Brusatol attenuated proliferation and invasion induced by KRAS in differentiated thyroid cancer through inhibiting Nrf2.

BACKGROUND: Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) can be developed from differentiated thyroid cancer, and this dedifferentiated transformation leads to poor prognosis and high mortality. The role of Nrf2 in the dedifferentiation of differentiated thyroid cancer (DTC) induced by KRAS remains unclear. METHODS AND MATERIALS: In this study, two DTC cell lines, BCPAP and WRO, were used to evaluate the function of Nrf2 in the dedifferentiation caused by wild-type KRAS (KRAS-WT) and G12V point mutation KRAS (KRAS-G12V). RESULTS: The overexpression of KRAS-WT and KRAS-G12V increased the proliferative and invasive ability of BCPAP and WRO cells. Aggressive morphology was observed in KRAS-WT and KRAS-G12V overexpressed WRO cells. These results suggested that overexpression of KRAS-WT or KRAS-G12V may induce dedifferentiation in DTC cells. The expression of Nrf2 was increased by KRAS-WT and KRAS-G12V in DTC cells. In addition, compared with normal thyroid tissues, the expression of Nrf2 protein was considerably higher in thyroid cancer tissues on immunohistochemistry (IHC) staining, and the increased expression of Nrf2 indicated a poor prognosis of thyroid cancer. These results indicated that Nrf2 is the KRAS downstream molecule in thyroid cancer. Functional studies showed that the Nrf2 inhibitor Brusatol counteracted the proliferative and invasive abilities induced by KRAS-WT and KRAS-G12V in BCPAP and WRO cells. In addition, the xenograft assay further confirmed that Brusatol inhibits tumor growth induced by KRAS-WT and KRAS-G12V. CONCLUSION: Collectively, this study suggests that Nrf2 could be a promising therapeutic target in KRAS-mediated dedifferentiation of thyroid cancer.

Estrogen as a guardian of auditory health: Tsp1-CD47 axis regulation and noise-induced hearing loss.

OBJECTIVES: This study aimed to analyze the role of estrogen in noise-induced hearing loss (NIHL) and uncover underlying mechanisms. METHODS: An ovariectomized Sprague-Dawley rat model (OVX) was constructed to investigate the hearing threshold and auditory latency before and after noise exposure using the auditory brainstem response (ABR) test. The morphological changes were assessed using immunofluorescence, scanning electron microscopy and transmission electron microscopy. Proteomics and bioinformatics were used to analyze the mechanism. The findings were further verified through western blot and Luminex liquid suspension chip technology. RESULTS: After noise exposure, OVX rats exhibited substantially elevated hearing thresholds. A conspicuous delay in ABR wave I latency was observed, alongside increased loss of outer hair cells, severe collapse of stereocilia and pronounced deformation of the epidermal plate. Accordingly, OVX rats with estrogen supplementation exhibited tolerance to NIHL. Additionally, a remarkable upregulation of the thrombospondin 1 (Tsp1)-CD47 axis in OVX rats was discovered and verified. CONCLUSIONS: OVX rats were more susceptible to NIHL, and the protective effect of estrogen was achieved through regulation of the Tsp1-CD47 axis. This study presents a novel mechanism through which estrogen regulates NIHL and offers a potential intervention strategy for the clinical treatment of NIHL.

Effect of wearing an N95 respirator on the internal nasal valve and the association with external nasal anatomy - a cohort study.

OBJECTIVES: To determine whether: the N95 respirator affects nasal valve patency; placement on the bony vault improves patency; and external nasal anatomy affects the outcome. METHODS: A prospective study with 50 participants was conducted. Nasal patency was measured by the minimal cross-sectional area via acoustic rhinometry, and using the Nasal Obstruction Symptom Evaluation survey, before and after wearing the N95 respirator and after adjustment. RESULTS: The minimal cross-sectional area was narrowed by 27 per cent when wearing the N95 respirator (p < 0.001), and improved by 9.2 per cent after adjustment (p = 0.003). The total Nasal Obstruction Symptom Evaluation score increased from 10.2 to 25.4 after donning the N95 respirator (p < 0.001), and decreased from 25.4 to 15.6 after adjustment (p < 0.001). There was no correlation with external nasal anatomy parameters. CONCLUSION: Wearing the N95 respirator causes narrowing of the nasal valve, and adjustment onto the bony vault improves symptoms. The findings were not affected by external nasal anatomy.

Efficacy of a Comprehensive Dysphagia Intervention Program Tailored for the Residents of Nursing Homes.

