A prospective, randomized comparison of the LMA-protector™ and i-gel™ in paralyzed, anesthetized patients

Background In the present study, we compare the LMA-Protector™ and the i-gel™ in terms of adequacy of the airway seal, insertion time, ease and accuracy of insertion, and the incidence of postoperative sore throat. Methods In 110 anesthetized and paralyzed adult patients, the i-gel™ (n = 55) or the LMA-Protector™ (n = 55) was inserted. The primary outcome was airway leak pressure. The secondary outcomes included the first-attempt success rate, insertion time, ease and accuracy of the device insertion, ease of gastric tube placement, blood staining on the device after removal, and incidence and severity of postoperative sore throat. Results The airway leak pressure was higher with the LMA-Protector™ than with the i-gel™ (31 [7] cmH2O vs. 27 [6] cmH2O, respectively; P = 0.016). Insertion time was longer with the LMA-Protector™ than with the i-gel™ (27 [16] sec vs. 19 [16] sec, respectively, P < 0.001), but ease of insertion and the first-attempt success rate were not different between the two groups. The LMA-Protector™ provided a worse fiberoptic view of the vocal cords and more difficult gastric tube insertion than the i-gel™ (both P < 0.001). Blood staining on the device was more frequent with the LMA-Protector™ than with the i-gel™ (P = 0.033). The incidence and severity of postoperative sore throat were not different between the two groups. Conclusion The LMA-Protector™ provided a better airway sealing effect than the i-gel™. However, it required a longer insertion time, provided a worse fiberoptic view of the vocal cords, and caused more mucosal injury compared to the i-gel™. Trial registration ClinicalTrials.gov(NCT03078517). Registered prior to patient enrollment, Date of registration: Mar 13, 2017

MDGA1 negatively regulates amyloid precursor protein-mediated synapse inhibition in the hippocampus

Abstract Balanced synaptic inhibition, controlled by multiple synaptic adhesion proteins, is critical for proper brain function. MDGA1 (meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu [MAM] domain-containing glycosylphosphatidylinositol anchor protein 1) suppresses synaptic inhibition in mammalian neurons, yet the molecular mechanisms underlying MDGA1-mediated negative regulation of GABAergic synapses remain unresolved. Here, we show that the MDGA1 MAM domain directly interacts with the extension domain of amyloid precursor protein (APP). Strikingly, MDGA1-mediated synaptic disinhibition requires the MDGA1 MAM domain and is prominent at distal dendrites of hippocampal CA1 pyramidal neurons. Down-regulation of APP in presynaptic GABAergic interneurons specifically suppressed GABAergic, but not glutamatergic, synaptic transmission strength and inputs onto both the somatic and dendritic compartments of hippocampal CA1 pyramidal neurons. Moreover, APP deletion manifested differential effects in somatostatin- and parvalbumin-positive interneurons in the hippocampal CA1, resulting in distinct alterations in inhibitory synapse numbers, transmission, and excitability. The infusion of MDGA1 MAM protein mimicked postsynaptic MDGA1 gain-of-function phenotypes that involve the presence of presynaptic APP. The overexpression of MDGA1 wild type or MAM, but not MAM-deleted MDGA1, in the hippocampal CA1 impaired novel object-recognition memory in mice. Thus, our results establish unique roles of APP-MDGA1 complexes in hippocampal neural circuits, providing unprecedented insight into trans-synaptic mechanisms underlying differential tuning of neuronal compartment-specific synaptic inhibition.Peer reviewe

