Association of rs2651899 Polymorphism in the Positive Regulatory Domain 16 and Common Migraine Subtypes: A Meta-Analysis.

BACKGROUND: Migraine is a neurovascular disease with recurrent headache attacks. A polymorphism (rs2651899) of the PRDM16 gene, which is associated with migraine, was identified in recent genome-wide association studies. The potential role of the PRDM16 rs2651899 polymorphism in migraine is still unknown. Therefore, we conducted this systematic review and meta-analysis to examine this issue. METHODS: We performed a comprehensive literature search of the PubMed, Embase, and Google Scholar databases to identify eligible studies published before October 2018. Individual odds ratio and 95% confidence interval was used to estimate the pooled strength of the association between the PRDM16 rs2651899 polymorphism and common migraine subtypes, including migraine with aura (MA) and migraine without aura (MO). RESULTS: Six studies with 2853 cases and 9319 controls that fulfilled the inclusion and exclusion criteria were selected for this meta-analysis. Of the 6 included studies, 4 studies had available data for MWA and another 4 studies had data for MWoA. Overall, significant migraine risks of 1.257, 1.305, and 1.419 were found under allele model (C vs T), dominant model (C/C+T/C vs T/T), and recessive model (C/C vs T/C+T/T), respectively. In the recessive model, significantly increased risks of 1.454 and 1.546 were found for MA and MO, respectively. CONCLUSION: Our major findings suggest that PRDM16 rs2651899 polymorphism is associated with the risk of migraine. Furthermore, we found that PRDM16 rs2651899 polymorphism is significantly related to common migraine subtypes (MA and MO).

Efficacy of vardenafil in human nasal mucosa.

OBJECTIVE: Levitra, a phosphodiesterase-5 (PDE5) inhibitor, is the trade name of vardenafil. It is applied to treatment of erectile dysfunction. PDE5 inhibitors dilate the penile blood vessels and cause prolonged erections. However, the effects of Levitra on human nasal mucosa are not yet fully explored. MATERIALS AND METHODS: We examined the effectiveness of Levitra on human nasal mucosa directly in vitro by testing: 1) effect on human nasal mucosa resting tension; 2) effect on contraction caused by 10-6 M methoxamine as a sympathetic mimetic; 3) effect of the drugs on electrically induced human nasal mucosa contractions. RESULTS: The results showed that addition of methoxamine to the incubation medium caused the nasal mucosa to contract in a dose-dependent manner. Addition of Levitra at doses of 10-4 M elicited a significant relaxation response to 10-6 M methoxamine-induced mucosa strip contraction. Levitra could not inhibit electrical field stimulation-induced spike contraction and had a minimal effect on the basal tension of nasal mucosa as the concentration increased. CONCLUSION: This study indicated that high concentrations of Levitra had a significant spasmolytic effect by antagonizing α-adrenoceptors. Moreover, nasal obstruction might not be relieved in patients suffering from erectile dysfunction and stuffy noses who were concomitant using α-adrenergic agonist and Levitra.

Enhanced basal tension in isolated rat tracheal smooth muscle stimulated by electric field stimulation under low temperature.

Exposure to cold causes cutaneous vasoconstriction to reduce body heat loss, while the airway warms up the inspired cold air, thus suggesting that cooling might evoke a response in tracheal smooth muscle different from that in cutaneous blood vessels. The aim of this study was to evaluate the effect of temperature on isolated rat trachea, with or without electric field stimulation (EFS). Tissue bath for isolated trachea was used. An in vitro isometric contraction of trachea from healthy male Sprague-Dawley rat (body weight: ≥ 200 g) was continuously recorded. Tension in strips of rat trachea that were untreated and treated with EFS, was continuously recorded in stepwise manner at temperatures varying from 37 °C to 7 °C or from 7 °C to 37 °C. Results indicated that descent and re-ascent of temperature produced temperature-dependent tension changes. Basal tension of the trachea decreased when temperature was reduced if EFS was not applied. EFS-induced spike contraction decreased when temperature was reduced, while basal tension increased at the same time. We concluded that low temperature induced rapid and reproducible contraction in isolated rat tracheal strip only if EFS was applied. Increasing temperature reduced basal tension and enhanced EFS-induced spike contraction of the trachea at the same time.

