Bi-Weekly Voice Therapy Versus Weekly Voice Therapy for Muscle Tension Dysphonia.

OBJECTIVES: To compare the outcomes of bi-weekly voice therapy (BWVT) with weekly voice therapy on perception, acoustics, and quality of life for individuals with muscle tension dysphonia (MTD). METHODS: Thirty participants with MTD were enrolled either BWVT (40 min/session, two sessions per week for 4 weeks) or weekly voice therapy (40 min/session, once a week for 8 weeks). Auditory perceptual ratings, acoustic parameters, and the Mandarin version of the voice-related quality of life questionnaire (MV-RQOL) scores were statistically analyzed before and after treatment. RESULTS: There were significant improvements in the voice qualities such as overall grade, roughness, asthenia, and strain in both groups after treatment. Acoustics analyses showed that fundamental frequency, speaking fundamental frequency, jitter, shimmer, and cepstral peak prominence significantly improved in both groups after treatment. For the MV-RQOL questionnaire scores, the result also demonstrated that both groups felt significant improvements in voice-related quality of life after treatment. However, there were no significant differences between the two groups of treatment effects. CONCLUSIONS: Patients with MTD can restore voice qualities and quality of life if they are able to complete a full course of voice therapy, regardless of the intensity of voice therapy. However, if they can receive the BWVT, they would be able to regain their voice faster. The results of this study can be provided as a reference for clinicians when treating patients with MTD.

Voice Outcomes of Straw Phonation Exercises for Telephone Customer Service Staff.

OBJECTIVE: This study aimed to investigate the effectiveness of a straw phonation exercise program in preventing voice problems in telephone customer service staff. STUDY DESIGN: Prospective study. METHODS: Twenty-eight participants with no obvious voice problems were placed into two groups: the experimental (n = 13) and control (n = 15) groups. The experimental group received voice hygiene instructions and participated in a 3-week straw phonation exercise program, while the control group only received voice hygiene instructions. The acoustic parameters and Mandarin Chinese version of the Vocal Fatigue Index (CVFI) scores were statistically analyzed before training, immediately after training, followed up one and 3 months after training. RESULTS: The results showed that speaking fundamental frequency (SF0), shimmer, and cepstral peak prominence (CPP) of the experimental group improved immediately after the straw phonation exercise program, and shimmer of the experimental group after training was also significantly lower than that of the control group. A higher SF0 and lower shimmer were noted in the experimental group during the follow-up phase, whereas factors 1 (voice load and fatigue) and 2 (physiological symptoms) of the CVFI did not differ significantly until the third month after training. CONCLUSION: The study results suggest that the straw phonation exercise program can help telephone service staff to establish an appropriate speaking pitch and prevent voice fatigue.

Montgomery T-Tube Airway Restoration and Swallowing Rehabilitation for a Near-Hanging Female.

Patients who fail to commit suicide by hanging often end up with laryngotracheal injuries, which may lead to a compromised airway, swallowing dysfunction, and dysphonia. Previous studies have mainly focused on airway management after near-hanging attempts. Few have shed light on the treatment of swallowing dysfunction after laryngotracheal injuries. Here, we present a near-hanging patient who developed complete dysphagia shortly afterward. We used a Montgomery T-tube as an endolaryngeal stent, combined with swallowing rehabilitation. The patient's swallowing ability was gradually restored one month after the surgery, and the stent was removed six months later. The present case report exemplifies the unique way of using the Montgomery T-tubes in clinical practice. Among the patients with airway stenosis affecting the larynx and extending to the vocal cords, Montgomery T-tube may be the only stent that can help manage strictures at the level of the vocal cords and in the supraglottic region, restoring swallowing function and maintaining the airway.

Functional divergence of a pair of Arabidopsis phospho-base methyltransferases, PMT1 and PMT3, conferred by distinct N-terminal sequences.

