Improvement in swallowing safety after injection laryngoplasty in patients with unilateral vocal paralysis complicated with aspiration.

BACKGROUND: The benefit of injection laryngoplasty (IL) on voice for unilateral vocal fold paralysis (UVFP) is supported increasingly in literatures, yet less is known for swallowing. Also, prevalence of patient-reported dysphagia is substantially higher than instrumental studies. This prospective study focused on swallowing outcomes, with predetermined flexible endoscopic evaluation of swallowing (FEES) protocol that simulates daily life situation. METHODS: Adult patients with UVFP and aspiration receiving IL were recruited. Voice outcome measurements, as well as swallowing outcomes including Eating Assessment Tool (EAT-10) and FEES, which challenged patients with different fluid volumes: 10 mL, 20 mL, and 90 mL cup sipping were evaluated. RESULTS: Significant improvements were demonstrated in all voice outcomes. Significant changes were also presented inEAT-10 (P < 0.01). Pre-operatively, penetration-aspiration scale (PAS) was 1.5 ± 1.3, 1.9 ± 1.7 and 2.3 ± 1.8 for 10 mL, 20 mL and 90 mL serial sipping, and improved to 1.1 ± 0.3, 1.1 ± 0.4 and 1.4 ± 0.7 post-operatively (P < 0.01). Safe swallowing (PAS ≤ 2) was achieved in all, except for one patient, who presented with a post-injection PAS of 4 (material enters the airway, contacts the vocal folds, and is ejected from the airway) on 90 mL cup sipping, whose pre-injection PAS was 7 (residue in trachea). CONCLUSION: Maintaining swallowing function suitable for social environment is important. Our results demonstrated the feasibility of the predetermined FEES protocol, and positive effects of IL on both voice and swallowing outcomes.

Effects of a swallowing and oral-care program on resuming oral feeding and reducing pneumonia in patients following endotracheal extubation: a randomized, open-label, controlled trial.

BACKGROUND: The resumption of oral feeding and free from pneumonia are important therapeutic goals for critically ill patients who have been successfully extubated after prolonged (≥ 48 h) endotracheal intubation. We aimed to examine whether a swallowing and oral-care (SOC) program provided to critically ill patients extubated from prolonged mechanical ventilation improves their oral-feeding resumption and reduces 30-day pneumonia incidence. METHODS: In this randomized, open-label, controlled trial, participants were consecutively enrolled and randomized to receive the SOC program or usual care. The interventions comprised three protocols: oral-motor exercise, sensory stimulation and lubrication, and safe-swallowing education. Beginning on the day following patient extubation, an SOC nurse provided the three-protocol care for seven consecutive days or until death or hospital discharge. With independent outcome assessors, oral-feeding resumption (yes, no) corresponded to level 6 or level 7 on the Functional Oral Intake Scale (censored seven days postextubation) along with radiographically documented pneumonia (yes, no; censored 30 days postextubation), abstracted from participants' electronic medical records were coded. RESULTS: We analyzed 145 randomized participants (SOC group = 72, control group = 73). The SOC group received, on average, 6.2 days of intervention (14.8 min daily) with no reported adverse events. By day 7, 37/72 (51.4%) of the SOC participants had resumed oral feeding vs. 24/73 (32.9%) of the control participants. Pneumonia occurred in 11/72 (15.3%) of the SOC participants and in 26/73 (35.6%) of the control participants. Independent of age and intubation longer than 6 days, SOC participants were likelier than their control counterparts to resume oral feeding (adjusted hazard ratio, 2.35; 95% CI 1.38-4.01) and had lower odds of developing pneumonia (adjusted odds ratio, 0.28; 95% CI 0.12-0.65). CONCLUSIONS: The SOC program effectively improved patients' odds that oral feeding would resume and the 30-day pneumonia incidence would decline. The program might advance dysphagia care provided to critically ill patients extubated from prolonged mechanical ventilation. TRIAL REGISTRATION: NCT03284892, registered on September 15, 2017.

Proactive Swallowing Rehabilitation in Patients with Recurrent Oral Cancer Receiving Salvage Treatment: Long-Term Swallowing-Related Outcomes.

