Spatially Resolved Anisotropic Natural Abundance Deuterium 2D-NMR Spectroscopy Using Bimesophasic Lyotropic Chiral Systems.

In this paper, we describe, for the first time, the combined and original use of spatially resolved anisotropic natural abundance deuterium (ANAD) 2D-NMR experiments and bimesophasic lyotropic chiral systems to extract two independent sets of anisotropic parameters such as 2H-RQCs from a single NMR sample. As a pioneering example, we focus on a mixture of immiscible polypeptides (PBLG) and polyacetylene helical polymers (L-MSP) dissolved in weakly polar organic solvents (chloroform). Nondeuterated (D)-(+)-camphor is used as a model chiral solute. By providing two series of 2H-RQCs, this new analytical approach paves the way for applications in 3D structure elucidation with increased reliability and also opens up original investigations in terms of spectral enantiomeric discriminations and mixing of helical polymers.

An Integrated Experimental-Computational Study of Vocal Fold Vibration in Type I Thyroplasty.

Subject-specific computational modeling of vocal fold (VF) vibration was integrated with an ex vivo animal experiment of type 1 thyroplasty to study the effect of the implant on the vocal fold vibration. In the experiment, a rabbit larynx was used to simulate type 1 thyroplasty, where one side of the vocal fold was medialized with a trans-muscular suture while the other side was medialized with a silastic implant. Vocal fold vibration was then achieved by flowing air through the larynx and was filmed with a high-speed camera. The three-dimensional computational model was built upon the pre-operative scan of the laryngeal anatomy. This subject-specific model was used to simulate the vocal fold medialization and then the fluid-structure interaction (FSI) of the vocal fold. Model validation was done by comparing the vocal fold displacement with postoperative scan (for medialization), and by comparing the vibratory characteristics with the high-speed images (for vibration). These comparisons showed the computational model successfully captured the effect of the implant and thus has the potential for presurgical planning.

Acute Effects of Systemic Glucocorticoids on the Vocal Folds in a Pre-Clinical Model.

OBJECTIVES/HYPOTHESIS: Systemic glucocorticoids (GC)s are employed to treat various voice disorders. However, GCs have varying pharmacodynamic properties with adverse effects ranging from changes in epithelial integrity, skeletal muscle catabolism, and altered body weight. We sought to characterize the acute temporal effects of systemic dexamethasone and methylprednisolone on vocal fold (VF) epithelial glucocorticoid receptor (GR) nuclear translocation, epithelial tight junction (ZO-1) expression, thyroarytenoid (TA) muscle fiber morphology, and body weight using an established pre-clinical model. We hypothesized dexamethasone and methylprednisolone will elicit changes in VF epithelial GR nuclear translocation, epithelial ZO-1 expression, TA muscle morphology, and body weight compared to placebo-treated controls. METHODS: Forty-five New Zealand white rabbits received intramuscular injections of methylprednisolone (4.5 mg; n = 15), dexamethasone (450 µg; n = 15), or volume matched saline (n = 15) into the iliocostalis/longissimus muscle for 6 consecutive days. Vocal folds from 5 rabbits from each treatment group were harvested at 1-, 3-, or 7 days following the final injection and subjected to immunohistochemistry for ZO-1 and GR as well as TA muscle fiber cross-sectional area (CSA) measures. RESULTS: Dexamethasone increased epithelial GR nuclear translocation and ZO-1 expression 1-day following injections compared to methylprednisolone (P = .024; P = .012). Dexamethasone and methylprednisolone increased TA CSA 1-day following injections (P = .011). Methylprednisolone decreased body weight 7 days following injections compared to controls (P = .004). CONCLUSIONS: Systemic dexamethasone may more efficiently activate GR in the VF epithelium with a lower risk of body weight loss, suggesting a role for more refined approaches to GC selection for laryngeal pathology.

Subject-Specific Modeling of Implant Placement for Type I Thyroplasty Surgery.

