An In-Silico Study on Integrated Mechanisms of Mechano-Electric Coupling in Ischaemic Arrhythmogenesis

Heterogeneous mechanical dyskinesis during acute myocardial ischaemia is thought to contribute to arrhythmogenic alterations to cardiac electrophysiology. Various forms of mechano-electric coupling (MEC) mechanisms have been suggested to contribute to these changes, with two primary mechanisms being: (1) myofilament-dependent calcium release events, and (2) the activation of stretch-activated currents (SACs). In this computational investigation, we assessed the collective impact of these processes on mechanically-induced alternans that create an arrhythmogenic substrate during acute ischaemia. To appraise the potential involvement of MEC in ischaemia-induced arrhythmias, we developed a coupled model of ventricular myocyte electrophysiology and contraction including SACs and stretch-dependent calcium buffering and release. The model, reflecting observed electrophysiological changes during ischaemia, was exposed to a series of stretch protocols that replicated both physiological and pathological mechanical conditions. Pathologically realistic myofiber stretch variations revealed calcium sensitivity changes dependent on myofilament, leading to alterations in cytosolic calcium concentrations. Under calcium overload conditions, these changes resulted in electrical alternans. The study implies that strain impacts cellular electrophysiology through myofilament calcium release and SAC opening in ventricular mechano-electrical models, parameterised to available data. This supports experimental evidence suggesting that both calcium-driven instability via MEC and SAC-induced effects contribute to electrical alternans in acute ischaemia.Comment: 20 pages; 8 figures; original pape

Cytotoxicity Effects of Different Surfactant Molecules Conjugated to Carbon Nanotubes on Human Astrocytoma Cells

Phase contrast and epifluorescence microscopy were utilized to monitor morphological changes in human astrocytoma cells during a time-course exposure to single-walled carbon nanotube (SWCNT) conjugates with different surfactants and to investigate sub-cellular distribution of the nanotube conjugates, respectively. Experimental results demonstrate that cytotoxicity of the nanotube/surfactant conjugates is related to the toxicity of surfactant molecules attached on the nanotube surfaces. Both sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) are toxic to cells. Exposure to CNT/SDS conjugates (0.5 mg/mL) for less than 5 min caused changes in cell morphology resulting in a distinctly spherical shape compared to untreated cells. In contrast, sodium cholate (SC) and CNT/SC did not affect cell morphology, proliferation, or growth. These data indicate that SC is an environmentally friendly surfactant for the purification and dispersion of SWCNTs. Epifluorescence microscopy analysis of CNT/DNA conjugates revealed distribution in the cytoplasm of cells and did not show adverse effects on cell morphology, proliferation, or viability during a 72-h incubation. These observations suggest that the SWCNTs could be used as non-viral vectors for diagnostic and therapeutic molecules across the blood–brain barrier to the brain and the central nervous system

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Multi-Band Bathymetry Mapping with Spiking Neuron Anomaly Detection

The developed method extracts bathymetry distributions from multiple satellite image bands. The automated remote sensing function is sparsely coded and combines spiking neural net anomaly filtration, spline, and multi-band fittings. Survey data were used to identify an activation threshold, decay rate, spline fittings, and multi-band weighting factors. Errors were computed for remotely sensed Landsat satellite images. Multi-band fittings achieved an average error of 25.3 cm. This proved sufficiently accurate to automatically extract shorelines to eliminate land areas in bathymetry mapping

Multi-Band Bathymetry Mapping with Spiking Neuron Anomaly Detection

The developed method extracts bathymetry distributions from multiple satellite image bands. The automated remote sensing function is sparsely coded and combines spiking neural net anomaly filtration, spline, and multi-band fittings. Survey data were used to identify an activation threshold, decay rate, spline fittings, and multi-band weighting factors. Errors were computed for remotely sensed Landsat satellite images. Multi-band fittings achieved an average error of 25.3 cm. This proved sufficiently accurate to automatically extract shorelines to eliminate land areas in bathymetry mapping

Didemnin-B Induces Cell-Death by Apoptosis - the Fastest Induction of Apoptosis Ever Described

Didemnin B, a cyclic N-methylated peptolide induces apoptosis in human HL-60 cells. When incubated with 1 mu M didemnin B, unsynchronized HL-60 cultures undergo apoptosis to 100% within 140 minutes. Apoptosis has been assessed by the typical apoptotic morphology, the presence of double-stranded DNA fragments within the cytosol and the generation of DNA ladders. None of these characteristics of apoptosis are seen when HL-60 cells are pretreated with 1 mM Zn2+ immediately before treatment with didemnin B. (C) 1995 Academic Press, Inc

Neurones express glutamine synthetase when deprived of glutamine or interaction with astrocytes

P>Glutamine synthetase (GS) forms glutamine by catalyzing the ATP-dependent amidation of glutamate. In healthy brains, GS is restricted to astrocytes but in Alzheimer's disease and cell culture, GS has been detected in neurones