The present study aimed to evaluate the impact of proactive swallowing rehabilitation on swallowing function and quality of life in patients with recurrent oral cancer in the first 2 years after salvage treatment. Consecutive adult patients with recurrent oral cancer who received salvage surgery and free flap reconstruction were recruited prospectively, to whom proactive swallowing rehabilitation was provided. Body weight (BW); fiberoptic endoscopic evaluation of swallowing (FEES), functional oral intake scale (FOIS), and diet level; 10-item eating assessment tool (EAT-10), and MD Anderson Dysphagia Inventory (MDADI); and adherence at baseline, 1, 3, 6, 12, 18 and 24 months were evaluated. A total of 50 patients were included during May 2018 to July 2020. Compared to the baseline, significant deterioration in BW, FOIS, and MDADI was noted at one month. However, a trend of recovery was observed in BW and FOIS from one month, and in MDADI from three months. All patients were free of tube feeding at 18-24 months and tolerated diet with special preparations or compensation. Safe swallowing could be achieved in approximately 80% participants after 12 months of diet modification or compensatory maneuvers. Proactive swallowing therapy was feasible in patients with recurrent oral cancer receiving salvage treatment. Although this patient population might have pre-existing dysphagia from previous treatments, rehabilitation could facilitate safe per oral intake and maintain adequate nutrition with adaptive maneuvers or compensatory strategies. Patients who underwent proactive swallowing rehabilitation had better recovery in the functional oral intake level.

Effects of surgery on the relationship between subglottic pressure and fundamental frequency in vocal fold dynamics in patients with benign laryngeal diseases.

PURPOSE: Subglottic pressure (Ps) and fundamental frequency (F0) play important roles in governing vocal fold (VF) dynamics. Theoretical description, model simulation, excised larynx and animal models have been used in previous studies, yet clinically applicable measurements are still lacking. This study aimed to evaluate the effects of surgery for benign laryngeal lesions by investigating the relationship between F0 and Ps. METHODS: Patients with benign laryngeal lesions who underwent phonosurgery were prospectively recruited. Participants were instructed to sustain voicing the vowel /o/ at three incremental frequencies four semitones apart in the modal register (F01, F02, F03). F0 was estimated by VF vibration on the accelerometer. Ps change was achieved and measured using the airflow interruption method. RESULTS: Thirteen patients with a mean age (SD) of 43.5 (12.4) years were included. The change in F0 per unit change of Ps, which is the slope (Hz/kPa) of the regression line of the frequency-pressure data pairs, decreased as the tension of the VF increased. The slopes significantly increased after the operation for F01 and F02 (36.43 ± 14.68 preoperatively, 53.91 ± 30.71 postoperatively, p = 0.011 and 26.02 ± 10.71; 34.85 ± 17.92, p = 0.046, respectively). In addition, there was a significant decrease in phonation threshold pressure and improvements in the grade, roughness, breathiness, asthenia, strain scale, and the voice handicap inventory-10. CONCLUSIONS: The relationship between F0 and Ps may serve as an objective assessment of the outcomes in the treatment of benign laryngeal diseases with clinical relevance.

Radiation-induced swallowing dysfunction in patients with head and neck cancer: A literature review.

Swallowing dysfunction is a prevailing state following radiotherapy in patients with head and neck cancer. Following the advancement of cancer treatment in recent years, the survival rate of head and neck cancer has gradually increased. Simultaneously, patients with head and neck cancer suffer due to the long-duration and more prominent swallowing dysfunction states. Based on an extensive literature review, we aimed to explore the mechanisms, risk factors, and clinical evaluations of swallowing dysfunction and their related symptoms following radiotherapy. These include functional changes of the muscles, trismus, xerostomia, neuropathy, and lymphedema. When swallowing dysfunction occurs, patients usually seek medical help and are referred for rehabilitation therapy, such as muscle strengthening and tongue resistance exercise. Furthermore, clinicians should discuss with patients how and when to place the feeding tube. Only through detailed evaluation and management can swallowing dysfunction resolve and improve the quality of life of patients with head and neck cancer following radiotherapy.

An alternative surgical technique for advanced tongue/tongue base cancer without free flap reconstruction.

