Sigma1 receptors (Sigma1R) are intracellular chaperone proteins that bind psychotropic drugs and also clinically used drugs such as ketamine and haloperidol. Co-expression of the Sigma1R has been reported to enhance the sensitivity of several voltage-gated ion channels to Sigma1R ligands. Kv1.3 is the predominant voltage-gated potassium channel expressed in T lymphocytes with a documented role in immune activation. To gain a better understanding of Sigma1R modulation of Kv ion channels, we investigated the effects of Sigma1R co-expression on Kv1.3 physiology and pharmacology in ion channels expressed in Xenopus oocytes. We also explored the protein domains of Kv1.3 necessary for protein:protein interaction between Kv1.3 and Sigma1R through co-immunoprecipitation studies. Slowly inactivating outward-going currents consistent with Kv1.3 expression were elicited on step depolarizations. The current characterized by Erev, V1/2, and slope factor remained unchanged when co-expressed with Sigma1R. Analysis of inactivation time constant revealed a faster Kv1.3 current decay when co-expressed with Sigma1R. However the sensitivity to Sigma1R ligands remained unaltered when co-expressed with the Sigma1R in contrast to the previously reported modulation of ligand sensitivity in closely related Kv1.4 and Kv1.5 voltage gated potassium channels. Co-immunoprecipitation assays of various Kv1.3 truncation constructs indicated that the transmembrane domain of the Kv1.3 protein was responsible for the protein:protein interaction with the Sigma1R. Sigma1R likely interacts with different domains of Kv ion channel family proteins resulting in distinct modulation of different channels.

PurposeThere is still no easy and highly useful method to comprehensively assess both preoperative and intraoperative patient statuses to predict postoperative outcomes. We attempted to develop a new scoring system that would enable a comprehensive assessment of preoperative and intraoperative patient statuses instantly at the end of anesthesia, predicting postoperative mortality.MethodsThe study included 32,555 patients who underwent surgery under general or regional anesthesia from 2008 to 2012. From the anesthesia records, extracted factors, including patient characteristics and American Society of Anesthesiologists physical status classification (ASA-PS), and three intraoperative indexes (the lowest heart rate, lowest mean arterial pressure, and estimated volume of blood loss) are used to calculate the surgical Apgar score (sAs). The sAs and ASA-PS, and surgical Apgar score combined with American Society of Anesthesiologists physical status classification (SASA), which combines the sAs and ASA-PS into a single adjusted scale, were compared and analyzed with postoperative 30-day mortality.ResultsIncreased severity of the sAs, ASA-PS and SASA was correlated with significantly higher mortality. The risk of death was elevated by 3.65 for every 2-point decrease in the sAs, by 6.4 for every 1-point increase in the ASA-PS, and by 9.56 for every 4-point decrease in the SASA. The ROC curves of the sAs and ASA-PS alone also individually demonstrated high validity (AUC = 0.81 for sAs and 0.79 for ASA-PS, P < 0.001). The SASA was even more valid (AUC = 0.87, P < 0.001).ConclusionsThe sAs and ASA-PS were shown to be extremely useful for predicting 30-day mortality after surgery. An even higher predictive ability was demonstrated by the SASA, which combines these simple and effective scoring systems.

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To the Editor: The Quality Standards Subcommittee of the American Academy of Neurology has endorsed guidelines for management of concussion in sports. 1 This practice parameter represented a consolidation and modification of previous concussion guidelines in sports. 2,3 A major limitation and criticism of most management guidelines for concussion in sports has been that the determination of criteria for return to play has been arbitrarily established, based on theoretical considerations and limited clinical investigation.In the absence of loss of consciousness, clinical grading scales for concussion in sports have focused on amnesia or confusion as possible criteria for assessing the severity of concussion. During the evaluation of concussion on the athletic field, the clinical distinction between amnesia and confusion is not practical. Posttraumatic amnesia is a clinical entity that features normal immediate recall and the inability to learn new material. 4 During posttraumatic amnesia, there is relatively well-preserved retrieval of previously learned information except in cases associated with retrograde amnesia. Confusion is characterized by impaired immediate recall; reduced ability to learn new information; inability to retrieve already learned information; and incoherence secondary to inattention, distractibility, or the inability to obtain, maintain, or shift set. 4 Because memory function is disrupted during amnesia and confusion, the determination of the specific type of memory impairment is beyond the scope of the athletic trainer or health care provider who is not trained in neuropsychology or neurology. Accordingly, any athlete exhibiting impairment in orientation, concentration, immediate memory, or delayed recall on the standardized assessment of concussion (SAC) 5 or other test of neuropsychological function should be considered to be experiencing cognitive dysfunction.Studies utilizing baseline neuropsychological testing 6 or the SAC 5 indicate that athletes who experience cognitive dysfunction after concussion do not recover immediately. According to a prospective investigation of concussion among college football players, 6 the recovery period for an athlete who exhibited cognitive dysfunction without loss of consciousness was approximately 1 week. McCrea et al. 5 observed that concussed athletes without impaired consciousness scored significantly lower than their preinjury baseline scores on the SAC and returned to their preinjury scores within 48 hours.Based on the above-mentioned clinical information, the following considerations are advocated. First, the clinical distinction between amnesia and confusion on the playing field is unrealistic and unnecessary because both of these conditions are indicative of cognitive dysfunction. Secondly, it is recommended that any athlete who experiences cognitive dysfunction after a concussion in sports should not be allowed to return to competition that same day. Athletes that could be allowed to return to competition on the same day of a concussion are ...