Faculty Bibliography

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Various animal models have been employed to investigate vocal fold (VF) and phonatory function. However, biomechanical testing techniques to characterize vocal fold structural properties vary and have not compared critical properties across species. We adapted a nondestructive, automated indentation mapping technique to simultaneously quantify VF structural properties (VF cover layer and intact VF) in commonly used species based on the hypothesis that VF biomechanical properties are largely preserved across species. STUDY DESIGN/METHODS:Ex vivo animal model. METHODS:Canine, leporine, and swine larynges (n = 4 each) were sagittally bisected, measured, and subjected to normal indentation mapping (indentation at 0.3 mm; 1.2 mm/s) with a 2-mm spherical indenter to quantify normal force along the VF cover layer, structural stiffness, and displacement at 0.8 mN; two-dimensional maps of the free VF edge through the conus elasticus were created for these characterizations. RESULTS:Structural stiffness was 7.79 gf/mm (0.15-74.55) for leporine, 2.48 gf/mm (0.20-41.75) for canine, and 1.45 gf (0.56-4.56) for swine. For each species, the lowest values were along the free VF edge (mean ± standard deviation; leporine: 0.40 ± 0.21 gf/mm, canine: 1.14 ± 0.49 gf/mm, swine: 0.89 ± 0.28 gf/mm). Similar results were obtained for the cover layer normal force at 0.3 mm. On the free VF edge, mean (standard deviation) displacement at 0.08 gf was 0.14 mm (0.05) in leporine, 0.11 mm (0.03) in canine, and 0.10 mm (0.02) in swine. CONCLUSIONS:Automated indentation mapping yielded reproducible biomechanical property measurement of the VF cover and intact VF. Divergent VF structural properties across canine, swine, and leporine species were observed. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2018.

OBJECTIVE:Age-related muscle atrophy of the laryngeal muscles contributes to presbyphonia. Remodeling of the neuromuscular junction is one aspect underlying age-related muscle atrophy. Although muscle disuse has been shown to exacerbate age-related neuromuscular changes in the limb muscles, it is unknown if reduced vocal use has a similar effect in the laryngeal muscles. The objective of this study was to examine the use of social isolation as a novel method to reduce vocal use in old rats-and the impact of that reduced vocal use on ultrasonic vocalization acoustics and neuromuscular junction morphology in the thyroarytenoid muscle. STUDY DESIGN/METHODS:Animal group comparison. METHODS:Old F344/BN rats (31 months of age) were socially isolated (n = 8) or communally housed (n = 8) for 8 weeks. Effect of housing condition on ultrasonic vocalization acoustics was assessed by calculating the changes in vocalization fundamental frequency and amplitude from baseline to 8 weeks. Neuromuscular junction morphology was measured in the lateral and medial portions of the thyroarytenoid muscle at the conclusion of the experiment. RESULTS:Vocalization amplitude decreased by a mean of -4.4 dB (standard deviation [SD], 4.49) after social isolation, whereas amplitude increased by a mean of 5.7 dB (SD, 5.07) in the communally housed rats (P = 0.002). There was no significant difference in the change in fundamental frequency between groups. Furthermore, there were no group differences in any measure of neuromuscular junction morphology. CONCLUSION/CONCLUSIONS:These results suggest that neuromuscular junctions in the thyroarytenoid muscle of old rats are unaffected by 8 weeks of social isolation, despite functional changes in vocalizations. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2018.

OBJECTIVES/OBJECTIVE:ties was hypothesized to differ from those in patients with twill ties. METHODS:ties. Patients were followed for the first seven postoperative days. The primary outcome was skin-related complications, which were further categorized into mild (irritation) and severe (breakdown). The secondary outcome was accidental decannulation. Rates of skin-related complication and accidental decannulation were compared across the two groups using chi-square analysis. RESULTS:ties was associated with a decreased rate of skin irritation (OR: 0.41; 95% CI: 0.17-0.97; P = 0.039). CONCLUSIONS:ties at the time of pediatric tracheotomy placement.