In seed plants, phospho-base N-methyltransferase (PMT) catalyzes a key step in the biosynthesis pathway of phosphatidylcholine (PC), the most abundant phospholipid class. Arabidopsis thaliana possesses three copies of PMT, with PMT1 and PMT3 play a primary role because the pmt1 pmt3 double mutant shows considerably reduced PC content with a pale seedling phenotype. Although the function of PMT1 and PMT3 may be redundant because neither of the parental single mutants showed a similar mutant phenotype, major developmental defects and possible functional divergence of these PMTs underlying the pale pmt1 pmt3 seedling phenotype are unknown. Here, we show the major developmental defect of the pale seedlings in xylem of the hypocotyl with partial impairments in chloroplast development and photosynthetic activity in leaves. Although PMT1 and PMT3 are localized at the endoplasmic reticulum, their tissue-specific expression pattern was distinct in hypocotyls and roots. Intriguingly, the function of PMT3 but not PMT1 requires its characteristic N-terminal sequence in addition to the promoter because truncation of the N-terminal sequence of PMT3 or substitution with PMT1 driven by the PMT3 promoter failed to rescue the pale pmt1 pmt3 seedling phenotype. Thus, PMT3 function requires the N-terminal sequence in addition to its promoter, whereas the PMT1 function is defined by the promoter.

Preliminary Clinical Outcomes of VOIS-Implant in Patients With Unilateral Vocal Fold Paralysis.

OBJECTIVES/HYPOTHESIS: Evaluation of the clinical outcomes after 6 months of treatment with a novel adjustable implant, the APrevent® Vocal-Implant-System (VOIS), in conjunction with medialization thyroplasty (MT) in patients with unilateral vocal fold paralysis. STUDY DESIGN: Prospective case series study at single tertiary referral center. METHODS: Preoperative and 1 week, 7 weeks, and 6 months postoperative glottal efficiency (maximum phonation time [MPT]), voice quality (including GRBAS-scores and acoustic parameters) and self-perceived voice-related handicap (voice handicap index [VHI-30]) were measured and analyzed, whereas type of vocal fold closure was evaluated and determined by flexible videolaryngoscopy based on Södersten and Lindestad classification (Wilcoxon signed-rank test). RESULTS: Thirteen patients underwent MT with VOIS under local anesthesia. Six months after surgery, the VHI-30 and MPT had improved from a preoperative mean of 75.0 ± 22.9 and 2.7 ± 2.1 s to a postoperative mean of 20.6 ± 19.7 and 6.3 ± 4.0 s, respectively. The mean GRBAS score improved from preoperative scores of Gpreop  = 2.7, Rpreop  = 2.6, Bpreop  = 2.6, Apreop  = 2.2, and Spreop  = 2.0 to Gpostop  = 0.3, Rpostop  = 0.3, Bpostop  = 0.2, Apostop  = 0.2, and Spostop  = 0.3 at 6 months postoperatively. Improved glottal closure was achieved in all patients (n = 13). Five patients received postoperative adjustment for the optimization of voice quality and glottal closure. No intra- or postoperative complications were observed. Significant improvements in acoustic parameters, including percentage jitter, percentage shimmer, and signal-to-noise ratio, were also observed after MT. All results were statistically significant (P < .05, Cohen's d > .8). CONCLUSIONS: APrevent® VOIS-Implantation is a safe procedure with good voice outcomes. Postoperative adjustments can be performed smoothly to optimize voice quality and glottal closure. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1622-1629, 2022.

A robust TDP-43 knock-in mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset degenerative disorder of motor neurons. The diseased spinal cord motor neurons of more than 95% of amyotrophic lateral sclerosis (ALS) patients are characterized by the mis-metabolism of the RNA/DNA-binding protein TDP-43 (ALS-TDP), in particular, the presence of cytosolic aggregates of the protein. Most available mouse models for the basic or translational studies of ALS-TDP are based on transgenic overexpression of the TDP-43 protein. Here, we report the generation and characterization of mouse lines bearing homologous knock-in of fALS-associated mutation A315T and sALS-associated mutation N390D, respectively. Remarkably, the heterozygous TDP-43 (N390D/+) mice but not those heterozygous for the TDP-43 (A315T/+) mice develop a full spectrum of ALS-TDP-like pathologies at the molecular, cellular and behavioral levels. Comparative analysis of the mutant mice and spinal cord motor neurons (MN) derived from their embryonic stem (ES) cells demonstrates that different ALS-associated TDP-43 mutations possess critical ALS-causing capabilities and pathogenic pathways, likely modified by their genetic background and the environmental factors. Mechanistically, we identify aberrant RNA splicing of spinal cord Bcl-2 pre-mRNA and consequent increase of a negative regulator of autophagy, Bcl-2, which correlate with and are caused by a progressive increase of TDP-43, one of the early events associated with ALS-TDP pathogenesis, in the spinal cord of TDP-43 (N390D/+) mice and spinal cord MN derived from their ES cells. The TDP-43 (N390D/+) knock-in mice appear to be an ideal rodent model for basic as well as translational studies of ALS- TDP.

