Developing forebrain synapses are uniquely vulnerable to sleep loss.

Sleep is an essential behavior that supports lifelong brain health and cognition. Neuronal synapses are a major target for restorative sleep function and a locus of dysfunction in response to sleep deprivation (SD). Synapse density is highly dynamic during development, becoming stabilized with maturation to adulthood, suggesting sleep exerts distinct synaptic functions between development and adulthood. Importantly, problems with sleep are common in neurodevelopmental disorders including autism spectrum disorder (ASD). Moreover, early life sleep disruption in animal models causes long lasting changes in adult behavior. Different plasticity engaged during sleep necessarily implies that developing and adult synapses will show differential vulnerability to SD. To investigate distinct sleep functions and mechanisms of vulnerability to SD across development, we systematically examined the behavioral and molecular responses to acute SD between juvenile (P21-28), adolescent (P42-49) and adult (P70-100) mice of both sexes. Compared to adults, juveniles lack robust adaptations to SD, precipitating cognitive deficits in the novel object recognition test. Subcellular fractionation, combined with proteome and phosphoproteome analysis revealed the developing synapse is profoundly vulnerable to SD, whereas adults exhibit comparative resilience. SD in juveniles, and not older mice, aberrantly drives induction of synapse potentiation, synaptogenesis, and expression of peri-neuronal nets. Our analysis further reveals the developing synapse as a convergent node between vulnerability to SD and ASD genetic risk. Together, our systematic analysis supports a distinct developmental function of sleep and reveals how sleep disruption impacts key aspects of brain development, providing mechanistic insights for ASD susceptibility.

Treatment of post-tonsillectomy hemorrhage with nebulized tranexamic acid: A retrospective study.

OBJECTIVE: To evaluate the association of treatment with nebulized tranexamic acid (TXA) with rates of operative intervention in post-tonsillectomy hemorrhage (PTH). METHODS: Single tertiary-referral center and satellite hospitals, retrospective cohort of adult and pediatric patients who were diagnosed with PTH in 2015-2022 and treated with nebulized TXA and standard care, compared with an age- and gender-matched control cohort treated with standard care. Patients were typically treated in the emergency department with a single dose of 500mg/5 mL TXA delivered via nebulizer. RESULTS: 1110 total cases of PTH were observed, and 83 were treated with nebulized TXA. Compared to 249 age- and gender-matched PTH controls, TXA-treated patients had a rate of operating room (OR) intervention of 36.1% versus 60.2% (p < 0.0001) and a rate of repeat bleeding of 4.9% versus 14.2% (p < 0.02). The odds ratio for OR intervention with TXA treatment was 0.37 (95% CI 0.22, 0.63). There were no adverse effects identified with an average follow-up time of 586 days. CONCLUSION: Treatment of PTH with nebulized TXA is associated with lower rates of operative intervention and lower rates of repeat bleeding events. Prospective studies are needed to further characterize efficacy and optimal treatment protocols.

Coordinated Regulation of CB1 Cannabinoid Receptors and Anandamide Metabolism Stabilizes Network Activity during Homeostatic Downscaling.

Neurons express overlapping homeostatic mechanisms to regulate synaptic function and network properties in response to perturbations of neuronal activity. Endocannabinoids (eCBs) are bioactive lipids synthesized in the postsynaptic compartments to regulate synaptic transmission, plasticity, and neuronal excitability primarily through retrograde activation of presynaptic cannabinoid receptor type 1 (CB1). The eCB system is well situated to regulate neuronal network properties and coordinate presynaptic and postsynaptic activity. However, the role of the eCB system in homeostatic adaptations to neuronal hyperactivity is unknown. To address this issue, we used Western blotting and targeted lipidomics to measure adaptations in eCB system to bicuculline (BCC)-induced chronic hyperexcitation in mature cultured rat cortical neurons, and used multielectrode array (MEA) recording and live-cell imaging of glutamate dynamics to test the effects of pharmacological manipulations of eCB on network activities. We show that BCC-induced chronic hyperexcitation triggers homeostatic downscaling and a coordinated adaptation to enhance tonic eCB signaling. Hyperexcitation triggers first the downregulation of fatty acid amide hydrolase (FAAH), the lipase that degrades the eCB anandamide, then an accumulation of anandamide and related metabolites, and finally a delayed upregulation of surface and total CB1. Additionally, we show that BCC-induced downregulation of surface AMPA-type glutamate receptors (AMPARs) and upregulation of CB1 occur through independent mechanisms. Finally, we show that endocannabinoids support baseline network activities before and after downscaling and is engaged to suppress network activity during adaptation to hyperexcitation. We discuss the implications of our findings in the context of downscaling and homeostatic regulation of in vitro oscillatory network activities.