Effect of budesonide and azelastine on histamine signaling regulation in human nasal epithelial cells.

Both glucocorticoids and H1-antihistamines are widely used on patients with airway diseases. However, their direct effects on airway epithelial cells are not fully explored. Therefore, we use the primary culture of human nasal epithelial cells (HNEpC) to delineate in vitro mucosal responses to above two drugs. HNEpC cells were cultured with/without budesonide and azelastine. The growth rate at each group was recorded and measured as population double time (PDT). The histamine1-receptor (H1R), muscarinic1-receptor (M1R) and M3R were measured using immunocytochemistry and western blotting after 7-days treatment. Then, we used histamine and methacholine to stimulate the mucus secretion from HNEpC and observed the MUC5AC expression in culture supernatants. Concentration-dependent treatment-induced inhibition of HNEpC growth rate was observed. Cells incubated with azelastine proliferated significantly slower than that with budesonide and the combined use of those drugs led to significant PDT prolong. The immunocytochemistry showed the H1R, M1R and M3R were obviously located in the cell membrane without apparent difference after treatment. However, western blotting showed that budesonide can significantly up-regulate the H1R, M1R and M3R level while azelastine had opposite effects. Histamine and methacholine stimulated MUC5AC secretion was greater in cells treated with budesonide but was lesser in those treated with azelastine, as compared to controls. Our data suggest that both budesonide and azelastine can significantly inhibit HNEpC proliferation, and therefore, be helpful in against airway remodeling. Long-term use of budesonide might amplify histamine signaling and result in airway hyperreactivity to stimulants by enhancing H1R, M1R and M3R expression while azelastine can oppose this effect. Therefore, combined use of those two drugs in patients with chronic inflammatory airway diseases may be an ideal option.

Menthol inhibiting parasympathetic function of tracheal smooth muscle.

Menthol is used as a constituent of food and drink, tobacco and cosmetics nowadays. This cold receptor agonist has been used as a nasal inhalation solution in the daily life. The effect of menthol on nasal mucosa in vivo is well known; however, the effect of the drug on tracheal smooth muscle has been rarely explored. Therefore, during administration of the drug for nasal symptoms, it might also affect the trachea via oral intake or inhalation. We used our preparation to test the effectiveness of menthol on isolated rat tracheal smooth muscle. A 5 mm long portion of rat trachea was submersed in 30 ml Krebs solution in a muscle bath at 37ºC. Changes in tracheal contractility in response to the application of a parasympathetic mimetic agent were measured using a transducer connected to a Pentium III computer equipped with polygraph software. The following assessments of menthol were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10-6 M methacholine as a parasympathetic mimetic; (3) effect of the drug on electrically induced tracheal smooth muscle contractions. Results indicated that addition of a parasympathetic mimetic to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of menthol at doses of 10-5 M or above elicited a relaxation response to 10-6 M methacholine-induced contraction. Menthol could also inhibit electrical field stimulation (EFS) induced spike contraction. However, it alone had a minimal effect on the basal tension of trachea as the concentration increased. We concluded that the degree of drug-induced tracheal contraction or relaxation was dose-dependent. In addition, this study indicated that high concentrations of menthol might actually inhibit parasympathetic function of the trachea.

Sudden sensorineural hearing loss associated with tension-type headache: a population-based study.

