An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

Citation: Shi, Z. Z., Chapes, S. K., Ben-Arieh, D., & Wu, C. H. (2016). An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data. Plos One, 11(8), 39. doi:10.1371/journal.pone.0161131We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as "sepsis". Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-a ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Repercussões da cardiomegalia na função pulmonar de indivíduos adultos com insuficiência cardíaca crônica: uma revisão sistemática Repercussions of the cardiomegaly on the pulmonary function of adult individuals with chronic heart failure: a systematic review

Para analisar as repercussões da cardiomegalia sobre a função pulmonar em indivíduos adultos com insuficiência cardíaca (IC) crônica, foram revisados artigos nas bases PUBMED, BIREME, ISI Web of Knowledge e COCHRANE, publicados na última década, estudos observacionais e sem restrição de idioma. Utilizados os descritores "cardiomegaly" e "Respiratory Function Tests", e negada a palavra "exercise". Foram incluídos artigos com IC crônica, de ambos os sexos, entre 19 e 64 anos, incluindo IC congestiva e cardiomiopatia dilatada e excluídos com IC aguda, com avaliações pós-intervenção clínica ou por exercício. Para avaliar a qualidade dos artigos foi utilizada a escala da Agency for Healthcare Research and Quality (AHRQ) e aceitos aqueles com escore>50 pontos (0-100). Foram selecionados cinco artigos do total de 1093 e agrupados por parâmetros relacionados aos fluxos e volumes pulmonares, padrão ventilatório e desempenho muscular. Na AHRQ, dois estudos ficaram na faixa de 50-75% e os demais >75%. Eles apontam para redução da capacidade vital inspiratória (CVI), volume expiratório forçado no 1º segundo (VEF1) e pressão inspiratória máxima (PImáx) em função da cardiomegalia, com discreta redução na relação VEF1/CVI e na capacidade de difusão para monóxido de carbono (DLCO). Portanto, segundo os estudos, a cardiomegalia leva a um padrão respiratório restritivo, com redução do volume alveolar que interfere na DLCO. As correlações mais fortes envolvem a redução da PImáx, CVI e VEF1.<br>To analyze the repercussions of the cardiomegaly on lung function in adults with chronic heart failure (CHF), the databases PUBMED, BIREME, ISI Web of Knowledge and COCHRANE were considered to review observational studies published in the last decade without language restriction. It was used the descriptors "cardiomegaly" and "respiratory function tests", and denied "exercise". It was included papers with CHF, of both sexes between 19 and 64 years accepting samples with congestive HF and dilated cardiomyopathy and excluding with acute heart failure, post-intervention assessment clinic or by exercise. The quality of papers was evaluated by using the scale of Agency for Healthcare Research and Quality (AHRQ) and accepted papers with score>50 points (0-100). We selected 5 studies from total of 1093 and grouped by parameters related to flows and lung volumes, respiratory pattern and muscle performance. At AHRQ, two studies were in the range of 50-75% and the others>75%. These studies showed lower inspiratory vital capacity (IVC), forced expiratory volume in 1st second (FEV1) and maximal inspiratory pressure (PImáx) as a function of cardiomegaly, with a slight reduction in the ratio VEF1/IVC and diffusion capacity for carbon monoxide (DLCO). Therefore, the studies suggest that the cardiomegaly leads to a restrictive lung pattern, with reduction in alveolar volume that interferes with DLCO. The strongest correlations involve the reduction of PImáx, IVC and FEV1 in this population