Hair cells, the sensory receptors of the inner ear, respond to mechanical forces originating from sounds and accelerations. An essential feature of each hair cell is an array of filamentous tip links, consisting of the proteins protocadherin 15 (PCDH15) and cadherin 23 (CDH23), whose tension is thought to directly gate the cell’s transduction channels. These links are considered far too stiff to represent the gating springs that convert hair bundle displacement into forces capable of opening the channels, and no mechanism has been suggested through which tip-link stiffness could be varied to accommodate hair cells of distinct frequency sensitivity in different receptor organs and animals. Consequently, the gating spring’s identity and mechanism of operation remain central questions in sensory neuroscience. Using a high-precision optical trap, we show that an individual monomer of PCDH15 acts as an entropic spring that is much softer than its enthalpic stiffness alone would suggest. This low stiffness implies that the protein is a significant part of the gating spring that controls a hair cell’s transduction channels. The tip link’s entropic nature then allows for stiffness control through modulation of its tension. We find that a PCDH15 molecule is unstable under tension and exhibits a rich variety of reversible unfolding events that are augmented when the Ca2+ concentration is reduced to physiological levels. Therefore, tip link tension and Ca2+ concentration are likely parameters through which nature tunes a gating spring’s mechanical properties.

Background The exceptional competitiveness of the orthopedic surgery specialty, combined with the unclear impact of the COVID-19 pandemic on residency recruitment, has presented significant challenges to applicants and residency program directors. With limited in-person opportunities in the 2020-2021 application cycle, applicants have been pressed to gauge chances and best fit by browsing program websites. Objective The aim of the study was to assess the accessibility and content of accredited orthopedic surgery residency program websites during the COVID-19 pandemic. Methods Using the online database of the Electronic Residency Application Service (ERAS), we compiled a list of accredited orthopedic surgery residency programs in the United States. Program websites were evaluated across four domains: program overview, education, research opportunities, and application details. Each website was assessed twice in July 2020, during a period of adjustment to the COVID-19 pandemic, and twice in November 2020, following the October ERAS application deadline. Results A total of 189 accredited orthopedic surgery residency programs were identified through ERAS. Of these programs, 3 (1.6%) did not have functional website links on ERAS. Data analysis of content in each domain revealed that most websites included program details, a description of the didactic curriculum, and sample rotation schedules. Between the two evaluation periods in July and November 2020, the percentage of program websites containing informative videos and virtual tours rose from 12.2% (23/189) to 48.1% (91/189; P<.001) and from 0.5% (1/189) to 13.2% (25/189; P<.001), respectively. However, the number of programs that included information about a virtual subinternship or virtual interview on their websites did not change. Over the 4-month period, larger residency programs with 5 or more residents were significantly more likely to add a program video (P<.001) or virtual tour (P<.001) to their websites. Conclusions Most residency program websites offered program details and an overview of educational and research opportunities; however, few addressed the virtual transition of interviews and subinternships during the COVID-19 pandemic.

Hair cells, the sensory receptors of the inner ear, respond to mechanical forces originating from 6 sounds and accelerations 1,2 . An essential feature of each hair cell is an array of filamentous tip 7 links, consisting of the proteins protocadherin 15 (PCDH15) and cadherin 23 (CDH23) 3 , whose 8 tension is thought to directly gate the cell's transduction channels 4,5,6 . These links are 9 considered far too stiff to represent the gating springs that convert hair-bundle displacement 10 into forces capable of opening the channels 7,8 , and no mechanism has been suggested through 11 which tip-link stiffness could be varied to accommodate hair cells of distinct frequency 12 sensitivity in different receptor organs and animals. As a consequence, the gating spring's 13 identity and mechanism of operation remain central questions in sensory neuroscience. Using 14 a high-precision optical trap, we show that an individual monomer of PCDH15 acts as an 15 entropic spring that is much softer than its enthalpic stiffness alone would suggest 7,8 . This low 16 stiffness implies that the protein is a significant part of the gating spring that controls a hair 17 cell's transduction channels. The tip link's entropic nature then allows for stiffness control 18 through modulation of its tension. We find that a PCDH15 molecule is unstable under tension 19 and exhibits a rich variety of reversible unfolding events that are augmented when the Ca 2+ 20 concentration is reduced to physiological levels. Tip-link tension and Ca 2+ concentration are 21 therefore likely parameters through which nature tunes a gating spring's mechanical 22properties. 23 24 2 . † These authors contributed equally to this 29 work. 30Mechanically gated ion channels are ubiquitous. In addition to underlying our senses of hearing, 31 balance, and touch, they are involved in the regulation of processes such as muscle extension, 32 blood pressure, pulmonary inflation, and visceral distension. These channels are opened and 33 closed through the action of gating springs, which are elastic elements that are tensioned by 34 mechanical stimulation and in turn communicate stress to the molecular gates of the respective 35 channels. Gating springs accordingly store mechanical energy and use it to regulate channels' 36 open probabilities. For bacterial mechanoreceptors, which respond to osmotic stress, the cellular 37 membrane itself serves as a gating spring 9 . The ubiquitous Piezo channels of vertebrates extend 38 three membrane-embedded arms that likely act as gating springs by flexing in response to 39 membrane stretching 10,11 . Other mechanosensitive channels, such as NOMPC (TRPN1) in 40Drosophila, appear to be gated by the tension in elastic ankyrin domains 12 . 41Gating springs were first posited for hair cells of the vertebrate inner ear, the sensors of 42 the auditory and vestibular systems 4 . Each hair cell is surmounted by a hair bundle-a cluster of 43 erect, actin-filled processes termed stereocilia-that is deflected by mechanical stimulation. 44However, ...