Boosting the enantioresolution of zwitterionic-teicoplanin chiral stationary phases by moving to wide-pore core-shell particles.

A novel zwitterionic-teicoplanin chiral stationary phase (CSP), based on superficially porous particles (SPPs) of 2.7 µm particle diameter and 160 Å pore size, has been prepared and evaluated towards the enantioseparation of important classes of compounds, including chiral drugs, pesticides, and N-derivatized amino acids. The comparison with two analogous CSPs prepared on SPPs with 2.7 and 2.0 µm particle diameter and 90 Å pore size has revealed that the use of large-pore particles allows to dramatically improve both the enantioselectivity and the resolution-per-analysis-time, at the point that the column prepared with the new CSP outperformed the one packed with the finest particles. On the novel wide-pore CSP, the separation of fifteen racemates of pratical importance was significantly improved in terms of both enantioselectivity and resolution-per-analysis time-compared to the CSPs based on SPPs with smaller pores (90 Å). Such a CSP would be suitable for very fast enantioseparations allowing the saving of solvent for greener high-efficiency/high-throughput applications.

Syndesmotic Screw Breakage May Be More Problematic Than Previously Reported: Increased Rates of Hardware Removal Secondary to Pain With Intraosseous Screw Breakage.

BACKGROUND: The majority of retained syndesmotic screws will either loosen or break once the patient resumes weight-bearing. While evidence is limited, anecdotal experience suggests that intraosseous screw breakage may be problematic for some patients due to painful bony erosion. This study seeks to identify the incidence of intraosseous screw breakage, variables that may predict intraosseous screw breakage, and whether intraosseous screw breakage is associated with higher rates of implant removal secondary to pain. METHODS: Five hundred thirty-one patients undergoing syndesmotic stabilization were screened, of which 43 patients (with 58 screws) experiencing postoperative screw breakage met inclusion criteria. Patient charts were retrospectively reviewed for demographic data, comorbidities, time to screw breakage, location of screw breakage, and implant removal. Several radiographic parameters were evaluated for their potential to influence the site of screw breakage. RESULTS: Intraosseous screw breakage occurred in 32 patients (74.4%). Screw breakage occurred exclusively in the tibiofibular clear space in the remaining 11 instances (25.6%). Intraosseous screw breakage was significantly associated with eventual implant removal after breakage (P = .034). Screws placed further from the tibiotalar joint were at less risk for intraosseous breakage (odds ratio 0.818, P = .002). Screws placed at a threshold height of 20 mm or greater were more likely to break in the clear space (odds ratio 12.1, P = .002). CONCLUSION: Syndesmotic screw breakage may be more problematic than previously described. Intraosseous breakage was associated with higher rates of implant removal secondary to pain in this study. Placement of screws 20 mm or higher from the tibiotalar joint may decrease risk of intraosseous breakage.Levels of Evidence: Level III: Retrospective study.

Aerosol and Droplet Generation from Open Rhinoplasty: Surgical Risk in the Pandemic Era.

