Faculty Bibliography

BACKGROUND:Post-tonsillectomy hemorrhage (PTH) is a highly studied outcome of tonsillectomy with serious consequences. Various treatments and interventions have been utilized to decrease post-tonsillectomy hemorrhage. The off-label use of tranexamic acid (TXA) is of growing interest to control PTH but has not been incorporated in management guidelines. This scoping review plans to summarize existing studies from the scientific literature on the use of tranexamic acid for post-tonsillectomy hemorrhage. METHODS/UNASSIGNED:We used the Preferred Reporting Items for Systematic Reviews or Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR). The review will cover studies including patients undergoing tonsillectomy who were treated with TXA in the peri-operative or post-operative period. We include randomized controlled trials, retrospective, prospective, and case series. A database-specific search strategy will be used to search records across. Two reviewers will independently screen and extract data. Tables and visual representations will be utilized to present the extracted data. REGISTRATION DETAILS/UNASSIGNED:The protocol will be registered in Open Science Framework and published in PLOS One.

OBJECTIVE:What we hear may influence postural control, particularly in people with vestibular hypofunction. Would hearing a moving subway destabilize people similarly to seeing the train move? We investigated how people with unilateral vestibular hypofunction and healthy controls incorporated broadband and real-recorded sounds with visual load for balance in an immersive contextual scene. DESIGN/METHODS:Participants stood on foam placed on a force-platform, wore the HTC Vive headset, and observed an immersive subway environment. Each 60-second condition repeated twice: static or dynamic visual with no sound or static white noise or real recorded subway station sounds [real] played from headphones. SETTING/METHODS:Human motion laboratory. PARTICIPANTS/METHODS:41 healthy controls (mean age 52 years, range 22-78) and 28 participants with unilateral peripheral vestibular hypofunction (mean age 61.5, 27-82). MAIN OUTCOME MEASURES/METHODS:We collected center-of-pressure (COP, anterior-posterior, medio-lateral) from the force-platform and head (anterior-posterior, medio-lateral, pitch, yaw, roll) from the headset and quantified root mean square velocity (cm/s or rad/s). RESULTS:Adjusting for age, the vestibular group showed significantly more sway than controls on: COP medio-lateral (no sound or real with static or dynamic visual); COP anterior-posterior (only on dynamic visuals in the presence of either sound); head medio-lateral and anterior-posterior (all conditions), head pitch and yaw (only on dynamic visuals in the presence of either sound). A significant increase in sway with sounds was observed for the vestibular group only on dynamic visuals COP anterior-posterior and head yaw (real) and head anterior-posterior and pitch (either sound). CONCLUSIONS:The addition of auditory stimuli, particularly contextually-accurate sounds, to a challenging, standing balance task in real-life simulation increased sway in people with vestibular hypofunction but not in healthy controls. TRIAL REGISTRATION/BACKGROUND:Clinical trial registrationThis study was registered on clinicaltrials.gov at the following link: https://clinicaltrials.gov/study/NCT04479761.

INTRODUCTION/UNASSIGNED:Patients with oral cancer often experience intense functional pain due to mechanical stimulation at the cancer site. The role of mechanosensitive ion channels in oral cancer pain, such as TRPV4, is not fully understood. OBJECTIVES/UNASSIGNED:Our objective was to investigate the role of Schwann cell TRPV4 in oral cancer pain. METHODS/UNASSIGNED:imaging, and patch-clamp electrophysiology. The effect of TRPV4 activation on Schwann cell responses to mechanical stimulation was evaluated using a piezo stimulator. Conditioned media (CM) from TRPV4-activated Schwann cells were injected into the mouse paw to evaluate the contribution of TRPV4 in Schwann cells to mechanical hypersensitivity. RESULTS/UNASSIGNED:responses and whole-cell membrane currents in human Schwann cells. Mechanoactivated currents in human Schwann cells were inhibited by the TRPV4 antagonist HC-067047. Schwann cell CM induced mechanical hypersensitivity in mice, which was blocked by pre-treatment with HC-067047. CONCLUSION/UNASSIGNED:TRPV4 activation plays a role in mediating mechanically induced pain of oral cancer.

