Highly Efficient Singlet Oxygen Generation by BODIPY-Ruthenium(II) Complexes for Promoting Neurite Outgrowth and Suppressing Tau Protein Aggregation.

Singlet oxygen (1O2) has been recently identified as a key molecule against toxic Aß aggregation, which is associated with the currently incurable Alzheimer's disease (AD). However, limited research has studied its efficiency against tau protein aggregation, the other major hallmark of AD. Herein, we designed and synthesized boron-dipyrromethene (BODIPY)-ruthenium conjugates and isolated three isomers. Under visible-light irradiation, the ε isomer can be photoactivated and efficiently generate singlet oxygen. Particularly, the complex demonstrated successful results in attenuating tauopathy─an appreciable decrease to 43 ± 2% at 100 nM. The photosensitizer was further found to remarkably promote neurite outgrowth and significantly increased the length and number of neurites in nerve cells. As a result of effective photoinduced singlet oxygen generation and proactive neurite outgrowth, the hybrid design has great potential for therapeutics for Alzheimer's disease.

Relationship Between Pharyngeal Residues Assessed by Bolus Residue Scale or Normalized Residue Ratio SCALE and Risk of Aspiration in Head and Neck Cancer Who Underwent Videofluoroscopy.

Dysphagia affects 60-75% of patients treated for head and neck cancer (HNC). We aimed to evaluate the association between residue severity and airway invasion severity using a videofluoroscopic swallowing study and identify risk factors for poor penetration-aspiration outcomes in patients with dysphagia treated for HNC. Penetration-Aspiration Scale (PAS) was used to assess airway invasion severity, while residue severity was assessed using both the Bolus Residue Scale (BRS) for residue location and the Normalized Residue Ratio Scale (NRRS) for residue amount. Relevant covariates were adjusted in the logistic regression models to account for potential confounding. Significantly higher abnormal PAS was reported for increased piriform sinus NRRS (NRRSp) [odds ratio (OR), 4.81; p = 0.042] with liquid swallowing and increased BRS value (OR, 1.52; p = 0.014) for semi-liquid swallowing in multivariate analysis. Tumor location, older age, and poorer Functional Oral Intake Scale (FOIS) were significant factors for abnormal PAS in both texture swallowings. After adjusting for confounding factors (sex, age, and FOIS score), NRRS model in liquid swallowing (area under the curve [AUC], 0.83; standard error = 0.04, 95% confidence interval [CI]: 0.75, 0.91) and BRS in semi-liquid swallowing (AUC, 0.83; SE = 0.04; 95% CI: 0.76, 0.91) predicted abnormal PAS. The results indicate that while assessing residue and swallowing aspiration in patients with HNC, it is important to consider age, tumor location, and functional swallowing status. The good predictability of abnormal PAS with BRS and NRRS indicated that residue location and amount were both related to the aspiration event in patients with HNC.

Green tea (-)-epigallocatechin gallate suppresses IGF-I and IGF-II stimulation of 3T3-L1 adipocyte glucose uptake via the glucose transporter 4, but not glucose transporter 1 pathway.

This study investigated the pathways involved in EGCG modulation of insulin-like growth factor (IGF)-stimulated glucose uptake in 3T3-L1 adipocytes. EGCG inhibited IGF-I and IGF-II stimulation of adipocyte glucose uptake with dose and time dependencies. EGCG at 20µM for 2h decreased IGF-I- and IGF-II-stimulated glucose uptake by 59% and 64%, respectively. Pretreatment of adipocytes with antibody against the EGCG receptor (also known as the 67-kDa laminin receptor; 67LR), prevented the effects of EGCG on IGF-increased glucose uptake, but pretreatment with normal rabbit immunoglobulin did not. This suggests that the 67LR mediates the anti-IGF effect of EGCG on adipocyte glucose uptake. Further analysis indicated EGCG, IGF-I, and IGF-II did not alter total levels of GLUT1 or GLUT4 protein. However, EGCG prevented the IGF-increased GLUT4 levels in the plasma membrane and blocked the IGF-decreased GLUT4 levels in low-density microsomes. Neither EGCG nor its combination with IGF altered GLUT1 protein levels in the plasma membrane and low-density microsomes. EGCG also suppressed the IGF-stimulated phosphorylation of IGF signaling molecules, PKCζ/λ, but not AKT and ERK1/2, proteins. This study suggests that EGCG suppresses IGF stimulation of 3T3-L1 adipocyte glucose uptake through inhibition of the GLUT4 translocation, but not through alterations of the GLUT1 pathway.

Balloon Dilation Eustachian Tuboplasty for Dilatory Dysfunction With and Without Effusion: A Comprehensive Outcome Analysis.

