Anesthesiology
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Inhalational anesthetics are known to disrupt PDZ2 domain-mediated protein-protein interactions of the postsynaptic density (PSD)-95 protein. The aim of this study is to investigate the underlying mechanisms in response to early isoflurane exposure on synaptic PSD-95 PDZ2 domain disruption that altered spine densities and cognitive function. The authors hypothesized that activation of protein kinase-G by the components of nitric oxide (NO) signaling pathway constitutes a mechanism that prevents loss of early dendritic spines and synapse in neurons and cognitive impairment in mice in response to disruption of PDZ2 domain of the PSD-95 protein. ⋯ Activation of soluble guanylyl cyclase or protein kinase-G prevents isoflurane or PSD-95 wild-type PDZ2 peptide-induced loss of dendritic spines and synapse. Prevention of recognition memory with YC-1, a NO-independent activator of guanylyl cyclase, supports a role for the soluble guanylyl cyclase mediated protein kinase-G signaling in countering the effects of isoflurane-induced cognitive impairment.
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The authors estimate the probability of successful development and duration of clinical trials for medications to treat neuropathic and nociceptive pain. The authors also consider the effect of the perceived abuse potential of the medication on these variables. ⋯ The authors' data suggest that the unique attributes of pain medications, such as their abuse potential and intended pathology, can influence the probability of successful development and duration of development.
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Heterogeneity among reported outcomes from enhanced recovery after cesarean delivery impact studies is high. This study aimed to develop a standardized enhanced recovery core outcome set for use in future enhanced recovery after cesarean delivery studies. ⋯ Results from an international consensus to develop a core outcome set for enhanced recovery after cesarean delivery are presented. These are outcomes that could be considered when designing future enhanced recovery studies.
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For the task of estimating a target benchmark dose such as the ED50 (the dose that would be effective for half the population), an adaptive dose-finding design is more effective than the standard approach of treating equal numbers of patients at a set of equally spaced doses. Up-and-down is the most popular family of dose-finding designs and is in common use in anesthesiology. ⋯ This article provides an overview of up-and-down properties, recent methodologic developments, and practical recommendations, illustrated with the help of simulated examples. Additional reference material is offered in the Supplemental Digital Content.