OBJECTIVES: This study explored the relationship between sudden sensorineural hearing loss (SSNHL) and prior tension-type headache (TTH) in a large nationwide population-based data set in Taiwan. METHODS: In this case-controlled study in Taiwan, participants with SSNHL (n = 4,683) were identified, and controls (n = 18,732) were randomly selected from the National Health Insurance database. Cases of TTH were identified by having been diagnosed as TTH prior to the index date of SSNHL diagnosis. A conditional logistic regression model was used to estimate the adjusted odds ratio (OR) and 95% confidence intervals (CI) for the association of sudden deafness with TTH among the sampled patients. RESULTS: Among the 23,415 patients, 2.5% (600/23,415) had TTH diagnoses prior to the index date; TTH was diagnosed in 4.5% (209/4,683) of the SSNHL group and 2.1% (391/18,732) of the control group. After adjusting for sociodemographic characteristics and comorbid medical disorders, we found that patients with SSNHL were more likely to have had a previous TTH than controls (OR, 1.86; 95% CI, 1.54-2.24; p < 0.01). CONCLUSION: Both male and female patients with SSNHL had a higher proportion of prior TTH than controls without SSNHL.

Tension-type headache associated with obstructive sleep apnea: a nationwide population-based study.

BACKGROUND: There is still controversy regarding the association between primary headaches and obstructive sleep apnea. We explored the relationship between tension-type headache (TTH) and obstructive sleep apnea (OSA) using a large nationwide population-based data set in Taiwan. METHODS: We identified 4759 patients diagnosed with OSA from the Taiwan Longitudinal Health Insurance Database, based on polysomnography, as the OSA group. We then randomly selected 19036 subjects without OSA, matched by sex and age, to serve as the non-OSA group. The multivariate Cox proportional hazards model with matching for age and sex was used to assess the possible associations between TTH and OSA among the patients. RESULTS: The prevalence of TTH was 10.2% among OSA patients and 7.7% among non-OSA patients (p < 0.001). The multivariate Cox proportional hazards model revealed patients with OSA were more likely to have TTH (hazard ratio, 1.18; 95% CI, 1.06-1.31) (p = 0.003) than patients in the non-OSA group. CONCLUSION: Patients with OSA had a higher likelihood of developing TTH than patients in the non-OSA group. Further studies of physiological patterns between OSA and TTH are needed to confirm the study findings.

Evaluation of the teratogenic effects of three traditional Chinese medicines, Si Jun Zi Tang, Liu Jun Zi Tang and Shenling Baizhu San, during zebrafish pronephros development.

The aim of this study was to evaluate the teratogenic effects of three common Chinese medical prescriptions, Si Jun Zi Tang (SJZT), Liu Jun Zi Tang (LJZT) and Shenling Baizhu San (SLBS), during zebrafish pronephros development. We used the transgenic zebrafish line Tg(wt1b:EGFP) to assess the teratogenic effects using 12 different protocols, which comprised combinations of 4 doses (0, 25, 250, 1,250 ng/mL) and 3 exposure methods [methods I, 12-36 hours post fertilization (hpf), II, 24-48 hpf, and III, 24-36 hpf]. As a result, few defects in the kidneys were observed in the embryos exposed to 25 ng/mL of each medical prescription. The percentage of kidney malformation phenotypes increased as the exposure concentrations increased (25 ng/mL, 0-10%; 250 ng/mL, 0-60%; 1,250 ng/mL, 80-100%). Immunohistochemistry for α6F, which is a basolateral and renal tubular differentiation marker, revealed no obvious defective phenotypes in either SJZT- or LJZT-treated embryos, indicating that these Chinese medical prescriptions had minimal adverse effects on the pronephric duct. However, SLBS-treated embryos displayed a defective phenotype in the pronephric duct. According to these findings, we suggest (1) that the Chinese medical prescriptions induced kidney malformation phenotypes that are dose dependent and (2) that the embryonic zebrafish kidney was more sensitive to SLBS than SJZT and LJZT.

The effect of temperature on basal tension and thyroarytenoid muscle contraction in an isolated rat glottis model.