OBJECTIVE: This study aimed (1) to demonstrate the efficacy of balloon dilation Eustachian tuboplasty (BDET) for dilatory Eustachian tube dysfunction (ETD) and (2) to determine whether adjunctive ventilation tube insertion (VTI) is superior to myringotomy in relieving symptoms for patients with ETD and concurrent middle ear effusion (MEE) treated with BDET. STUDY DESIGN: A retrospective cohort study. SETTING: Tertiary care academic center. METHODS: Patients with dilatory ETD undergoing BDET with a ≥6-month follow-up period were enrolled and evaluated mainly using Eustachian tube function (ETF) tests and Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7). Participants with concurrent MEE were further classified into 2 subgroups, BDET with VTI and BDET with myringotomy. An intergroup comparison and comprehensive outcome evaluation were performed. RESULTS: In total, 35 patients with 50 symptomatic ears were enrolled. According to ETF test results, the normalized ETF rate was 94% on the last visit. The mean ETDQ-7 scores decreased significantly from 3.7 ± 1.4 to 2.0 ± 0.9 after interventions, with the most improvement in symptoms occurring for "ear fullness" and "muffled hearing." For the final visit, strong correlations among ETF tests, tympanometry, and Valsalva results were noted. The aforementioned assessment results did not significantly differ between (1) the patients with MEE and patients without MEE and (2) "BDET with VTI" subgroup and "BDET with myringotomy" subgroup. CONCLUSION: BDET was effective for dilatory ETD, even in cases with concurrent MEE. For patients with ETD and MEE, further research is required to evaluate the benefits of adjunctive myringotomy with or without VTI.

Evaluation of Fine Needle Aspiration Cytopathology in Salivary Gland Tumors under Milan System: Challenges, Misdiagnosis Rates, and Clinical Recommendations.

(1) Background: Salivary gland tumors are rare in the head and neck. To determine the need and extent of surgical intervention, fine needle aspiration (FNA) is a widely accepted tool to approach salivary gland lesions. However, the FNA cytology varies between entities, while the lack of uniform terminology makes diagnosis more challenging. Since establishing the Milan system for reporting salivary gland cytopathology (MSRSGC) has become an increasingly accepted reporting standard, further examination and detailed recommendations were needed. (2) Methods: Between April 2013 and October 2021, 375 cases with FNA and salivary gland resection were retrospectively collected. All FNA specimens were reclassified according to the criteria of MSRSGC. After surgical excision, the FNA data were compared with the histological diagnosis to estimate the risk of malignancy (ROM), the risk of neoplasm (RON), and the diagnostic accuracy for each diagnostic category. (3) Results: Our cohort's distribution of ROM and RON was similar to the MSRSGC's recommendation. Carcinoma ex pleomorphic adenoma (CXPA) has the highest rate (66.7%) of misdiagnosed as a nonneoplastic lesion or benign salivary gland tumor. Pleomorphic adenoma (PA) and Warthin's tumor were the most common benign salivary gland tumors, while the cytology diagnosis of Warthin's tumor seems more challenging than PAs. (4) Conclusions: Despite the convenience and effectiveness of MSRSGC, we suggest close follow-up, re-biopsy, or surgical removal for salivary lesions even in Milan IVA-Benign for possibly missing FNA of malignancy, mixed lesions, or prevention of malignant transformation.

Evaluation of Objective and Subjective Swallowing Outcomes in Patients with Dysphagia Treated for Head and Neck Cancer.

We evaluated objective and subjective swallowing function outcomes in patients with dysphagia treated for head and neck cancer (HNC) and identified risk factors for poor swallowing outcomes. Patients undergoing videofluoroscopic swallowing studies (VFSS) between January 2016 and March 2021 were divided into four groups according to primary tumor sites; post-treatment dysphagia was assessed. The penetration-aspiration scale (PAS) and bolus residue scale (BRS) were used to objectively assess swallowing function through VFSS. The Functional Oral Intake Scale (FOIS) was used for subjective analyses of swallowing statuses. To account for potential confounding, important covariates were adjusted for in logistic regression models. Oropharyngeal tumors were significantly more likely to have poor PAS and BRS scores than oral cavity tumors, and the patients with nasopharyngeal tumors were significantly less likely to have poor FOIS scores. Old age, having multiple HNCs, and a history of radiotherapy were associated with an increased odds of poor PAS scores (for all types of swallows), poor BRS scores (for semiliquid and solid swallows), and poor FOIS scores, respectively. This indicates using only subjective assessments may not allow for accurate evaluations of swallowing function in patients treated for HNC. Using both objective and subjective assessments may allow for comprehensive evaluations.

Demethylation of an artificial hydrogenase agent for prolonged CO release and enhanced anti-tau aggregation activity.