OBJECTIVES/OBJECTIVE:To investigate fall risk among older adults with bilateral sensorineural hearing loss (BHL) by comparing single task (ST) and dual task (DT) performance on the instrumented "Timed Up & Go" test (iTUG). The TUG is a well-validated clinical tool for fall risk; addition of wireless sensors increases the test's sensitivity and allows for subcomponent analysis. METHODS:Adults with audiometrically confirmed normal hearing or BHL were prospectively recruited and screened for visual, musculoskeletal, neurologic, or vestibular pathology and Dizziness Handicap Inventory (DHI) < 10. Total and sub-component iTUG data in the ST and DT condition (serial subtraction) was collected. RESULTS:35 adults (50-78 years) were included: 20 (mean 69 years) with BHL and 15 controls (mean age 63 years). Total iTUG duration did not differ between groups in either the ST or DT condition. In sit-to-stand, BHL were significantly slower than controls (p < 0.03) in both ST and DT conditions. In the final subcomponent (stand-to-sit), a significant interaction was observed such that the BHL group were significantly slower with DT compared to the control group. CONCLUSIONS:BHL performed slower on sub-component analysis of the iTUG compared with age-matched normal hearing controls. Slower times on the final iTUG phase for BHL may suggest a lower threshold for attentional capacity that may be cumulative. Further investigation into the impact of treatment (including amplification and training) is warranted.

Oral cavity cancer is associated with high morbidity and mortality, particularly with advanced stage diagnosis. Oral cavity cancer, typically squamous cell carcinoma (OSCC), is often preceded by oral potentially malignant disorders (OPMDs), which comprise eleven disorders with variable risks for malignant transformation. While OPMDs are clinical diagnoses, conventional oral exam followed by biopsy and histopathological analysis is the gold standard for diagnosis of OSCC. There is vast heterogeneity in the clinical presentation of OPMDs, with possible visual similarities to early-stage OSCC or even to various benign oral mucosal abnormalities. The diagnostic challenge of OSCC/OPMDs is compounded in the non-specialist or primary care setting. There has been significant research interest in technology to assist in the diagnosis of OSCC/OPMDs. Artificial intelligence (AI), which enables machine performance of human tasks, has already shown promise in several domains of medical diagnostics. Computer vision, the field of AI dedicated to the analysis of visual data, has over the past decade been applied to clinical photographs for the diagnosis of OSCC/OPMDs. Various methodological concerns and limitations may be encountered in the literature on OSCC/OPMD image analysis. This narrative review delineates the current landscape of AI clinical photograph analysis in the diagnosis of OSCC/OPMDs and navigates the limitations, methodological issues, and clinical workflow implications of this field, providing context for future research considerations.

Communication between intracellular organelles including lysosomes and mitochondria has recently been shown to regulate cellular proliferation and fitness. The way lysosomes and mitochondria communicate with each other (lysosomal/mitochondrial interaction, LMI) is, emerging as a major determinant of tumor proliferation and growth. About 30% of squamous carcinomas (including squamous cell carcinoma of the head and neck, SCCHN) overexpress TMEM16A, a calcium-activated chloride channel, which promotes cellular growth and negatively correlates with patient survival. We have recently shown that TMEM16A drives lysosomal biogenesis, but its impact on mitochondrial function has not been explored. Here, we show that in the context of high TMEM16A SCCHN, (1) patients display increased mitochondrial content, specifically complex I; (2) In vitro and in vivo models uniquely depend on mitochondrial complex I activity for growth and survival; (3) NRF2 signaling is a critical linchpin that drives mitochondrial function, and (4) mitochondrial complex I and lysosomal function are codependent for proliferation. Taken together, our data demonstrate that coordinated lysosomal and mitochondrial activity and biogenesis via LMI drive tumor proliferation and facilitates a functional interaction between lysosomal and mitochondrial networks. Therefore, inhibition of LMI instauration may serve as a therapeutic strategy for patients with SCCHN. Implications: Intervention of lysosome-mitochondria interaction may serve as a therapeutic approach for patients with high TMEM16A expressing SCCHN.