The pitch of voice is closely related to the vocal fold tension, which is the end result of coordinated movement of the intralaryngeal muscles, and especially the thyroarytenoid muscle. It is known that vocal quality may be affected by surrounding temperature; however, the effect of temperature on vocal fold tension is mostly unknown. Thus, the aim of this study was to evaluate the effect of temperature on isolated rat glottis and thyroarytenoid muscle contraction induced by electrical field stimulation. In vitro isometric tension of the glottis ring from 30 Sprague-Dawley rats was continuously recorded by the tissue bath method. Electrical field stimulation was applied to the glottis ring with two wire electrodes placed parallel to the glottis and connected to a direct-current stimulator. The tension changes of the rat glottis rings that were either untreated or treated with electrical field stimulation were recorded continuously at temperatures from 37 to 7 °C or from 7 to 37 °C. Warming from 7 to 37 °C increased the basal tension of the glottis rings and decreased the electrical field stimulation-induced glottis ring contraction, which was chiefly due to thyroarytenoid muscle contraction. In comparison, cooling from 37 to 7 °C decreased the basal tension and enhanced glottis ring contraction by electrical field stimulation. We concluded that warming increased the basal tension of the glottis in vitro and decreased the amplitude of electrical field stimulation-induced thyroarytenoid muscle contraction. Thus, vocal pitch and the fine tuning of vocal fold tension might be affected by temperature in vivo.

Antibacterial nanostructured composite films for biomedical applications: microstructural characteristics, biocompatibility, and antibacterial mechanisms.

Hydrogenated Cu-incorporated diamond-like carbon (a-C:H/Cu) films were prepared in the present study using a radio-frequency plasma magnetron sputtering system at various CH4/Ar gas ratios. The a-C:H/Cu films were characterized by scanning electron microscopy, atomic force microscopy, Raman spectroscopy, transmission electron microscopy, nano-indentation and a contact angle goniometer. The antibacterial properties and cell cytotoxicity of a-C:H/Cu films were evaluated as per JIS Z2801:2010 and ISO 10993-5 specifications, respectively. The analytical results revealed that the production of a-C:H/Cu films varied with the CH4/Ar ratio, and the phase transformation (amorphous-like → nano-polycrystalline structure) was induced by Cu doping/ion bombardment and radical reactions. Moreover, it was found that the microhardness of the a-C:H/Cu films decreased with increasing Ar fraction in the gas ratio. The a-C:H/Cu films exhibited a high hydrophobic surface feature. The film which contained 77.3 ± 4.4 at.% Cu did not influence cell adhesion and proliferation behaviors. Antibacterial tests also demonstrated that a-C:H/Cu films possessed excellent antibacterial properties. Therefore, a-C:H/Cu films could be developed as promising antibacterial coatings for biomedical applications.

Effect of all-trans retinoic acid on the growth of two nasopharyngeal cancer cell lines and its treatment potential in combination with cisplatin.

The purpose of this study was to determine the effect of all-trans retinoid acid (ATRA) on two nasopharyngeal cancer (NPC) cell lines and to evaluate the synergistic effect of ATRA used in combination with cisplatin, a standard chemotherapeutic agent for NPC. Two NPC cell lines (NPC-TW01 and NPC-TW04) were used, and the MTT assay was used to analyze cell growth inhibition under various concentrations of ATRA and cisplatin. Under low concentrations of ATRA, the growth of both cell lines was significantly inhibited. When ATRA was used in combination with cisplatin, the resulting synergistic effects were robust and significant. Only a low concentration of ATRA was required to produce a synergistic effect when combined with cisplatin, indicating the potential usefulness of a combination therapy regimen. Therefore, the combination of ATRA and cisplatin is a viable treatment option for NPC and should be further investigated.

An integrative OSCE methodology for enhancing the traditional OSCE program at Taipei Medical University Hospital--a feasibility study.

