Introduction of an agent-based multi-scale modular architecture for dynamic knowledge representation of acute inflammation

<p>Abstract</p> <p>Background</p> <p>One of the greatest challenges facing biomedical research is the integration and sharing of vast amounts of information, not only for individual researchers, but also for the community at large. Agent Based Modeling (ABM) can provide a means of addressing this challenge via a unifying translational architecture for dynamic knowledge representation. This paper presents a series of linked ABMs representing multiple levels of biological organization. They are intended to translate the knowledge derived from in vitro models of acute inflammation to clinically relevant phenomenon such as multiple organ failure.</p> <p>Results and Discussion</p> <p>ABM development followed a sequence starting with relatively direct translation from in-vitro derived rules into a cell-as-agent level ABM, leading on to concatenated ABMs into multi-tissue models, eventually resulting in topologically linked aggregate multi-tissue ABMs modeling organ-organ crosstalk. As an underlying design principle organs were considered to be functionally composed of an epithelial surface, which determined organ integrity, and an endothelial/blood interface, representing the reaction surface for the initiation and propagation of inflammation. The development of the epithelial ABM derived from an in-vitro model of gut epithelial permeability is described. Next, the epithelial ABM was concatenated with the endothelial/inflammatory cell ABM to produce an organ model of the gut. This model was validated against in-vivo models of the inflammatory response of the gut to ischemia. Finally, the gut ABM was linked to a similarly constructed pulmonary ABM to simulate the gut-pulmonary axis in the pathogenesis of multiple organ failure. The behavior of this model was validated against in-vivo and clinical observations on the cross-talk between these two organ systems</p> <p>Conclusion</p> <p>A series of ABMs are presented extending from the level of intracellular mechanism to clinically observed behavior in the intensive care setting. The ABMs all utilize cell-level agents that encapsulate specific mechanistic knowledge extracted from in vitro experiments. The execution of the ABMs results in a dynamic representation of the multi-scale conceptual models derived from those experiments. These models represent a qualitative means of integrating basic scientific information on acute inflammation in a multi-scale, modular architecture as a means of conceptual model verification that can potentially be used to concatenate, communicate and advance community-wide knowledge.</p

Use of Intralesional and Perilesional Human Recombinant Epidermal Growth Factor (hrEGF) in the Local Treatment of Venous Ulcer &ndash; Review Article &ndash; Expert Recommendation

Maria Teresa Cacua Sanchez,1 Lina M Vargas Abello,2 Álvaro Orrego,3 Paola Ortiz,4 Héctor Segura,5 Jhon Jairo Berrio Caicedo,6 Luz Marina Zuluaga,7 José Ordoñez,8 José Ignacio Fernández Montequin,9 Jorge Ulloa10 1Ambulatory Surgery Center, Kennedy Hospital, Vascular Laboratory SURA, Bogotá, Colombia; 2Lumina Vein & Aesthetic Institute, Windermere, FL, USA; 3Laser & Veins Clinic, Viña del Mar, Chile; 4Uruguay Vein Center, Universidad de la República Oriental de Uruguay, Montevideo, Uruguay; 5Vascular and Endovascular Surgery Department, Hospital Español, Mexico City, Mexico; 6Universidad Del Valle, San José de Buga Hospital Foundation, Buga, Colombia; 7San Juan de Dios Hospital, Cartago Valle, Colombia; 8Department of Vascular Surgery, Fundación Santa Fe, Bogotá, Colombia; 9National Institute of Angiology and Vascular Surgery, Havana, Cuba; 10Department of Vascular Surgery, Fundación Santa Fe de Bogotá, Universidad de los Andes, Bogota, ColombiaCorrespondence: Maria Teresa Cacua Sanchez, Email [email protected]: Venous Ulcers (VU) represent 60– 80% of all leg ulcers and are the final stage of the disease secondary to venous hypertension or valve insufficiency. Conventional treatment that focuses on its etiological factors continues to be the gold standard; however, 30% of ulcers do not heal with this treatment; thus, it has been seen that the use of growth factor can be used as an adjuvant for this pathology. A literature review was carried out to evaluate the evidence from systematic reviews, meta-analyses, case studies, and quantitative studies that respond to the objective of this analysis review in the different databases with specific inclusion criteria with publications between 2002 and 2022, initially finding the topical application of the factor and later, more recently, the intralesional and perilesional application, the latter being an alternative treatment for this type of pathology and generating some recommendations for using the Factor.Keywords: chronic venous fibroblast dysfunctions, recombinant human epidermal growth factor, rhEGF, intralesional, perilesional, fibroblast dysfunction