BACKGROUND/PURPOSE: Locally advanced tongue or tongue base cancer is recommended to be treated by radical resection that is usually detrimental to physiological functions. This study reports the efficacy and treatment outcome of the patients who had received total glossectomy and laryngeal suspension without lip-split mandibulotomy and free flap reconstruction to preserve laryngopharyngeal function. METHODS: From 2010 to 2018, 37 consecutive patients who had received the surgery were retrospectively recruited. RESULTS: The overall five-year survival is 72%. The postoperative dependent rate of feeding tube and tracheostomy largely decreases within 1-year follow-up. Treated by this surgical method, these patients are free from facial disfiguration, donor site morbidity, and destructive mastication and occlusion. It is also feasible to perform this surgical technique in the recurrent cases previously treated by chemoradiation. CONCLUSION: Total glossectomy with laryngeal suspension can be successfully applied to locally advanced tongue or tongue base cancer, and benefits the patients with improved survival and preserved physiological function. Especially surgeons for free flap reconstruction are understaffed at some regional or district hospitals.

Anatomical and physiological characteristics in patients with Laryngopharyngeal Reflux Symptoms: A case-control study utilizing high-resolution impedance manometry.

BACKGROUND/PURPOSE: This study aimed to explore the anatomical and physiological characteristics of patients with laryngopharyngeal reflux (LPR) symptoms, such as hoarseness, throat clearing, throat pain, globus, and chronic cough, with the novel high-resolution impedance manometry (HRIM). METHODS: Consecutive patients exhibited at least one LPR symptom for ≥4 weeks after 2-month proton-pump inhibitor treatment were enrolled during November 2014 and March 2018 from single tertiary medical center. All patients completed validated symptom questionnaires, esophagogastroduodenoscopy, and HRIM. Healthy volunteers were also recruited for comparison of esophageal parameters on HRIM. RESULTS: Eighty-nine LPR patients and 63 healthy volunteers were analyzed. Compared with healthy volunteers, LPR patients had significantly shorter upper and lower esophageal sphincters (UES and LES), a shorter intraabdominal esophagus (all P < 0.01), higher 4-s integrated relaxation pressures (IRP-4s) (P = 0.011) of the LES. After adjusted for age, sex, body weight, body height and alcohol consumption, multiple regression analysis showed that age, LES IRP-4s and the UES length were independent risk factors for LPR symptoms (OR 1.056, 95% CI 1.019-1.094; OR 1.107, 95% CI 1.004-1.222; OR 0.432, 95% CI 0.254-0.736, respectively). In subgroup analysis, patients with moderate LPR symptoms had lower IRP-4s (6.64 ± 4.55 vs. 8.69 ± 5.10, P = 0.049) and more failed peristalsis (27.33 ± 29.26 vs. 11.36 ± 21.20, P = 0.004) than those with mild LPR symptoms. CONCLUSION: Our study suggests that esophageal structural factors and LES IRP-4s may contribute to the occurrence of LPR symptoms. Patients with moderate LPR symptoms were more likely to present with failed peristalsis.

Predicting feeding-tube dependence in patients following endotracheal extubation: a two-item swallowing screen.

BACKGROUND: To meet the surging demands for intubation and invasive ventilation as more COVID-19 patients begin their recovery, clinicians are challenged to find an ultra-brief and minimally invasive screen for postextubation dysphagia predicting feeding-tube dependence persisting for 72 h after extubation. METHODS: This study examined the predictive validity of a two-item swallowing screen on feeding-tube dependence over 72 h in patients following endotracheal extubation. Intensive-care-unit (ICU) patients (≥ 20 years) successfully extubated after ≥ 48 h endotracheal intubation were screened by trained nurses using the swallowing screen (comprising oral stereognosis and cough-reflex tests) 24 h postextubation. Feeding-tube dependence persisting for 72 h postextubation was abstracted from the medical record by an independent rater. To verify the results and cross-check whether the screen predicted penetration and/or aspiration during fiberoptic endoscopic evaluation of swallowing (FEES), participants agreeing to receive FEES were analyzed within 30 min of screening. RESULTS: The results showed that 95/123 participants (77.2%) failed the screen, which predicted ICU patients' prolonged (> 72 h) feeding-tube dependence, yielding sensitivity of 0.83, specificity of 0.35, and accuracy of 0.68. Failed-screen participants had 2.96-fold higher odds of feeding-tube dependence (95% CI, 1.13-7.76). For the 38 participants receiving FEES, the swallowing screen had 0.89 sensitivity to detect feeding-tube dependence and 0.86 sensitivity to predict penetration/aspiration, although specificity had room for improvement (0.36 and 0.21, respectively). CONCLUSION: This ultra-brief swallowing screen is sufficiently sensitive to identify high-risk patients for feeding-tube dependence persisting over 72 h after extubation. Once identified, a further assessment and care are indicated to ensure the prompt return of patients' oral feeding. TRIAL REGISTRATION: NCT03284892, registered on September 15, 2017.