Type I thyroplasty is widely used to improve voice production in patients affected by unilateral vocal fold paralysis. Almost two-thirds of laryngologists report using Silastic® implants to medialize the vocal fold, with implant size, shape, and location determined experientially. However, post-surgical complications arising from this procedure (extrusion, migration, resizing) necessitate revision in 4.5-16% of patients. To improve initial surgical outcomes, we have developed a subject-specific modeling tool, PhonoSim, which uses model reconstruction from MRI scans to predict the optimal implantation location. Eleven vocal fold sample sides from eight larynges of New Zealand white rabbits were randomized to two groups: PhonoSim informed (n = 6), and control (no model guidance, n = 5). Larynges were scanned ex vivo in the abducted configuration using a vertical-bore 11.7 T microimaging system, and images were used for subject-specific modeling. The PhonoSim tool simulated vocal fold adduction for multiple implant location placements to evaluate vocal fold adduction at the medial surface. The best implant placement coordinates were output for the 6 samples in the PhonoSim group. Control placements were determined by the same surgeon based on anatomical landmarks. Post-surgical MRI scans were performed for all samples to evaluate medialization in implanted vocal folds. Results show that PhonoSim-guided implantation achieved higher vocal fold medialization relative to controls (28 to 55% vs. - 29 to 39% respectively, in the glottal area reduction), suggesting that this tool has the potential to improve outcomes and revision rates for type I thyroplasty.

Custom Laser-Cut Silastic® Implants for Type I Thyroplasty in a Preclinical Model.

This study aimed to produce customized silicone elastomer implants of varied size and shape for optimization of type I thyroplasty procedures in a rabbit model. Computer-aided design models of different implant designs were designed and used to program laser cutting of a medical-grade Silastic® sheet. Laser-cut implants were produced rapidly and cost-efficiently. Surgical implantation demonstrated vocal fold medialization and phonation in 5 test subjects. This technique may provide a low-cost alternative or adjunct method to hand-carving or commercial implants.

Acute In Vitro and In Vivo Effects of Dexamethasone in the Vocal Folds: a Pilot Study.

OBJECTIVES/HYPOTHESIS: Glucocorticoids (GC)s are commonly employed to treat vocal fold (VF) pathologies. However, VF atrophy has been associated with intracordal GC injections. Dexamethasone-induced skeletal muscle atrophy is well-documented in other tissues and believed to be mediated by increased muscle proteolysis via upregulation of Muscle Ring Finger (MuRF)-1 and Atrogin-1. Mechanisms of dexamethasone-mediated VF atrophy have not been described. This pilot study employed in vitro and in vivo models to investigate the effects of dexamethasone on VF epithelium, thyroarytenoid (TA) muscle, and TA-derived myoblasts. We hypothesized that dexamethasone will increase atrophy-associated gene expression in TA muscle and myoblasts and decrease TA muscle fiber size and epithelial thickness. STUDY DESIGN: In vitro, pre-clinical. METHODS: TA myoblasts were isolated from a female Sprague-Dawley rat and treated with 1 µM dexamethasone for 24-h. In vivo, 15 New Zealand white rabbits were randomly assigned to three treatment groups: (1) bilateral intracordal injection of 40 µL dexamethasone (10 mg/ml; n = 5), (2) volume-matched saline (n = 5), and (3) untreated controls (n = 5). Larynges were harvested 7-days post-injection. Across in vivo and in vitro experimentation, MuRF-1 and Atrogin-1 mRNA expression were measured via RT-qPCR. TA muscle fiber cross-sectional area (CSA) and epithelial thickness were also quantified in vivo. RESULTS: Dexamethasone increased MuRF-1 gene expression in TA myoblasts. Dexamethasone injection, however, did not alter atrophy-associated gene expression, TA CSA, or epithelial thickness in vivo. CONCLUSION: Dexamethasone increased atrogene expression in TA myoblasts, providing foundational insight into GC induced atrophic gene transcription. Repeated dexamethasone injections may be required to elicit atrophy in vivo. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2264-2270, 2023.

Epithelial response to vocal fold microflap injury in a preclinical model.

