A review of quantitative systems pharmacology models of the coagulation cascade: opportunities for improved usability

Despite the numerous therapeutic options to treat bleeding or thrombosis, a comprehensive quantitative mechanistic understanding of the effects of these and potential novel therapies is lacking. Recently, the quality of quantitative systems pharmacology (QSP) models of the coagulation cascade has improved, simulating the interactions between proteases, cofactors, regulators, fibrin, and therapeutic responses under different clinical scenarios. We aim to review the literature on QSP models to assess the unique capabilities and reusability of these models. We systematically searched the literature and BioModels database reviewing systems biology (SB) and QSP models. The purpose and scope of most of these models are redundant with only two SB models serving as the basis for QSP models. Primarily three QSP models have a comprehensive scope and are systematically linked between SB and more recent QSP models. The biological scope of recent QSP models has expanded to enable simulations of previously unexplainable clotting events and the drug effects for treating bleeding or thrombosis. Overall, the field of coagulation appears to suffer from unclear connections between models and irreproducible code as previously reported. The reusability of future QSP models can improve by adopting model equations from validated QSP models, clearly documenting the purpose and modifications, and sharing reproducible code. The capabilities of future QSP models can improve from more rigorous validation by capturing a broader range of responses to therapies from individual patient measurements and integrating blood flow and platelet dynamics to closely represent in vivo bleeding or thrombosis risk.Pharmacolog

The effects of the bacterial interaction with visible-light responsive titania photocatalyst on the bactericidal performance

Bactericidal activity of traditional titanium dioxide (TiO2) photocatalyst is effective only upon irradiation by ultraviolet light, which restricts the potential applications of TiO2 for use in our living environments. Recently carbon-containing TiO2 was found to be photoactive at visible-light illumination that affords the potential to overcome this problem; although, the bactericidal activity of these photocatalysts is relatively lower than conventional disinfectants. Evidenced from scanning electron microscopy and confocal Raman spectral mapping analysis, we found the interaction with bacteria was significantly enhanced in these anatase/rutile mixed-phase carbon-containing TiO2. Bacteria-killing experiments indicate that a significantly higher proportion of all tested pathogens including Staphylococcus aureus, Shigella flexneri and Acinetobacter baumannii, were eliminated by the new nanoparticle with higher bacterial interaction property. These findings suggest the created materials with high bacterial interaction ability might be a useful strategy to improve the antimicrobial activity of visible-light-activated TiO2

A Western single-center experience with endoscopic submucosal dissection for early gastrointestinal cancers

Endoscopic submucosal dissection (ESD) has gained worldwide acceptance as a treatment for early gastrointestinal cancers (EGICs). However, the management of these tumors in the Western world is still mainly surgical. Our aim was to evaluate the safety and feasibility of ESD at a European center. Based on the knowledge transferred by one of the most experienced Japanese institutions, we conducted a pilot study on 25 consecutive patients with EGICs located in the esophagus (n = 3), stomach (n = 7), duodenum (n = 1), and colon (n = 14) at our tertiary center over a 2-year-period. The main outcome measurements were complete (R0) resection, as well as en-bloc resection and the management of complications. The R0 and en-bloc resection rates were 100% and 84%, respectively. There were three cases of bleeding and five cases of perforation. With a median follow up of 18 months, two recurrences were observed. We conclude that ESD for early esophageal and gastric cancers is feasible and effective, while colonic ESD requires more expertise

Dalitz plot analysis of D_s+ and D+ decay to pi+pi-pi+ using the K-matrix formalism

FOCUS results from Dalitz plot analysis of D_s+ and D+ to pi+pi-pi+ are presented. The K-matrix formalism is applied to charm decays for the first time to fully exploit the already existing knowledge coming from the light-meson spectroscopy experiments. In particular all the measured dynamics of the S-wave pipi scattering, characterized by broad/overlapping resonances and large non-resonant background, can be properly included. This paper studies the extent to which the K-matrix approach is able to reproduce the observed Dalitz plot and thus help us to understand the underlying dynamics. The results are discussed, along with their possible implications on the controversial nature of the sigma meson.Comment: To be submitted to Phys.Lett.B A misprint corrected in formula