Introduction: The coronavirus disease 2019 pandemic has led to concerns over transmission risk from head and neck operations including facial cosmetic surgeries. Objectives: To quantify droplet and aerosol generation from rhinoplasty techniques in a human anatomic specimen model using fluorescein staining and an optical particle sizer. Methods: Noses of human anatomic specimens were infiltrated using 0.1% fluorescein. Droplets and aerosols were measured during rhinoplasty techniques including opening the skin-soft tissue envelope, monopolar electrocautery, endonasal rasping, endonasal osteotomy, and percutaneous osteotomy. Results: No visible droplet contamination was observed for any rhinoplasty techniques investigated. Compared with the negative control of anterior rhinoscopy, total 0.300-10.000 µm aerosols were increased after monopolar electrocautery (p < 0.001) and endonasal rasp (p = 0.003). Opening the skin-soft tissue envelope, endonasal osteotomies, and percutaneous osteotomies did not generate a detectable increase in aerosols (p > 0.15). Discussion and Conclusions: In this investigation, droplets were not observed under ultraviolet light, and aerosol generation was noted only with cautery and endonasal rasping.

Pediatric intraosseous cranial myxoma: A case report and review of literature.

While intraosseous cranial myxoma is a rare pathology, it is important for providers to be aware of it, as early diagnosis and treatment is imperative for prognosis. Long-term follow-up is needed as high rates of recurrence have been documented.

Schizophrenia-Linked Protein tSNARE1 Regulates Endosomal Trafficking in Cortical Neurons.

TSNARE1, which encodes the protein tSNARE1, is a high-confidence gene candidate for schizophrenia risk, but nothing is known about its cellular or physiological function. We identified the major gene products of TSNARE1 and their cytoplasmic localization and function in endosomal trafficking in cortical neurons. We validated three primary isoforms of TSNARE1 expressed in human brain, all of which encode a syntaxin-like Qa SNARE domain. RNA-sequencing data from adult and fetal human brain suggested that the majority of tSNARE1 lacks a transmembrane domain that is thought to be necessary for membrane fusion. Biochemical data demonstrate that tSNARE1 can compete with Stx12 for incorporation into an endosomal SNARE complex, supporting its possible role as an inhibitory SNARE. Live-cell imaging in cortical neurons from mice of both sexes demonstrated that brain tSNARE1 isoforms localized to the endosomal network. The most abundant brain isoform, tSNARE1c, localized most frequently to Rab7+ late endosomes, and endogenous tSNARE1 displayed a similar localization in human neural progenitor cells and neuroblastoma cells. In mature rat neurons from both sexes, tSNARE1 localized to the dendritic shaft and dendritic spines, supporting a role for tSNARE1 at the postsynapse. Expression of either tSNARE1b or tSNARE1c, which differ only in their inclusion or exclusion of an Myb-like domain, delayed the trafficking of the dendritic endosomal cargo Nsg1 into late endosomal and lysosomal compartments. These data suggest that tSNARE1 regulates endosomal trafficking in cortical neurons, likely by negatively regulating early endosomal to late endosomal trafficking.SIGNIFICANCE STATEMENT Schizophrenia is a severe and polygenic neuropsychiatric disorder. Understanding the functions of high-confidence candidate genes is critical toward understanding how their dysfunction contributes to schizophrenia pathogenesis. TSNARE1 is one of the high-confidence candidate genes for schizophrenia risk, yet nothing was known about its cellular or physiological function. Here we describe the major isoforms of TSNARE1 and their cytoplasmic localization and function in the endosomal network in cortical neurons. Our results are consistent with the hypothesis that the majority of brain tSNARE1 acts as a negative regulator to endolysosomal trafficking.

Aerosol and droplet generation from orbital repair: Surgical risk in the pandemic era.

