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The terms used to describe vocal fold motion impairment are confusing and not standardized. This results in a failure to communicate accurately and to major limitations of interpreting research studies involving vocal fold impairment. We propose standard nomenclature for reporting vocal fold impairment. Overarching terms of vocal fold immobility and hypomobility are rigorously defined. This includes assessment techniques and inclusion and exclusion criteria for determining vocal fold immobility and hypomobility. In addition, criteria for use of the following terms have been outlined in detail: vocal fold paralysis, vocal fold paresis, vocal fold immobility/hypomobility associated with mechanical impairment of the crico-arytenoid joint and vocal fold immobility/hypomobility related to laryngeal malignant disease. This represents the first rigorously defined vocal fold motion impairment nomenclature system. This provides detailed definitions to the terms vocal fold paralysis and vocal fold paresis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the in vitro rheometric properties of the canine vocal fold lamina propria and muscle at phonatory frequencies, and their changes with anatomic location. Methods: Six canine larynges were harvested immediately postmortem. Viscoelastic shear properties of anterior, middle, and posterior portions of the vocal fold cover (lamina propria) as well as those of the medial thyroarytenoid (TA) muscle (vocalis muscle) were quantified by a linear, controlled-strain simple-shear rheometer. Measurements of elastic shear modulus (G′) and dynamic viscosity (η′) of the specimens were conducted with small-amplitude sinusoidal shear deformation over a frequency range of 1–250Hz. Results: All specimens showed similar frequency dependence of the viscoelastic functions, with G′ gradually increasing with frequency and η′ decreasing with frequency monotonically. G′ and η′ of the canine vocalis muscle were significantly higher than those of the canine vocal fold cover, and η′ of the canine vocal fold cover was significantly higher than that of the human vocal fold cover. There were no significant differences in G′ and in η′ between different portions of the canine vocal fold cover. Conclusion: These preliminary data based on the canine model suggested that the vocalis muscle, while in a relaxed state in vitro, is significantly stiffer and more viscous than the vocal fold cover during vibration at phonatory frequencies. For large-amplitude vocal fold vibration involving the medial portion of the TA muscle, such distinct differences in viscoelastic properties of different layers of the vocal fold should be taken into account in multi-layered biomechanical models of phonation. [Copyright &y& Elsevier]

Examines the specific interactions required for catalysis of α-lytic protease folding. Factors affecting the folding catalysis; Enhancement of resistance on proteolysis; Instability of energetic penalty required for folding.

Traditional radiation therapy for early-stage larynx cancer irradiates the whole larynx over 5.5 to 6 weeks. Phase 1 data suggest that stereotactic ablative radiotherapy (SABR) is a viable strategy to reduce the irradiated volume and compress treatment time. This phase 2 study evaluated the efficacy of gLoTtic larynx-SABR in 5 or 16 fractions. Eligibility required stage 0 to II squamous cell carcinoma of the glottic larynx. The arytenoid cartilage could not be involved beyond the vocal process, and patients smoking more than one pack per day were excluded. The treatment volume consisted of the gross tumor volume, with a 3 mm margin (5 mm craniocaudal) to create the planning target volume. Patients without active smoking and planning target volume <10 cc received 4250 cGy in 5 fractions, twice per week; other patients received 58.08 Gy in 16 daily fractions. The primary endpoint was the 2-year incidence of local failure. Twenty-five patients were accrued to this study, with 21 and 4 treated with 5 and 16 fractions, respectively. The stage distribution was in situ (n = 1, 4%), T1a/b (n = 16/5, 64%/20%), and T2 (n = 3, 12%). The median age was 72 years, with a prior smoking history in 16 (64%) and active smoking in 1 (4%). At a median follow-up for surviving patients of 3.7 years (IQR, 3.1-4.4 years), there have been 2 in-field recurrences (1 in each dose cohort). The cumulative incidences of local failure were 4% (90% CI, 0.8%-20%) and 8% (90% CI, 3%-24%) at 1 and 2 years, respectively. There have been no acute or late grade 3+ toxicities in disease-free patients. The median baseline, 1, 6, 12, and 24 months Voice Handicap Index scores were 57 (IQR, 32-69), 28.5 (8-48), 4 (0-12), 7.5 (0-12), and 5 (0-24), respectively. Highly conformal stereotactic radiation therapy appears safe and efficacious for early-stage glottic larynx cancer, with encouraging patient-reported outcomes. These results need to be interpreted with caution given the small sample size and large noninferiority margin. Additional follow-up and ultimately comparative studies are necessary to validate this paradigm. [ABSTRACT FROM AUTHOR]

Investigates the complex of a monomer of the GAL4 protein with DNA by two-dimensional H nuclear magnetic resonance (NMR) spectroscopy. Discovery of structure in which a dimer of the N-terminal 65-residue fragment of GAL4 forms a complex; Development of a smaller system amenable for analysis using NMR; Basis for chemical shift data for free GAL4 protein.

