Enhanced Molecular Dynamics Method to Efficiently Increase the Discrimination Capability of Computational Protein-Protein Docking

Protein-protein docking typically consists of the generation of putative binding conformations, which are subsequently ranked by fast heuristic scoring functions. The simplicity of these functions allows for computational efficiency but has severe repercussions on their discrimination capabilities. In this work, we show the effectiveness of suitable descriptors calculated along short scaled molecular dynamics runs in recognizing the nearest-native bound conformation among a set of putative structures generated by the HADDOCK tool for eight protein-protein systems

A distributed bio-inspired method for multisite grid mapping

Computational grids assemble multisite and multiowner resources and represent the most promising solutions for processing distributed computationally intensive applications, each composed by a collection of communicating tasks. The execution of an application on a grid presumes three successive steps: the localization of the available resources together with their characteristics and status; the mapping which selects the resources that, during the estimated running time, better support this execution and, at last, the scheduling of the tasks. These operations are very difficult both because the availability and workload of grid resources change dynamically and because, in many cases, multisite mapping must be adopted to exploit all the possible benefits. As the mapping problem in parallel systems, already known as NP-complete, becomes even harder in distributed heterogeneous environments as in grids, evolutionary techniques can be adopted to find near-optimal solutions. In this paper an effective and efficient multisite mapping, based on a distributed Differential Evolution algorithm, is proposed. The aim is to minimize the time required to complete the execution of the application, selecting from among all the potential ones the solution which reduces the use of the grid resources. The proposed mapper is tested on different scenarios

Molecular docking simulations on histone deacetylases (Hdac)-1 and-2 to investigate the flavone binding

Histone modifications through acetylation are fundamental for remodelling chromatin and consequently activating gene expression. The imbalance between acetylation and deacetylation activity causes transcriptional dysregulation associated with several disorders. Flavones, small molecules of plant origin, are known to interfere with class I histone deacetylase (HDAC) enzymes and to enhance acetylation, restoring cell homeostasis. To investigate the possible physical interactions of flavones on human HDAC1 and 2, we carried out in silico molecular docking simulations. Our data have revealed how flavone, and other two flavones previously investigated, i.e., apigenin and luteolin, can interact as ligands with HDAC1 and 2 at the active site binding pocket. Regulation of HDAC activity by dietary flavones could have important implications in developing epigenetic therapy to regulate the cell gene expression

Mid-Term Outcome of Mitral Valve Repair and Coronary Artery Bypass Grafting for Ischemic or Degenerative Mitral Regurgitation

Aim of the study. To verify the impact of the etiology of mitral valve regurgitation on a 5-year outcome after repair and concomitant coronary artery bypass grafting (CABG). Methods. One hundred and eleven consecutive patients (mean age of 69±8 years) who underwent mitral valve repair, 65 for ischemic and 46 for degenerative mitral regurgitation, and concomitant CABG, were retrospectively analyzed. The mean follow-up was 40±28 (9-104) months. Five-year survival (including operative mortality), and survival free from events (postoperative low output syndrome, progression of mitral regurgitation, onset or worsening of congestive heart failure, recurrence of myocardial infarction, and the need for mitral valve replacement) were analyzed. Results. Compared with degenerative, ischemic mitral regurgitation was associated with a higher incidence of previous myocardial infarction (P<0.0001), left ventricular ejection fraction (LVEF) <0.45 (P<0.0001), and more diseased coronary vessels per patient (P<0.0001). Five-year all-cause mortality was 18% (20/111). Independent predictors of mortality were older age at operation (P=0.0008), LVEF<0.45 (P=0.04), and the ischemic etiology of mitral regurgitation (P=0.03). At five years, survival was 69%±7.6% for ischemic versus 87%±6.5% for degenerative etiology (P=0.03); event-free survival was 58%±8.4% versus 75%±8% (P=0.02), and freedom from late cardiac death was 85%±6.6% versus 100% (P=0.02). Freedom from mitral valve reoperation was 97±2.4%. Conclusions. Ischemic mitral regurgitation “per se” predicted limited survival and event-free survival. Left ventricular dysfunction is frequently associated with the ischemic etiology. An early surgical indication to prevent left ventricular dysfunction could be important to improve the mid-term outcom

Surgical "elephant trunk" arch replacement with a branched arch prosthesis: two alternative operative techniques

Introduction: Elephant trunk repair of the aortic arch cannot be performed with a branched prosthesis. Aim: We conceived two different modifications of the original technique to perform an arch replacement with a branched graft, while arranging an adequate landing zone for a subsequent thoracic endovascular aortic repair, without the need of dedicated material. Material and methods: Eight consecutive patients underwent arch replacement with one of our techniques. Five were emergency patients with acute aortic dissection, and 3 suffered chronic expansive disease. The "modified elephant trunk" includes a separate anastomosis of an endo-luminal prosthetic segment in the descending aorta. Subsequently, the branched arch prosthesis is anastomosed to the distal aortic stump with the attached trunk. In the "prophylactic debranching", a tail is left on the distal end of the arch prosthesis, so that the branches for the supra-aortic vessels will remain displaced proximally, allowing a "zone 1" available for landing. Results: Three patients experienced transient cerebral deficits (1 transient ischemic attack and post-operative delirium in 2 cases), 1 required re-operation for bleeding and 2 needed prolonged intubation. One died of multi-organ failure. Conclusions: Both techniques proved to be easily reproducible, and allow an adequate landing zone for a subsequent endovascular procedure, while retaining the advantages of using a tetra-furcated prosthesis. They are a viable alternative when a hybrid prosthesis cannot be implanted

Surgical Treatment for Recurrent Refractory Skenitis

We report a case of persistent skenitis that was initially misdiagnosed and treated as a urinary infection. Despite an adequate course of antibiotics, the symptoms failed to improve. The case was ultimately resolved with surgical intervention, which resulted in its prompt and complete resolution

Perspective: Cancer Patient Management Challenges During the COVID-19 Pandemic

On March 11, 2020, the WHO has declared the coronavirus disease 2019 (COVID-19) a global pandemic. As the last few months have profoundly changed the delivery of health care in the world, we should recognize the effort of numerous comprehensive cancer centers to share experiences and knowledge to develop best practices to care for oncological patients during the COVID-19 pandemic. Patients as well as physicians must be aware of all these constraints and profound social, personal, and medical challenges posed by the tackling of this deadly disease in everyday life in order to adjust to such a completely novel scenario. This review will discuss facing the challenges and the current approaches that cancer centers in Italy and United States are adopting in order to cope with clinical and research activities

Thrombosis of the left anterior descending artery due to compression from giant pseudoaneurysm late after a bentall operation.

BACKGROUND: A postoperative pseudoaneurysm may develop and gradually expand in the mediastinal space even late following Bentall operation for aortic root replacement, particularly in patients with dissection of the aorta. METHODS: A very large (148 mm) pseudoaneurysm originating of the right coronary ostium suture line was observed in a patient admitted with unstable angina 6 years after Bentall procedure for type A aortic dissection. Angiograms showed reduced flow in the right coronary and thrombotic subocclusion of the left anterior descending (LAD) coronary artery due to extrinsic compression from the expanding mediastinal mass. RESULTS: Reoperation was performed during femoro-femoral cardiopulmonary bypass and brief period of circulatory arrest to clamp the tubular graft. After closure of the detected right coronary ostium in the tubular graft double bypass, grafting to the right coronary and LAD arteries was required. Postoperative course was uneventful. CONCLUSIONS: Close long-term follow-up after a Bentall procedure is required to minimize the risk of developing a large pseudoaneurysmal mass, in particular, after dissection of the aorta