LWD-TCP complex activates the morning gene CCA1 in Arabidopsis.

A double-negative feedback loop formed by the morning genes CIRCADIAN CLOCK ASSOCIATED1 (CCA1)/LATE ELONGATED HYPOCOTYL (LHY) and the evening gene TIMING OF CAB EXPRESSION1 (TOC1) contributes to regulation of the circadian clock in Arabidopsis. A 24-h circadian cycle starts with the peak expression of CCA1 at dawn. Although CCA1 is targeted by multiple transcriptional repressors, including PSEUDO-RESPONSE REGULATOR9 (PRR9), PRR7, PRR5 and CCA1 HIKING EXPEDITION (CHE), activators of CCA1 remain elusive. Here we use mathematical modelling to infer a co-activator role for LIGHT-REGULATED WD1 (LWD1) in CCA1 expression. We show that the TEOSINTE BRANCHED 1-CYCLOIDEA-PCF20 (TCP20) and TCP22 proteins act as LWD-interacting transcriptional activators. The concomitant binding of LWD1 and TCP20/TCP22 to the TCP-binding site in the CCA1 promoter activates CCA1. Our study reveals activators of the morning gene CCA1 and provides an action mechanism that ensures elevated expression of CCA1 at dawn to sustain a robust clock.

Plantar Purpura as the Initial Presentation of Viridians Streptococcal Shock Syndrome Secondary to Streptococcus gordonii Bacteremia.

Viridians streptococcal shock syndrome is a subtype of toxic shock syndrome. Frequently, the diagnosis is missed initially because the clinical features are nonspecific. However, it is a rapidly progressive disease, manifested by hypotension, rash, palmar desquamation, and acute respiratory distress syndrome within a short period. The disease course is generally fulminant and rarely presents initially as a purpura over the plantar region. We present a case of a 54-year-old female hospital worker diagnosed with viridians streptococcal shock syndrome caused by Streptococcus gordonii. Despite aggressive antibiotic treatment, fluid hydration, and use of inotropes and extracorporeal membrane oxygenation, the patient succumbed to the disease. Early diagnosis of the potentially fatal disease followed by a prompt antibiotic regimen and appropriate use of steroids are cornerstones in the management of this disease to reduce the risk of high morbidity and mortality.

Changes in the nasalance of vowels within the first week following uvulopalatopharyngoplasty.

We conducted a retrospective study to evaluate the short-term effect of uvulopalatopharyngoplasty (UPPP) on changes in the nasalance of five vowels: /a/, /ε/, /i/, /ɔ/, and /u/. Our study group was made up of 20 patients-15 males and 5 females, aged 16 to 57 years (mean: 37.3 ± 11.5)-who had undergone UPPP as a treatment for mild to moderate obstructive sleep apnea. Nasometry was used to obtain nasalance scores in all patients on the morning of the operation (day 1) and subsequently on day 4 or 5 (mean: 4.5 ± 0.5). Preoperatively, nasalance scores were highest for /i/ (mean: 29.8 ± 12.6) and /a/ (mean: 24.1 ± 10.3). After the operation, nasalance scores for all five studied vowels increased; they were highest for /i/ (mean: 40.7 ± +17.8) and /ε/ (mean: 30.0 ± 10.8). The increases in the nasalance of /i/, /ε/, and /u/ were statistically significant (p < 0.05). Our findings indicate that UPPP has a significant impact on nasalance immediately after surgery.

microRNA Expression in Prospectively Collected Blood as a Potential Biomarker of Breast Cancer Risk in the BCFR.