Oropharyngeal dysphagia is a widespread condition in older people and thus poses a serious health threat to the residents of nursing homes. The management of dysphagia relies mainly on compensatory strategies, such as diet and environmental modification. This study investigated the efficacy of an intervention program using a single-arm interventional study design. Twenty-two participants from nursing homes were included and had an average of 26 hours of intervention, including oromotor exercises, orosensory stimulation and exercises to target dysphagia and caregiver training. Four of the 22 participants exhibited improvement in functional oral intake scale (FOIS) but was not statistically significant as a group. All oromotor function parameters, including the range, strength, and coordination of movements, significantly improved. These results indicate that this intervention program could potentially improve the oromotor function, which were translated into functional improvements in some participants' recommended diets. The validity of this study could be improved further by using standardized swallowing and feeding assessment methods or an instrumental swallowing assessment.

The Bonebridge semi-implantable bone conduction hearing device: experience in an Asian patient.

For over three decades, bone conduction hearing aids have been changing the lives of patients with impaired hearing. The size, appearance and fitting discomfort of early generations of bone conduction hearing aids made them unpopular. The advent of bone-anchored hearing aids in the 1970s offered patients improved sound quality and fitting comfort, due to the application of osseointegration. However, the issue of post-operative peri-abutment pin tract wound infection persisted. The Bonebridge system incorporates the first active bone conduction device, and aims to resolve peri-abutment issues. Implantation of this system in an Asian patient is presented.

Vibrant Soundbridge system: application of the stapes coupling technique.

INTRODUCTION: The use of the stapes coupling technique, employed in the Vibrant Soundbridge system, is technically less demanding than the vibroplasty technique, and is more likely to generate a positive outcome without significantly changing residual hearing or resulting in medical or surgical complication. METHOD: We report a patient with repeated left ossiculoplasty failure, who was successfully implanted with a Vibrant Soundbridge. CONCLUSION: We believe that the stapes coupling technique can provide natural stimulation to the inner ear, resulting in a better perceived sound quality.

Perceptions and experiences of post-irradiation swallowing difficulties in nasopharyngeal cancer survivors.

This study aimed to explore the perceptions and experiences of swallowing difficulties in irradiated survivors of nasopharyngeal carcinoma (NPC). Qualitative semi-structured interviews were conducted with 60 post-irradiation NPC patients after they had answered a set of self-report questions. The interviews were transcribed verbatim for analysis. Results of the self-report data showed that in response to a global question 'Do you have any swallowing difficulties?' eight-five per cent of the respondents reported a certain degree of difficulty. The qualitative interview findings, however, suggested that this figure might have been underestimated. Patient interpretations of swallowing difficulties had excluded part of the symptoms. Some respondents who claimed to have no difficulty swallowing, in fact, were suffering from oral retention of food bolus, regurgitation of food or liquids through the nose, and/or even choking. The risk of aspiration was generally neglected. Informants' concerns focused more on the threat of cancer recurrence, thus paid less attention to the radiation-induced swallowing complication. Respondents did not possess sufficient knowledge to judge their swallowing abilities at a general level. This study suggests ways to enhance patient-provider communication and health education to improve patient knowledge.

Psychometric properties of the Chinese (Cantonese) Tinnitus Handicap Inventory.

OBJECTIVES: To establish the reliability and validity of the Chinese (Cantonese) version of the Tinnitus Handicap Inventory to measure the self-perceived handicapping effect and severity of the condition in patients with chronic tinnitus. DESIGN: Cross-sectional psychometric validation study. SETTING: Audiology clinics in a hospital setting. PARTICIPANTS: Subjects were 114 adult Chinese who attended the audiology clinics with a complaint of tinnitus. MAIN OUTCOME MEASURES: Test-retest and internal consistency reliability; construct validity. RESULTS: The Chinese version of the Tinnitus Handicap Inventory and its subscales showed good internal consistency reliabilities (alpha = 0.72-0.94) that are comparable to those of the original version. High correlations were observed between the Tinnitus Handicap Inventory and psychological distress, tinnitus-related problem ratings and severity ratings. Factor analysis showed that the Chinese version of the Tinnitus Handicap Inventory has a unifactorial structure. A high degree of test-retest reliability was observed (intraclass correlation coefficient = 0.88). CONCLUSIONS: The results suggest that the Chinese (Cantonese) version of the Tinnitus Handicap Inventory is a reliable and valid measure of general tinnitus-related distress that can be used in clinical settings to quantify the impact of tinnitus on daily life.

'Steam-boat' supraglottic laryngoplasty for treatment of chronic refractory aspiration: a modification of Biller's technique.

