Scientific reports
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In contrast to mammals, adult fish display a remarkable ability to fully regenerate central nervous system (CNS) axons, enabling functional recovery from CNS injury. Both fish and mammals normally undergo a developmental downregulation of axon growth activity as neurons mature. Fish are able to undergo damage-induced "reprogramming" through re-expression of genes necessary for axon growth and guidance, however, the gene regulatory mechanisms remain unknown. ⋯ Our analyses reveal a regeneration program characterized by sequential activation of stage-specific pathways, regulated by a temporally changing cast of transcription factors that bind to stably accessible DNA regulatory regions. Strikingly, we also find a discrete set of regulatory regions that change in accessibility, consistent with higher-order changes in chromatin organization that mark (1) the beginning of regenerative axon growth in the optic nerve, and (2) the re-establishment of synaptic connections in the brain. Together, these data provide valuable insight into the regulatory logic driving successful vertebrate CNS axon regeneration, revealing key gene regulatory candidates for therapeutic development.
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Opioid drugs are the mainstay of pain management but present the side-effect of respiratory depression that can be lethal with overdose. In addition to their respiratory effect, opioids also induce a profound sedative state and produce electrocortical features characteristic of a state of reduced brain arousal, similar to anaesthesia or sleep. In such states, respiratory activity depends more on the integrity of the brainstem respiratory network than it does during wakefulness. ⋯ Fentanyl increased δ (1-3 Hz) frequency power (P < 0.001), but reduced α (7.5-13.5 Hz) and β2 (20-30 Hz) powers (P = 0.012 and P < 0.001, respectively), when compared to wakefulness. Interestingly, respiratory rate depression by fentanyl was significantly correlated with increased θ power (R = 0.61, P < 0.001), therefore showing a clear association between electrocortical activity and the magnitude of respiratory rate depression. Overall, we provide new evidence linking specific electrocortical changes to the severity of respiratory depression by opioids, which highlights the importance of considering the cortical and subcortical effects of opioids in addition to their impacts on breathing when evaluating opioid-induced respiratory depression.
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Bispectral index (BIS), a useful marker of anaesthetic depth, is calculated by a statistical multivariate model using nonlinear functions of electroencephalography-based subparameters. However, only a portion of the proprietary algorithm has been identified. We investigated the BIS algorithm using clinical big data and machine learning techniques. ⋯ The average of median absolute errors of regression models was 4.1 as BIS value. A data driven BIS calculation algorithm using multiple electroencephalography subparameters with different weights depending on BIS ranges has been proposed. The results may help the anaesthesiologists interpret the erroneous BIS values observed during clinical practice.
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An object's location can be represented either relative to an observer's body effectors (egocentric reference frame) or relative to another external object (allocentric reference frame). In non-spatial tasks, an object's task-irrelevant egocentric position conflicts with the side of a task-relevant manual response, which defines the classical Simon effect. Growing evidence suggests that the Simon effect occurs not only based on conflicting positions within the egocentric but also within the allocentric reference frame. ⋯ The right precentral gyrus, extending to the right SMA, was generally activated by Simon conflicts, irrespective of the spatial reference frame involved, and showed no additive activity to Simon conflicts. In contrast, the right postcentral gyrus was specifically involved in Simon conflicts induced by task-irrelevant allocentric, rather than egocentric, representations. Furthermore, a right lateral frontoparietal network showed increased neural activity whenever the egocentric and allocentric target locations were incongruent, indicating its functional role as a mismatch detector that monitors the discrepancy concerning allocentric and egocentric object locations.
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Cardiac arrest (CA) may occur due to a variety of causes with heterogeneity in their clinical presentation and outcomes. This study aimed to identify clinical patterns or subphenotypes of CA patients admitted to the intensive care unit (ICU). The clinical and laboratory data of CA patients in a large electronic healthcare database were analyzed by latent profile analysis (LPA) to identify whether subphenotypes existed. ⋯ Profile 2 was associated with a significantly higher risk of death (OR: 2.09; 95% CI: 1.30 to 3.38) whilst the mortality rates of Profiles 3 was not significantly different from Profile 1 in multivariable model. LPA using routinely collected clinical data could identify three distinct subphenotypes of CA; those with multiple organ failure were associated with a significantly higher risk of mortality than other subphenotypes. LPA profiling may help researchers to identify the most appropriate subphenotypes of CA patients for testing effectiveness of a new intervention in a clinical trial.