OBJECTIVES: Functional outcomes following microflap surgery for vocal fold pathology are favorable. Although the stratified squamous epithelium appears to heal rapidly, persistent physiologic tissue alterations are likely. We sought to elucidate key biochemical processes including recruitment of immune cells, regulation of cellular junction proteins, and long-term alterations to epithelial tissue permeability following microflap with an eye toward enhanced clinical outcomes. METHODS: Forty New Zealand rabbits were assigned to eight groups (n = 5/group): no-injury control or bilateral microflap with survival for 0 h, 12 h, 1 day, 3 days, 7 days, 30 days, and 60 days post-microflap. The epithelium was dissected from one vocal fold and transepithelial resistance was quantified. The contralateral fold was subjected to transmission electron microscopy. Images were evaluated by a blinded rater and paracellular space dilation was quantified using ImageJ. Immune cell infiltration was evaluated and recorded qualitatively. RESULTS: Increased innate immune response was observed 12 h as well as 7 and 30 days after microflap. At 60 days following injury, decreased epithelial resistance was observed. Paracellular spaces were dilated at all time-points following injury. CONCLUSIONS: The vocal fold epithelium was significantly altered at 60 days following microflap. The implications for this tissue phenotype are unclear. However, compromised epithelial barrier function is implicated in various diseases and may increase the risk of subsequent injury. LEVEL OF EVIDENCE: NA Laryngoscope, 133:350-356, 2023.

Modeling Method for Semicrystalline Polymers Controlling Aspects of the Morphology at the Molecular Scale for the Study of Mechanical and Physicochemical Properties.

A novel method is presented to build semicrystalline polymer models used in molecular dynamics simulations. The method allows controlling certain aspects of the molecular morphology of the material. It relies on the generation of the polymer sections in the amorphous phase of the semicrystalline structure according to the statistical polymer physics theory proposed by Adhikari and Muthukumar ( J. Chem. Phys.2019, 151, 114905). The amorphous phase is first built based on the method initially developed by Theodorou and Suter ( Macromolecules1985,18 (7), 1467-1478). Then, the amorphous phase is stacked between crystallites, and a connection algorithm proposed by Rigby et al. ( Advanced Composites for Aerospace, Marine, and Land Applications; Springer: Cham, Switzerland, 2014), initially developed to build polymer thermosets, is employed to link the two phases. For a given set of degree of crystallinity, semicrystalline long period, densities of the crystalline and amorphous phases, and polymer molecular weight, the characteristic ratio is used to control the relative fractions of different types of polymer sections in the amorphous phase as well as the distribution of their lengths. There are three types of amorphous polymer sections: the ones that are reentering in the same crystallite called loops, those that are bonding two different crystallites called tie chains, and the chain tails ending in the amorphous region. The higher the imposed characteristic ratio is, the higher the fraction of the tie chains is. The full implementation of the theory is described and then applied to high-density polyethylene (HDPE). Several samples are generated. The obtained structures are characterized. Their elastic coefficients are computed, and high uniaxial deformations are performed. It is shown that the higher the degree of crystallinity, the higher the elastic coefficients. An entanglement analysis shows that the quantity of tie chains is more decisive than the entanglements in acting as stress transmitters to rigidify the structure.

Subject-Specific Computational Fluid-Structure Interaction Modeling of Rabbit Vocal Fold Vibration.

A full three-dimensional (3D) fluid-structure interaction (FSI) study of subject-specific vocal fold vibration is carried out based on the previously reconstructed vocal fold models of rabbit larynges. Our primary focuses are the vibration characteristics of the vocal fold, the unsteady 3D flow field, and comparison with a recently developed 1D glottal flow model that incorporates machine learning. The 3D FSI model applies strong coupling between the finite-element model for the vocal fold tissue and the incompressible Navier-Stokes equation for the flow. Five different samples of the rabbit larynx, reconstructed from the magnetic resonance imaging (MRI) scans after the in vivo phonation experiments, are used in the FSI simulation. These samples have distinct geometries and a different inlet pressure measured in the experiment. Furthermore, the material properties of the vocal fold tissue were determined previously for each individual sample. The results demonstrate that the vibration and the intraglottal pressure from the 3D flow simulation agree well with those from the 1D flow model based simulation. Further 3D analyses show that the inferior and supraglottal geometries play significant roles in the FSI process. Similarity of the flow pattern with the human vocal fold is discussed. This study supports the effective usage of rabbit larynges to understand human phonation and will help guide our future computational studies that address vocal fold disorders.