While the majority of proteins fold rapidly and spontaneously to their native states, the extracellular bacterial protease α-lytic protease (αLP) has a t1/2 for folding of ~2,000 years, corresponding to a folding barrier of 30 kcal mol?1. αLP is synthesized as a pro-enzyme where its pro region (Pro) acts as a foldase to stabilize the transition state for the folding reaction. Pro also functions as a potent folding catalyst when supplied as a separate polypeptide chain, accelerating the rate of αLP folding by a factor of 3 × 109. In the absence of Pro, αLP folds only partially to a stable molten globule-like intermediate state. Addition of Pro to this intermediate leads to rapid formation of native αLP. Here we report the crystal structures of Pro and of the non-covalent inhibitory complex between Pro and native αLP. The C-shaped Pro surrounds the C-terminal ß-barrel domain of the folded protease, forming a large complementary interface. Regions of extensive hydration in the interface explain how Pro binds tightly to the native state, yet even more tightly to the folding transition state. Based on structural and functional data we propose that a specific structural element in αLP is largely responsible for the folding barrier and suggest how Pro can overcome this barrier. [ABSTRACT FROM AUTHOR]

The effective depth of vocal fold vibration is self-regulated and generally not known a priori in vocalization. In this study, the effective depth was quantified systematically under various phonatory conditions using a fiber-gel finite element vocal fold model. The horizontal and vertical excursions of each finite element nodal point trajectory were recorded to compute trajectory areas. The extent of vibration was then studied based on the variation of trajectory radii as a function of depth in several coronal sections along the anterior-posterior direction. The results suggested that the vocal fold nodal trajectory excursions decrease systematically as a function of depth but are affected by the layered structure of the vocal folds. The effective depth of vibration was found to range between 15 and 55% of the total anatomical depth across all phonatory conditions. The nodal trajectories from the current study were compared qualitatively with the results from excised human hemi-larynx experiments published in Döllinger and Berry [(2006). J. Voice. 20(3), 401–413]. An estimate of the effective mass of a one-mass vocal fold model was also computed based on the effective depth of vibration observed in this study under various phonatory conditions. [ABSTRACT FROM AUTHOR]

Abstract Vibratory function of the vocal folds is largely determined by the rheological properties or viscoelastic shear properties of the vocal fold lamina propria. To date, investigation of the sample size estimation and statistical experimental design for vocal fold rheological studies is nonexistent. The current work provides the closed-form sample size formulas for two major study designs (i.e. paired and two-group designs) in vocal fold research. Our results demonstrated that the paired design could greatly increase the statistical power compared to the two-group design. By comparing the variance of estimated treatment effect, this study also confirms that ignoring within-subject and within-vocal fold correlations during rheological data analysis will likely increase type I errors. Finally, viscoelastic shear properties of intact and scarred rabbit vocal fold lamina propria were measured and used to illustrate theoretical findings in a realistic scenario and project sample size requirement for future studies. [ABSTRACT FROM AUTHOR]

Thyroplasty with arytenoid adduction, a combined procedure for treatment of unilateral vocal fold paralysis, is typically performed under local anesthesia with sedation to allow for intraoperative voice assessment. However, the need for patient immobility and suppression of laryngeal responses to surgical manipulation can make sedation-analgesia challenging. We describe our first 26 consecutive cases undergoing thyroplasty and arytenoid adduction with a standardized technique consisting of a combination of general anesthesia with tracheal intubation followed by sedation-analgesia. Most patients (69 %) were women, with age of 53 ± 15 years (mean ± SD). Neck surgery was the cause of vocal fold paralysis in 50 % of patients. Initially, general anesthesia was maintained with desflurane and remifentanil with dexmedetomidine added just before tracheal extubation. During the sedation-analgesia phase, patients received infusions of remifentanil and dexmedetomidine. Duration of general anesthesia and sedation-analgesia phases was 162 ± 68.2 and 79 ± 18.3 min, respectively. Mean (SD) wake-up time was 8.0 ± 4.0 min after desflurane discontinuation. Extubation occurred without coughing, bucking, or agitation in 96 % of patients. All the patients were able to phonate appropriately and remained comfortable after emergence. This technique allowed improved surgical conditions with reduced patient discomfort and may be advantageous for other laryngeal and neck surgeries in which intraoperative patient feedback is required. [ABSTRACT FROM AUTHOR]

