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Objectives: With an ever-expanding medical knowledge base and requirements for clinical training, medical schools struggle to incorporate subspecialty education, such as otolaryngology (OTO), into curricula. This study aims to assess the current state of OTO education, and evaluate factors contributing to the extent of OTO teaching in United States (U.S.) medical schools., Methods: A 48-question survey evaluated the extent and practices of OTO teaching. The survey was distributed by email to all 155 LCME accredited U.S. allopathic medical schools in 2020 and 2021., Results: Sixty-eight unique responses were received (43.9% of U.S. allopathic medical schools). 36.8% (n = 25) of schools reported having formal expectations of OTO knowledge in their core curriculum. Only 1 school (1.5%) had a required OTO rotation; the majority of schools offered an optional third or fourth year clerkship rotation (76.5% and 95.6%, respectively). Schools with residency programs and who employ their faculty through an OTO or surgery department were more likely to have otolaryngologists teach basic science lectures and the Head & Neck exam, offer an optional third year rotation, and have formal expectations of rotating students., Conclusions: Medical schools with residency programs and who employ their faculty through an OTO or surgery department have more robust OTO curricula. Despite the ubiquity of OTO presentations across specialties, incorporation of OTO knowledge in U.S. medical school curricula remains variable, and at times limited.

Objective: Otolaryngology (OTO) is a competitive specialty, and medical school factors outside an applicant's control, such as presence of OTO student resources and an affiliated OTO residency program, can impact the competitiveness of a student's application. This study sought to evaluate the extent of OTO resources United States (U.S.) allopathic medical schools provide to help their students be successful, and to evaluate for medical school factors which may bias toward inequitable distribution of student OTO resources., Methods: A 48-question cross-sectional survey evaluating the extent of OTO resources was distributed by email to LCME accredited U.S. allopathic medical schools in 2020 and 2021., Results: Schools with residency programs and where faculty were employed through an OTO or surgery department were more likely to have an Otolaryngology Interest Group (OIG), an Otolaryngology Medical Student Education Director (OMSED), and were more likely to provide opportunities for OTO research., Competing Interests: Conflicts of interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Radiation therapy for head and neck cancers causes salivary gland dysfunction leading to permanent xerostomia. Limited progress in the discovery of new therapeutic strategies is attributed to the lack of in vitro models that mimic salivary gland function and allow high-throughput drug screening. We address this limitation by combining engineered extracellular matrices with microbubble (MB) array technology to develop functional tissue mimetics for mouse and human salivary glands. We demonstrate that mouse and human salivary tissues encapsulated within matrix metalloproteinase-degradable poly(ethylene glycol) hydrogels formed in MB arrays are viable, express key salivary gland markers, and exhibit polarized localization of functional proteins. The salivary gland mimetics (SGm) respond to calcium signaling agonists and secrete salivary proteins. SGm were then used to evaluate radiosensitivity and mitigation of radiation damage using a radioprotective compound. Altogether, SGm exhibit phenotypic and functional parameters of salivary glands, and provide an enabling technology for high-content/throughput drug testing.

Purpose: In a combined retrospective and prospective study, human salivary glands were investigated after radiation treatment for head and neck cancers. The aim was to assess acinar cell loss and morphologic changes after radiation therapy and to determine whether irradiated salivary glands have regenerative potential., Methods and Materials: Irradiated human submandibular and parotid salivary glands were collected from 16 patients at a range of time intervals after completion of radiation therapy (RT). Control samples were collected from 14 patients who had not received radiation treatments. Tissue sections were analyzed using immunohistochemistry to stain for molecular markers., Results: Human submandibular and parotid glands isolated less than 1 year after RT showed a near complete loss of acinar cells. However, acinar units expressing functional secretory markers were observed in all samples isolated at later intervals after RT. Significantly lower acinar cell numbers and increased fibrosis were found in glands treated with combined radiation and chemotherapy, in comparison to glands treated with RT alone. Irradiated samples showed increased staining for duct cell keratin markers, as well as many cells coexpressing acinar- and duct cell-specific markers, in comparison to nonirradiated control samples., Conclusions: After RT, acinar cell clusters are maintained in human submandibular glands for years. The surviving acinar cells retain proliferative potential, although significant regeneration does not occur. Persistent DNA damage, increased fibrosis, and altered cell identity suggest mechanisms that may impair regeneration., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To develop treatments for salivary gland dysfunction, it is important to understand how human salivary glands are maintained under normal homeostasis. Previous data from our lab demonstrated that murine salivary acinar cells maintain the acinar cell population through self-duplication under conditions of homeostasis, as well as after injury. Early studies suggested that human acinar cells are mitotically active, but the identity of the resultant daughter cells was not clear. Using markers of cell cycle activity and mitosis, as well as an ex vivo 5-Ethynyl-2´-deoxyuridine assay, we show that human salivary gland acinar cells divide to generate daughter acinar cells. As in mouse, our data indicate that human salivary gland homeostasis is supported by the intrinsic mitotic capacity of acinar cells., (© 2019 Federation of European Biochemical Societies.)