BACKGROUND: Continuous development and use of new technologies and methodologies are key features in improving the learning, performance, and skills of medical students and students of all health care professions. Although significant improvements in teaching methodologies have been made in all areas of medicine and health care, studies reveal that students in many areas of health care taking an objective structured clinical examination (OSCE) express difficulties. Thus, this study was planned as a feasibility study to assess the educational effectiveness of an integrated objective structured clinical examination (iOSCE) using both standardized patients and virtual patients. METHODS: Thirty (30) medical students in their first year of internship at Taipei Medical University volunteered to be part of a feasibility study for demonstrating the concept of iOSCE. They divided themselves into five groups of six students each and were requested to evaluate two cases: 1) a patient with abdominal pain and 2) a patient with headache using a combination of a standardized patient and a virtual patient. For each of the two cases, five stations were designed in which students were given ten minutes per station leading to a final diagnosis and concluded with a debriefing. The five stations were: Station 1) Interacting with the standardized patient. Station 2) Writing the patient note and developing a differential diagnosis. Station 3) Selecting appropriate laboratory and imaging studies. Station 4) Making a final diagnosis and stating the evidence for it. Station 5) Having the debriefing. Each group of 6 students was assigned 2 hours per day for each case. All participants completed a survey regarding the usefulness and efficiency of the iOSCE. RESULTS: All medical students (30/30; 100%) found the iOSCE program to be very satisfactory, and all expressed that they would like to have further iOSCE experiences if given the opportunity. In terms of ease and helpfulness, the students rated the program an average of 4.4 for the 1st case (abdominal pain) and 4.5 for the 2nd case (headache) on a scale of 1-5, with 5 being the highest and 1 being the lowest score. CONCLUSIONS: The participants felt that the iOSCE program can offer certain advantages over the traditional OSCE with the SP alone. They cited that the iOSCE provided improved clarity of what was being assessed as well as providing an opportunity to improve their diagnostic reasoning.

Cryptococcal infection of the vocal folds.

Cryptococcosis of the larynx is rare. In this manuscript we present a case of laryngeal cryptococcosis with a clear history of pigeon exposure. Cryptococcal laryngitis may present as hoarseness without other typical symptoms, even in immunocompetent individuals.

Causes of Vocal Fold Paralysis.

BACKGROUND: Vocal fold paralysis (VFP) can result from a variety of diseases or surgeries and has various causes. This study determined concurrent etiologies in patients who were treated in a teaching hospital (tertiary medical center). METHODS: A retrospective review of medical records of patients with VFP from September 2010 to December 2019 was performed to determine the etiology. Patients with laryngeal/hypopharyngeal malignancies, those with incomplete examination and follow-up data were excluded from the study. During the follow-ups, cases involving recovery were also excluded. RESULTS: One hundred and ninety-four patients with a determined etiology were included: 113 males and 81 females. Unilateral VFP was present in 178 patients, and 16 presented with bilateral VFP. The causes of unilateral VFP were surgical for 61.3%, neoplastic for 17.5%, idiopathic for 10.3%, traumatic for 1.5%, central for 4.7%, cardiovascular for 2%, radiation-induced for 1.5%, and inflammatory for 1%. Thyroidectomy was the most common surgery for unilateral VFP and was the cause for 54 patients. Lung cancer was responsible for 15 cases and was the most common neoplastic etiology of unilateral VFP. For those who presented with bilateral VFP, surgery was the most common cause and accounted for 56.3% of the incidences. In terms of gender, surgery was the most common cause for both sexes, accounting for 62 of 113 male patients and 57 of 81 female patients. Four cases recovered during the follow-ups and these were excluded. CONCLUSION: Surgery and in particular, thyroidectomy, was the most common cause of VFP for these series. Central nervous system disorders were the cause of VFP (4.5%). Central nervous system disorders, especially cerebrovascular accidents that induced VFP, could not be neglected. Radiation-induced cranial nerve paralysis in the head and neck cancer was possible causes. The percentage for the causes of unilateral VFP, surgery increased and the percentage for neoplasm decreased for Taiwan.

Mechanisms of adiponectin-mediated COX-2 induction and protection against iron injury in mouse hepatocytes.