Voice Handicap Index Changes After Microflap Surgery for Benign Vocal Fold Lesions Are Not Associated With Recommended Absolute Voice Rest Duration.

PURPOSE: Voice rest is frequently prescribed after phonosurgery, but optimal type and duration for voice outcomes have not been demonstrated. Studies to date have been characterized by heterogeneity in surgical procedures and laryngeal diagnoses. We sought to analyze the effect of recommended absolute voice rest duration on outcomes of microflap surgery for benign vocal fold lesions. A secondary purpose was to identify patient factors associated with postoperative voice outcomes. METHOD: Forty-three patients were included in this retrospective review of patients aged 18 years and above who underwent direct microlaryngoscopy with microflap for vocal fold polyp or cyst over a 5-year period at a multidisciplinary voice center. Duration of recommended postoperative absolute voice rest was classified as less than 7 days, 7 days, and more than 7 days. Demographic and vocal hygiene data and voice treatment history were collected. Outcome measures consisted of one pre- and two postoperative Voice Handicap Index (VHI) scores. Effects of recommended voice rest on outcomes were analyzed using mixed models for repeated measures. Effects of patient factors on outcomes were analyzed as exploratory measures. Stroboscopy ratings were analyzed descriptively. RESULTS: Thirteen patients were recommended 7 days of absolute voice rest, 15 were recommended less than 7 days, and 15 were recommended more than 7 days. Postoperatively, VHI scores significantly improved for all patients. Voice rest as a continuous variable was associated with the Functional subscale score in the short term, but there was no effect on VHI total score and no longer term effect of voice rest on any outcome. Age, sex, and preoperative voice therapy were associated with at least one VHI subscale score on at least one time point. CONCLUSION: VHI outcomes of microflap surgery for polyps and cysts do not differ by duration of recommended absolute postoperative voice rest. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.19178459.

Numerical and experimental investigations on vocal fold approximation in healthy and simulated unilateral vocal fold paralysis.

We have developed a novel surgical/computational model for the investigation of unilateral vocal fold paralysis (UVFP) which will be used to inform future in silico approaches to improve surgical outcomes in type I thyroplasty. Healthy phonation (HP) was achieved using cricothyroid suture approximation on both sides of the larynx to generate symmetrical vocal fold closure. Following high-speed videoendoscopy (HSV) capture, sutures on the right side of the larynx were removed, partially releasing tension unilaterally and generating asymmetric vocal fold closure characteristic of UVFP (sUVFP condition). HSV revealed symmetric vibration in HP, while in sUVFP the sutured side demonstrated a higher frequency (10 - 11%). For the computational model, ex vivo magnetic resonance imaging (MRI) scans were captured at three configurations: non-approximated (NA), HP, and sUVFP. A finite-element method (FEM) model was built, in which cartilage displacements from the MRI images were used to prescribe the adduction and the vocal fold deformation was simulated before the eigenmode calculation. The results showed that the frequency comparison between the two sides were consistent with observations from HSV. This alignment between the surgical and computational models supports the future application of these methods for the investigation of treatment for UVFP.

Mycoplasma affects baseline gene expression and the response to glucocorticoids in vocal fold fibroblasts.