Objective evaluation of biomaterial effects after injection laryngoplasty - Introduction of artificial intelligence-based ultrasonic image analysis.

OBJECTIVE: Hyaluronic acid (HA) can be degraded over time. However, persistence of the effects after injection laryngoplasty (IL) for unilateral vocal fold paralysis (UVFP), longer than expected from HA longevity, has been observed. The purpose of the study was to develop a methodology with clinical utility for objective evaluation of the temporal change in HA volume after IL using artificial intelligence (AI)-based ultrasonic assessment. DESIGN, SETTING AND PARTICIPANTS: Imaging phantoms simulating injected HA were built in different volumes for designing the algorithm for machine learning. Subsequently, five adult patients who had undergone IL with HA for UVFP were recruited for clinical evaluation. MAIN OUTCOME MEASURES: Estimated volumes were evaluated for injected HA by the automatic algorithm as well as voice outcomes at 2 weeks, and 2 and 6 months after IL. RESULTS: On imaging phantoms, contours on each frame were described well by the algorithm and the volume could be estimated accordingly. The error rates were 0%-9.2%. Moreover, the resultant contours of the HA area were captured in detail for all participants. The estimated volume decreased to an average of 65.76% remaining at 2 months and to a minimal amount at 6 months while glottal closure remained improved. CONCLUSION: The volume change of the injected HA over time for an individual was estimated non-invasively by AI-based ultrasonic image analysis. The prolonged effect after treatment, longer than HA longevity, was demonstrated objectively for the first time. The information is beneficial to achieve optimal cost-effectiveness of IL and improve the life quality of the patients.

Estimating vocal fold stiffness: Using the relationship between subglottic pressure and fundamental frequency of phonation as an analog.

OBJECTIVE: The stiffness of the vocal folds is an important factor in voice production, yet clinically applicable measurements are still lacking. It has been demonstrated in an in vivo canine model that fundamental frequency (F0 ) increased linearly as subglottic pressure (Ps ) increased, but with a lesser slope for higher levels of vocal fold tension. In this study, the relationship between F0 and Ps was investigated using the airflow interruption method in awake patients non-invasively. DESIGN: Healthy volunteers enrolled for evaluation. SETTING: Single-centre. PARTICIPANTS: Thirty-three healthy volunteers aged 20 and older were recruited, with one excluded for a recent asthma attack. MAIN OUTCOME MEASURES: The relationships between F0 and Ps , described as the slope (Hz/kPa), were investigated when the participants sustained voicing the vowel/o/at 3 incremental frequencies 4 semitones apart in the modal register (F1, F2 and F3). RESULTS: Thirty-two healthy volunteers (20 females, 12 males) aged 20-47 years were enrolled for final analyses. There was a statistically significant difference in the slopes of the linear regression lines of F0 -Ps , depending on the frequency with which the vowel/o/ was produced (P < .001). The slope differed significantly between F2 and F1 (P < .001; P = .015), F3 and F1 (P < .001; P = .002) and F3 and F2 (P < .001; P = .005) for both women and men, respectively. CONCLUSIONS: It was demonstrated that the higher the vocal fold tension, the smaller the slope between F0 and Ps . Using the relationship between F0 and Ps as an analog of vocal fold stiffness is potentially practical for clinical application.

Nonintubated laryngomicrosurgery with Transnasal Humidified Rapid-Insufflation Ventilatory Exchange: A case series.