BACKGROUND/AIM: Current breast cancer risk assessment models have moderate discriminatory ability. We evaluated whether microRNA (miRNA) expression profiles in peripheral blood mononuclear cells (PBMC) could be a useful biomarker of risk in high-risk women. MATERIALS AND METHODS: Next-generation sequencing evaluated miR expression in PBMCs of 20 women who were unaffected at the time of recruitment and later diagnosed with breast cancer and 20 unaffected women. RESULTS: Out of the 5 miRNAs identified as potential risk markers, miR-144-3p, miR-451a, miR-144-5p and miR-183-5p were up-regulated, while miR-708-5p was down-regulated. We then evaluated these miRs in 28 additional case/control pairs using quantitative reverse transcription polymerase chain reaction (PCR). None of the results in the validation sample were statistically significant possibly due to the much longer interval between blood collection and diagnosis in the validation set. CONCLUSIONS: Differentially expressed miRNAs from PBMCs may be potential non-invasive biomarkers for breast cancer prediction. Larger prospective studies are required to confirm whether our findings with specific miRNA loci were related to timing before diagnosis.

Acoustic characteristics of different target vowels during the laryngeal telescopy.

OBJECTIVE: The aim of this study was to investigate the acoustic characteristics of target vowels phonated in normal voice persons while performing laryngeal telescopy. The acoustic characteristics are compared to show the extent of possible difference to speculate their impact on phonation function. METHODS: Thirty-four male subjects aged 20-39 years with normal voice were included in this study. The target vowels were /i/ and /ɛ/. Recording of voice samples was done under natural phonation and during laryngeal telescopy. The acoustic analysis included the parameters of fundamental frequency, jitter, shimmer and noise-to-harmonic ratio. RESULTS: The sound of a target vowel /ɛ/ was perceived identical in more than 90% of the subjects by the examiner and speech language pathologist during the telescopy. Both /i/ and /ɛ/ sounds showed significant difference when compared with the results under natural phonation. There was no significant difference between /i/ and /ɛ/ during the telescopy. CONCLUSION: The present study showed that change in target vowels during laryngeal telescopy makes no significant difference in the acoustic characteristics. The results may lead to the speculation that the phonation mechanism was not affected significantly by different vowels during the telescopy. This study may suggest that in the principle of comfortable phonation, introduction of the target vowels /i/ and /ɛ/ is practical.

Anterior-posterior axis specification in Drosophila oocytes: identification of novel bicoid and oskar mRNA localization factors.

The Drosophila melanogaster anterior-posterior axis is established during oogenesis by the localization of bicoid and oskar mRNAs to the anterior and posterior poles of the oocyte. Although genetic screens have identified some trans-acting factors required for the localization of these transcripts, other factors may have been missed because they also function at other stages of oogenesis. To circumvent this problem, we performed a screen for revertants and dominant suppressors of the bicaudal phenotype caused by expressing Miranda-GFP in the female germline. Miranda mislocalizes oskar mRNA/Staufen complexes to the oocyte anterior by coupling them to the bicoid localization pathway, resulting in the formation of an anterior abdomen in place of the head. In one class of revertants, Miranda still binds Staufen/oskar mRNA complexes, but does not localize to the anterior, identifying an anterior targeting domain at the N terminus of Miranda. This has an almost identical sequence to the N terminus of vertebrate RHAMM, which is also a large coiled-coil protein, suggesting that it may be a divergent Miranda ortholog. In addition, we recovered 30 dominant suppressors, including multiple alleles of the spectroplakin, short stop, a lethal complementation group that prevents oskar mRNA anchoring, and a female sterile complementation group that disrupts the anterior localization of bicoid mRNA in late oogenesis. One of the single allele suppressors proved to be a mutation in the actin nucleator, Cappuccino, revealing a previously unrecognized function of Cappuccino in pole plasm anchoring and the induction of actin filaments by Long Oskar protein.