INTRODUCTION: The highly contagious COVID-19 has resulted in millions of deaths worldwide. Physicians performing orbital procedures may be at increased risk of occupational exposure to the virus due to exposure to secretions. The goal of this study is to measure the droplet and aerosol production during repair of the inferior orbital rim and trial a smoke-evacuating electrocautery handpiece as a mitigation device. MATERIAL AND METHODS: The inferior rim of 6 cadaveric orbits was approached transconjunctivally using either standard or smoke-evacuator electrocautery and plated using a high-speed drill. Following fluorescein inoculation, droplet generation was measured by counting under ultraviolet-A (UV-A) light against a blue background. Aerosol generation from 0.300-10.000 µm was measured using an optical particle sizer. Droplet and aerosol generation was compared against retraction of the orbital soft tissue as a negative control. RESULTS: No droplets were observed following the orbital approach using electrocautery. Visible droplets were observed after plating with a high-speed drill for 3 of 6 orbits. Total aerosol generation was significantly higher than negative control following the use of standard electrocautery. Use of smoke-evacuator electrocautery was associated with significantly lower aerosol generation in 2 of 3 size groups and in total. There was no significant increase in total aerosols associated with high-speed drilling. DISCUSSION AND CONCLUSIONS: Droplet generation for orbital repair was present only following plating with high-speed drill. Aerosol generation during standard electrocautery was significantly reduced using a smoke-evacuating electrocautery handpiece. Aerosols were not significantly increased by high-speed drilling.

Aerosol generation during routine rhinologic surgeries and in-office procedures.

OBJECTIVE: Cadaveric simulations have shown endonasal drilling and cautery generate aerosols, which is a significant concern for otolaryngologists during the COVID-19 era. This study quantifies aerosol generation during routine rhinologic surgeries and in-office procedures in live patients. METHODS: Aerosols ranging from 0.30 to 10.0 µm were measured in real-time using an optical particle sizer during surgeries and in-office procedures. Various mask conditions were tested during rigid nasal endoscopy (RNE) and postoperative debridement (POD). RESULTS: Higher aerosol concentrations (AC) ranging from 2.69 to 10.0 µm were measured during RNE (n = 9) with no mask vs two mask conditions (P = .002 and P = .017). Mean AC (0.30-10.0 µm) were significantly higher during POD (n = 9) for no mask vs a mask covering the patient's mouth condition (mean difference = 0.16 ± 0.03 particles/cm3, 95% CI 0.10-0.22, P < .001). There were no discernible spikes in aerosol levels during endoscopic septoplasty (n = 3). Aerosol spikes were measured in two of three functional endoscopic sinus surgeries (FESS) with microdebrider. Using suction mitigation, there were no discernible spikes during powered drilling in two anterior skull base surgeries (ASBS). CONCLUSION: Use of a surgical mask over the patient's mouth during in-office procedures or a mask with a slit for an endoscope during RNE significantly diminished aerosol generation. However, whether this reduction in aerosol generation is sufficient to prevent transmission of communicable diseases via aerosols was beyond the scope of this study. There were several spikes in aerosols during FESS and ASBS, though none were associated with endonasal drilling with the use of suction mitigation. LEVEL OF EVIDENCE: 4.

Aerosol generation during cadaveric simulation of otologic surgery and live cochlear implantation.

OBJECTIVE: The risk of SARS-CoV-2 transmission to healthcare workers through airborne aerosolization during otologic surgery has not been characterized. The objective of this study was to describe and quantify the aerosol generation during common otologic procedures in both cadaveric surgical simulation and live patient surgery. METHODS: The number concentrations of generated aerosols in the particle size range of 0.30 to 10.0 µm were quantified using an optical particle sizer during both a cadaveric simulation of routine otologic procedures as well as cochlear implant surgery on live patients in the operating room. RESULTS: In the cadaveric simulation, temporalis fascia graft harvest using cold techniques (without electrocautery) (n = 4) did not generate aerosols above baseline concentrations. Tympanoplasty (n = 3) and mastoidectomy (n = 3) both produced statistically significant increases in concentrations of aerosols (P < 0.05), predominantly submicron particles (< 1.0 µm). High-speed, powered drilling of the temporal bone during mastoidectomy with a Multi Flute cutting burr resulted in higher peak concentrations and greater number of spikes in aerosols than with a diamond burr. In the operating room, spikes in aerosols occurred during both cochlear implant surgeries. CONCLUSION: In the cadaveric simulation, temporalis fascia graft harvest without electrocautery did not generate aerosol levels above baseline, while significant aerosol levels were generated during mastoidectomy and to a much less degree during tympanoplasty. Aerosol spikes were appreciated during cochlear implantation surgery in live patients. LEVEL OF EVIDENCE: 2.