BACKGROUND: Nonintubation anaesthesia for laryngomicrosurgery (LMS) provides both excellent visualization of the surgical field and complete examination on vocal cord. However, adequate oxygenation remains challenging during nonintubated LMS. Recently, transnasal humidified rapid-insufflation ventilator exchange (THRIVE) has been reported effectively maintaining apneic oxygenation in patient with difficult airways. The feasibility and safety of nonintubated LMS with THRIVE was evaluated in this case series. METHODS: From September 2016 to February 2017, a total of 23 patients receiving nonintubated LMS were included. Anaesthesia was induced and maintained through target-controlled propofol infusion and muscle relaxation with THRIVE oxygen support. Perioperative data were collected from medical records and analysed. RESULTS: The mean (±SD) duration of the operation was 12.4 (±4.4) min. The mean (±SD) total anaesthesia time (from induction to emergence) was 24.1 (±6.4) min. 22 patients received nonintubated LMS with surgical satisfaction without intraoperative desaturation. One patient who underwent laryngeal tumour biopsy experienced a single episode of desaturation. A 5.5-mm tracheal tube was needed for short-term mechanical ventilation to regain SpO2 to 100%. No significant complication was noted in all patients. All patients discharged as per schedule on the next day after surgery as intubated LMS patients in our hospital. CONCLUSION: Nonintubated LMS with THRIVE is a feasible and safe alternative to intubated LMS with a small size tracheal tube to provide a better surgical field. However, for patients with easy-bleeding tumor, intubated LMS remains suggestive for better airway protection.

Extended bandwidth nonlinear frequency compression in Mandarin-speaking hearing-aid users.

BACKGROUND/PURPOSE: The high frequency information of consonant messages is important for recognition of speech. Recently, the nonlinear frequency compression (NLFC) technique has been shown to improve the speech perception in patients with high frequency hearing loss. In Mandarin, seven consonants are located over 10-16 kHz. Extended-bandwidth (EB) NLFC may provide an additional benefit for recognition of Mandarin words. The purpose of this study was to explore the effects of NLFC and EB-NLFC on Mandarin word recognition in patients with high frequency hearing loss. METHODS: Fourteen native Mandarin-speaking adult patients, aged 20-65 years with bilateral, moderate to severe, sensorineural hearing loss, specifically high frequency hearing loss were included in single-blind randomized study. The assessment tools included the Mandarin Monosyllable Recognition Test (MMRT), Mandarin Hearing in Noise Test (MHINT), and International Outcome Inventory for Hearing Aids (IOI-HA) and sound quality scale of the hearing aids. The patients were tested under unaided condition, after which they were randomly assigned to wear NLFC and EB-NLFC hearing aids, alternatively, in a crossover fashion. After each 4-week block, the patients were tested again to obtain the test outcomes. RESULTS: Patients with hearing aids with EB-NLFC had a significantly better word and consonant recognition using the MMRT (p<0.05). The MHINT was better for the EB-NLFC group without significant differences. The EB-NLFC group had better scores in both the IOI-HA and sound quality scale but not statistically significant. CONCLUSION: Patients with high-frequency hearing loss may benefit more from using EB-NLFC for word and consonant recognition; however, the improvement was small under a noisy listening environment. The subjective questionnaires did not show significant benefit of EB-NLFC either.

Induced-Fit Recognition of CCG Trinucleotide Repeats by a Nickel-Chromomycin Complex Resulting in Large-Scale DNA Deformation.

Small-molecule compounds targeting trinucleotide repeats in DNA have considerable potential as therapeutic or diagnostic agents against many neurological diseases. NiII (Chro)2 (Chro=chromomycin A3) binds specifically to the minor groove of (CCG)n repeats in duplex DNA, with unique fluorescence features that may serve as a probe for disease detection. Crystallographic studies revealed that the specificity originates from the large-scale spatial rearrangement of the DNA structure, including extrusion of consecutive bases and backbone distortions, with a sharp bending of the duplex accompanied by conformational changes in the NiII chelate itself. The DNA deformation of CCG repeats upon binding forms a GGCC tetranucleotide tract, which is recognized by NiII (Chro)2 . The extruded cytosine and last guanine nucleotides form water-mediated hydrogen bonds, which aid in ligand recognition. The recognition can be accounted for by the classic induced-fit paradigm.

Migrated Implant Causing Refractory Headache in Rhinoplasty.

