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Background: Nasal epithelial cells are the first site of encounter of the influenza virus, and their innate immune response might define subsequent inflammatory direction. Aims/objectives: We used metabolomics analysis to identify metabolic changes and the regulation of inflammatory cytokines in nasal epithelial cells upon influenza virus infection. Material and methods: We cultured nasal epithelial cells using air-liquid interface (ALI) model. Influenza virus (PR8) infection followed by metabolomic analysis was performed. Furthermore, cytokine expression was analyzed by cytokine array and RT-qPCR. Results: Metabolomic analysis revealed depletion of the tryptophan and accumulation of its metabolite, kynurenine, within 48 h. The major enzyme involved in the tryptophan metabolic pathway, indoleamine 2,3-dioxygenase (IDO), was overexpressed after infection. Cytokine expression array after infection showed increased levels of IL-1α, CCL2, IL-6, CXCL10, CCL5, and CXCL11, and after using 1-methyltryptophan (1-MT) as inhibitor, the expression levels of IL-6 and G-CSF were reduced. Conclusions and significance: Viral infection results in depletion of tryptophan and accumulation of kynurenine via increased cellular IDO activity. Inhibition of IDO activity or replenishment of tryptophan by local application may be a good therapeutic strategy for limiting the initial damage caused by influenza virus in nasal epithelial cells.

Background: The role of allergy in the development of chronic rhinosinusitis (CRS) in East Asians is not clear., Aims/objectives: The aim was to investigate the impact of allergies in the clinical characteristics of chronic rhinosinusitis., Material and Methods: A total of 138 CRS patients who underwent endoscopic sinus surgery were included. A brief history of rhinosinusitis symptoms, blood eosinophil count, blood-specific allergen tests, computed tomography (CT) scan findings, Lund-Mackay (LM) CT scores, and Sino-Nasal Outcome Test (SNOT-22) Questionnaire scores, and sinoscopy findings at 3 and 6 months postoperatively., Results: The ImmunoCAP test was positive in 71(51%) patients and negative in 67(49%) patients. The mean age of those who received endoscopic sinus surgery was 7-years younger in the allergic group compared with the non-allergic group (p = .008). The peripheral eosinophil count in the allergic group was higher than that of the non-allergic group (p = .008). The LM scores and SNOT-22 scores were not significantly different between the two groups. The recurrence rate of nasal polyps in the allergic group was higher but without statistical significance., Conclusions and Significance: Allergy may accelerate the disease progression of CRS. The presence of the serum-specific IgE was correlated with peripheral eosinophil percentage, especially in the CRSwNP patients.

Objectives: To assess population-level data for pediatric adenoidectomy., Methods: Using data from the Taiwan National Health Insurance Research Database for the 1997-2012 period, all inpatients <18 years who received adenoidectomies were identified by codes from the International Classification of Diseases, 9th Revision., Results: A total of 20,599 children underwent adenoidectomy (mean age, 7.4 years; 67% boys). The overall incidence rate was 24.5 per 100,000 children. The highest incidence was observed for the ages of 3-5 years in both genders (p < .001). Boys exhibited higher incidence rates than did girls (p < .001). Longitudinal data revealed an increase in the incidence rates from 1997 (14.8/100,000) to 2012 (26.9/100,000) (p trend < .001). The proportion of adenoidectomies performed at medical centers decreased from 60.5 to 46.9%, whereas those performed at regional hospitals increased from 36.4 to 47.2% (all p trend < .001). The proportion of pediatric adenoidectomies performed for sleep-disordered breathing (SDB) increased significantly from 10.1 to 35.6%, whereas those for infections decreased from 32.3 to 8.0% (all p trend < .001)., Conclusions: This study revealed an increasing trend of pediatric inpatient adenoidectomy incidence rates during 1997-2012 in Taiwan. Moreover, surgical indications have shifted from infections to SDB.

Conclusions: In patients with malignant external otitis (MEO), mortality was not related to age, sex, degree of glucose tolerance, duration of diabetes mellitus (DM), microorganism, comorbid disease, or involvement of a single cranial nerve. Severe complications such as skull base osteomyelitis, intracranial extension, and involvement of multiple cranial nerves were correlated with mortality., Objectives: To analyze the factors that affect the survival of patients with MEO in today's era of advanced antibiotics., Patients and Methods: Patients with a diagnosis of MEO from 1993 to 2005 were collected., Results: A total 26 patients with a mean age of 63.7+/-10.2 years were included. All had a history of DM. Pseudomonas aeruginosa (26.9%), Klebsiella pneumoniae (19.2%), and fungus (15.4%) were most frequently found in pus cultures. Cranial nerves were involved in 11 patients: the facial nerve was most frequently (38.46%) involved. Complications such as osteomyelitis (11 patients) and intracranial involvement (3 patients) were noted in this series. Mastoidectomy was performed in 12 patients. A total of five patients died.