Aerosol Generation During Myringotomy With Tympanostomy Tube Insertion: Implications for Otolaryngology in the COVID-19 Era.

The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission to health care workers during myringotomy and tympanostomy tube (MT) insertion is unknown. To determine the need for enhanced precautions to prevent potential spread via aerosolized particles, we used an optical particle sizer to measure aerosol generation intraoperatively during a case series of MT insertion. We also discuss our institutional experience with safe pandemic-era perioperative practices. There was no measured increase in aerosol particle number during the procedure at a distance of 30 cm from the external auditory canal. These initial data are reassuring regarding the risk of SARS-CoV-2 transmission to the operating room team due to aerosol generation, but further study is necessary before making definitive recommendations.

Mitigation of Aerosols Generated During Rhinologic Surgery: A Pandemic-Era Cadaveric Simulation.

OBJECTIVE: After significant restrictions initially due to the COVID-19 pandemic, otolaryngologists have begun resuming normal clinical practice. However, the risk of SARS-CoV-2 transmission to health care workers through aerosolization and airborne transmission during rhinologic surgery remains incompletely characterized. The objective of this study was to quantify the number concentrations of aerosols generated during rhinologic surgery with and without interventions involving 3 passive suction devices. STUDY DESIGN: Cadaver simulation. SETTING: Dedicated surgical laboratory. SUBJECTS AND METHODS: In a simulation of rhinologic procedures with and without different passive suction interventions, the concentrations of generated aerosols in the particle size range of 0.30 to 10.0 µm were quantified with an optical particle sizer. RESULTS: Functional endoscopic sinus surgery with and without microdebrider, high-speed powered drilling, use of an ultrasonic aspirator, and electrocautery all produced statistically significant increases in concentrations of aerosols of various sizes (P < .05). Powered drilling, ultrasonic aspirator, and electrocautery generated the highest concentration of aerosols, predominantly submicroparticles <1 µm. All interventions with a suction device were effective in reducing aerosols, though the surgical smoke evacuation system was the most effective passive suction method in 2 of the 5 surgical conditions with statistical significance (P < .05). CONCLUSION: Significant aerosol concentrations were produced in the range of 0.30 to 10.0 µm during all rhinologic procedures in this cadaver simulation. Rhinologic surgery with a passive suction device results in significant mitigation of generated aerosols.

Aerosol and droplet generation from mandible and midface fixation: Surgical risk in the pandemic era.

PURPOSE: The COVID-19 pandemic has led to concerns over transmission risk from healthcare procedures, especially when operating in the head and neck such as during surgical repair of facial fractures. This study aims to quantify aerosol and droplet generation from mandibular and midface open fixation and measure mitigation of airborne particles by a smoke evacuating electrocautery hand piece. MATERIALS AND METHODS: The soft tissue of the bilateral mandible and midface of two fresh frozen cadaveric specimens was infiltrated using a 0.1% fluorescein solution. Surgical fixation via oral vestibular approach was performed on each of these sites. Droplet splatter on the surgeon's chest, facemask, and up to 198.12 cm (6.5 ft) away from each surgical site was measured against a blue background under ultraviolet-A (UV-A) light. Aerosol generation was measured using an optical particle sizer. RESULTS: No visible droplet contamination was observed for any trials of mandible or midface fixation. Total aerosolized particle counts from 0.300-10.000 µm were increased compared to baseline following each use of standard electrocautery (n = 4, p < 0.001) but not with use of a suction evacuating electrocautery hand piece (n = 4, p = 0.103). Total particle counts were also increased during use of the powered drill (n = 8, p < 0.001). CONCLUSIONS: Risk from visible droplets during mandible and midface fixation is low. However, significant increases in aerosolized particles were measured after electrocautery use and during powered drilling. Aerosol dispersion is significantly decreased with the use of a smoke evacuating electrocautery hand piece.

Droplet Exposure Risk to Providers From In-Office Flexible Laryngoscopy: A COVID-19 Simulation.

