Blood potassium concentration ([K+]) influences the electrocardiogram (ECG), particularly T-wave morphology. We developed a new method to quantify [K+] from T-wave analysis and tested its clinical applicability on data from dialysis patients, in whom [K+] varies significantly during the therapy. To elucidate the mechanism linking [K+] and T-wave, we also analysed data from long QT syndrome type 2 (LQT2) patients, testing the hypothesis that our method would have underestimated [K+] in these patients. Moreover, a computational model was used to explore the physiological processes underlying our estimator at the cellular level. We analysed 12-lead ECGs from 45 haemodialysis and 12 LQT2 patients. T-wave amplitude and downslope were calculated from the first two eigenleads. The T-wave slope-to-amplitude ratio (TS/A) was used as starting point for an ECG-based [K+] estimate (KECG). Leave-one-out cross-validation was performed. Agreement between KECG and reference [K+] from blood samples was promising (error: −0.09 ± 0.59 mM, absolute error: 0.46 ± 0.39 mM). The analysis on LQT2 patients, also supported by the outcome of computational analysis, reinforces our interpretation that, at the cellular level, delayed-rectifier potassium current is a main contributor of KECG correlation to blood [K+]. Following a comprehensive validation, this method could be effectively applied to monitor patients at risk for hyper/hypokalemia.
3D cell cultures are in-vitro models representing a significant improvement with respect to traditional monolayers. Their diffusion and applicability, however, are hampered by the complexity of 3D systems, that add new physical variables for experimental analyses. In order to account for these additional features and improve the study of 3D cultures, we here present SALSA (ScAffoLd SimulAtor), a general purpose computational tool that can simulate the behavior of a population of cells cultured in a 3D scaffold. This software allows for the complete customization of both the polymeric template structure and the cell population behavior and characteristics. In the following the technical description of SALSA will be presented, together with its validation and an example of how it could be used to optimize the experimental analysis of two breast cancer cell lines cultured in collagen scaffolds. This work contributes to the growing field of integrated in-silico/in-vitro analysis of biological systems, which have great potential for the study of complex cell population behaviours and could lead to improve and facilitate the effectiveness and diffusion of 3D cell culture models. Cell culture is currently experiencing a fundamental shift from traditional 2D to 3D systems, that are more realistic representations of a biological tissue. These novel approaches, that integrate important aspects of cellular habitat, such as a non-uniform microenvironment, more complex diffusion processes and cell interactions with local physical features of the synthetic extracellular matrix (ECM), are bound to provide fundamental insights into cell biology, generating a closer approximation of reality as shown in 1-4. However, in order for 3D systems to become the standard in-vitro cell culturing technique, several issues still need to be addressed. In fact, the increased complexity in structural properties is, at the same time, the added value of these experimental systems and the limitation in optimising biological assays and protocols originally standardised for cells grown on 2D plastic surfaces. This complicates experimental design and data collection. While innovative 3D native assays are being developed 5,6 , computational models can complement the wet-lab experimental activity and help to address some of the limitations of 3D culture settings 7-9. The mathematical formalization of complex behaviours, however, is often maintained separate from the experimental analysis. As an example there are multiple models describing cancer-related cellular processes 10-17 and the effect of antineoplastic therapies 18-24 but most of them are presented as theoretical frameworks that do not aim at driving the experimental activity. To integrate this important functionality we developed a general purpose scaffold simulator named SALSA that can be programmed to reproduce the behaviour of a population of arbitrary cells, grown in 3D scaffolds of tunable size and material. It relies on a custom hybrid continuous/discrete framework that is particularly b...
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