mPins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression.

Appropriate trafficking and targeting of glutamate receptors (GluRs) to the postsynaptic density is crucial for synaptic function. We show that mPins (mammalian homologue of Drosophila melanogaster partner of inscuteable) interacts with SAP102 and PSD-95 (two PDZ proteins present in neurons), and functions in the formation of the NMDAR-MAGUK (N-methyl-D-aspartate receptor-membrane-associated guanylate kinase) complex. mPins enhances trafficking of SAP102 and NMDARs to the plasma membrane in neurons. Expression of dominant-negative constructs and short-interfering RNA (siRNA)-mediated knockdown of mPins decreases SAP102 in dendrites and modifies surface expression of NMDARs. mPins changes the number and morphology of dendritic spines and these effects depend on its Galphai interaction domain, thus implicating G-protein signalling in the regulation of postsynaptic structure and trafficking of GluRs.

Intensive Care Unit Readmission in Patients With Primary Brain Injury and Tracheostomy.

BACKGROUND: Readmission for ventilator support in tracheostomy patients with primary brain injury is often attributed to failure of airway protection and aspiration pneumonia. Data regarding the incidence of intensive care unit readmissions and associated factors in these patients are limited. OBJECTIVES: To determine the factors associated with intensive care unit readmission among tracheostomy patients with primary brain injury, as compared with tracheostomy patients without primary brain injury. METHODS: Prospectively acquired data from an ongoing tracheostomy registry at an academic health center were reviewed retrospectively. A total of 164 patients more than 18 years of age who received an elective tracheostomy and had at least 1 readmission to the intensive care unit between 2007 and 2013 were included. RESULTS: The incidence of mechanical ventilation resumption and readmission was significantly higher in patients with than without primary brain injury (P = .005). Patients requiring tracheostomy for airway protection were at a higher risk for atelectasis (odds ratio, 8.23; P = .05). In patients with primary brain injury, a higher Glasgow Coma Scale score was associated with a lower risk for atelectasis (odds ratio, 0.84; P = .04). Mean (SD) Glasgow Coma Scale score was higher in patients without primary brain injury (10.64 [3.98]) than in patients with primary brain injury (8.62 [4.57]; P = .006). CONCLUSIONS: Tracheostomy patients with primary brain injury may have central nervous system-mediated respiratory compromise associated with reduced Glasgow Coma Scale score, increased atelectasis, and shorter duration of ventilator dependency.

Multidisciplinary Difficult Airway Course: An Essential Educational Component of a Hospital-Wide Difficult Airway Response Program.

OBJECTIVE: A hospital-wide difficult airway response team was developed in 2008 at The Johns Hopkins Hospital with three central pillars: operations, safety monitoring, and education. The objective of this study was to assess the outcomes of the educational pillar of the difficult airway response team program, known as the multidisciplinary difficult airway course (MDAC). DESIGN: The comprehensive, full-day MDAC involves trainees and staff from all provider groups who participate in airway management. The MDAC occurs within the Johns Hopkins Medicine Simulation Center approximately four times per year and uses a combination of didactic lectures, hands-on sessions, and high-fidelity simulation training. Participation in MDAC is the main intervention being investigated in this study. Data were collected prospectively using course evaluation survey with quantitative and qualitative components, and prepost course knowledge assessment multiple choice questions (MCQ). Outcomes include course evaluation scores and themes derived from qualitative assessments, and prepost course knowledge assessment MCQ scores. SETTING: Tertiary care academic hospital center PARTICIPANTS: Students, residents, fellows, and practicing physicians from the departments of Surgery, Otolaryngology Head and Neck Surgery, Anesthesiology/Critical Care Medicine, and Emergency Medicine; advanced practice providers (nurse practitioners and physician assistants), nurse anesthetists, nurses, and respiratory therapists. RESULTS: Totally, 23 MDACs have been conducted, including 499 participants. Course evaluations were uniformly positive with mean score of 86.9 of 95 points. Qualitative responses suggest major value from high-fidelity simulation, the hands-on skill stations, and teamwork practice. MCQ scores demonstrated significant improvement: median (interquartile range) pre: 69% (60%-81%) vs post: 81% (72%-89%), p < 0.001. CONCLUSIONS: Implementation of a MDAC successfully disseminated principles and protocols to all airway providers. Demonstrable improvement in prepost course knowledge assessment and overwhelmingly positive course evaluations (quantitative and qualitative) suggest a critical and ongoing role for the MDAC course.