Objective: The objective of this study was to characterize the mechanism by which salivary gland cells (SGC) aggregate in vitro., Design: Timelapse microscopy was utilized to analyze the process of salivary gland aggregate formation using both primary murine and human salivary gland cells. The role of cell density, proliferation, extracellular calcium, and secretory acinar cells in aggregate formation was investigated. Finally, the ability of cells isolated from irradiated glands to form aggregates was also evaluated., Results: Salivary gland cell self-organization rather than proliferation was the predominant mechanism of aggregate formation in both primary mouse and human salivary gland cultures. Aggregation was found to require extracellular calcium while acinar lineage cells account for ∼80% of the total aggregate cell population. Finally, aggregation was not impaired by irradiation., Conclusions: The data reveal that aggregation occurs as a result of heterogeneous salivary gland cell self-organization rather than from stem cell proliferation and differentiation, contradicting previous dogma. These results suggest a re-evaluation of aggregate formation as a criterion defining salivary gland stem cells., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Radiotherapy for head and neck cancers commonly causes damage to salivary gland tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and quality-of-life issues. Amifostine is the only Food and Drug Administration-approved radioprotective drug used clinically to prevent xerostomia. However, systemic administration of amifostine is limited by severe side effects, including rapid decrease in blood pressure (hypotension), nausea, and a narrow therapeutic window. In this study, we demonstrate that retroductal delivery of amifostine and its active metabolite, WR-1065, to murine submandibular glands prior to a single radiation dose of 15 Gy maintained gland function and significantly increased acinar cell survival. Furthermore, in vivo stimulated saliva secretion was maintained in retrograde-treated groups at levels significantly higher than irradiated-only and systemically treated groups. In contrast to intravenous injections, retroductal delivery of WR-1065 or amifostine significantly attenuated hypotension. We conclude that localized delivery to salivary glands markedly improves radioprotection at the cellular level, as well as mitigates the adverse side effects associated with systemic administration. These results support the further development of a localized delivery system that would be compatible with the fractionated dose regimen used clinically.

Hyposalivation is commonly observed in the autoimmune reaction of Sjögren's syndrome or following radiation injury to the major salivary glands. In these cases, questions remain regarding disease pathogenesis and effective interventions. An optimized technique that allows functional assessment of the salivary glands is invaluable for investigating exocrine gland biology, dysfunction, and therapeutics. Here, we present a step by step approach to performing pilocarpine stimulated saliva secretion, including tracheostomy and the dissection of the three major murine salivary glands. We also detail the appropriate murine head and neck anatomy accessed during these techniques. This approach is scalable, allowing for multiple mice to be processed simultaneously, thus improving the efficiency of the work flow. We aim to improve the reproducibility of these methods, each of which has further applications within the field. In addition to saliva collection, we discuss metrics for quantifying and normalizing functional capacity of these tissues. Representative data are included from submandibular glands with depressed salivary gland function 2 weeks following fractionated radiation (4 doses of 6.85 Gy).

Two common goals of salivary gland therapeutics are prevention and cure of tissue dysfunction following either autoimmune or radiation injury. By locally delivering bioactive compounds to the salivary glands, greater tissue concentrations can be safely achieved versus systemic administration. Furthermore, off target tissue effects from extra-glandular accumulation of material can be dramatically reduced. In this regard, retroductal injection is a widely used method for investigating both salivary gland biology and pathophysiology. Retroductal administration of growth factors, primary cells, adenoviral vectors, and small molecule drugs has been shown to support gland function in the setting of injury. We have previously shown the efficacy of a retroductally injected nanoparticle-siRNA strategy to maintain gland function following irradiation. Here, a highly effective and reproducible method to administer nanomaterials to the murine submandibular gland through Wharton's duct is detailed (Figure 1). We describe accessing the oral cavity and outline the steps necessary to cannulate Wharton's duct, with further observations serving as quality checks throughout the procedure.