Conclusions: Facial palsy in children might be an alarming sign of serious underlying disease such as tumor, systemic disease or congenital anomalies and the recovery is poor in those cases. Therefore, careful investigation and differential diagnosis are essential in children. Prednisolone does not make a significant difference in the outcome in the treatment of children with Bell's palsy. The prognosis of Bell's palsy in the pediatric group is good; patients usually recover within 3 months., Objectives: To review and analyze the etiology, management, and outcome of facial palsy in children., Patients and Methods: Using a retrospective chart review, patients under the age of 15 years with a diagnosis of facial palsy were collected from 1996 to 2002., Results: A total of 56 cases (29 male, 27 female) with a mean age of 6.9±4.5 years were included in this analysis. Causes of facial palsy were Bell's palsy (44 patients, 78.6%), neoplastic (4 patients, 7.1%), head injury (3 patients, 5.4%), congenital (3 patients, 5.4%), or infectious (2 patients, 3.6%). In Bell's palsy there was no significant difference in the recovery rate between the groups with or without prednisolone treatment and between the groups that received medication within 1 week of syndrome onset or after more than 1 week.

Conclusions: Our study demonstrated that high resolution animal positron emission tomography (PET) can non-invasively assess the change in glucose metabolism of the central auditory pathway including the inferior colliculus and auditory cortex in the rat., Objectives: The traditional in vitro approach with immunohistochemical staining or autoradiography to assess chronological changes or topographic arrangement of central auditory pathway required sacrificing a large number of animals. Inter-individual difference is also a major concern. Therefore, development of an in vivo animal model using PET imaging would be a rational method to overcome these shortcomings., Materials and Methods: Small animal PET scan using (18)F-fluorodeoxyglucose (FDG) as a functional marker was performed in rats. Each animal was serially scanned before and after unilateral cochlear ablation, with and without acoustic stimulation. The images were analyzed by the region of interest (ROI) method. Ratios of radioactivity at the inferior colliculus and auditory cortex and a referenced cerebral cortex between bilateral hemispheres were measured., Results: These scans demonstrated several brain structures including the inferior colliculus (IC) and cortex (B). Moreover, unilateral cochlear ablation decreased the radioactivity at contralateral IC and auditory cortex (C) areas. Differences may reach 33% in IC and 27% in C, and average radioactivity ratios were 1.24+/-0.08 and 1.18+/-0.07 in selected adjacent sections, respectively.

Conclusions: Nasal epithelial cells are constitutively equipped with all Toll-like receptors (TLRs) which are essential for innate immunity. Both mRNA and protein levels of TLR3 expression increased in more differentiated nasal epithelial cells. Considering that the ligand for TLR3 is viral dsRNA, this result is in good accordance with previous reports demonstrating that more differentiated airway epithelial cells have increased resistance to rhinovirus infection., Objective: Nasal epithelial cells use innate immune responses to combat inspired potential pathogens. TLRs are receptors that recognize pathogen-associated molecular patterns of microbes. Therefore, we investigated the expression of TLRs in cultured nasal epithelial cells obtained from nasal polyps., Materials and Methods: Submerged single layer (SSL) and air-liquid interface (ALI) nasal epithelial cell cultures with or without 10(-7) M retinoid acid (+/- RA) were created., Results: ALI + RA culture developed ciliary differentiation as observed by light and scanning electron microscopic examination in 3 weeks. It had higher interleukin (IL)-8 basal secretion (21.9 vs 0.82-1.45 ng/ml) and transepithelial potential (-20.4 mV). TLR1-10 mRNA expression in cultured nasal epithelial cells was determined by RT-PCR. Only TLR3 mRNA significantly increased at day 20 vs day 1 (n=5, p=0.02) in ALI + RA cell culture. Higher TLR3 protein was also expressed at day 20 in ALI + RA cell culture but not in SSL culture by western blotting.

Conclusions: Broad-spectrum antibiotics are advocated for treating deep neck infection. Anaerobic coverage is necessary, especially in odontogenic cases. The presence of diabetes, infection of the parotid space and an obvious odontogenic source of infection can aid in determining the causative organisms., Objectives: This study aimed to analyze the bacteriology in deep neck infections and identify the factors that influenced the causative pathogens., Materials and Methods: The records of 212 patients who were diagnosed as having deep neck infections at the National Taiwan University Hospital between 1997 and 2003 were reviewed; 128 patients with bacterial isolation from their pus cultures were enrolled., Results: The cultures of 46 patients (35.9%) were polymicrobial. Viridans Streptococcus was the most commonly isolated organism (38.3%), followed by Klebsiella pneumoniae (32.0%) and Peptostreptococcus (17.2%). The most common organism in 44 diabetic patients was K. pneumoniae (54.5%), versus viridans streptococcus (48.8%) in 84 nondiabetic patients. In patients with dental sources of infections, the culture rate of anaerobes was 59.3%; in upper airway infections and other sources of infections they were 22.7% and 21.5%, respectively (Chi(2) test, p = 0.0008). The differences in age, sex, and climate did not show any significant changes in the common causative pathogens. Common pathogens in the infection of parapharyngeal, submandibular, and extended spaces were the same as viridans streptococcus, but in the parotid space K. pneumoniae was the most common pathogen.

