Articles: function.
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Critical care medicine · Feb 2015
Inhibition of the mitochondrial fission protein dynamin-related protein 1 improves survival in a murine cardiac arrest model.
Survival following sudden cardiac arrest is poor despite advances in cardiopulmonary resuscitation and the use of therapeutic hypothermia. Dynamin-related protein 1, a regulator of mitochondrial fission, is an important determinant of reactive oxygen species generation, myocardial necrosis, and left ventricular function following ischemia/reperfusion injury, but its role in cardiac arrest is unknown. We hypothesized that dynamin-related protein 1 inhibition would improve survival, cardiac hemodynamics, and mitochondrial function in an in vivo model of cardiac arrest. ⋯ Post-cardiac arrest inhibition of dynamin-related protein 1 improves time to return of spontaneous circulation and myocardial hemodynamics, resulting in improved survival and neurological outcomes in a murine model of cardiac arrest. Pharmacological targeting of mitochondrial fission may be a promising therapy for cardiac arrest.
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Bump attractors are localized activity patterns that can self-sustain after stimulus presentation, and they are regarded as the neural substrate for a host of perceptual and cognitive processes. One of the characteristic features of bump attractors is that they are neutrally stable, so that noisy inputs cause them to drift away from their initial locations, severely impairing the accuracy of bump location-dependent neural coding. Previous modeling studies of such noise-induced drifting activity of bump attractors have focused on normal diffusive dynamics, often with an assumption that noisy inputs are uncorrelated. ⋯ We demonstrate that subdiffusive dynamics can significantly improve the coding accuracy of bump attractors, since the variance of the bump displacement increases sublinearly over time and is much smaller than that of normal diffusion. Furthermore, we reanalyze existing psychophysical data concerning the spread of recalled cue position in spatial working memory tasks and show that its variance increases sublinearly with time, consistent with subdiffusive dynamics of bump attractors. Based on the probability density function of bump position, we also show that the subdiffusive dynamics result in a long-tailed decay of firing rate, greatly extending the duration of persistent activity.
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Respiratory complications occur in 20% to 65% of patients who have undergone esophagectomy. While noninvasive positive pressure ventilation (NPPV) is associated with fewer complications than endotracheal intubation (ET), it is relatively contraindicated after esophagectomy due to potential injury to the anastomosis. We created ex vivo and in vivo pig models to determine the pressure tolerance of an esophagectomy anastomosis and compare it to esophageal pressure during NPPV. ⋯ Our pig model suggests that an esophagectomy anastomosis can tolerate a considerably higher pressure than is transmitted to the esophagus during NPPV. NPPV may be a safe alternative to ET after esophagectomy.