Adiponectin (APN)-mediated cyclooxygenase (COX)-2 induction is known to have various protective effects on cardiovascular diseases. However, the molecular mechanisms of APN-mediated COX-2 induction and its protection against iron-mediated injury in hepatocytes are still unclear. Herein, we show that AMP-mediated peroxisome proliferator-activated receptor (PPAR)alpha activation was attributable to COX-2 induction by APN, which was further confirmed by identifying novel functional PPAR responsive elements (PPREs) in the mouse COX-2 promoter region. Prostaglandin (PG)I2 and PGE2, metabolites of COX-2, time-dependently increased in hepatocytes treated with APN. Interestingly, beraprost and misoprostol, respective agonists for PGI2 and PGE2, mimicked the protective effects of APN in iron-mediated inflammation in hepatocytes. The iron dextran-activated nuclear factor (NF)-kappaB pathway was correlated with the increased production of inflammatory cytokines including tumor necrosis factor-alpha, intercellular adhesion molecule-1, and monocyte chemotactic protein-1. This was eliminated by administration of APN, whereas blockage of PPARalpha activation, an upstream regulator of COX-2 induction by APN, and COX-2 activation reversed the anti-inflammatory effect of APN, suggesting the crucial role of COX-2 in this event. Herein, we demonstrate that APN-mediated COX-2 induction through a PPARalpha-dependent mechanism, and COX-2 exerted an anti-inflammatory effect of APN in hepatocytes subjected to iron challenge.

FOXD1 Repression Potentiates Radiation Effectiveness by Downregulating G3BP2 Expression and Promoting the Activation of TXNIP-Related Pathways in Oral Cancer.

Radiotherapy is commonly used to treat oral cancer patients in the current clinics; however, a subpopulation of patients shows poor radiosensitivity. Therefore, the aim of this study is to identify a biomarker or druggable target to enhance the effectiveness of radiotherapy on oral cancer patients. By performing an in silico analysis against public databases, we found that the upregulation of FOXD1, a gene encoding forkhead box d1 (Foxd1), is extensively detected in primary tumors compared to normal tissues and associated with a poor outcome in oral cancer patients receiving irradiation treatment. Moreover, our data showed that the level of FOXD1 transcript is causally relevant to the effective dosage of irradiation in a panel of oral cancer cell lines. The FOXD1 knockdown (FOXD1-KD) dramatically suppressed the colony-forming ability of oral cancer cells after irradiation treatment. Differentially expressed genes analysis showed that G3BP2, a negative regulator of p53, is predominantly repressed after FOXD1-KD and transcriptionally regulated by Foxd1, as judged by a luciferase-based promoter assay in oral cancer cells. Gene set enrichment analysis significantly predicted the inhibition of E2F-related signaling pathway but the activation of the interferons (IFNs) and p53-associated cellular functions, which were further validated by luciferase reporter assays in the FOXD1-KD oral cancer cells. Robustly, our data showed that FOXD1-KD fosters the expression of TXNIP, a downstream effector of IFN signaling and activator of p53, in oral cancer cells. These findings suggest that FOXD1 targeting might potentiate the anti-cancer effectiveness of radiotherapy and promote immune surveillance on oral cancer.

Erratum: Lee, H.H., et al. Histone 2A Family Member J Drives Mesenchymal Transition and Temozolomide Resistance in Glioblastoma Multiforme. Cancers 2020, 12, 98.

The authors wish to make the following changes to this paper [...].

The prevalence of chronic otitis media and its complication rates in teenagers and adult patients.