A pilot study comparing three bend angles for lighted stylet intubation

Background For successful lighted stylet intubation, bending the lighted stylet with an appropriate angle is a prerequisite. The purpose of this study was to compare three different bend angles of 70, 80, and 90 degrees for lighted stylet intubation. Methods The patient trachea was intubated with a lighted stylet bent at 70, 80, or 90 degrees according to the randomly allocated groups (group I, II, and III, respectively). A lighted stylet combined with a tracheal tube was prepared with a bend angle of 70, 80, or 90 degrees according to the assigned group. We checked the success rate at the first attempt and overall success rate for the two attempts. Additionally, we measured search time, which was time from insertion of the bent union into the patient mouth to the start of advancing the tracheal tube while separating it from the lighted stylet, and evaluated postoperative sore throat (POST) at 2, 4, and 24 h after the recovery from anesthesia. Results There was no statistically significant difference between group I, II, and III for success rate at first attempt (73.9 %, 88.2 %, and 94.7 %, respectively, p = 0.178), even though there was a trend of increasing success rate with increasing bend angles. For overall success rate, there was similar result to that in the first attempt between the groups I, II, and III (82.6 %, 94.1 %, and 100 %, respectively, p = 0.141). However, search time took significantly longer in group I than groups II and III (p < 0.001). When group II and III were compared for POST with numeric rating scale (0–10), it was significantly lower in group II than III at 2, 4 h after the recovery (0.5 vs. 2.3, p = 0.016, and 0.4 vs. 1.8, p = 0.011, respectively). Conclusions The bend angle of the lighted stylet affected the time required for tracheal intubation and POST in our study. 80 and 90 degrees as a bend angle seem to be acceptable for clinicians in regard to success rate of lighted stylet intubation. Considering the success rate of lighted stylet intubation and POST, the bend angle of 80 degrees might be better than 70 and 90 degrees. Trial registration ClinicalTrials.gov Identifier NCT03693235 , registered on 30 September 2018

Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions

Members of the Slitrk (Slit- and Trk-like protein) family of synaptic cell-adhesion molecules control excitatory and inhibitory synapse development through isoform-dependent extracellular interactions with leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs). However, how Slitrks participate in activation of intracellular signaling pathways in postsynaptic neurons remains largely unknown. Here we report that, among the six members of the Slitrk family, only Slitrk2 directly interacts with the PDZ domain-containing excitatory scaffolds, PSD-95 and Shank3. The interaction of Slitrk2 with PDZ proteins is mediated by the cytoplasmic COOH-terminal PDZ domain-binding motif (Ile-Ser-Glu-Leu), which is not found in other Slitrks. Mapping analyses further revealed that a single PDZ domain of Shank3 is responsible for binding to Slitrk2. Slitrk2 forms in vivo complexes with membrane-associated guanylate kinase (MAGUK) family proteins in addition to PSD-95 and Shank3. Intriguingly, in addition to its role in synaptic targeting in cultured hippocampal neurons, the PDZ domain-binding motif of Slitrk2 is required for Slitrk2 promotion of excitatory synapse formation, transmission, and spine development in the CA1 hippocampal region. Collectively, our data suggest a new molecular mechanism for conferring isoform-specific regulatory actions of the Slitrk family in orchestrating intracellular signal transduction pathways in postsynaptic neurons. © 2019, The Author(s).1

Effect of neck extension on the advancement of tracheal tubes from the nasal cavity to the oropharynx in nasotracheal intubation: a randomized controlled trial

Background Clinicians sometimes encounter resistance in advancing a tracheal tube, which is inserted via a nostril, from the nasal cavity into the oropharynx during nasotracheal intubation. The purpose of this study was to investigate the effect of neck extension on the advancement of tracheal tubes from the nasal cavity into the oropharynx during nasotracheal intubation. Methods Patients were randomized to the neck extension group (E group) or neutral position group (N group) for this randomized controlled trial. After induction of anesthesia, a nasal RAE tube was inserted via a nostril. For the E group, an anesthesiologist advanced the tube from the nasal cavity into the oropharynx with the patients neck extended. For the N group, an anesthesiologist advanced the tube without neck extension. If the tube was successfully advanced into the oropharynx within two attempts by the same maneuver according to the assigned group, the case was defined as success. We compared the success rate of tube advancement between the two groups. Results Thirty-two patients in the E group and 33 in the N group completed the trial. The success rate of tube passage during the first two attempts was significantly higher in the E group than in the N group (93.8% vs. 60.6%; odds ratio = 9.75, 95% CI = [1.98, 47.94], p = 0.002). Trial registration: ClinicalTrials.gov Identifier NCT03377114, registered on 13 December 2017

Loss of IQSEC3 Disrupts GABAergic Synapse Maintenance and Decreases Somatostatin Expression in the Hippocampus

