We next sought to examine whether 1NN truly identified the decision time point in the magic size

We next sought to examine whether 1NN truly identified the decision time point in the magic size. but for a given amount GLPG2451 of ischemia, increasing the number of reperfusion events also increases damage (2h, 5 cycles v 1h, 10 cycles).(DOCX) pcbi.1004309.s005.docx (116K) GUID:?0E12D060-6E03-4E69-BA71-C4653A0E0E96 S2 Fig: Histogram of ulceration versus % initial injury. A 30% initial injury prospects to ulceration roughly 50% of the time.(DOCX) pcbi.1004309.s006.docx (159K) GUID:?F8FEF732-D4EC-408F-BC83-CDE43C12603A S3 Fig: Histogram and GMM Estimate of tissue damage at t = 1000 for 30% initial injury. Two disparate levels of tissue damage suggest two results from simulations starting with the same initial conditions. Lower tissue damage is associated with no ulcer formation.(DOCX) pcbi.1004309.s007.docx (224K) GUID:?5825BD55-B2DE-4380-83D3-E87E17B40596 S4 Fig: Time courses for each feature in resolved versus ulcerated simulations. Blue time programs are from simulations that led to ulcers whereas reddish did not. Total counts of cells, mediators, and cells health are plotted for 1000 ticks. Time programs of some features are very related for both results, but for additional the variations are stark.(DOCX) pcbi.1004309.s008.docx (739K) GUID:?8969BFC4-118B-43E9-BB91-302665D78FF4 S5 Fig: 1NN over individual features. GLPG2451 Classification accuracy (resolved versus ulcerated) for 1NN over each feature separately. Features were input as time vectors, using either all earlier time points or the previous 50 ticks.(DOCX) pcbi.1004309.s009.docx (779K) GUID:?993A3813-5A66-47D1-B88D-57FB6AD1B94C S6 Fig: Implementation of corticosteroid treatment in magic size rules. Local concentrations of corticosteroid functionally disable macrophages and neutrophils in the model, causing them to no longer create or respond to mediators.(DOCX) pcbi.1004309.s010.docx (273K) GUID:?6371D013-B07E-4A0C-91D1-C54083DBBAA4 S7 Fig: Implementation of anti-DAMPs antibody in magic size rules. Anti-DAMPs antibodies are simulated as eliminating DAMPs from your model, lowering local concentrations inside a quenching Rabbit Polyclonal to E2F4 reaction.(DOCX) pcbi.1004309.s011.docx (276K) GUID:?80F676D4-3F15-449F-B7AC-C6FBB12702E3 Data Availability StatementAll relevant data are within the paper and its Supporting Information documents. Abstract People with spinal cord injury (SCI) are predisposed to pressure ulcers (PU). PU remain a significant burden in cost of care and quality of life despite improved mechanistic understanding and advanced interventions. An agent-based model (ABM) of ischemia/reperfusion-induced swelling and PU (the PUABM) was created, calibrated to serial images of post-SCI PU, and used to investigate potential treatments tests of anti-inflammatory treatments such as corticosteroids and a neutralizing antibody targeted at Damage-Associated Molecular Pattern molecules (DAMPs) suggested that, at best, early software at a sufficiently high dose could attenuate local swelling and reduce pressure-associated tissue damage, but could not reduce PU incidence. The PUABM therefore shows promise as an adjunct for mechanistic understanding, diagnosis, and design of therapies in the establishing of PU. Author Summary A virtual GLPG2451 pressure ulcer was created as a platform to test therapies and determine the mechanisms most correlated with unfavorable results. A coating of tissue fed with oxygen and diffusible molecules via blood vessels could develop an ulcer if pressure was applied, by simulating constriction of blood vessels in a circular region. Simulated ulcers were visually much like GLPG2451 digital photographs of ulcers in individuals with spinal cord injury in their irregular shapes, jagged edges, and overall progression in time. Statistical analyses of simulation outputs exposed that swelling was an important determinant of ulcer severity and overall tissue damage. However, simulated medical trials exposed that obstructing the negative effects of swelling could not prevent ulceration, and in order to be beneficial whatsoever for this specific type of ulcer, anti-inflammatory treatments must be applied during the earliest phases of ulcer formationbefore many medical indications of ulceration appear. Intro Pressure ulcers (PU) impact 2.5 million US acute care patients and cost up to $1 billion per year [1]. They are a significant source of morbidity in both hospitalized individuals and community-dwelling individuals with impaired mobility. PUs are especially common in individuals.