OBJECTIVE: To determine the annual complication rates of chronic otitis media (COM) and its management. STUDY DESIGN: Retrospective. SUBJECTS AND METHODS: Data were extracted from 3,223 adult patients, aged 15.1 years and older, under the diagnosis of COM from 1998 to 2007. Complications secondary to COM were identified in a total of 115 patients. RESULTS: The incidence of COM in adults decreased from 407 to 145 cases per year (R(2) = 0.845, P < 0.001) from 1998 to 2007. The mean age of patients with COM increased from 44.67 to 49.43 years (R(2) = 0.896, P < 0.001). The prevalence of COM decreased considerably during the study period. However, the annual extracranial complication rate (R(2) = 0.109, P = 0.352) and intracranial rate (R(2) = 0.382, P = 0.057) did not reduce during the past 10 years. CONCLUSION: The complication rate for COM remained steady in the past 10 years, regardless of the overall reduction in the prevalence of COM with use of antibiotics. A high index of suspicion and imaging studies for early identification are recommended. Pneumococcal vaccination is recommended, particularly for the elderly patients who are treated conservatively because of relatively poor general health conditions.

The Epidemiology of Benign Voice Disorders in Taiwan: A Nationwide Population-Based Study.

OBJECTIVE: Because there are few population-based studies regarding the epidemiology of benign voice diseases, the present study used a nationwide population-based claims database (the National Health Insurance Research Database) to investigate the epidemiology of benign voice diseases among the general adult population in Taiwan. METHODS: Study participants were retrieved for those patients who were 20 to 90 years old with a diagnosis of benign voice diseases that were defined by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes from 2006 to 2014. Patient visits were grouped into infectious (ICD-9-CM: 012.3, 032.3, 034.0, 090.5, 095.8,101, 464.0, 464.20, 464.21, 465.x, 476.0, 476.1) and noninfectious (ICD-9-CM: 306.1, 478.3x, 478.4, 478.5, 748.3, 784.4x) dysphonia groups. RESULTS: Benign voice disorders have a prevalence of approximately 3.6% in Taiwan as of 2014. The year-to-year prevalence decreased gradually in the query period. Infectious dysphonia diagnoses were higher than noninfectious ones. Dysphonia caused by noninfectious diagnoses was most prevalent in the 60 to 79 years age group. Dysphonia caused by infectious diagnoses was highest in 20 to 39 years group. Noninfectious dysphonia diagnoses were more common in women. CONCLUSION: The prevalence of voice disorders among the adult population in Taiwan was 3.6% in 2014. Voice disorders are more common in women and occur primarily in the 20 to 39 years age group. Infectious dysphonia is more common than noninfectious dysphonia. The results may be underestimated due to limitation of the database. This is the first population-based epidemiology study of adult voice disorders.

Nicotinic Acetylcholine Receptor Subunit Alpha-5 Promotes Radioresistance via Recruiting E2F Activity in Oral Squamous Cell Carcinoma.

Radiotherapy is commonly used to treat patients with oral squamous cell carcinoma (OSCC), but a subpopulation of OSCC patients shows a poor response to irradiation treatment. Therefore, identifying a biomarker to predict the effectiveness of radiotherapy in OSCC patients is urgently needed. In silico analysis of public databases revealed that upregulation of CHRNA5, the gene encoding nicotinic acetylcholine receptor subunit alpha-5, is extensively detected in primary tumors compared to normal tissues and predicts poor prognosis in OSCC patients. Moreover, CHRNA5 transcript level was causally associated with the effective dose of irradiation in a panel of OSCC cell lines. Artificial silencing of CHRNA5 expression enhanced, but nicotine reduced, the radiosensitivity of OSCC cells. Gene set enrichment analysis demonstrated that the E2F signaling pathway is highly activated in OSCC tissues with high levels of CHRNA5 and in those derived from patients with cancer recurrence after radiotherapy. CHRNA5 knockdown predominantly suppressed E2F activity and decreased the phosphorylation of the Rb protein; however, nicotine treatment dramatically promoted E2F activity and increased Rb phosphorylation, which was mitigated after CHRNA5 knockdown in OSCC cells. Notably, the signature combining increased mRNA levels of CHRNA5 and the E2F signaling gene set was associated with worse recurrence-free survival probability in OSCC patients recorded to be receiving radiotherapy. Our findings suggest that CHRNA5 is not only a useful biomarker for predicting the effectiveness of radiotherapy but also a druggable target to enhance the cancericidal effect of irradiation on OSCC.