Roughly half of all vestibular nucleus neurons without eye movement sensitivity respond to both angular rotation and linear acceleration. Linear acceleration signals arise from otolith organs, and rotation signals arise from semicircular canals. In the vestibular nerve, these signals are carried by different afferents. Vestibular nucleus neurons represent the first point of convergence for these distinct sensory signals. This study systematically evaluated how rotational and translational signals interact in single neurons in the vestibular nuclei: multisensory integration at the first opportunity for convergence between these two independent vestibular sensory signals. Single-unit recordings were made from the vestibular nuclei of awake macaques during yaw rotation, translation in the horizontal plane, and combinations of rotation and translation at different frequencies. The overall response magnitude of the combined translation and rotation was generally less than the sum of the magnitudes in responses to the stimuli applied independently. However, we found that under conditions in which the peaks of the rotational and translational responses were coincident these signals were approximately additive. With presentation of rotation and translation at different frequencies, rotation was attenuated more than translation, regardless of which was at a higher frequency. These data suggest a nonlinear interaction between these two sensory modalities in the vestibular nuclei, in which coincident peak responses are proportionally stronger than other, off-peak interactions. These results are similar to those reported for other forms of multisensory integration, such as audio-visual integration in the superior colliculus. NEW & NOTEWORTHY This is the first study to systematically explore the interaction of rotational and translational signals in the vestibular nuclei through independent manipulation. The results of this study demonstrate nonlinear integration leading to maximum response amplitude when the timing and direction of peak rotational and translational responses are coincident.

After vestibular labyrinth injury, behavioral measures of vestibular performance recover to variable degrees (vestibular compensation). Central neuronal responses after unilateral labyrinthectomy (UL), which eliminates both afferent resting activity and sensitivity to movement, have been well-studied. However, unilateral semicircular canal plugging (UCP), which attenuates angular-velocity detection while leaving afferent resting activity intact, has not been extensively studied. The current study reports response properties of yaw-sensitive non-eye-movement rhesus macaque vestibular neurons after compensation from UCP. The responses at a series of frequencies (0.1-2 Hz) and peak velocities (15-210°/s) were compared between neurons recorded before and at least 6 wk after UCP. The gain (sp/s/°/s) of central type I neurons (responding to ipsilateral yaw rotation) on the side of UCP was reduced relative to normal controls at 0.5 Hz, ±60°/s [0.48 ± 0.30 (SD) normal, 0.32 ± 0.15 ipsilesion; 0.44 ± 0.2 contralesion]. Type II neurons (responding to contralateral yaw rotation) after UCP have reduced gain (0.40 ± 0.27 normal, 0.35 ± 0.25 ipsilesion; 0.25 ± 0.18 contralesion). The difference between responses after UCP and after UL is primarily the distribution of type I and type II neurons in the vestibular nuclei (type I neurons comprise 66% in vestibular nuclei normally; 51% ipsilesion UCP; 59% contralesion UCP; 38% ipsilesion UL; 65% contralesion UL) and the magnitude of the responses of type II neurons ipsilateral to the lesion. These differences suggest that the need to compensate for unilateral loss of resting vestibular nerve activity after UL necessitates a different strategy for recovery of dynamic vestibular responses compared to after UCP., (Copyright © 2016 the American Physiological Society.)

Objectives: (1) Determine factors influencing survival in patients diagnosed with spindle cell carcinoma (SpCC), a rare variant of head and neck squamous cell carcinoma (SCC). (2) Compare survival of patients with SpCC to those with conventional SCC., Study Design: Retrospective cohort study., Setting: Surveillance, Epidemiology, and End Results 18 database (years 2004-2009)., Subjects and Methods: Among patients receiving treatment for a single primary in the oral cavity, oropharynx, hypopharynx, or larynx, 118 subjects with SpCC and 18,298 subjects with SCC were identified with complete data for the variables of age, sex, grade, tumor size, stage group, and TNM stage. Disease-specific survival curves were compared. Univariate and multivariate analyses were used to examine the effects of each factor on survival over all sites and within each of 3 sites., Results: Univariate analysis of the combination of the 3 anatomic subsites showed survival with SpCC was worse than with conventional SCC (P < .001). Three-year disease-specific survival with SpCC was 49.5%, and 5-year disease-specific survival was 40.2%. Compared with conventional SCC, survival was worse for SpCC of the oral cavity (P < .001) and oropharynx (P < .001) but no different for the larynx and hypopharynx site (P = .15). Multivariate analysis identified age (P = .02), tumor size (P = .006), and M stage (P < .001) as the only variables significantly affecting survival with SpCC. All variables significantly affected survival with conventional SCC., Conclusions: Spindle cell carcinoma carries a worse prognosis than SCC. Larger tumor size, older age, and metastatic disease portend worse survival with SpCC of the head and neck., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)