Motherhood in mammals involves tremendous changes throughout the body and central nervous system, which support attention and nurturing of infants. Maternal care consists of complex behaviors, such as nursing and protection of the offspring, requiring new mothers to become highly sensitive to infant needs. Long-lasting neural plasticity in various regions of the cerebral cortex may enable the perception and recognition of infant cues, important for appropriate caregiving responses. Recent findings have demonstrated that the neuropeptide oxytocin is involved in a number of physiological processes, including parturition and lactation and dynamically shaping neuronal responses to infant stimuli as well. Here, we review experience-dependent changes within the cortex occurring throughout motherhood, focusing on plasticity of the somatosensory and auditory cortex. We outline the role of oxytocin in gating cortical plasticity and discuss potential mechanisms regulating oxytocin release in response to different sensory stimuli.

OBJECTIVES:/UNASSIGNED:Prognostic information about the return of vocal fold mobility in patients with iatrogenic unilateral vocal fold immobility (UVFI) can help with informed decisions about temporary and permanent treatment options. Although many variables can influence the likelihood of recovery, clinical experience suggests that cervical versus thoracic injury is a determining factor. The purpose of this study was to compare recovery rates from UVFI between cervical and thoracic injuries. METHODS:/UNASSIGNED:analyses. RESULTS:/UNASSIGNED:Overall, 15% of patients recovered vocal fold mobility at a median of 4.1 months. Patients with cervical injury (65 of 329 [20%]) were significantly more likely to recover mobility than patients with thoracic injury (11 of 173 [6.4%]) (odds ratio, 3.63). The cervical cohort contained more women (68% vs 31%) and was younger (mean age, 60.4 ± 13.8 vs 64.1 ± 16.1 years; Cohen's D = 0.25). CONCLUSIONS:/UNASSIGNED:Patients with cervical injuries resulting in UVFI are 4 times more likely to recover mobility than patients with thoracic injuries. This information can be valuable in counseling patients with UVFI and may affect clinical decision making.

Previous studies have shown that tumor necrosis factor alpha (TNFα) is significantly increased in complete Freund's adjuvant (CFA)-treated temporomandibular joint (TMJ) tissues. However, it is unclear whether TNFα in the trigeminal nociceptive system contributes to the development of TMJ pain. In the present study, we investigated the role of TNFα in trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in CFA-induced inflammatory TMJ pain. Intra-TMJ injection of CFA (10 μl, 5 mg/ml) induced inflammatory pain in the trigeminal nerve V2- and V3-innervated skin areas of WT mice, which was present on day 1 after CFA and persisted for at least 10 days. TNFα in both TG and Sp5C of WT mice was upregulated after CFA injection. The CFA-induced TMJ pain was significantly inhibited in TNFα KO mice. The immunofluorescence staining showed that intra-TMJ CFA injection not only enhanced co-localization of TNFα with Iba1 (a marker for microglia) in both TG and Sp5C but also markedly increased the expression of TNFα in the Sp5C neurons. By the methylated DNA immunoprecipitation assay, we also found that DNA methylation at the TNF gene promoter region in the TG was dramatically diminished after CFA injection, indicating that epigenetic regulation may be involved in the CFA-enhanced TNFα expression in our model. Our results suggest that TNFα in the trigeminal nociceptive system plays a critical role in CFA-induced inflammatory TMJ pain.

