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5% to 10.4%; P less then 0.001) and at 18 cases for CR-IM (30.7% to 18.6%; P less then 0.001) from RA-CUSUM curve analysis. CONCLUSION Our data suggest that 18 supervised cases of endoscopic ablation may be required before competency in endoscopic treatment of Barrett’s dysplasia can be achieved. The difference in outcomes between a high-volume and low-volume center does not support further centralization of services to only high-volume centers. BACKGROUND AND AIMS In recent years, the feasibility and safety of endoscopic placement of different biodegradable biliary stents has been investigated. New, helicoidally shaped, biliary and pancreatic biodegradable stents have been developed for endoscopic use. Stents are provided in different sizes and with 3 expected speeds of degradation slow (11 weeks), medium (20 days), and fast (12 days). The aim of this study was to evaluate degradation time, technical outcomes, and safety of these stents (NCT03767166). METHODS This was a single-center, prospective, pilot study (August 2018 – January 2019) of consecutive patients with indication to biliary or pancreatic plastic stent positioning during ERCP. The primary outcome was the evaluation of degradation time of the stents which was controlled by abdominal radiograph. Secondary outcomes were the evaluation of specific stent-related technical features (loadability, pushability and fluoroscopic visibility), as compared with commonly used plastic stents and adversimes, and technically successful in a variety of indications. Further randomized multicenter studies are required to validate our preliminary findings. BACKGROUND AND AIMS The management of ampullary adenomas in familial adenomatous polyposis (FAP) is challenging due to multiple adenomas in the duodenum, history of prior major abdominal surgery, and desmoid lesions. In this study, we aim to define the optimum management for ampullary adenomas, particularly in FAP. METHODS This is a retrospective study of all patients with a pathology-confirmed ampullary adenomas in M.D. Anderson Cancer Center from 2002 to 2018. Relevant data were extracted including patient demographics, treatments, outcomes, and adverse events. RESULTS There were 137 patients with ampullary adenomas who underwent 159 procedures; 95 of the 137 patients had FAP and were placed under close observation; 29 underwent endoscopic ampullectomy; 4 surgical ampullectomy; and 31 panreaticoduodenectomy (PD). In the close observation group, 12.6% progressed to advanced adenoma, and subsequently underwent resection. There was no ampullary cancer detected in this group. The endoscopic ampullectomy group had postprocedure adverse event of 10.2%. Eleven patients had residual/recurrent disease postendoscopic ampullectomy with 3 requiring surgery. Four patients underwent initial surgical ampullectomy with 2 subsequently requiring PD. Patients who underwent PD had a adverse event rate of 29%. In this group, there were no residual disease or recurrence. CONCLUSIONS The management of ampullary adenomas in FAP should be carefully selected for the best outcome. Although these can be managed by endoscopic ampullectomy, careful surveillance for recurrence should be followed along with prompt management of the recurrence when detected. Although pancreaticoduodenectomy provides a definitive treatment, it is limited by the patient’s comorbid conditions and high adverse event rates. The plant defensin HsAFP1 is characterized by broad-spectrum antifungal activity and induces apoptosis in Candida albicans. In this study, we performed a transcriptome analysis on C. albicans cultures treated with HsAFP1 to gain further insight in the antifungal mode of action of HsAFP1. Various genes coding for cell surface proteins, like glycosylphosphatidylinositol (GPI)-anchored proteins, and proteins involved in cation homeostasis, autophagy and in cell cycle were differentially expressed upon HsAFP1 treatment. The biological validation of these findings was performed in the model yeast Saccharomyces cerevisiae. To discriminate between events linked to HsAFP1’s antifungal activity and those that are not, we additionally used an inactive HsAFP1 mutant. We demonstrated that (i) HsAFP1-resistent S. cerevisiae mutants that are characterized by a defect in processing GPI-anchors are unable to internalize HsAFP1, and (ii) moderate doses (FC50, fungicidal concentration resulting in 50% killing) of HsAFP1 induce autophagy in S. cerevisiae, while high HsAFP1 doses result in vacuolar dysfunction. Vacuolar function is an important determinant of replicative lifespan (RLS) under dietary restriction (DR). In line, HsAFP1 specifically reduces RLS under DR. Lastly, (iii) HsAFP1 affects S. cerevisiae cell cycle in the G2/M phase. However, the latter HsAFP1-induced event is not linked to its antifungal activity, as the inactive HsAFP1 mutant also impairs the G2/M phase. In conclusion, we demonstrated that GPI-anchored proteins are involved in HsAFP1’s internalization, and that HsAFP1 induces autophagy, vacuolar dysfunction and impairment of the cell cycle. Collectively, all these data provide novel insights in the mode of action of HsAFP1 as well as in S. cerevisiae tolerance mechanisms against this peptide. Living matter is a quasi-stationary out-of-equilibrium system; in this physical condition, structural fluctuations at nano- and meso-scales are needed to understand the physics behind its biological functionality. Myelin has a simple ultrastructure whose fluctuations show correlated disorder in its functional out-of-equilibrium state. However, there is no information on the relationship between this correlated disorder and the dynamics of the intrinsically disordered Myelin Basic Protein (MBP) which is expected to influence the membrane structure and overall functionality. In this work, we have investigated the role of this protein structural dynamics in the myelin ultrastructure fluctuations in various conditions, by using synchrotron Scanning micro X Ray Diffraction and Small Angle X ray Scattering. We