling yeast cells makes this platform convenient for screening potential GLUT2 and GLUT3 inhibitors in a growth-based manner, amenable to high-throughput approaches. Moreover, our expression system is less laborious for detailed kinetic characterization of inhibitors than alternative methods such as the preparation of proteoliposomes or uptake assays in Xenopus oocytes. We show that functional expression of GLUT2 in yeast requires the deletion of the extended extracellular loop connecting transmembrane domains TM1 and TM2, which appears to negatively affect the trafficking of the transporter in the heterologous expression system. Furthermore, single amino acid substitutions at specific positions of the transporter sequence appear to positively affect the functionality of both GLUT2 and GLUT3 in yeast. We show that these variants are sensitive to known inhibitors phloretin and quercetin, demonstrating the potential of our expression systems to significantly accelerate the discovery of compounds that modulate the hexose transport activity of GLUT2 and GLUT3.Background Multivisceral transplantation entails the en-bloc transplantation of stomach, duodenum, pancreas, liver and bowel following resection of the native organs. Diffuse portomesenteric thrombosis, defined as the complete occlusion of the portal system, can lead to life-threatening gastrointestinal bleeding, malnutrition and can be associated with liver and intestinal failure. Multivisceral transplantation is the only procedure that offers a definitive solution by completely replacing the portal system. However, this procedure is technically challenging in this setting. The aim of this study is to describe our experience, highlight the challenges and propose technical solutions. Materials and Methods We performed a retrospective analysis of our cohort undergoing multivisceral transplantation for diffuse portomesenteric thrombosis at our institution from 2000 to 2020. Donor and recipient demographics and surgical strategies were reviewed in detail and posttransplant complications and survival were analyzed. Results Five patients underwent MVTx. Median age was 47 years (23-62). All had diffuse portomesenteric thrombosis with life-threatening variceal bleeding. Major blood loss during exenteration was avoided by combining two techniques embolization of the native organs followed by a novel, staged extraction. This prevented major perioperative blood loss [median intra-operative transfusion of 3 packed red blood cell units (0-5)]. Median CIT was 330 min (316-416). There was no perioperative death. One patient died due to invasive aspergillosis. Four others are alive and well with a median follow-up of 4.1 years (0.3-5.9). Conclusions Multivisceral transplantation should be considered in patients with diffuse portomesenteric thrombosis that cannot be treated by any other means. Asunaprevir chemical structure We propose a standardized surgical approach to limit the operative risk and improve the outcome.Introduction The Clavien-Dindo classification is a broadly accepted surgical complications classification system, grading complications by the extent of therapy necessary to resolve them. A drawback of the method is that it does not consider why the patient was operated on primarily. Methods We designed a novel index based on Clavien-Dindo but with respect to the surgical indication. We surveyed an international panel of otolaryngologists who filled out a questionnaire with 32 real case-inspired scenarios. Each case was graded for the surgical complication, surgical indication, and a subjective rating whether the complication was acceptable or not. Results Seventy-seven otolaryngologists responded to the survey. Mean subjective rating and surgical complication grading for each scenario showed an inverse correlation (r2 = 0.147, p = 0.044). When grading the surgical complication with respect to the surgical indication, the correlation with the subjective rating increased dramatically (r2 = 0.307, p = 0.0022). Conclusion We describe a novel index grading surgical complications with respect to the surgical indication. In our survey, most respondents judged a complication as acceptable or not according to its grade but kept in mind the surgical indication. This subjective judgment could be quantified with our novel index.Purpose The study aimed to investigate the risk factors for postoperative ileus (POI) after small intestinal fistula excision (SIFE) in patients with diffuse extensive abdominal adhesions. Methods From October 2010 to December 2019, we enrolled patients who underwent SIFE and had diffuse extensive abdominal adhesions. Patients were divided into the POI group and the non-POI group according to its occurrence. We then investigated and analyzed the clinical characteristics of both groups. Result A total of 247 patients were enrolled into the study. There were 100 patients in the POI group, and 147 patients in the non-POI group. A multi-variable logistic regression analysis revealed that blood loss during SIFE (OR = 1.001; 95% CI 1.000-1.259; P = 0.012), postoperative lactate(OR = 1.212; 95% CI 1.001-1.304; P = 0.015), grade V abdominal adhesions (OR = 2.518; 95% CI 1.814-3.44; P = 0.024), and time for recovery of lactate less then 2 mmol/L (OR = 2.079; 95% CI 1.599-3.616; P = 0.026) were associated with POI. Moreover, POI was also associated with prolonged postoperative stay in the hospital (HR = 3.291; 95% CI 2.511-4.172; P = 0.014). Conclusion Blood loss during operation, grade V abdominal adhesions, positive fluid balance within 48 h of operation, and time for recovery of lactate were the risk factors for POI after SIFE in patients with diffuse extensive abdominal adhesions.