Plos One
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Tracking the physiological conditions of a patient developing infection is of utmost importance to provide optimal care at an early stage. This work presents a procedure to integrate multiple measures of heart rate variability into a unique measure for the tracking of sepsis development. An early warning system is used to illustrate its potential clinical value. ⋯ Simulating a real-time monitoring setting, the sum of the energy over the very low frequency range of the composite measure was used to classify the probability of developing sepsis. The composite revealed information about the onset of sepsis about 60 hours (median value) before of sepsis diagnosis. In a real monitoring setting this quicker detection time would be associated to increased efficacy in the treatment of sepsis, therefore highlighting the potential clinical utility of a composite measure of variability.
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The effectiveness of sodium bicarbonate (SB) has recently been questioned although it is often used to correct metabolic acidosis of neonates. The aim of the present study was to examine its effect on hemodynamic changes and hydrogen peroxide (H(2)O(2)) generation in the resuscitation of hypoxic newborn animals with severe acidosis. ⋯ Despite enhancing the normalization of acid-base imbalance, SB administration during resuscitation did not provide any beneficial effects on hemodynamic recovery in asphyxiated newborn piglets. SB treatment also reduced the H(2)O(2) accumulation in the cerebral cortex without significant effects on oxidative stress markers presumably by suppressing superoxide dismutase but not catalase activity.
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The recent history of activity input onto granule cells (GCs) in the main olfactory bulb can affect the strength of lateral inhibition, which functions to generate contrast enhancement. However, at the plasticity level, it is unknown whether and how the prior modification of lateral inhibition modulates the subsequent induction of long-lasting changes of the excitatory olfactory nerve (ON) inputs to mitral cells (MCs). ⋯ The regulation of spike timing-dependent plasticity (STDP) was achieved by the regulation of the inter-spike-interval (ISI) of the postsynaptic bursts. This novel form of inhibition-dependent regulation of plasticity may contribute to the encoding or processing of olfactory information in the olfactory bulb.
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Chaperone-mediated autophagy (CMA) is a selective autophagy-lysosome protein degradation pathway. The role of CMA in normal neuronal functions and in neural disease pathogenesis remains unclear, in part because there is no available method to monitor CMA activity at the single-cell level. ⋯ In the present study, we established a novel fluorescent-based method to evaluate CMA activity in a single neuron. This novel method should be useful and valuable for evaluating the role of CMA in various neuronal functions and neural disease pathogenesis.
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Etiology of aberrant social behavior consistently points to a strong polygenetic component involved in fundamental developmental pathways, with the potential of being enhanced by defects in bioenergetics. To this end, the occurrence of social deficits and mitochondrial outcomes were evaluated in conditional Pten (Phosphatase and tensin homolog) haplo-insufficient mice, in which only one allele was selectively knocked-out in neural tissues. Pten mutations have been linked to Alzheimer's disease and syndromic autism spectrum disorders, among others. ⋯ This mechanism was confirmed in Pten-deficient striatal neurons and, HCT 116 cells with different p53 gene dosage. These results suggest a unique pathogenic mechanism of the Pten-p53 axis in mice with aberrant social behavior: loss of Pten (via p53) impairs mitochondrial function elicited by an early defective assembly of CCO and later enhanced by the accumulation of mtDNA deletions. Consistent with our results, (i) SCO2 deficiency and/or CCO activity defects have been reported in patients with learning disabilities including autism and (ii) mutated proteins in ASD have been found associated with p53-signaling pathways.