Carbon monoxide (CO) plays an important role in signaling in cells, making its use as a therapeutic tool highly intriguing. Reduced burst emissions are important to avoid the cytotoxicity and tissue damage caused by CO. Here, we developed a stable diiron carbonyl [FeFe] hydrogenase agent that enables prolonged CO release activity (half-life of over 9 h) in cells. The integrated analysis allowed the identification of the key intermediate sites and CO accumulations with subcellular resolution. We observed that the [FeFe]A complex was enriched in neurons with S-methyl bond rupture. Furthermore, the [FeFe]A complex efficiently reduced the aggregation of tau proteins (49.3% reduction) and showed superior biocompatibility in nerve cells (∼ 95% survival).

The Additive Effectiveness of Inspiratory Muscle Training on Glottic Closure and Subjective Voice Outcomes of Patients With Benign Lesion After Hyaluronic Acid Laryngoplasty.

OBJECTIVES: For patients with glottic insufficiency disease, injection laryngoplasty is a rapid and efficient management option that complements voice therapy. Some studies have indicated that respiratory muscle training may also show promise in patients with voice disorders. However, the effect of respiratory muscle training in patients with glottic insufficiency was reported to be limited, and whether it provides additional benefit after standard management requires further evaluation. We aimed to investigate the effectiveness of inspiratory muscle training on glottis closure and patient-reported voice quality in glottic insufficiency patients who had been treated with hyaluronic acid injection. STUDY DESIGN: Retrospective observational study. METHODS: We included 46 patients with glottic insufficiency who had undergone hyaluronic acid injection. Twenty of them had undergone inspiratory muscle training during three months. We measured patients' changes in glottic status according to the normalized glottal gap area and bowing index, as well as voice quality of life according to the voice handicap index 10 and the voice outcome survey, before and after training. RESULTS: Patients who underwent inspiratory muscle training had higher odds of experiencing better improvement in all scores. The range of odds ratios ranged from 2.5 to 6.3 for changes in scores, and from 3.8 to 22.2 for changes in score percentages. Of note, the effect of training on percentage changes in the normalized glottal gap area score was significant (P= 0.0127) after adjustment for the duration of vocal disease, body mass index and BMI, and history of gastroesophageal reflux disease. CONCLUSIONS: Inspiratory muscle training can improve the glottal gap after injection laryngoplasty, and may be applied in clinical practice.

Operative and Conservative Management of Laryngeal Contact Granuloma: A Network Analysis and Systematic Review.

OBJECTIVE: Laryngeal contact granuloma is a disease of benign hypertrophic granulation tissue at the medial side of vocal process. Numerous studies of conservative and surgical management have reported effectiveness, yet optimal treatment has not been standardized. We compared primary and secondary outcomes of conservative and surgical treatment using endoscopic grading, Voice Handicap Index-10 (VHI-10), maximum phonation time (MPT), and recurrence rate. METHODS: We performed literature searches of MEDLINE, PubMed, and EMBASE from November 1985 to October 2017, with randomized controlled trials and case control studies of at least three months follow-up as the inclusion criteria. Outcomes included laryngoscopic findings, MPT, and VHI-10. Data regarding study design, outcome analysis, follow-up time, and disease remission were systematically collected. RESULTS: A total of 1069 patients were abstracted from 19 papers. With conservative treatment, 98% of patients' laryngeal granuloma resolved within three months, and 84% for the surgical group. There was a decrease in VHI-10 of 2.69 (95% credible interval (CI) -9.52 to 3.82) and 6.48 (95% CI -15.00 to 1.94) for conservative and surgical management, respectively. MPT improvement was 1.27 s (95% CI: 2.03-5.84) for conservative treatment and 5.02 s (95% CI: 0.78-8.07) for surgical. For all 19 studies, absolute recurrence risk for control, conservative, and surgical measures were respectively 4%, 16%, and 29%. CONCLUSIONS: Most patients treated conservatively or surgically alone responded to treatment, but conservative management was favored. VHI-10 and MPT improvement in surgical patients were noted, but only the latter was statistically significant. In regard to recurrence, conservative management had better outcome than surgical. Taken together, the results suggest that minimally symptomatic granulomas have higher response rate and lower recurrence risk when treated conservatively, while larger, symptomatic granulomas may favor surgical excision followed by medical management to reduce risk of recurrence.

Early Injection Laryngoplasty After Surgery: 30 Cases and Proposed Aspiration Assessment Protocol.