OBJECTIVE: The surgical treatment of intractable aspiration usually requires sacrifice of the patient's natural voice to prevent food entering the airway. Biller described a tubed supraglottic laryngoplasty to control aspiration while allowing patients to phonate with their larynx. Our preliminary experience with this technique in Chinese patients has been disappointing, as tension in the mucosa on wound closure led to wound dehiscence. Our objective was to modify Biller's technique in order to achieve a better outcome. METHOD: We modified Biller's technique by trimming the epiglottic cartilage and by inserting a tibial periosteal graft to reinforce closure of the mucosa, creating an arrangement resembling a Chinese steam boat. RESULTS: Three Chinese patients underwent the modified Biller's technique. No wound dehiscence occurred, the surgery controlled aspiration, and the patients were able to phonate with their own larynx. All patients resumed oral feeding, and previously placed gastrostomy tubes were removed. CONCLUSION: The 'steam-boat' supraglottic laryngoplasty is a viable surgical alternative to total laryngectomy or tracheal diversion for controlling intractable aspiration, and preserves a phonating larynx.

Rhinitis symptoms and quality of life in patients with chronic perennial rhinitis treated with desloratadine.

OBJECTIVE: To evaluate the outcome and the change in quality of life of patients with chronic rhinitis after treatment with desloratadine. STUDY DESIGN: A prospective, open-label, non-blinded, non-randomised study of patients in a secondary and tertiary ENT referral centre. METHODS: Chinese patients with chronic rhinitis were recruited. The patients were assessed by a questionnaire that included rhinitis symptoms score and SF-36 health survey components. Endoscopic assessment was performed with a rigid nasoendoscope and scored according to the modified endoscopic appearance score of Lund and Kennedy. A 12-week course of desloratadine 5 mg daily was prescribed. Patients were re-evaluated after treatment. A total of 47 subjects completed the study. RESULTS: There were significant reductions in median rhinitis symptoms score, from six to five (p < 0.001), and in median endoscopic appearance score, from five to three (p < 0.001). Patients' general health perception was also improved after treatment (p == 0.022). CONCLUSION: Desloratadine may be an effective treatment which provides symptomatic relief and improves the quality of life in patients with chronic rhinitis.

A simple method for re-dilatation of an acute tracheostoma stenosis.

Tracheostomy or laryngectomy stomas may sometimes re-stenose, resulting in respiratory distress for the patient unless the stoma is rapidly re-dilated and an adequate airway re-established. This article describes a simple and effective method for the acute re-dilatation of a tracheostoma stenosis, using an aural speculum, prior to the insertion of a patent airway tube. This technique has been successfully used in our department since 1995 and, in our experience, causes significantly less distress to our patients when compared with other means employed previously.

Acquired posterior choanal stenosis and atresia: management of this unusual complication after radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To report on acquired posterior choanal stenosis and atresia after radiotherapy for nasopharyngeal carcinoma. MATERIALS AND METHODS: Four patients with acquired bilateral choanal atresia and 2 with severe unilateral choanal stenosis in the posterior choanae were identified after treatment of nasopharyngeal carcinoma with radiotherapy. The mean age was 42 years (range, 29 to 48 years). Two patients had stage II, and 4 had stage III disease, according to Ho's classification. They all received a 66 Gy dose of external irradiation delivered to the nasopharynx, and a mean dose of 62.6 Gy to the neck. Five patients had an additional 20 Gy delivered to the parapharyngeal region, and 1 patient had intracavitatory brachytherapy of 18 Gy delivered to the nasopharynx. The mean onset of symptoms was 10.5 months (range, 2 to 40 months) postirradiation. All patients were treated by transnasal endoscopic resection. Merocel epsitaxis packing (Medtronic Xomed, Jacksonville, FL) was used to stent the nasal airway for 2 weeks postoperatively. RESULTS: The mean follow-up was 16.2 months (range, 14 to 18 months) after surgery. Four patients (67%) were symptom-free. Two patients (33%) had unilateral restenosis in the postnasal space that required revision surgery and further nasal stenting for 2 weeks, and both were subsequently free from further restenosis. No adverse postoperative complication occurred. CONCLUSION: Acquired posterior choanal stenosis and atresia is an unusual long-term complication after radiotherapy that can be successfully treated with transnasal endoscopic resection. A 2-week Merocel nasal stent is recommended to prevent restenosis in the posterior choanae.

Middle ear effusions after radiotherapy: correlation with pre-radiotherapy nasopharyngeal tumor patterns.