Alloplastic materials are popular and readily available for use in nasal augmentations. Among them, silicone implant is one of the most widely used, especially in certain areas in Asia for its reasonable cost and relatively simple operative technique. A major disadvantage of silicone is its notorious mobility after implantation and rate of extrusion if traumatized or exposed. Here, an unusual complication of a silicone implant for rhinoplasty was presented. We report a case of a 58-year-old woman who had augmentation rhinoplasty 20 years ago suffered from headache for over a year. Brain lesion and neurologic causes were ruled out by neurologists and physician in family medicine. Local finding showed upwardly deviated nasion and vague shape of silicone implant underneath the skin on nasal dorsum.

The structural basis of actinomycin D-binding induces nucleotide flipping out, a sharp bend and a left-handed twist in CGG triplet repeats.

The potent anticancer drug actinomycin D (ActD) functions by intercalating into DNA at GpC sites, thereby interrupting essential biological processes including replication and transcription. Certain neurological diseases are correlated with the expansion of (CGG)n trinucleotide sequences, which contain many contiguous GpC sites separated by a single G:G mispair. To characterize the binding of ActD to CGG triplet repeat sequences, the structural basis for the strong binding of ActD to neighbouring GpC sites flanking a G:G mismatch has been determined based on the crystal structure of ActD bound to ATGCGGCAT, which contains a CGG triplet sequence. The binding of ActD molecules to GCGGC causes many unexpected conformational changes including nucleotide flipping out, a sharp bend and a left-handed twist in the DNA helix via a two site-binding model. Heat denaturation, circular dichroism and surface plasmon resonance analyses showed that adjacent GpC sequences flanking a G:G mismatch are preferred ActD-binding sites. In addition, ActD was shown to bind the hairpin conformation of (CGG)16 in a pairwise combination and with greater stability than that of other DNA intercalators. Our results provide evidence of a possible biological consequence of ActD binding to CGG triplet repeat sequences.

Precision-Targeted Injection Laryngoplasty and Longitudinal Biomaterial Effects Evaluation Using High-resolution Ultrasonography in a Rat Model.

OBJECTIVE: Current laryngeal injection models rely on the transoral route and are suboptimal due to limited view, narrowed working space, and the need to sacrifice animals for investigation of the injectables. In the present study, a novel surgical model for laryngeal intervention therapy utilizing an ultra-high frequency ultrasound imaging system was proposed. Based on this system, we developed a systemic evaluation approach, from guidance of the injection process, documentation of the injection site of the material, to in vivo longitudinal follow-up on the augmentation and medialization effect by analyzing the ultrasonography data. STUDY DESIGN: In vivo animal study. SETTING: Academic institution. METHODS: Injection laryngoplasty with hyaluronic acid under ultrasonography guidance was performed on Sprague-Dawley rats one week after induced unilateral vocal paralysis. Ultrasonography was performed at preinjection, immediately postinjection, on Day 2, Day 7 and then weekly for 4 weeks to obtain measurements, including the glottic area, angle between bilateral folds, and vocal fold width ratio. Laryngoscopic and histologic studies were also performed. RESULTS: Unilateral injections to the paralyzed fold were successfully performed as demonstrated by ultrasonographic, laryngoscopic, and histologic studies. The width ratio was significantly increased after injection for 4 weeks, while the glottic airway area was unchanged. CONCLUSION: Here, a novel surgical model for laryngeal injection utilizing ultrasonography in rats was established. In addition to providing visual guidance for precise localization of the injection, robust documentation of the treatment effect was also demonstrated. This methodology could be beneficial for screening therapeutic agents for treatment of glottic insufficiency.

Identification and analysis of Nonlinear behaviors of vocal fold biomechanics during phonation to assess efficacy of surgery for benign laryngeal Diseases.

BACKGROUND: Current voice assessments focus on perceptive evaluation and acoustic analysis. The interaction of vocal tract pressure (PVT) and vocal fold (VF) vibrations are important for volume and pitch control. However, there are currently little non-invasive ways to measure PVT. Limited information has been provided by previous human trials, and interactions between PVT and VF vibrations and the potential clinical application remain unclear. Here, we propose a non-invasive method for monitoring the nonlinear characteristics of PVT and VF vibrations, analyze voices from pathological and healthy individuals, and evaluate treatment efficacy. METHOD: Healthy volunteers and patients with benign laryngeal lesions were recruited for this study. PVT was estimated using an airflow interruption method, VF vibrational frequency was calculated from accelerometer signals, and nonlinear relationships between PVT and VF vibrations were analyzed. Results from healthy volunteers and patients, as well as pre- and post-operation for the patients, were compared. RESULTS: For healthy volunteers, nonlinearity was exhibited as an initial increase and then prompt decrease in vibrational frequency at the end of phonation, coinciding with PVT equilibrating with the subglottal pressure upon airflow interruption. For patients, nonlinearity was present throughout the phonation period pre-operatively, but showed a similar trend to healthy volunteers post-operatively. CONCLUSION: This novel method simultaneously monitors PVT and VF vibration and helps clarify the role of PVT. The results demonstrate differences in nonlinear characteristics between healthy volunteers and patients, and pre-/post-operation in patients. The method may serve as an analysis tool for clinicians to assess pathological phonation and treatment efficacy.

