The ER membrane complex (EMC) can functionally replace the Oxa1 insertase in mitochondria.

Two multisubunit protein complexes for membrane protein insertion were recently identified in the endoplasmic reticulum (ER): the guided entry of tail anchor proteins (GET) complex and ER membrane complex (EMC). The structures of both of their hydrophobic core subunits, which are required for the insertion reaction, revealed an overall similarity to the YidC/Oxa1/Alb3 family members found in bacteria, mitochondria, and chloroplasts. This suggests that these membrane insertion machineries all share a common ancestry. To test whether these ER proteins can functionally replace Oxa1 in yeast mitochondria, we generated strains that express mitochondria-targeted Get2-Get1 and Emc6-Emc3 fusion proteins in Oxa1 deletion mutants. Interestingly, the Emc6-Emc3 fusion was able to complement an Δoxa1 mutant and restored its respiratory competence. The Emc6-Emc3 fusion promoted the insertion of the mitochondrially encoded protein Cox2, as well as of nuclear encoded inner membrane proteins, although was not able to facilitate the assembly of the Atp9 ring. Our observations indicate that protein insertion into the ER is functionally conserved to the insertion mechanism in bacteria and mitochondria and adheres to similar topological principles.

Hunger Games: Impact of Fasting Guidelines for Orthopedic Procedural Sedation in the Pediatric Emergency Department.

BACKGROUND: Fasting guidelines for pediatric procedural sedation have historically been controversial. Recent literature suggests that there is no difference in adverse events regardless of fasting status. OBJECTIVES: The goal of this study was to examine adverse outcomes and departmental efficiency when fasting guidelines are not considered during pediatric emergency department (PED) sedation for orthopedic interventions. METHODS: Retrospective chart review identified 2674 patients who presented to a level I PED and required procedural sedation for orthopedic injuries between February 2011 and July 2018. This was a level III, retrospective cohort study. Patients were categorized into the following groups: already within American Society of Anesthesiologists (ASA) fasting guidelines on presentation to the PED (n = 671 [25%]), had procedural sedation not within the ASA guidelines (n = 555 [21%]), and had procedural sedation after fasting in the PED to meet ASA guidelines (n = 1448 [54%]). Primary outcomes were length of stay, time from admission to start of sedation, length of sedation, time from end of sedation to discharge, and adverse events. DISCUSSION: There was a significant difference in the length of stay and time from admission to sedation-both approximately 80 min longer in those with procedural sedation after fasting in the PED to meet ASA guidelines (p < 0.001). There was no significant difference among groups in length of sedation or time to discharge after sedation. Adverse events were uncommon, with only 55 total adverse events (0.02%). Vomiting during the recovery phase was the most common (n = 17 [0.006%]). Other notable adverse events included nine hypoxic events (0.003%) and five seizures (0.002%). There was no significant difference in adverse events among the groups. CONCLUSIONS: Length of stay in the PED was significantly longer if ASA fasting guidelines were followed for children requiring sedation for orthopedic procedures. This is a substantial delay in a busy PED where beds and resources are at a premium. Although providing similar care with equivalent outcomes, the value of spending less time in the PED is evident. Overall, adverse events related to sedation are rare and not related to fasting guidelines.

Resident operative experience in pediatric neurosurgery across the United States.