OBJECTIVE: The purpose of this study was to assess whether pretreatment tumor patterns of nasopharyngeal carcinoma (NPC) can predict the status of the middle ear after radiation treatment. MATERIALS AND METHODS: Pretreatment and follow-up magnetic resonance imaging (MRI) was performed in 32 patients (64 ears) who had radiation therapy for NPC. For the purpose of analysis, the ears were placed into their pre-radiation therapy tumor pattern groups and the presence of middle ear effusion (MEE) with regard to eustachian tube (ET) invasion or displacement was identified. RESULTS: MEEs were present in 31 (48.4%) ears after radiation therapy. All of the MEEs that resolved were in the preradiation therapy groups where tumor invasion of the eustachian tube was present irrespective of the amount of ET displacement. There was, however, no significant difference for resolved MEEs between ears with ET invasion or displacement (p = 0.32 and p = 0.71, respectively, Fisher's exact test). The MEEs occurred with significantly greater frequency in ears with minor ET displacement than in those with major ET displacement (p = 0.013, Fisher's exact test) as well as in previously normal ears compared with other groups (p = 0.008, Mann-Whitney U test). CONCLUSION: A pre-radiation therapy NPC tumor pattern was not found that clearly predicted the outcome of MEE after radiation treatment. The findings, however, suggest that approximately one third of MEEs in patients with invasion of ET or paratubal structures, irrespective of the amount of ET displacement, resolve after therapy. The MEEs that were present in ears with ET displacement and no invasion did not resolve despite reversal of the displacement after treatment, which suggests that ET position plays a less important role than invasion in the resolution of MEE. It is, however, difficult to be certain, because ears with invasion were invariably associated with ET displacement, and the contribution of radiation therapy to the development of MEE further complicates the issue.

Giant benign sinonasal squamous papilloma: report of a case.

We treated a patient with a giant squamous papilloma in the nasal cavity and maxillary sinus that extended through a bony defect into the oral cavity. The mass was excised with a combined endoscopic, Caldwell-Luc, and transoral approach. Lesions of this type are rare, but when they do occur, the rate of recurrence is high. Therefore, long-term followup, including endoscopic examination, is important.

Screening for otitis media with effusion to measure its prevalence in Chinese children in Hong Kong.

In an attempt to gain a better understanding of the prevalence of otitis media with effusion (OME) in the Hong Kong community, and to compare the characteristics of the disease here with OME as it is described in the Western literature, we screened more than 6,000 6- and 7-year-old children with both clinical and audiologic examinations. The initial positive screening rate was 5.3%. Upon further evaluation, we determined that the overall prevalence of persistent OME was 2.2%. We found that the disease pattern and natural history of persistent OME in Hong Kong children are similar to those reported in the Western literature.

Efficacy of ondansetron for prevention of postoperative nausea and vomiting after outpatient ear surgery under local anesthesia.

OBJECTIVE: To assess the efficacy and safety of intravenous ondansetron (4 mg) for the prevention of nausea and vomiting after middle ear surgery under local anesthesia. SETTING: The study was conducted by Division of Otorhinolaryngology in Prince of Wales Hospital, which is a tertiary referral center and teaching hospital for The Chinese University of Hong Kong. STUDY DESIGN: A double-blind randomized controlled trial. PATIENTS: Fifty-eight Chinese patients undergoing tympanoplasty under local anesthesia from July 1995 to June 1997 were recruited. The mean age of patients was 42.8 years (range 18-71 years). INTERVENTION: Patients were randomly allocated to receive a single dose of intravenous ondansetron (4 mg) (n = 29) or placebo (n = 29) immediately before surgery. MAIN OUTCOME MEASURES: Patients were assessed for severity and frequency of postoperative nausea and vomiting at the 1st, 2nd, 4th, 8th, and 24th hours after middle ear surgery. RESULTS: Female patients showed a higher prevalence of postoperative nausea and vomiting. Twenty-eight percent of the patients experienced postoperative nausea, of whom 14% also experienced vomiting. Although the ondansetron group demonstrated a lower prevalence of postoperative nausea and vomiting (PONV) (24% nausea and 10% vomiting) than the placebo group (31% nausea and 17% vomiting), significant reduction in postoperative vomiting only occurred in the first postoperative hour (p = 0.038). No complications or adverse side effects were found to be associated with the use of ondansetron. CONCLUSIONS: Single-dose ondansetron (4 mg) given intravenously preoperatively significantly reduces postoperative vomiting in patients after tympanoplasty under local anesthesia and causes no adverse effects.