Decreased connexin 43 (Cx43) expression as a result of application of lipopolysaccharide (LPS) may limit the diffusion of intercellular signaling molecules that is essential to the coordinated function of neighboring cells. Therefore, it may be related to a ciliary beating defect in nasal epithelial cells and result in accumulation of harmful substances.Gap junction intercellular communication (GJIC) is altered during inflammation in tracheal epithelial cells. Thus, we aimed to investigate whether LPS affects the expression of Cx43, the elementary protein composing the gap junction of nasal epithelial cells, in vitro.LPS (Pseudomonas aeruginosa serotype 10) was applied to epithelial cells obtained from nasal polyp for 24 h in vitro. As an inflammatory indicator, IL-8 secretion was measured using a commercially available ELISA kit. Cx43 protein was detected semi-quantitatively using Western blotting. The nasal epithelial cells constitutively secreted IL-8 at a concentration of 0.45+/-0.03 ng/microg protein. In the presence of 10(-2) mg/ml LPS, the concentration of IL-8 was significantly increased to 0.55+/-0.05 ng/microg protein (n=8). Expression of the Cx43:beta-actin ratio decreased in a time- and dose-dependent fashion (10(-3)-10(-1) mg/ml LPS).

Objective: Although the mutation in the Gap Junction Beta 2-encoding gap junction protein connexin 26 (Cx26) has been related to hereditary non-syndromic deafness and maturation of cochlear development, the physiological role of Cx26 in the cochlear lateral wall remains unclear. It has been suggested to be responsible for the recycling of K+ in the endolymph and for maintenance of the endocochlear potential (EP). In noise-induced hearing loss, alterations in the EP and the K+ concentration in endolymph have been observed. Thus Cx26, which is widely expressed in the cochlear lateral wall, may play a role in the mechanism of acoustic trauma., Material and Methods: We used a rat model of noise-induced hearing impairment to detect changes in Cx26 expression in the cochlear lateral wall. By means of immunofluorescent staining and Western blotting, we investigated whether Cx26 was involved in the pathophysiological mechanism of acoustic trauma., Results: The results indicated that abundant Cx26 protein was found on fibrocytes of the spiral ligament in the cochlear lateral wall. Protein extract of cochlear lateral wall expressed Cx26 with a molecular weight of approximately 21 kDa. After noise exposure, with an increasing threshold of the auditory brainstem response (ABR) of approximately 54.2 +/- 21.8 dB SPL, the expression of Cx26 protein increased significantly (p < 0.05) as revealed by semi-quantitative analysis from Western blotting., Conclusion: Cx26 protein was present in the cochlear lateral wall of rats and was upregulated when the ABR threshold shifted after intense noise exposure. Cx26 protein was involved in the pathogenesis of acoustic trauma.

Objective: Recent studies have suggested that inositol triphosphate is transmitted through the gap junction of adjacent epithelial cells and communicates the intracellular calcium wave that controls the beating of cilia. Therefore, gap junction-mediated intercellular communication may modulate the metachronal ciliary beating of respiratory mucosa., Material and Methods: The expression and function of gap junctions were evaluated in nasal mucosa using immunofluorescent staining, Western blotting and Lucifer Yellow dye coupling in both whole nasal mucosa and cultured nasal epithelial cells., Results: Among connexins (Cxs) 26, 32 and 43, only Cx43 was found in the nasal mucosa, in both the epithelial cells and submucosa tissue. Using Western blotting, Cx43 protein was found in protein extracts of both whole mucosa and cultured epithelial cells. The Cx43 protein content increased twofold between the 3rd and 6th days of culture. Lucifer Yellow dye, microinjected into single cultured epithelial cells, had spread to the adjacent cells., Conclusion: Cx43 is present in nasal mucosa. The expression of Cx43 on epithelial cells increases after culture. The dye-coupling study in epithelial cells indicated that the signal may be transmitted to neighboring cells via a gap junction composed of Cx43. Thus, Cx43 may be involved in the regulation of metachronal ciliary beating in ciliated epithelial cells and growth or differentiation in nasal tissue.