Introduction. In vitro experimentation is intentionally contrived to isolate specific phenomena in the context of profound biological complexity. Mycoplasmas in the upper airway likely contribute to this complexity and play a largely unknown role in both health and disease. Similarly, the presence and role of mycoplasma in in vitro investigation are largely unknown.Hypothesis. We hypothesize mycoplasma in human vocal fold fibroblasts (VFF) will affect both basal gene-expression patterns as well as the cell response to exogenous stimuli.Aim. We sought to determine mycoplasma presence across vocal fold fibroblast cultures, basal transcriptional changes as a function of mycoplasma, and responsiveness to exogenous glucocorticoids in mycoplasma-positive and -negative VFF.Methodology. PCR-based mycoplasma detection was performed in an immortalized human VFF line as well as rat and rabbit primary VFF cultures and extracted rat laryngeal tissue. RNA sequencing was performed in mycoplasma-positive and -negative human cells at baseline and in response to dexamethasone.Results. Mycoplasma was identified in the human cell line as well as primary culture from rabbits. Mycoplasma was not detected in tissue or primary culture from rat vocal folds. Basal mRNA expression in human VFF differed significantly following mycoplasma treatment. In addition, differential responses to dexamethasone were observed across multiple pathways as a function of mycoplasma presence in these cells. Pathways including apoptosis, DNA damage repair, and G1 to S cell cycle signalling were significantly enriched in mycoplasma-positive cells.Conclusion. Variability of mycoplasma presence across culture conditions and differential responses to exogenous stimuli as a function of mycoplasma presence are potentially problematic for the translation of in vitro experimentation in the upper aerodigestive tract. It remains unclear if these findings represent contamination or the baseline state of this specialized tissue.

Protein Substrate Alters Cell Physiology in Primary Culture of Vocal Fold Epithelial Cells.

The basement membrane interacts directly with the vocal fold epithelium. Signaling between the basement membrane and the epithelium modulates gene regulation, differentiation, and proliferation. The purpose of this study was to identify an appropriate simple single-protein substrate for growth of rabbit vocal fold epithelial cells. Vocal folds from 3 New Zealand white rabbits (Oryctolagus cuniculus) were treated to isolate epithelial cells, and cells were seeded onto cell culture inserts coated with collagen I, collagen IV, laminin, or fibronectin. Transepithelial electrical resistance (TEER) was measured, and phase contrast microscopy, PanCK, CK14, and E-cadherin immunofluorescence were utilized to assess for epithelial cell-type characteristics. Further investigation via immunofluorescence labeling was conducted to assess proliferation (Ki67) and differentiation (Vimentin). There was a significant main effect of substrate on TEER, with collagen IV eliciting the highest, and laminin the lowest resistance. Assessment of relative TEER across cell lines identified a larger range of TEER in collagen I and laminin. Phase contrast imaging identified altered morphology in the laminin condition, but cell layer depth did not appear to be related to TEER, differentiation, or morphology. Ki67 staining additionally showed no significant difference in proliferation. All conditions had confluent epithelial cells and dispersed mesenchymal cells, with increased mesenchymal cell numbers over time; however, a higher proportion of mesenchymal cells was observed in the laminin condition. The results suggest collagen IV is a preferable basement membrane substrate for in vitro vocal fold epithelial primary cell culture, providing consistent TEER and characteristic cell morphology, and that laminin is an unsuitable substrate for vocal fold epithelial cells and may promote mesenchymal cell proliferation.

A one-dimensional flow model enhanced by machine learning for simulation of vocal fold vibration.

A one-dimensional (1D) unsteady and viscous flow model that is derived from the momentum and mass conservation equations is described, and to enhance this physics-based model, a machine learning approach is used to determine the unknown modeling parameters. Specifically, an idealized larynx model is constructed and ten cases of three-dimensional (3D) fluid-structure interaction (FSI) simulations are performed. The flow data are then extracted to train the 1D flow model using a sparse identification approach for nonlinear dynamical systems. As a result of training, we obtain the analytical expressions for the entrance effect and pressure loss in the glottis, which are then incorporated in the flow model to conveniently handle different glottal shapes due to vocal fold vibration. We apply the enhanced 1D flow model in the FSI simulation of both idealized vocal fold geometries and subject-specific anatomical geometries reconstructed from the magnetic resonance imaging images of rabbits' larynges. The 1D flow model is evaluated in both of these setups and shown to have robust performance. Therefore, it provides a fast simulation tool that is superior to the previous 1D models.

Medialization Laryngoplasty: A Review for Speech-Language Pathologists.

