In an inflammatory setting, macrophages can be polarized to an inflammatory M1 phenotype or to an anti-inflammatory M2 phenotype, as well as existing on a spectrum between these two extremes. Dysfunction of this phenotypic switch can result in a population imbalance that leads to chronic wounds or disease due to unresolved inflammation. Therapeutic interventions that target macrophages have therefore been proposed and implemented in diseases that feature chronic inflammation such as diabetes mellitus and atherosclerosis. We have developed a model for the sequential influx of immune cells in the peritoneal cavity in response to a bacterial stimulus that includes macrophage polarization, with the simplifying assumption that macrophages can be classified as M1 or M2. With this model, we were able to reproduce the expected timing of sequential influx of immune cells and mediators in a general inflammatory setting. We then fit this model to in vivo experimental data obtained from a mouse peritonitis model of inflammation, which is widely used to evaluate endogenous processes in response to an inflammatory stimulus. Model robustness is explored with local structural and practical identifiability of the proposed model a posteriori . Additionally, we perform sensitivity analysis that identifies the population of apoptotic neutrophils as a key driver of the inflammatory process. Finally, we simulate a selection of proposed therapies including points of intervention in the case of delayed neutrophil apoptosis, which our model predicts will result in a sustained inflammatory response. Our model can therefore provide hypothesis testing for therapeutic interventions that target macrophage phenotype and predict outcomes to be validated by subsequent experimentation.

The model is able to reproduce the time course of change in LM in response to RE and can be used to generate a simulated cohort for in silico clinical studies. Simulations suggest that the additional LM generated by RE may shift the body composition to a healthier state.

During the COVID-19 pandemic, mathematical modeling of disease transmission has become a cornerstone of key state decisions. To advance the state-of-the-art host viral modeling to handle future pandemics, many scientists working on related issues assembled to discuss the topics. These discussions exposed the reproducibility crisis that leads to inability to reuse and integrate models. This document summarizes these discussions, presents difficulties, and mentions existing efforts towards future solutions that will allow future model utility and integration. We argue that without addressing these challenges, scientists will have diminished ability to build, disseminate, and implement high-impact multi-scale modeling that is needed to understand the health crises we face.

Con la llegada a España del SARS-CoV-2, el incremento exponencial de enfermos de COVID-19 y sus lamentables consecuencias para un número importante de personas, la @SCSL ha tenido que adaptarse a esta nueva situación. El virus se ha propagado en muchos hogares, en numerosas empresas y en todos los centros sanitarios, sociosanitarios y residenciales del país, llegando incluso a situarnos al borde del colapso asistencial. Esta nueva variable, en forma de riesgo biológico, llegó provocando en la población trabajadora un desequilibrio de la siempre compleja relación bidireccional entre el trabajo y la salud…