OBJECTIVE: Neurosurgical residents receive exposure to the subspecialty of pediatric neurosurgery during training. The authors sought to determine resident operative experience in pediatric neurosurgery across Accreditation Council for Graduate Medical Education (ACGME)-accredited neurosurgical programs. METHODS: During 2018-2019, pediatric neurosurgical case logs for recent graduates or current residents who completed their primary pediatric exposure were collected from US continental ACGME training programs. Using individual resident reports and procedure designations, operative volumes and case diversity were analyzed collectively, according to training site characteristics, and also correlated with the recently described Resident Experience Score (RES). RESULTS: Of the 114 programs, a total of 316 resident case logs (range 1-19 residents per program) were received from 86 (75%) programs. The median cumulative pediatric case volume per resident was 109 (IQR 75-161). Residents at programs with a pediatric fellowship reported a higher median case volume (143, IQR 96-187) than residents at programs without (91, IQR 66-129; p < 0.0001). Residents at programs that outsource their pediatric rotation had a lower median case volume (84, IQR 52-114) compared with those at programs with an in-house experience (117, IQR 79-170; p < 0.0001). The case diversity index among all programs ranged from 0.61 to 0.80, with no statistically significant differences according to the Accreditation Council for Pediatric Neurosurgery Fellowships designation or pediatric experience site (p > 0.05). The RES correlated moderately (r = 0.44) with median operative volumes per program. A program's annual pediatric operative volume and duration of pediatric experience were identified as significant predictive factors for median resident operative volume. CONCLUSIONS: Resident experience in pediatric neurosurgery is variable within and between programs. Case volumes are generally higher for residents at programs with in-house exposure and an accredited fellowship, but case diversity is relatively uniform across all programs. RES provides some insight on anticipated case volume, but other unexplained factors remain.

Innovation, Royalties, and Introduction of the Patent Hirsch Index within U.S. Academic Neurosurgery.

BACKGROUND: Historically, practicing neurosurgeons have been key drivers of neurosurgical innovation. We sought to describe the patents held by U.S. academic neurosurgeons and to explore the relationship between patents and royalties received. METHODS: The Centers for Medicare and Medicaid CMS Open Payments Data was used to identify academic neurosurgeons who had received royalties and royalty amounts during a 5-year period (2013-2017). Online patent databases were used to gather patent details. Patent citations and 5-year individual and departmental patent Hirsch (h)-indexes were calculated. Royalties were correlated with the number of patents, patent citations, and patent h-index. RESULTS: We found that 119 academic neurosurgeons (7.8%) from 57 U.S. teaching programs (48.3%) had received royalty payments; 72 (60.5%) had published 648 patents. All surgeons were men, with approximately one half in the "late" stages of their career (45.3%) and subspecializing in spinal surgery (50.4%). The patented products or devices were most commonly used for spinal surgery (72.1%), with 2010-2019 the most productive period (n = 455; 70.2%). The median number of citations per patent was 32 (range, 0-620), with 33% having ≥100 citations. The highest individual and institutional patent h-index was 95; 25 (34.7%) neurosurgeons had a patent h-index of ≥5. The median total royalty payment per individual neurosurgeon was $111,011 (range, $58.05-$76,715,750.34). Royalties were correlated with the number of patents (Spearman r = 0.37; P ≤ 0.001), citations (Spearman r, 0.38; P ≤ 0.001), and inventor h-index (Spearman r = 0.38; P ≤ 0.001). CONCLUSIONS: Few U.S. academic neurosurgeons (7.8%) receive royalties and hold patents (4.7%), with an even smaller select group having a patent h-index of ≥5 (1.6%).

Transcriptome signatures associated with meningioma progression.

Meningiomas are the most common primary brain tumor of adults. The majority are benign (WHO grade I), with a mostly indolent course; 20% of them (WHO grade II and III) are, however, considered aggressive and require a more complex management. WHO grade II and III tumors are heterogeneous and, in some cases, can develop from a prior lower grade meningioma, although most arise de novo. Mechanisms leading to progression or implicated in de novo grade II and III tumorigenesis are poorly understood. RNA-seq was used to profile the transcriptome of grade I, II, and III meningiomas and to identify genes that may be involved in progression. Bioinformatic analyses showed that grade I meningiomas that progress to a higher grade are molecularly different from those that do not. As such, we identify GREM2, a regulator of the BMP pathway, and the snoRNAs SNORA46 and SNORA48, as being significantly reduced in meningioma progression. Additionally, our study has identified several novel fusion transcripts that are differentially present in meningiomas, with grade I tumors that did not progress presenting more fusion transcripts than all other tumors. Interestingly, our study also points to a difference in the tumor immune microenvironment that correlates with histopathological grade.