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Atrial fibrillation (AF) is nowadays the most common human arrhythmia and it is considered a marker of an increased risk of embolic stroke. It is known that 99% of AF-related thrombi are generated in the left atrial appendage (LAA), an anatomical structure located within the left atrium (LA). Left atrial appendage occlusion (LAAO) has become a good alternative for nonvalvular AF patients with contraindications to anticoagulants. However, there is a non-negligible number of device-related thrombus (DRT) events, created next to the device surface. In silico fluid simulations can be a powerful tool to better understand the relation between LA anatomy, haemodynamics, and the process of thrombus formation. Despite the increasing literature in LA fluid modelling, a consensus has not been reached yet in the community on the optimal modelling choices and boundary conditions for generating realistic simulations. In this line, we have performed a sensitivity analysis of several boundary conditions scenarios, varying inlet/outlet and LA wall movement configurations, using patient-specific imaging data of six LAAO patients (three of them with DRT at follow-up). Mesh and cardiac cycle convergence were also analysed. The boundary conditions scenario that better predicted DRT cases had echocardiography-based velocities at the mitral valve outlet, a generic pressure wave from an AF patient at the pulmonary vein inlets, and a dynamic mesh approach for LA wall deformation, emphasizing the need for patient-specific data for realistic simulations. The obtained promising results need to be further validated with larger cohorts, ideally with ground truth data, but they already offer unique insights on thrombogenic risk in the left atria. [ABSTRACT FROM AUTHOR]

Streptomyces clavuligerus is a filamentous Gram-positive bacterial producer of the β-lactamase inhibitor clavulanic acid. Antibiotics biosynthesis in the Streptomyces genus is usually triggered by nutritional and environmental perturbations. In this work, a new genome scale metabolic network of Streptomyces clavuligerus was reconstructed and used to study the experimentally observed effect of oxygen and phosphate concentrations on clavulanic acid biosynthesis under high and low shear stress. A flux balance analysis based on experimental evidence revealed that clavulanic acid biosynthetic reaction fluxes are favored in conditions of phosphate limitation, and this is correlated with enhanced activity of central and amino acid metabolism, as well as with enhanced oxygen uptake. In silico and experimental results show a possible slowing down of tricarboxylic acid (TCA) due to reduced oxygen availability in low shear stress conditions. In contrast, high shear stress conditions are connected with high intracellular oxygen availability favoring TCA activity, precursors availability and clavulanic acid (CA) production. [ABSTRACT FROM AUTHOR]