In nature, animal vocalizations can provide crucial information about identity, including kinship and hierarchy. However, lab-based vocal behavior is typically studied during brief interactions between animals with no prior social relationship, and under environmental conditions with limited ethological relevance. Here, we address this gap by establishing long-term acoustic recordings from Mongolian gerbil families, a core social group that uses an array of sonic and ultrasonic vocalizations. Three separate gerbil families were transferred to an enlarged environment and continuous 20-day audio recordings were obtained. Using a variational autoencoder (VAE) to quantify 583,237 vocalizations, we show that gerbils exhibit a more elaborate vocal repertoire than has been previously reported and that vocal repertoire usage differs significantly by family. By performing gaussian mixture model clustering on the VAE latent space, we show that families preferentially use characteristic sets of vocal clusters and that these usage preferences remain stable over weeks. Furthermore, gerbils displayed family-specific transitions between vocal clusters. Since gerbils live naturally as extended families in complex underground burrows that are adjacent to other families, these results suggest the presence of a vocal dialect which could be exploited by animals to represent kinship. These findings position the Mongolian gerbil as a compelling animal model to study the neural basis of vocal communication and demonstrates the potential for using unsupervised machine learning with uninterrupted acoustic recordings to gain insights into naturalistic animal behavior.

BACKGROUND:Accurate intraoperative diagnosis is crucial for differentiating between primary CNS lymphoma (PCNSL) and other CNS entities, guiding surgical decision-making, but represents significant challenges due to overlapping histomorphological features, time constraints, and differing treatment strategies. We combined stimulated Raman histology (SRH) with deep learning to address this challenge. METHODS:We imaged unprocessed, label-free tissue samples intraoperatively using a portable Raman scattering microscope, generating virtual H&E-like images within less than three minutes. We developed a deep learning pipeline called RapidLymphoma based on a self-supervised learning strategy to (1) detect PCNSL, (2) differentiate from other CNS entities, and (3) test the diagnostic performance in a prospective international multicenter cohort and two additional independent test cohorts. We trained on 54,000 SRH patch images sourced from surgical resections and stereotactic-guided biopsies, including various CNS neoplastic/non-neoplastic lesions. Training and test data were collected from four tertiary international medical centers. The final histopathological diagnosis served as ground-truth. RESULTS:In the prospective test cohort of PCNSL and non-PCNSL entities (n=160), RapidLymphoma achieved an overall balanced accuracy of 97.81% ±0.91, non-inferior to frozen section analysis in detecting PCNSL (100% vs. 77.77%). The additional test cohorts (n=420, n=59) reached balanced accuracy rates of 95.44% ±0.74 and 95.57% ±2.47 in differentiating IDH-wildtype diffuse gliomas and various brain metastasis from PCNSL. Visual heatmaps revealed RapidLymphoma's capabilities to detect class-specific histomorphological key features. CONCLUSIONS:RapidLymphoma proves reliable and valid for intraoperative PCNSL detection and differentiation from other CNS entities. It provides visual feedback within three minutes, enabling fast clinical decision-making and subsequent treatment strategy planning.

BACKGROUND:Oral cancer causes intense pain at the primary site, and such pain can impair oral functions. However, the underlying mechanisms for oral cancer pain are still not fully understood. In the present study, it is investigated whether programmed cell death protein 1 (PD-1) is involved in the development of oral cancer pain. METHODS:RMP1-14, a specific anti-PD-1 antibody, was injected into spinal trigeminal nucleus caudalis (Sp5C) and measured pain behaviors using von Frey filaments and dolognawmeter. Western blotting and immunofluorescence staining were performed to analyze the expression of PD-1 and tumor necrosis factor alpha (TNFα) in the Sp5C. RESULTS:It was observed that the PD-1 antibody significantly inhibited mechanical hypersensitivity and functional allodynia in our oral cancer pain mouse model. Moreover, we found that TNFα was highly upregulated in the Sp5C following the induction of oral cancer pain and that intra-Sp5C injection of the PD-1 antibody diminished the upregulation of TNFα. It was found that genetic deletion of TNFα or its receptor antagonism synergized the analgesic effect of PD-1 antibody on oral cancer pain. CONCLUSION/CONCLUSIONS:Our results suggest that PD-1 in the Sp5C contributes to oral cancer pain by altering TNFα signaling in the trigeminal nociceptive system, and PD-1 could be targeted to develop a novel approach for oral cancer pain management.