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        Analysis and Temporal Evolution of Extubation Parameters for Patients Undergoing Single-Stage Circumferential Cervical Spine Surgery

        Ricardo B.V. Fontes,Mena G. Kerolus,Ryan B. Kochanski,Rajeev K. Garg,Anthony DelaCruz,Vincent C. Traynelis 대한척추신경외과학회 2020 Neurospine Vol.17 No.3

        Objective: Airway obstruction after postoperative extubation is a dreaded but uncommon complication in patients undergoing circumferential cervical spine surgery (CCSS). The cuff leak test (CLT) has been utilized to assess air leak around the endotracheal tube which may reflect airway swelling. In this prospective observational study, we analyze the temporal evolution of CLT and perioperative factors that may influence it. Methods: Twenty patients undergoing single-stage CCSS were managed according to our extubation protocol. Patients were maintained intubated overnight following surgery. They were extubated if a CLT > 200 mL and both intensive care unit (ICU) and Neurosurgery teams agreed that it was safe. Patients extubated in the first postoperative day (8 of 20) comprised the early group, and the remaining patients (12 of 20) the delayed group. Patient and operative data were analyzed as a single group and comparing both groups. Results: The main indication for surgery was cervical deformity. Median number of levels fused was 5 anteriorly (range, 1–6) and 6 (range, 1–13) posteriorly. Patients were kept intubated for an average of 73.6 hours (range, 26–222 hours) and stayed in the ICU for 119.1 hours (range, 36–360 hours). There were 4 failed extubations and 3 patients (15%) required a tracheostomy. Patient profiles between both groups were very similar across most patient variables but differed significantly regarding infraglottic luminal area (p < 0.05). Patients with larger preoperative cuff leak values tended to have a shorter intubation period (p = 0.053). Conclusion: This study objectively demonstrates the difficulties in airway management following CCSS and provides useful insight for preoperative planning and counseling. Local anatomic factors influence airway outcome more than operative factors. The study format does not allow for testing of interventions but we suggest that patients with favorable anatomy (larger infraglottic luminal area) may benefit from a less strict airway management protocol.

      • P2Y1 receptor signaling is controlled by interaction with the PDZ scaffold NHERF-2

        Fam, S. R.,Paquet, M.,Castleberry, A. M.,Oller, H.,Lee, C. J.,Traynelis, S. F.,Smith, Y.,Yun, C. C.,Hall, R. A. Proceedings of the National Academy of Sciences 2005 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.102 No.22

        <P>P2Y(1) purinergic receptors (P2Y(1)Rs) mediate rises in intracellular Ca(2+) in response to ATP, but the duration and characteristics of this Ca(2+) response are known to vary markedly in distinct cell types. We screened the P2Y(1)R carboxyl terminus against a recently created proteomic array of PDZ (PSD-95/Drosophila Discs large/ZO-1 homology) domains and identified a previously unrecognized, specific interaction with the second PDZ domain of the scaffold NHERF-2 (Na(+)/H(+) exchanger regulatory factor type 2). Furthermore, we found that P2Y(1)R and NHERF-2 associate in cells, allowing NHERF-2-mediated tethering of P2Y(1)R to key downstream effectors such as phospholipase Cbeta. Finally, we found that coexpression of P2Y(1)R with NHERF-2 in glial cells prolongs P2Y(1)R-mediated Ca(2+) signaling, whereas disruption of the P2Y(1)R-NHERF-2 interaction by point mutations attenuates the duration of P2Y(1)R-mediated Ca(2+) responses. These findings reveal that NHERF-2 is a key regulator of the cellular activity of P2Y(1)R and may therefore determine cell-specific differences in P2Y(1)R-mediated signaling.</P>

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      • Bestrophin-1 encodes for the Ca2+-activated anion channel in hippocampal astrocytes.

        Park, Hyungju,Oh, Soo-Jin,Han, Kyung-Seok,Woo, Dong Ho,Park, Hyekyung,Mannaioni, Guido,Traynelis, Stephen F,Lee, C Justin The Society 2009 The Journal of neuroscience Vol.29 No.41

        <P>In mammalian brain, neurons and astrocytes are reported to express various chloride and anion channels, but the evidence for functional expression of Ca(2+)-activated anion channel (CAAC) and its molecular identity have been lacking. Here we report electrophysiological evidence for the CAAC expression and its molecular identity by mouse Bestrophin 1 (mBest1) in astrocytes of the mouse brain. Using Ca(2+) imaging and perforated-patch-clamp analysis, we demonstrate that astrocytes displayed an inward current at holding potential of -70 mV that was dependent on an increase in intracellular Ca(2+) after G(alphaq)-coupled receptor activation. This current was mediated mostly by anions and was sensitive to well known anion channel blockers such as niflumic acid, 5-nitro-2(3-phenylpropylamino)-benzoic acid, and flufenamic acid. To find the molecular identity of the anion channel responsible for the CAAC current, we analyzed the expression of candidate genes and found that the mRNA for mouse mBest1 is predominantly expressed in acutely dissociated or cultured astrocytes. Whole-cell patch-clamp analysis using HEK293T cells heterologously expressing full-length mBest1 showed a Ca(2+)-dependent current mediated by mBest1, with a complete impairment of the current by a putative pore mutation, W93C. Furthermore, mBest1-mediated CAAC from cultured astrocytes was significantly reduced by expression of mBest1-specific short hairpin RNA (shRNA), suggesting that the CAAC is mediated by a channel encoded by mBest1. Finally, hippocampal CA1 astrocytes in hippocampal slice also showed mBest1-mediated CAAC because it was inhibited by mBest1-specific shRNA. Collectively, these data provide molecular evidence that the mBest1 channel is responsible for CAAC function in astrocytes.</P>

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