To provide data on risk of respiratory droplets from common otolaryngologic procedures during the COVID-19 pandemic, a novel simulation of droplet exposure from flexible laryngoscopy was performed. After completion of a nasal symptom questionnaire, topical fluorescein spray was administered into the nasal and oropharynx of 10 healthy volunteers, who then underwent flexible laryngoscopy under 2 conditions: routine without provoked response and with prompted sneeze/cough. After each, droplets on the proceduralist and participant were counted under ultraviolet A light. Droplets were observed on 1 of 10 volunteers after routine laryngoscopy and 4 of 10 during laryngoscopy with sneeze/cough. A nasal symptom score based on congestion and rhinorrhea was significantly elevated among droplet producers after sneeze/cough (P = .0164). No droplets were observed on the provider. Overall, with adequate personal protective equipment, flexible laryngoscopy poses minimal droplet risk to providers. Nasal symptoms can identify patients more likely to produce droplets after sneeze/cough.

Anterior Syndesmotic Augmentation Technique Using Nonabsorbable Suture-Tape for Acute and Chronic Syndesmotic Instability.

Syndesmotic instability is a source of significant pain and disability. Both subtle instability and gross diastasis, whether acute or chronic, require stabilization and may benefit from reconstruction with ligamentous augmentation. The use of nonabsorbable suture-tape has emerged as a promising operative strategy, allowing surgeons to anatomically reconstruct the syndesmosis, in particular the anterior inferior tibiofibular ligament. The current work provides a detailed description of the technique and preliminary results of a patient cohort treated using nonabsorbable suture-tape for syndesmotic augmentation.Level of Evidence: Level V, expert opinion.

Intraoperative ketorolac for pediatric tonsillectomy: Effect on post-tonsillectomy hemorrhage and perioperative analgesia.

OBJECTIVE: Determine the impact of ketorolac on post-tonsillectomy hemorrhage (PTH) and narcotic administration in children undergoing tonsillectomy. METHODS: Retrospective case series from 2013 to 2017. Patients younger than 18 years undergoing tonsillectomy were included. PTH was the primary outcome measured. Secondary measures include percentage of patients requiring surgical intervention for PTH, average time to PTH, the number of post-operative opioid doses, and average post-operative opioid dose. Statistical methods include Chi-square, Wilcoxon rank sum, and binary logistic regression analyses. RESULTS: During the study period, 669 patients received a single intraoperative dose of ketorolac (K+) and 653 patients did not receive ketorolac (K-). No differences were found in the rate of PTH (K- 6.5% vs. K+ 5.3%, RR = 0.82, 95% CI = 0.53 to 1.29, p = 0.40), surgical control of PTH (K- 4.0% vs. K+ 3.5%, RR = 0.87, CI = 0.51 to 1.51, p = 0.62), or average time [SD] to PTH (K- 6.0 [4.2] vs. K+ 5.2 [4.9] days; difference = 0.8 days; 95% CI, -1.3 to 2.9; p = 0.45). K+ patients had fewer post-operative opioid doses [SD] (K- 1.86 [1.14] vs. K+ 1.59 [1.23]; difference = -0.27; 95% CI, -0.053 to -0.49, Cohen d = 0.23) and a lower average opioid dose [SD] (K- 0.041 [0.032] vs. K+ 0.035 [0.030] mg/kg; difference = -0.006 mg/kg; 95% CI, -0.0003 to -0.012; Cohen d = 0.19). CONCLUSION: Ketorolac did not increase risk of hemorrhage following tonsillectomy and decreased narcotic use.

Acute and Chronic Syndesmotic Instability: Role of Surgical Stabilization.

Acute and chronic syndesmotic injuries significantly impact athletic function and activities of daily living. Patient history, examination, and judicious use of imaging modalities aid diagnosis. Surgical management should be used when frank diastasis, instability, and/or chronic pain and disability ensue. Screw and suture-button fixation remain the mainstay of treatment of acute injuries, but novel syndesmotic reconstruction techniques hold promise for treatment of acute and chronic injuries, especially for athletes. This article focuses on anatomy, mechanisms of injury, diagnosis, and surgical reduction and stabilization of acute and chronic syndesmotic instability. Fixation methods with a focus on considerations for athletes are discussed.