Vocal fold movement impairment may significantly compromise postoperative recovery and quality of life of patients following thoracic or cardiothoracic surgery or prolonged intubation. The literature is limited and there is no standard screening protocol for the optimal postoperative swallowing and aspiration evaluations. We performed retrospective review of adult patients undergoing early vocal fold (VF) injection laryngoplasty for acute postoperative Vocal fold movement impairment (<30 days) that had both pre- and postinjection speech language pathologist (SLP) performed swallowing/aspiration evaluations. Records were reviewed for demographics, clinical characteristics, procedural details, and short-term outcome measures of oral intake. In total, 30 patients were included, and had data on swallowing/aspiration studies before and after the VF injection laryngoplasty. Most of the patients were injected within 5 days following the laryngologist evaluation and within 14 days following the iatrogenic recurrent laryngeal nerve injury (23/30, 76.7%). The majority of patients were injected at the bedside by awake transcutaneous injection (22/30, 73.3%), six patients were injected in the operating room under general anesthesia, and two at the outpatient clinic. Pre- and postinjection SLP evaluations included clinical bedside assessment or instrumental evaluation. Following VF injection laryngoplasty, oral diet advancement was noted in 81.8% of the patients that were nil per os before the injection (18/22). No complications were noted. In conclusions, acute VFMI following surgery requires immediate diagnosis and therapeutic strategy to minimize postoperative complications and to overcome impairments in the voice, swallow, and cough. Otolaryngology-SLP interdisciplinary aspiration and swallowing assessment protocol is proposed based on our experience and an extensive literature review.

The Clinical Course of Idiopathic Bilateral Vocal Fold Motion Impairment in Adults: Case Series and Review of the Literature.

AIM: Steps for assessment and successful management of bilateral vocal fold motion impairment (VFMI) are (1) recognition of its presence, (2) identifying the etiology and factors restricting vocal fold motion, (3) evaluation of airway patency, and (4) establishing a management plan. No large series documenting the course and outcome of adult idiopathic bilateral VFMI has been published within the past 15 years. METHODS: Retrospective chart review of adult patients with idiopathic bilateral VFMI at a tertiary academic center. A diagnosis was established if history, physical examination with laryngoscopy, and initial imaging excluded a cause. Records were reviewed for demographics, clinical characteristics, surgical intervention details, and length of follow-up. RESULTS: Nine adult patients with idiopathic bilateral VFMI were identified. There were five males and four females with a mean age of 59.6 years. The mean follow-up period was 54.4 months (range, 6-111 months). Upon presentation to our laryngology service, three patients were advised observation, three patients were advised to undergo urgent tracheostomy, and three patients were advised to undergo elective surgery for airway management. By the end of the follow-up period, only four patients (4/9, 44.4%) were tracheostomy dependent, one of them was lost to follow-up after tracheostomy tub downsizing for decannulation. CONCLUSIONS: To our best knowledge, this is the largest series so far of adult patients with idiopathic bilateral VFMI. Conservative treatment can be considered as an alternative to surgery in select cases.

Resected specimen size: A reliable predictor of severe Frey syndrome after parotidectomy.

BACKGROUND: Frey syndrome is a common complication after parotidectomy. This study aimed to investigate the potential predictors for developing severe Frey syndrome after parotidectomy and to identify patients who may benefit from additional preventive maneuvers. METHODS: A total of 485 patients received parotidectomy because of parotid tumors at the Otolaryngology Department of the National Cheng Kung University Hospital, from July 2009 to November 2015. Only 115 of 485 patients were included in this study and to fill in a questionnaire to determine the occurrence and severity of Frey syndrome. RESULTS: A total of 115 parotidectomies were identified. 84 (73%, 84/115) patients were aware of the discomfort and were thus considered symptomatic. 39 (34%, 39/115) patients considered the symptoms apparently affected their quality of life. MSI tests showed that 56 (49%, 56/115) patients had a positive MSI test. By combining the results from symptom questionnaire and MSI test, 23 patients (20%, 23/115) had a severe form of Frey syndrome. Among all clinicopathological variables, the resected specimen size was the only significant predictor of the severe Frey syndrome group (P = 0.04). Disease pathology, tumor size, and adjuvant radiotherapy did not correlate with the severe Frey syndrome. Using receiver operating curve analysis, the best cutoff value of the resected specimen size (in largest dimension) for predicting severe Frey syndrome was 40 mm(sensitivity: 71.7%, specificity: 42.0%; area under the curve = 0.6483). The odds ratio of severe Frey syndrome with every 10 mm increase in the largest diameter of resected specimen was 1.30 (95% confidence interval, 1.01-1.68; P = 0.04). CONCLUSIONS: Resected specimen size is the only significant predictor of developing severe Frey syndrome after parotidectomy. Preventive interventions may have to be considered in high-risk patients whose resected specimen size (in largest dimension) is greater than 40 mm.