Purpose The purpose of this study is to familiarize speech-language-pathologists with the current state of the science regarding medialization laryngoplasty in the treatment of voice disorders, with emphasis on current evidence-based practice, voice outcomes, and future directions for research. Method A literature review was performed in PubMed and Embase using the keywords vocal fold/cord and laryngoplasty, thyroplasty, augmentation, or laryngeal framework. Articles published between 2010 and 2020 were reviewed for data about clinical applications, technical approach, voice-related outcomes, and basic science or clinical innovations with the potential to improve patient care. A synthesis of data was performed from articles meeting the outlined search criteria. Conclusions As key members in the multidisciplinary care of voice disorders, speech-language pathologists need to be informed of current research in medialization laryngoplasty, a procedure commonly used for patients with glottic insufficiency. Advances in anesthetic technique, office-based procedures, and the development of materials with increased bio-tolerability over the past decade have led to innovations in treatment and improved patient outcomes. Recent applications of computational and bioengineering approaches have the potential to provide new directions in the refinement of currently available techniques and the improvement of patient-based treatment outcomes.

A 3D In Vitro Model of the Human Airway Epithelium Exposed to Tritiated Water: Dosimetric Estimate and Cytotoxic Effects.

Tritium has been receiving worldwide attention, particularly because of its production and use in existing fission reactors and future nuclear fusion technologies, leading to an increased risk of release in the environment. Linking human health effects to low-dose tritium exposures presents a challenge for many reasons. Among these: biological effects strongly depend on the speciation of tritiated products and exposure pathway; large dosimetric uncertainties may exist; measurements using in vitro cell cultures generally lack a description of effects at the tissue level, while large-scale animal studies might be ethically questionable and too highly demanding in terms of resources. In this context, three-dimensional models of the human airway epithelium are a powerful tool to investigate potential toxicity induced upon inhalation of radioactive products in controlled physiological conditions. In this study we exposed such a model to tritiated water (HTO) for 24 h, with a range of activity levels (up to ∼33 kBq µl-1 cm-2). After the exposures, we measured cell viability, integrity of epithelial layer and pro-inflammatory response at different post-exposure time-points. We also quantified tritium absorption and performed dosimetric estimates considering HTO passage through the epithelial layer, leading to reconstructed upper limits for the dose to the tissue of less than 50 cGy cumulative dose for the highest activity. Upon exposure to the highest activity, cell viability was not decreased; however, we observed a small effect on epithelial integrity and an inflammatory response persisting after seven days. These results represent a reference condition and will guide future experiments using human airway epithelium to investigate the effects of other peculiar tritiated products.

Different Vibratory Conditions Elicit Different Structural and Biological Vocal Fold Changes in an In-Vivo Rabbit Model of Phonation.

OBJECTIVE: Vibration of the vocal folds can disrupt the tissue and induce structural, functional, and molecular changes; the presence or absence of contact between the vocal folds during vibration can affect the type and extent of these changes. The purpose of this study was to characterize vocal fold changes following 2 hours of contact phonation or phonation without vibratory contact. METHODS: Six New Zealand white breeder rabbits underwent 120 minutes of phonation with or without vibratory contact, and four served as nonphonated controls. The larynx was exposed and current was applied to the cricothyroids bilaterally to achieve vocal fold adduction while humidified airflow was delivered to induce vocal fold vibration. Laryngeal position, airflow, and stimulation levels were adjusted to obtain phonation with or without contact, and phonation was elicited for 120 minutes. Following excision, larynges were stained using Hematoxylin & Eosin, Elastica van Gieson, and Grocott's Methenamine Silver, or labeled with immunofluorescent markers for E-cadherin, CD31, CD11b, and Vimentin. All images were captured using a Nikon 90i microscope and analyzed using ImageJ. RESULTS: Differences between vibratory conditions and control samples were observed. There was more extensive epithelial thinning, reduced epithelial integrity and increased vascularity in the contact phonation group, while both phonatory groups demonstrated a decreased presence of mucous on the luminal surface and a decrease in elastin band thickness and lamina propria depth. Neither condition showed differences in inflammatory cell presence compared to control tissue. CONCLUSIONS: By showing that these two vibratory conditions result in structural changes of different types and magnitude, we have provided the first empirical evidence that vocal fold tissue is sensitive to differences in forces, and that changes in vibratory pattern can elicit different downstream biological changes within the tissue. The differences described herein are an important step toward understanding the vocal folds' potential for differential response to phonotraumatic damage following different vibratory behaviors.