Background Tracheal intubation is a hazardous aerosolizing procedure with a potential risk of spreading SAR-CoV-2 between patients and physicians. Aim The purpose of this study was to explore the impact of COVID-19 specific simulation training in improving provider level of comfort during the intubation of COVID-19 patients. Methods In this cross-sectional national study, an electronic survey was disseminated using a snowball sample approach to intubators from 55 hospitals across the United States. The survey assessed providers’ comfort of intubating and fear of contracting the virus during COVID-19 intubations. Results A total of 329 surveys from 55 hospitals were analyzed. Of 329 providers, 111 providers (33.7%) reported participating in simulation training. Of those, 86 (77.5%) reported that the simulation training helped reduce their fear of intubating COVID-19 patients. Providers in the simulation training group also reported a higher level of comfort level with intubating both general patients (median [range] no-simulation training group 9 [3–10], simulation training group 9 [6–10]; p = 0.015) and COVID-19 patients (no-ST 8 [1–10], ST group 9 [4–10]; p < 0.0005) than providers in the no-simulation training group. Conclusions Our study suggests that COVID-19 specific intubation simulation training promotes provider comfort. Simulation training may be implemented as part of airway management training during the current and novel pandemic situations.

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The use of invasive intracranial electroencephalogram (EEG) monitoring in the patient with a cerebrospinal fluid (CSF) diversionary shunt presents a conundrum --the presence of a percutaneous electrode passing into the intracranial compartment presents a pathway for entry of pathogens to which a chronically implanted device like a shunt is especially susceptible to infection. In this case report, we describe the clinical and radiological features, medical and surgical management, and treatment outcomes of pediatric patients with shunted hydrocephalus who underwent invasive intracranial monitoring over an eight-year period. Three cases of children undergoing invasive intracranial monitoring were included in this study. Invasive monitoring for each patient occurred over three to six days. In each case, invasive intracranial monitoring was completed successfully, without resulting infection or shunt malfunction. While the second procedure was complicated by the formation of a pneumocephalus, there was no associated midline shift, and invasive intracranial monitoring was completed without incidence. Each patient received further surgery that successfully reduced seizure frequency. This study suggests that, while children with CSF diversionary shunts are at an inherently increased risk for infection and other complications, invasive intracranial monitoring is a relatively safe and feasible option in these patients. Future studies should explore the optimal duration for intracranial monitoring in pediatric patients with chronically implanted devices.

ObjectivePrevious studies have highlighted the poor survival of patients with cutaneous angiosarcoma of the head and neck. Therapeutic options are limited, and effective treatment strategies are yet to be discovered. The objective of this study is to evaluate overall survival following intensified adjuvant treatment for high‐risk resected angiosarcoma of the head and neck.Study DesignRetrospective observational.SettingNational Cancer Database (NCDB).MethodsPatients diagnosed with nonmetastatic cutaneous angiosarcoma of the head and neck from 2004 to 2016 were identified by NCDB. We retrospectively compared demographics and overall survival between patients who received surgery and radiation therapy (SR) and patients who received surgery and chemoradiation (SRC). The χ2 test, Kaplan‐Meier method, and Cox regression models were used to analyze data.ResultsA total of 249 patients were identified, of which 79.5% were treated with surgery and radiation alone and 20.5% were treated with surgery and chemoradiation. The addition of chemotherapy, regardless of the sequence of administration, was not associated with significantly higher overall survival. Factors associated with worse survival in both groups included positive nodal status and positive margins. Patients with positive nodes had higher overall survival with radiation doses >50.4 Gy compared to ≤50.4 Gy (hazard ratio: 2.93, confidence interval: 1.60‐5.36, p < 0.001).ConclusionAdjuvant chemotherapy was not significantly associated with higher overall survival for resected nonmetastatic angiosarcoma of the head and neck. Higher radiation doses appear to be prognostic for high‐risk diseases.

BACKGROUND The exceptional competitiveness of the orthopaedic surgery specialty, combined with the unclear impact of the COVID-19 pandemic on residency recruitment, has presented significant challenges to applicants and residency program directors.1 With limited in-person opportunities in the 2020-2021 application cycle, applicants have been pressed to gauge chances and best fit by browsing program websites. OBJECTIVE The objective of the study was to assess the accessibility and content of accredited orthopaedic surgery residency program websites during the COVID-19 pandemic. METHODS Using the online database of the Electronic Residency Application Series (ERAS), we compiled a list of accredited orthopaedic residency programs in the United States. Program websites were evaluated across four domains: program overview, education, research opportunities, and application details. Each website was assessed twice in July, during a period of adjustment to the COVID-19 pandemic, and twice in November, following the October ERAS application deadline. RESULTS 189 accredited orthopaedic surgery residency programs were identified through ERAS. Three programs did not have a website and were not evaluated for content. Data analysis of content in each domain revealed that most websites included program details, a description of the didactic curriculum, and sample rotation schedules. Between the two evaluation periods in July and November, the percentage of program websites containing informative videos and virtual tours rose from 12% to 48% and 1% to 13%, respectively (p<0.005). However, the number of programs that included information about a virtual sub-internship or virtual interview to their websites did not change. CONCLUSIONS Most residency program websites offered program details and an overview of educational and research opportunities; however, few addressed the virtual transition of interviews and sub-internships during the COVID-19 pandemic.