Livingston, E. | Search bioRxiv

bioRxiv2020

CRIMSON: An Open-Source Software Framework for Cardiovascular Integrated Modelling and Simulation

In this work, we describe the CRIMSON (CardiovasculaR Integrated Modelling and SimulatiON) software environment. CRIMSON provides a powerful, customizable and user-friendly system for performing three-dimensional and reduced-order computational haemodynamics studies via a pipeline which involves: 1) segmenting vascular structures from medical images; 2) constructing analytic arterial and venous geometric models; 3) performing finite element mesh generation; 4) designing, and 5) applying boundary conditions; 6) running incompressible Navier-Stokes simulations of blood flow with fluid-structure interaction capabilities; and 7) post-processing and visualizing the results, including velocity, pressure and wall shear stress fields. A key aim of CRIMSON is to create a software environment that makes powerful computational haemodynamics tools accessible to a wide audience, including clinicians and students, both within our research laboratories and throughout the community. The overall philosophy is to leverage best-in-class open source standards for medical image processing, parallel flow computation, geometric solid modelling, data assimilation, and mesh generation. It is actively used by researchers in Europe, North and South America, Asia, and Australia. It has been applied to numerous clinical problems; we illustrate applications of CRIMSON to real-world problems using examples ranging from pre-operative surgical planning to medical device design optimization. CRIMSON binaries for Microsoft Windows 10, documentation and example input files are freely available for download from www.crimson.software, and the source code with compilation instructions is available on GitHub https://github.com/carthurs/CRIMSONFlowsolver (CRIMSON Flowsolver) under the GPL v3.0 license, and https://github.com/carthurs/CRIMSONGUI (CRIMSON GUI), under the AGPL v3.0 license. Support is available on the CRIMSON Google Groups forum, located at https://groups.google.com/forum/#!forum/crimson-users.

bioengineering↗

bioRxiv2020

INNATE IMMUNE INTERFERENCE ATTENUATES INFLAMMATION IN BACILLUS ENDOPHTHALMITIS

PURPOSEBacillus endophthalmitis is a sight-threatening bacterial infection that sometimes requires enucleation. Inflammation in this disease is driven by activation of innate Toll-like receptor (TLR) pathways. Here, we explored the consequences of innate immune interference on intraocular inflammatory responses during Bacillus endophthalmitis. METHODSEndophthalmitis was induced in mice by injecting 100 CFU Bacillus thuringiensis in to the mid-vitreous. We interfered with activation of the TLR2 and TLR4 pathways by 1) injecting a group of mice with S layer protein-deficient ({Delta}slpA) B. thuringiensis or 2) injecting a group of wild type (WT)-infected mice with a TLR2/4 inhibitor, oxidized phospholipid (OxPAPC). At 10 hours postinfection, infected eyes were removed and total RNA was purified. mRNA expression was then analyzed by NanoString using a murine inflammation panel. We compared findings with expression data from eyes infected with eyes injected with WT B. thuringiensis, eyes injected with OxPAPC alone, and uninfected eyes. RESULTSInterference of TLR2 and TLR4 pathways resulted in differential expression of mouse inflammatory genes compared to expression in WT-infected eyes. In WT-infected eyes, 56% of genes were significantly upregulated compared to that of uninfected controls. However, compared to WT-infected eyes, the expression of 27% and 50% of genes were significantly reduced in WT+OxPAPC and {Delta}slpA-infected eyes, respectively. The expression of 61 genes which were significantly upregulated in WT-infected eyes was decreased in WT+OxPAPC or {Delta}slpA-infected eyes. Interference with activation of the TLR2 and TLR4 pathways resulted in blunted expression of complement factors (C3, Cfb, and C6) and several innate genes such as TLR2, TLR4, TLR6, TLR8, MyD88, Nod2, Nlrp3, NF-{kappa}B, STAT3, RelA, RelB, and Ptgs2. Interference with activation of the TLR2 and TLR4 pathways also reduced the expression of several inflammatory cytokines such as CSF3, IL-6, IL-1{beta}, CSF2, IL-1, TNF, IL-23, TGF{beta}1, and IL-12{beta} and chemokines CCL2, CCl3, CXCL1, CXCL2, CXCL3, CXCL5, CXCL9, and CXCL10. All of the aforementioned genes were significantly upregulated in WT-infected eyes. CONCLUSIONSThese results suggest that interfering with the activation of innate immune pathways during Bacillus endophthalmitis significantly reduced the intraocular inflammatory response. This positive clinical outcome could be a strategy for anti-inflammatory therapy of an infection typically refractory to corticosteroid treatment.

microbiology↗