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

Kaempferol, myricetin and fisetin in prostate and bladder cancer: A systematic review of the literature

Prostate and bladder cancer represent the two most frequently diagnosed genito-urinary malignancies. Diet has been implicated in both prostate and bladder cancer. Given their prolonged latency and high prevalence rates, both prostate and bladder cancer represent attractive candidates for dietary preventive measures, including the use of nutritional supplements. Flavonols, a class of flavonoids, are commonly found in fruit and vegetables and are known for their protective effect against diabetes and cardiovascular diseases. Furthermore, a higher dietary intake of flavonols was associated with a lower risk of both bladder and prostate cancer in epidemiological studies. In this systematic review, we gathered all available evidence supporting the anti-cancer potential of selected flavonols (kaempferol, fisetin and myricetin) against bladder and prostate cancer. A total of 21, 15 and 7 pre-clinical articles on bladder or prostate cancer reporting on kaempferol, fisetin and myricetin, respectively, were found, while more limited evidence was available from animal models and epidemiological studies or clinical trials. In conclusion, the available evidence supports the potential use of these flavonols in prostate and bladder cancer, with a low expected toxicity, thus providing the rationale for clinical trials that explore dosing, settings for clinical use as well as their use in combination with other pharmacological and non-pharmacological interventions

Resources and tools for rare disease variant interpretation

Collectively, rare genetic disorders affect a substantial portion of the world’s population. In most cases, those affected face difficulties in receiving a clinical diagnosis and genetic characterization. The understanding of the molecular mechanisms of these diseases and the development of therapeutic treatments for patients are also challenging. However, the application of recent advancements in genome sequencing/analysis technologies and computer-aided tools for predicting phenotype-genotype associations can bring significant benefits to this field. In this review, we highlight the most relevant online resources and computational tools for genome interpretation that can enhance the diagnosis, clinical management, and development of treatments for rare disorders. Our focus is on resources for interpreting single nucleotide variants. Additionally, we present use cases for interpreting genetic variants in clinical settings and review the limitations of these results and prediction tools. Finally, we have compiled a curated set of core resources and tools for analyzing rare disease genomes. Such resources and tools can be utilized to develop standardized protocols that will enhance the accuracy and effectiveness of rare disease diagnosis

Pandemic Drugs at Pandemic Speed: Infrastructure for Accelerating COVID-19 Drug Discovery with Hybrid Machine Learning- and Physics-based Simulations on High Performance Computers

The race to meet the challenges of the global pandemic has served as a reminder that the existing drug discovery process is expensive, inefficient and slow. There is a major bottleneck screening the vast number of potential small molecules to shortlist lead compounds for antiviral drug development. New opportunities to accelerate drug discovery lie at the interface between machine learning methods, in this case, developed for linear accelerators, and physics-based methods. The two in silico methods, each have their own advantages and limitations which, interestingly, complement each other. Here, we present an innovative infrastructural development that combines both approaches to accelerate drug discovery. The scale of the potential resulting workflow is such that it is dependent on supercomputing to achieve extremely high throughput. We have demonstrated the viability of this workflow for the study of inhibitors for four COVID-19 target proteins and our ability to perform the required large-scale calculations to identify lead antiviral compounds through repurposing on a variety of supercomputers