Vocal folds are used as sound sources in various species, but it is unknown how vocal fold morphologies are optimized for different acoustic objectives. Here we identify two main variables affecting range of vocal fold vibration frequency, namely vocal fold elongation and tissue fiber stress. A simple vibrating string model is used to predict fundamental frequency ranges across species of different vocal fold sizes. While average fundamental frequency is predominantly determined by vocal fold length (larynx size), range of fundamental frequency is facilitated by (1) laryngeal muscles that control elongation and by (2) nonlinearity in tissue fiber tension. One adaptation that would increase fundamental frequency range is greater freedom in joint rotation or gliding of two cartilages (thyroid and cricoid), so that vocal fold length change is maximized. Alternatively, tissue layers can develop to bear a disproportionate fiber tension (i.e., a ligament with high density collagen fibers), increasing the fundamental frequency range and thereby vocal versatility. The range of fundamental frequency across species is thus not simply one-dimensional, but can be conceptualized as the dependent variable in a multi-dimensional morphospace. In humans, this could allow for variations that could be clinically important for voice therapy and vocal fold repair. Alternative solutions could also have importance in vocal training for singing and other highly-skilled vocalizations. [ABSTRACT FROM AUTHOR]

Creation of sub-epithelial voids within scarred vocal folds via ultrafast laser ablation may help in localization of injectable therapeutic biomaterials towards an improved treatment for vocal fold scarring. Several ultrafast laser surgery probes have been developed for precise ablation of surface tissues; however, these probes lack the tight beam focusing required for sub-surface ablation in highly scattering tissues such as vocal folds. Here, we present a miniaturized ultrafast laser surgery probe designed to perform sub-epithelial ablation in vocal folds. The requirement of high numerical aperture for sub-surface ablation, in addition to the small form factor and side-firing architecture required for clinical use, made for a challenging optical design. An Inhibited Coupling guiding Kagome hollow core photonic crystal fiber delivered micro-Joule level ultrashort pulses from a high repetition rate fiber laser towards a custom-built miniaturized objective, producing a 1/e2 focal beam radius of 1.12 ± 0.10 μm and covering a 46 × 46 μm2 scan area. The probe could deliver up to 3.8 μJ pulses to the tissue surface at 40% transmission efficiency through the entire system, providing significantly higher fluences at the focal plane than were required for sub-epithelial ablation. To assess surgical performance, we performed ablation studies on freshly excised porcine hemi-larynges and found that large area sub-epithelial voids could be created within vocal folds by mechanically translating the probe tip across the tissue surface using external stages. Finally, injection of a model biomaterial into a 1 × 2 mm2 void created 114 ± 30 μm beneath the vocal fold epithelium surface indicated improved localization when compared to direct injection into the tissue without a void, suggesting that our probe may be useful for pre-clinical evaluation of injectable therapeutic biomaterials for vocal fold scarring therapy. With future developments, the surgical system presented here may enable treatment of vocal fold scarring in a clinical setting. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to test the hypothesis that stretch-and-flow voice therapy (SnF) is noninferior to resonant voice therapy (RVT) for speakers with muscle tension dysphonia. Method: Participants with primary muscle tension dysphonia were randomly assigned to 1 of 2 treatment groups. Participants received 6 sessions of either SnF or RVT for 6 weeks (1 session per week). Pretreatment and posttreatment audio recordings of sustained vowels and connected speech were acquired. Response to treatment was assessed using the voice handicap index (VHI) as the primary outcome measure. Secondary outcome measures included the acoustic voice quality index, the smoothed cepstral peak prominence, and scales from the Consensus Auditory-Perceptual Evaluation of Voice instrument. Data were analyzed for 21 participants who completed the study (12 in the SnF group, 9 in the RVT group). Results: Direction of change for the primary outcome measure and all 3 secondary outcome measures at posttreatment was in the direction of improvement for both SnF and RVT. Confidence intervals for VHI measures did not cross the null effect line on forest plots, suggesting significant effects for both treatments on the primary outcome measure. The effect sizes for pretreatment to posttreatment changes in VHI were large for both treatment groups. Similar results were found for the secondary acoustic outcome measures. There were statistically significant pretreatment to posttreatment changes in the primary and secondary outcome measures for patients receiving both treatments, indicating significant improvement in response to both RVT and SnF. There were no statistically significant differences in pretreatment to posttreatment changes in the primary outcome measure or any secondary outcome measure between the two groups. The within-group pretreatment to posttreatment changes in Consensus Auditory-Perceptual Evaluation of Voice scales did not reach statistical significance for either RVT or SnF. Conclusions: Both SnF and RVT produced positive treatment response in speakers with muscle tension dysphonia, with no statistically significant difference in the outcome measures between the two treatments. This suggests that SnF is noninferior to RVT and that both are effective options for treating vocal hyperfunction. Results from this study also support previous findings documenting the sensitivity of multidimensional acoustic measurements to treatment response. [ABSTRACT FROM AUTHOR]