The effects of loop size on Sac7d-hairpin DNA interactions.

Hairpin structure is a common feature of DNA molecules. They are located near functional loci, such as regulation and promotion sites, as well as in cruciform structures, and they provide potential binding sites for endogenous proteins. The effects of different hairpin loops that are composed of one to five thymidines, designated as L1-L5, and have a common self-complementary stem, CTATATAG, on the interactions with Sac7d were studied. In thermostability studies, Sac7d stabilized a tetra-loop hairpin DNA and hairpin DNA with GTTC tetra-loop regions better than it stabilized tri- and penta-loops. Circular dichroism (CD) spectra showed that hairpins retained primarily a B-type conformation upon Sac7d binding. Intermolecular interactions between hairpins were likely decreased, due to the Sac7d-induced kinks, as shown by an increase at 220nm in the CD spectra. Surface plasmon resonance (SPR) observations suggested that the rates of Sac7d binding to hairpin DNA depend on the loop size of the hairpin duplexes. At a fixed stem length, Sac7d binds to tetra-loop hairpin DNA duplexes with a higher association rate and lower dissociation rate, compared with their tri- and penta-loop counterparts. In addition, the tri-loop and GTC tri-loop hairpin DNA had lower affinity for Sac7d because of the smaller and tighter loop size. Our study indicates that Sac7d binding affinity to hairpin DNA is primarily determined by loop size and stem integrity, and the results presented here provide a model for studies concerning other minor groove DNA-binding proteins that kink hairpin DNA.

Proton Pump Inhibitor-unresponsive Laryngeal Symptoms Are Associated With Psychological Comorbidities and Sleep Disturbance: A Manometry and Impedance-pH Monitoring Study

Background/Aims: Laryngeal symptoms are largely treated with empiric proton pump inhibitor (PPI) therapy if no apparent pathology shown on ear, nose, and throat evaluation and reflux-related etiologies are suspected. However, treatment response remains unsatisfactory. This study aimed to investigate the clinical and physiological characteristics of patients with PPI-refractory laryngeal symptoms. Methods: Patients with persistent laryngeal symptoms despite PPI treatment for ≥ 8 weeks were recruited. A multidisciplinary evaluation comprising validated questionnaires for laryngeal symptoms (reflux symptom index [RSI]), gastroesophageal reflux disease symptoms, psychological comorbidity (5-item brief symptom rating scale [BSRS-5]) and sleep disturbance (Pittsburgh sleep quality index [PSQI]), esophagogastroduodenoscopy, ambulatory impedance-pH monitoring, and high-resolution impedance manometry were performed. Healthy asymptomatic individuals were also recruited for comparison of psychological morbidity and sleep disturbances. Results: Ninety-seven adult patients and 48 healthy volunteers were analyzed. The patients had markedly higher prevalence of psychological distress (52.6% vs 2.1%, P < 0.001) and sleep disturbance (82.5% vs 37.5%, P < 0.001) than the healthy volunteers. There were significant correlations between RSI and BSRS-5 scores, and between RSI and PSQI scores (r = 0.26, P = 0.010, and r = 0.29, P = 0.004, respectively). Fifty-eight patients had concurrent gastroesophageal reflux disease symptoms. They had more prominent sleep disturbances (89.7% vs 71.8%, P < 0.001) than those with laryngeal symptoms alone but similar reflux profiles and esophageal motility. Conclusions: PPI-refractory laryngeal symptoms are mostly associated with psychological comorbidities and sleep disturbances. Recognition of these psychosocial comorbidities may help optimize management in these patients.