have induced the crossover from out-of-equilibrium functional state to in-equilibrium degeneration changing the pH to values far from physiological condition. The observed compression of the cytosolic layer thickness probes that the intrinsic large MBP fluctuations preserve the cytosol structure also in the degraded state. Thus, the transition of myelin ultrastructure from correlated to uncorrelated disordered state, is principally affected by the deformation of the membrane and extracellular domain. Daptomycin is a lipopeptide antibiotic that is important in the treatment of infections with Gram-positive bacteria. In the presence of calcium, daptomycin binds to phosphatidylglycerol in the bacterial cytoplasmic membrane and then forms oligomers that mediate its bactericidal effect. The structure of these bactericidal oligomers has not been elucidated. We here explore the feasibility of structural studies on the oligomer by solution-state NMR. To this end, we use nanodiscs that contain DMPC and DMPG, stabilized with a styrene-maleic acid copolymer that has been modified to minimize calcium chelation. We show that these nanodiscs bind daptomycin and induce the formation of stable oligomers under physiologically relevant conditions. GCN2IN1 The findings suggest that this membrane model is suitable for structural and functional characterization of oligomeric daptomycin, and possibly of other calcium-dependent lipopeptide antibiotics. We show that these nanodiscs bind daptomycin and induce the formation of stable oligomers, under conditions that are suitable for biomolecular NMR. The findings suggest that this membrane model is suitable for structural elucidation of oligomeric daptomycin, and possibly of other calcium-dependent lipopeptide antibiotics. The influence of several antimicrobial trivalent cyclic hexapeptides on the mixing behavior of bilayer lipid membranes containing phosphatidylglycerol (PG) and phosphatidylethanolamine (PE) with varying composition was studied using DSC and ITC. The peptides contained three arginines and three aromatic amino acids and had different sequences. All of them induce clustering of PG-rich clusters with bound peptides after binding. In a previous publication we could show that a correlation between clustering efficacy and the antimicrobial activity of the peptides exists (S. Finger et al., Biochim. Biophys. Acta 1848 (2015) 2998-3006). In the current study we investigated whether the non-ideality of the lipid mixture had any effect on the clustering efficacy and the critical peptide/lipid clustering ratio. We could show that for PG/PE membranes containing 11 M ratios and lipids with equal or unequal chain lengths, the amount of clustered PG depended only slightly on the absolute chain length and on the chain length re of the cyclic peptide influences the clustering efficacy but also the mixing behavior of the lipids in the bilayers has an influence on the amount of clustering induced by binding of cyclic peptides. OBJECTIVE To examine if eight weeks of high-intensity interval training (HIIT) in addition to standard care would increase and maintain peak oxygen uptake (VO2peak) more than standard care alone in patients with stroke. DESIGN This was a single-blind, multicenter, parallel group, randomized controlled trial. SETTING Specialized rehabilitation units at three Norwegian hospitals. PARTICIPANTS Participants, three months to five years after first-ever stroke, were randomly assigned to the intervention group (n=36) or the control group (n=34), 42% women, mean (SD) age was 57.6 (9.3) years and 26.4 (14.5) months post-stroke. INTERVENTION The intervention was eight weeks, three times a week high-intensity interval treadmill training with work periods of 4×4 minutes at 85-95% of peak heart rate (HRpeak), interspersed with 3 minutes of active recovery at 50-70% of HRpeak. The control group received standard care according to national guidelines. OUTCOMES The primary outcome, analyzed by intention-to-treat, was VO2peak measured as liters per minute (L·min-1) 12 months after inclusion. Secondary outcome measures were blood pressure and blood profile. RESULTS Mean (SD) baseline VO2peak was 2.63 (1.08) versus 2.87 (0.71) L·min-1, while at 12 months VO2peak was 2.70 (1.00) versus 2.67 (0.76) L·min-1, p=0.068, in the intervention and control groups, respectively. There was a significant and greater improvement in the intervention group compared to the control group at 12 months in three out of six secondary outcomes from the peak test, but no significant differences for the blood pressure or blood profile. CONCLUSIONS The HIIT intervention, which was well-tolerated in this sample of well-functioning stroke survivors, was not superior to standard care in improving and maintaining VO2peak at the 12-month follow-up. However, secondary results from the peak test showed a significant improvement from before to immediately after the intervention. OBJECTIVE To investigate the feasibility and benefits of Whole Body Vibration (WBV) exercise as a safe and effective training-tool for countering sarcopenia and age-related declines in mobility and function in the frail elderly. DESIGN An open, randomised control trial. SETTING Residential care-facilities PARTICIPANTS 117 male and female volunteers (82.5 ± 7.9 years) INTERVENTIONS After pre-screening for contra-indications, participants were randomly allocated to a Control (CON), Simulated-WBV (SIM) or WBV-exercise (WBV) group. All participants received regular care, whilst WBV- and SIM- participants also underwent thrice-weekly exercise sessions for 16 weeks. Delivered by overload principle, WBV-training began with 5 x 1-min bouts at 6 Hz/2 mm (11min exerciserest), progressing to 10 x 1-min at up-to 26 Hz/4 mm, maintaining knee-flexion. Training for SIM participants mimicked WBV-exercise stance and duration only MAIN OUTCOME MEASURES Timed-Up-and-Go, Parallel Walk and 10-m Timed-Walk test performance were assessed, in addition to the Barthel Index Questionnaire, at baseline, 8- and 16-weeks of exercise, and 3-, 6- and 12-months post-exercise.