Purpose: Non-tuberculous mycobacteria (NTM) is an intracellular microorganism that causes cavitary disease and nodular bronchiectatic disease of the lung. Common symptoms include chronic cough, sputum production and frequent pneumonias. Patients with NTM appear to have impaired swallow function as represented by impaired airway protection. Our aim is to determine bolus clearance in patients with NTM compared with a control. Method(s): Videofluoroscopy (VF) was prospectively collected from 195 patients:132 patients with NTM (90 females; ages 30-90) and 63 age-and sex-matched normal controls with normal pulmonary function tests and no pulmonary disease (39 females; ages 27-92).Two boluses of 3, 5, 10 mL thin liquid, two 5 mL puree Varibar, and cracker were analyzed per subject (N = 1,755 swallows).Outcome measures included ordinal ratings of residue in the valleculae and pyriform sinuses. The correlation between clinical information and the present of pharyngeal residue structures was analyzed by Fisher's exact test for categorical variables and Wilcoxon's rank sum test for comparisons of continuous variables between groups. Result(s): Inter-and intra-rater reliability of the ordinal ratings were assessed using two-way random intraclass correlation coefficients (ICC(2,1)) on 20% of the data with good results (intra-rater: ICC = 0.92, 95% CI 0.70-0.97 and inter-rater: ICC = 0.92, 95% CI 0.81-0.97).The ratings of residue in the valleculae were significantly higher in the NTM group compared to the control group for one of the 3 mL bolus (p = 0.008), for 5 mL boluses (p = 0.009 and p = 0.004), 10 mL boluses (p = 0.0005 and p = 0.0006), puree (p = 0.006), cracker (p = 0.005).The ratings of residue in the pyriform sinuses were also significantly higher in the NTM group for 3 mL boluses (p = 0.0002 and p = 0.01), 5 mL boluses (p = 0.0003 and p = 0.002), 10 mL boluses (p = 0.001 and p = 0.001), puree trials (p<0.0001 and p<0.0001).Wilcoxon's rank sum test determined no age difference and Fisher's exact test determined no gender difference between the NTM and control groups. Conclusions (Including Clinical Relevance): Patients with NTM appear to have reduced bolus clearance than healthy individuals with no pulmonary disease, as represented by ratings of residue in the valleculae and pyriform sinuses.Future work is needed to elucidate the interaction between the respiratory-swallowing systems and airway protection and responsiveness to swallowing treatment for patients with NTM

Oral cancer patients report severe function-induced pain; severity is greater in females. We hypothesize that a neutrophil-mediated endogenous analgesic mechanism is responsible for sex differences in nociception secondary to oral squamous cell carcinoma (SCC). Neutrophils isolated from the cancer-induced inflammatory microenvironment contain β-endorphin protein and are identified by the Ly6G⁺ immune marker. We previously demonstrated that male mice with carcinogen-induced oral SCC exhibit less nociceptive behavior and a higher concentration of neutrophils in the cancer microenvironment compared to female mice with oral SCC. Oral cancer cells secrete granulocyte colony stimulating factor (G-CSF), a growth factor that recruits neutrophils from bone marrow to the cancer microenvironment. We found that recombinant G-CSF (rG-CSF, 5 μg/mouse, intraperitoneal) significantly increased circulating Ly6G⁺ neutrophils in the blood of male and female mice within 24 h of administration. In an oral cancer supernatant mouse model, rG-CSF treatment increased cancer-recruited Ly6G⁺ neutrophil infiltration and abolished orofacial nociceptive behavior evoked in response to oral cancer supernatant in both male and female mice. Local naloxone treatment restored the cancer mediator-induced nociceptive behavior. We infer that rG-CSF-induced Ly6G⁺ neutrophils drive an endogenous analgesic mechanism. We then evaluated the efficacy of chronic rG-CSF administration to attenuate oral cancer-induced nociception using a tongue xenograft cancer model with the HSC-3 human oral cancer cell line. Saline-treated male mice with HSC-3 tumors exhibited less oral cancer-induced nociceptive behavior and had more β-endorphin protein in the cancer microenvironment than saline-treated female mice with HSC-3 tumors. Chronic rG-CSF treatment (2.5 μg/mouse, every 72 h) increased the HSC-3 recruited Ly6G⁺ neutrophils, increased β-endorphin protein content in the tongue and attenuated nociceptive behavior in female mice with HSC-3 tumors. From these data, we conclude that neutrophil-mediated endogenous opioids warrant further investigation as a potential strategy for oral cancer pain treatment.