Assessment of an anisotropic coarse-grained model for cis-1,4-polybutadiene: a bottom-up approach.

The spherical representation usually utilized for the coarse-grained particles of soft matter systems is an assumption and pertinent studies have shown that both structural and dynamical properties can depend on anisotropic effects. On these grounds, we develop coarse-grained equations of motion which take into account explicitly the anisotropy of the beads. As a first step, this model incorporates only conservative terms. Inclusion of the dissipative and random terms is in principle possible but is beyond the scope of this study. The translational dynamics of the beads is tracked using the position and momentum of their center of mass, while their rotational dynamics is modeled by representing their orientation through the use of quaternions, similarly to the case of rigid bodies. The associated force and torque controlling the motion are derived from atomistic molecular dynamics (MD) simulations via a bottom-up approach and define a coarse-grained potential. The assumptions of the model are clearly stated and checked for a reference system of a cis-1,4-polybutadiene melt. In particular, the choice of the angular velocity as a slow variable is justified by comparing its dynamics to atomic vibrations. The accuracy of this approach to reproduce static structural features of the polymer melt is assessed.

A Comparison of the Localization of Integral Membrane Proteins in Human and Rabbit Vocal Folds.

OBJECTIVES: This study's objective was to identify and compare the localization of Aquaporin (AQP) 1, 4, 7, Na+/K + -ATPase, E-cadherin, zona occludin (ZO)-1, and occludin in human and rabbit vocal folds (VF)s to inform the design of future studies to explore the function of these proteins in the regulation of VF homeostasis. METHODS: Four human larynges and five New Zealand white rabbit larynges were used. Samples were immunolabeled for primary antibodies against AQP1, AQP4, AQP7, the alpha subunit of Na+/K + -ATPase, E-cadherin, and ZO-1 and occludin and then captured digitally using a Nikon Eclipse 90i microscope and Hamamatsu C10600 Camera. Two raters familiar with human and rabbit VF histology identified positive labeling in tissue structures, including the apical epithelium, basal epithelium/basement membrane, and lamina propria (LP). RESULTS: Samples from both species showed positive labeling for AQP1 in the basal epithelium/basement membrane, superficial LP, and deep/intermediate LP. Aquaporin 4, Aquaporin 7, Na+/K + -ATPase, and E-cadherin were primarily localized to the epithelium of both species. Zona occludin-1 was primarily localized apical epithelium and the superficial LP of both species. Occludin was primarily present in the apical epithelium in rabbit samples but not human. CONCLUSION: These data provide evidence of the presence of key ion transport channels and cell adhesion proteins in human and rabbit VFs. Aquaporin 1, 4, 7, Na+/K + -ATPase, E-cadherin, and ZO-1 were similarly localized in both species. These findings will be useful to investigators interested in the exploration of VF homeostasis and barrier integrity in future studies. LEVEL OF EVIDENCE: N/A Laryngoscope, 131:E1265-E1271, 2021.

A reduced-order flow model for vocal fold vibration: from idealized to subject-specific models.

We present a reduced-order model for fluid-structure interaction (FSI) simulation of vocal fold vibration during phonation. This model couples the three-dimensional (3D) tissue mechanics and a one-dimensional (1D) flow model that is derived from the momentum and mass conservation equations for the glottal airflow. The effects of glottal entrance and pressure loss in the glottis are incorporated in the flow model. We consider both idealized vocal fold geometries and subject-specific anatomical geometries segmented from the MRI images of rabbits. For the idealized vocal fold geometries, we compare the simulation results from the 1D/3D hybrid FSI model with those from the full 3D FSI simulation based on an immersed-boundary method. For the subject-specific geometries, we incorporate previously estimated tissue properties for individual samples and compare the results with those from the high-speed imaging experiment of in vivo phonation. In both setups, the comparison shows good agreement in the vibration frequency, amplitude, phase delay, and deformation pattern of the vocal fold, which suggests potential application of the present approach for future patient-specific modeling.