Accuracy evaluation of RBC velocity measurement in nail-fold capillaries.

Cutaneous red blood cell velocity in vivo can be measured by using capillaroscopy with image processing techniques. However, unlike simulated blood flow images, there is no standard to determine the accuracy of the techniques for computing blood flow velocities. In this paper, we quantitatively evaluated the accuracy of previously proposed optical flow method for measuring red blood cell velocity in nail-fold capillaries. Blood flow images of subjects under normal and occlusion-release conditions were examined by a capillaroscope. To obtain velocity values, the images were further analyzed by using optical flow, cross-correlation and visual inspection methods, respectively. Visual inspection method was taken as the golden standard to determine the accuracy of blood flow velocity measurement using optical flow and cross-correlation techniques. Results showed that optical flow estimation provided superior accuracy to cross-correlation when assessing real blood flow velocity in nail-fold capillaries. Optical flow estimation is able to measure red blood cell velocity with a high accuracy of 91% and 86% when the observed velocity is less than 0.5mm/s under normal and occlusion-release conditions, respectively. In addition, optical flow method showed good agreement with visual inspection in determining blood flow velocity in both normal and occlusion-release conditions when the high-velocity zone is excluded.

Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to rapidly screen for albuminuria.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is used as an alternative method for the rapid diagnosis of albuminuria. This technique requires no further sample pretreatment than simply mixing the urine sample with a MALDI matrix and drying under ambient conditions. The resulting MALDI mass spectra reveal albumin ions having charges ranging from +1 to +5. The detection of albumin is possible using any of the three most common MALDI matrices - sinapinic acid (SA), 2,5-dihydroxybenzoic acid (2,5-DHB), or 4-hydroxy-alpha-cyanocinnamic acid (alpha-CHC). Using this analytical approach, the limit of detection for albumin in urine is 10(-6) M, approximately 5 to 10 times lower than that detectable through conventional chemical testing.

Early radiation effects on tongue function for patients with nasopharyngeal carcinoma: a preliminary study.

The purpose of this study was to investigate early radiation effects on tongue function for patients with nasopharyngeal carcinoma (NPC) and to provide a scientific database for early intervention plans. Twelve subjects with NPC and 12 age- and sex-matched normal subjects were included. Tongue maximum isometric strength and endurance at 50% of maximum strength were obtained once from normal subjects with the Iowa Oral Performance Instrument (IOPI) and twice from the NPC subjects: before and 2 months after radiation treatment. No significant differences were found in tongue function evaluation for normal or NPC groups in either pre- or post-treatments. However, this study showed that significant decreases in tongue function may not start until 2 months after treatment.

Miranda couples oskar mRNA/Staufen complexes to the bicoid mRNA localization pathway.

The double-stranded RNA binding protein Staufen is required for the microtubule-dependent localization of bicoid and oskar mRNAs to opposite poles of the Drosophila oocyte and also mediates the actin-dependent localization of prospero mRNA during the asymmetric neuroblast divisions. The posterior localization of oskar mRNA requires Staufen RNA binding domain 2, whereas prospero mRNA localization mediated the binding of Miranda to RNA binding domain 5, suggesting that different Staufen domains couple mRNAs to distinct localization pathways. Here, we show that the expression of Miranda during mid-oogenesis targets Staufen/oskar mRNA complexes to the anterior of the oocyte, resulting in bicaudal embryos that develop an abdomen and pole cells instead of the head and thorax. Anterior Miranda localization requires microtubules, rather than actin, and depends on the function of Exuperantia and Swallow, indicating that Miranda links Staufen/oskar mRNA complexes to the bicoid mRNA localization pathway. Since Miranda is expressed in late oocytes and bicoid mRNA localization requires the Miranda-binding domain of Staufen, Miranda may play a redundant role in the final step of bicoid mRNA localization. Our results demonstrate that different Staufen-interacting proteins couple Staufen/mRNA complexes to distinct localization pathways and reveal that Miranda mediates both actin- and microtubule-dependent mRNA localization.