bProper functioning of intracellular membranes is critical for many cellular processes. A key feature of membranes is their ability to adapt to changes in environmental conditions by adjusting their composition so as to maintain constant biophysical properties, including fluidity and flexibility. Similar changes in the biophysical properties of membranes likely occur when intracellular processes, such as vesicle formation and fusion, require dramatic changes in membrane curvature. Similar modifications must also be made when nuclear pore complexes (NPCs) are constructed within the existing nuclear membrane, as occurs during interphase in all eukaryotes. Here we report on the role of the essential nuclear envelope/endoplasmic reticulum (NE/ER) protein Brl1 in regulating the membrane composition of the NE/ER. We show that Brl1 and two other proteins characterized previously-Brr6, which is closely related to Brl1, and Apq12-function together and are required for lipid homeostasis. All three transmembrane proteins are localized to the NE and can be coprecipitated. As has been shown for mutations affecting Brr6 and Apq12, mutations in Brl1 lead to defects in lipid metabolism, increased sensitivity to drugs that inhibit enzymes involved in lipid synthesis, and strong genetic interactions with mutations affecting lipid metabolism. Mutations affecting Brl1 or Brr6 or the absence of Apq12 leads to hyperfluid membranes, because mutant cells are hypersensitive to agents that increase membrane fluidity. We suggest that the defects in nuclear pore complex biogenesis and mRNA export seen in these mutants are consequences of defects in maintaining the biophysical properties of the NE. T he nuclear envelope (NE) of eukaryotic cells compartmentalizes the nuclear material and separates it from the cytoplasm. The double membrane of the NE consists of an outer and an inner nuclear membrane (ONM and INM) that differ in protein and lipid composition. The NE is structurally and functionally related to the endoplasmic reticulum (ER), and the ONM is contiguous with the ER (1, 2). Embedded in the NE are the nuclear pore complexes (NPCs) and, in budding yeast, the spindle pole body (SPB). NPCs are extremely large and are constructed from multiple copies of about 30 different nucleoporins (nups) (3, 4). NPCs mediate selective trafficking of proteins and other macromolecules between the nucleus and the cytoplasm but also serve other important functions, including gene activation and mRNA surveillance (5, 6). The biogenesis of NPCs and their distribution over the NE are highly regulated processes and are coordinated with the cell cycle (7). During interphase, the number of NPCs doubles. In budding yeast, the NE remains intact throughout the cell cycle, and all the formation of NPCs occurs through de novo construction within the NE.In addition to the ONM and the INM, the NE contains a pore membrane domain (POM), formed by the fusion of the INM and ONM at sites where NPCs are assembled (8). The POM is a highly curved region of the NE that is i...

Objectives: Penetrating abdominal aortic injury (PAAI) is a highly acute injury requiring prompt surgical management. When compared to surgeons at level-II trauma centers, surgeons at level-I trauma centers are more likely to take in-house call, and may more often be available within 15 minutes of patient arrival. Thus, we hypothesized that level-I trauma centers would have a lower mortality rate than level-II trauma centers in patients with PAAI. Methods: We queried the Trauma Quality Improvement Program database for patients with PAAI, and compared patients treated at American College of Surgeons (ACS)-verified level-I centers to those treated at ACS level-II centers. Results: PAAI was identified in 292 patients treated at level-I centers and 86 patients treated at level-II centers. Patients treated at the 2 center types had similar median age, injury severity scores and prevalence of diabetes, hypertension, and smoking (p > 0.05). There was no difference in the frequency of additional intra-abdominal vascular injuries (p > 0.05). Median time to hemorrhage control (level-I: 40.8 vs level-II: 49.2 minutes, p = 0.21) was similar between hospitals at the 2 trauma center levels. We found no difference in the total hospital length of stay or post-operative complications (p > 0.05). When controlling for covariates, we found no difference in the risk of mortality between ACS verified level-I and level-II trauma centers (OR:1.01, CI:0.28-2.64, p = 0.99). Conclusion: Though the majority of PAAIs are treated at level-I trauma centers, we found no difference in the time to hemorrhage control, or the risk of mortality in those treated at level-I centers when compared to those treated at level-II trauma centers. This finding reinforces the ACS-verification process, which strives to achieve similar outcomes between level-I and level-II centers.

Objectives: To determine whether, similar to adults, early tracheostomy in pediatric patients with severe traumatic brain injury (TBI) improves inhospital outcomes including ventilator days, intensive care unit (ICU) length of stay (LOS), and total hospital LOS when compared to late tracheostomy. Design: Retrospective cohort analysis. Setting: The Pediatric Trauma Quality Improvement Program (TQIP) database Patients: One hundred twenty-seven pediatric patients <16 years old with severe (>3) abbreviated injury scale TBI who underwent early (days 1-6) or late (day ≥7) tracheostomy between 2014 and 2016. Interventions: Not applicable. Measurements and Main Results: The Pediatric TQIP database was queried for patients <16 years old with severe TBI, who underwent tracheostomy. Patient demographics and outcomes of early versus late tracheostomy were compared using Student t test, Mann-Whitney U test, and χ2 analysis. Sixteen patients underwent early tracheostomy while 111 underwent late tracheostomy. The groups had similar distributions of age, gender, mechanism of injury, and mean injury severity scores (P > .05). Early tracheostomy was associated with decreased ICU LOS (early: 17 vs late: 32 days, P < .05) and ventilator days (early: 9.7 vs late: 27.1 days, P < .05). There was no difference in total LOS (early: 26.7 vs late: 41.3 days, P = .06), the incidence of acute respiratory distress syndrome (early: 6.3% vs late: 2.7%, P = .45), pneumonia (early: 12.5% vs late: 29.7%, P = .15), or mortality (early: 0% vs late: 2%, P = .588) between the 2 groups. Conclusion: Similar to adults, early tracheostomy in pediatric patients with severe TBI is associated with decreased ICU LOS and ventilator days. Future prospective trials are needed to confirm these findings. Article Tweet: Early tracheostomy in pediatric patients with severe TBI is associated with decreased ICU LOS and ventilator days.

Traumatic esophageal injury is a highly lethal but rare injury with minimal data in the trauma population. We sought to provide a descriptive analysis of esophageal trauma (ET) to identify the incidence, associated injuries, interventions, and outcomes. We hypothesized that blunt trauma is associated with higher risk of death than penetrating trauma. The Trauma Quality Improvement Program (2010–2016) was queried for patients with ET. Patients with blunt and penetrating trauma were compared using chi-square and Mann-Whitney U tests. A multivariable logistic regression model was used to determine risk of mortality. Of 1,403,466 adult patients, 651 (<0.01%) presented with ET. The most common associated thoracic injuries were rib fractures (38.7%) and pneumothorax (26.7%). More patients with a penetrating mechanism underwent open repair of the esophagus than those with blunt mechanism (46.2% vs 11.7%, P < 0.001). After controlling for covariates, there was no difference in risk of mortality between blunt and penetrating trauma ( P = 0.65). The mortality rate for patients with esophageal injury surviving greater than 24 hours was 7.5 per cent. In this large national database analysis, ET was rare and most commonly associated with rib fractures and pneumothorax. Contrary to our hypothesis, the risk of mortality was equivalent between blunt and penetrating ET.

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