Gephyrin interacts with various GABAergic synaptic proteins to organize GABAergic synapse development. Among the multitude of gephyrin-binding proteins is IQSEC3, a recently identified component at GABAergic synapses that acts through its ADP ribosylation factor-guanine nucleotide exchange factor (ARF-GEF) activity to orchestrate GABAergic synapse formation. Here, we show that IQSEC3 knockdown (KD) reduced GABAergic synaptic density in vivo, suggesting that IQSEC3 is required for GABAergic synapse maintenance in vivo. We further show that IQSEC3 KD in the dentate gyrus (DG) increases seizure susceptibility and triggers selective depletion of somatostatin (SST) peptides in the DG hilus in an ARF-GEP activity-dependent manner. Strikingly, selective introduction of SST into SST interneurons in DG-specific IQSEC3-KD mice reverses GABAergic synaptic deficits. Thus, our data suggest that IQSEC3 is required for linking gephyrin-GABAA receptor complexes with ARF-dependent pathways to prevent aberrant, runaway excitation and thereby contributes to the integrity of SST interneurons and proper GABAergic synapse maintenance. © 2020 The Author(s) In this study, Kim et al. investigate the effect of loss of function of IQSEC3, a gephyrin-binding GABAergic synapse-specific ARF-GEF, using hippocampal dentate gyrus (DG)-specific IQSEC3-knockdown (KD) mice. Strikingly, IQSEC3 KD causes a massive reduction of somatostatin (SST) expression. The restricted SST expression in SST+ interneurons reverses the pathological phenotypes. © 2020 The Author(s)1

Calsyntenin-3 Interacts With Both α- And β-Neurexins in the Regulation of Excitatory Synaptic Innervation in Specific Schaffer Collateral Pathways

Calsyntenin-3 (Clstn3) is a postsynaptic adhesion molecule that induces presynaptic differentiation via presynaptic neurexins (Nrxns), but whether Nrxns directly bind to Clstn3 has been a matter of debate. Here, using LC-MS/MS-based protein analysis, confocal microscopy, RNAscope assays, and electrophysiological recordings, we show that β-Nrxns directly interact via their LNS domain with Clstn3 and Clstn3 cadherin domains. Expression of splice site 4 (SS4) insert-positive β-Nrxn variants, but not insert-negative variants, reversed the impaired Clstn3 synaptogenic activity observed in Nrxn-deficient neurons. Consistently, Clstn3 selectively formed complexes with SS4-positive Nrxns in vivo Neuron-specific Clstn3 deletion caused significant reductions in number of excitatory synaptic inputs. Moreover, expression of Clstn3 cadherin domains in CA1 neurons of Clstn3 conditional knockout mice rescued structural deficits in excitatory synapses, especially within the stratum radiatum layer. Collectively, our results suggest that Clstn3 links to SS4-positive Nrxns to induce presynaptic differentiation and orchestrate excitatory synapse development in specific hippocampal neural circuits, including Schaffer collateral afferents. © 2020 Kim et al.1

Npas4 regulates IQSEC3 expression in hippocampal somatostatin interneurons to mediate anxiety-like behavior

Activity-dependent GABAergic synapse plasticity is important for normal brain functions, but the underlying molecular mechanisms remain incompletely understood. Here, we show that Npas4 (neuronal PAS-domain protein 4) transcriptionally regulates the expression of IQSEC3, a GABAergic synapse-specific guanine nucleotide-exchange factor for ADP-ribosylation factor (ARF-GEF) that directly interacts with gephyrin. Neuronal activation by an enriched environment induces Npas4-mediated upregulation of IQSEC3 protein specifically in CA1 stratum oriens layer somatostatin (SST)-expressing GABAergic interneurons. SST+ interneuron-specific knockout (KO) of Npas4 compromises synaptic transmission in these GABAergic interneurons, increases neuronal activity in CA1 pyramidal neurons, and reduces anxiety behavior, all of which are normalized by the expression of wild-type IQSEC3, but not a dominant-negative ARF-GEF-inactive mutant, in SST+ interneurons of Npas4-KO mice. Our results suggest that IQSEC3 is a key GABAergic synapse component that is directed by Npas4 and ARF activity, specifically in SST+ interneurons, to orchestrate excitation-to-inhibition balance and control anxiety-like behavior.1