Search

In the inner ear, endolymph fluid surrounds the organ of Corti, which is important for auditory function; notably, even slight environmental changes mediated by trauma or infection can have significant consequences. However, it is unclear how the immune response is modulated in these tissues. Here, we report the local immune surveillance role of cleaved cochlin LCCL (Limulus factor C, Cochlin, and Lgl1) during Pseudomonas aeruginosa infection in the cochlea. Upon infection, the LCCL domain is cleaved from cochlin and secreted into the perilymph. This cleaved fragment sequesters infiltrating bacteria in the scala tympani and subsequently recruits resident immune cells to eliminate the bacteria. Importantly, hearing loss in a cochlin knockout mouse model is remedied by treatment with a cochlin LCCL peptide. These findings suggest cleaved cochlin LCCL constitutes a critical factor in innate immunity and auditory function and may be a potential therapeutic target to treat chronic otitis media-induced hearing loss.

OBJECTIVE Various anatomical structures of upper airway and physical differences are known to be risk factors for obstructive sleep apnoea (OSA). Torus mandibularis is a structure that can appear on the inside of the mandible. Therefore, it is possible for tori to influence airway volume by occupying the space for tongue and cause sleep apnoea. The purpose of this study is to investigate the effect of torus mandibularis on the severity of OSA as one of the craniofacial risk factors. DESIGN Retrospective case-control study. SETTING University-based tertiary medical centre. PARTICIPANTS Adult patients over 19-years-old who visited outpatient clinics with complaints of sleep-disordered breathing symptoms between January 2010 and December 2017 were investigated. MAIN OUTCOME MEASURES The presence of torus mandibularis in oral cavity was confirmed by physical examination or CT image. We analysed demographic findings including age, sex, medical history, previous operation history, physical findings of upper airway and result of polysomnography. To evaluate the effect of torus mandibularis on OSA, polysomnography data of the two groups according to presence or absence of torus mandibularis were compared and analysed. RESULTS Two-hundred and thirty-two OSA patients with BMI

Abnormalities in the human microbiota are associated with the etiology of allergic diseases. Although disease site-specific microbiota may be associated with disease pathophysiology, the role of the nasal microbiota is unclear. We sought to characterize the microbiota of the site of allergic rhinitis, the inferior turbinate, in subjects with allergic rhinitis ( n = 20) and healthy controls ( n = 12) and to examine the relationship of mucosal microbiota with disease occurrence, sensitized allergen number, and allergen-specific and total IgE levels. Microbial dysbiosis correlated significantly with total IgE levels representing combined allergic responses but not with disease occurrence, the number of sensitized allergens, or house dust mite allergen-specific IgE levels. Compared to the populations in individuals with low total IgE levels (group IgE low ), low microbial biodiversity with a high relative abundance of Firmicutes phylum ( Staphylococcus aureus ) and a low relative abundance of Actinobacteria phylum ( Propionibacterium acnes ) was observed in individuals with high total serum IgE levels (group IgE high ). Phylogeny-based microbial functional potential predicted by the 16S rRNA gene indicated an increase in signal transduction-related genes and a decrease in energy metabolism-related genes in group IgE high as shown in the microbial features with atopic and/or inflammatory diseases. Thus, dysbiosis of the inferior turbinate mucosa microbiota, particularly an increase in S. aureus and a decrease in P. acnes , is linked to high total IgE levels in allergic rhinitis, suggesting that inferior turbinate microbiota may be affected by accumulated allergic responses against sensitized allergens and that site-specific microbial alterations play a potential role in disease pathophysiology.

Moonlighting proteins exhibit multiple activities in different cellular compartments, and their abnormal regulation could play an important role in many diseases. To date, many proteins have been identified with moonlighting activity, and more such proteins are being gradually identified. Among the proteins that possess moonlighting activity, several secreted proteins exhibit multiple activities in different cellular locations, such as the extracellular matrix, nucleus, and cytoplasm. While acute inflammation starts rapidly and generally disappears in a few days, chronic inflammation can last for months or years. This is generally because of the failure to eliminate the cause of inflammation, along with repeated exposure to the inflammatory agent. Chronic inflammation is now considered as an overwhelming burden to the general wellbeing of patients and noted as an underlying cause of several diseases. Moonlighting proteins can contribute to the process of chronic inflammation; therefore, it is imperative to overview some proteins that exhibit multiple functions in inflammatory diseases. In this review, we will focus on inflammation, particularly unravelling several well-known secreted proteins with multiple functions in different cellular locations.

Considerable number of patients with obstructive sleep apnea (OSA) failed to respond to positive airway pressure therapy and so turned to surgical procedures. A wide variety of surgical procedures have been developed and advanced, according to obstruction and target site through nasal cavity to trachea. We introduced our overlapping lateral pharyngoplasty (OLP) technique as a surgical option for OSA and evaluated its surgical outcomes both with and without endoscope-guided coblator tongue base resection (CobTBR). Sixty-five patients underwent either OLP alone or OLP combined with CobTBR to treat OSA at academic tertiary center. Twenty-nine patients underwent postoperative polysomnography and were divided into two groups, as an OLP group and an OLP combined CobTBR group. Various parameters from physical examinations and polysomnographic results were compared and analyzed. Most enrolled patients improved on various polysomnographic parameters, including AHI and oxygen levels. In the OLP group, 91.7% of patients showed a surgical response and the overall success rate was 66.7%. Mean AHI improved significantly from 36.3 to 14.8. In the OLP + CobTBR group, all patients showed improvement in AHI and the surgical response rate was 100%. The overall success rate was 70.6% and mean AHI improved from 38.8 to 13.1. In both groups, various parameters such as RDI, lowest O2 saturation, mean O2 saturation, oxygen desaturation index, supine AHI, and ESS significantly improved after surgery. Our OLP technique appears to be safe and effective among OSA patients. Multi-level OLP surgery combined with CobTBR can be a good surgical strategy for patients experiencing retroglossal obstruction.

BRAF (V600E) mutation is the most commonly detected genetic alteration in thyroid cancer. Unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response in thyroid cancer is reported to be low. The purpose of this study is to investigate the resistance mechanism responsible for this low treatment response to BRAF inhibitor in order to maximize the effect of targeted therapy. We examined the expression of feedback regulation mechanisms and alterations in the upper signal transduction pathway in thyroid cancer cell lines harboring BRAF mutation. Also, we investigated the effect of dual inhibition from combinatorial therapy. Two thyroid cancer cell lines, 8505C (anaplastic thyroid cancer) and BCPAP (papillary thyroid cancer) were selected and treated with PLX4032 and its drug sensitivity were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on orthotopic xenograft mouse models. Unlike BCPAP cells, 8505C cells presented drug resistance to PLX4032 treatment and this was mainly due to increased expression of c-Met. Effective inhibitions of c-Met, p-AKT, and p-ERK were achieved after dual treatment with BRAF inhibitor (PLX4032) and c-Met inhibitor (PHA665752). Similar results were confirmed by in vivo study with orthotopic xenograft mouse model. c-Met-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF (V600E) mutant anaplastic thyroid cancer cells to PLX4032. Dual inhibition of BRAF and c-Met leads to sustained treatment response. © 2015 Wiley Periodicals, Inc.

We studied the relative roles of Duox2-derived reactive oxygen species (ROS) in host defense against influenza A virus (IAV) infection in normal human nasal epithelial cells and mouse nasal mucosa. We found that Duox2 primarily generated ROS rapidly after IAV infection in normal human nasal epithelial cells and that knockdown of Duox2 aggravated IAV infection. In addition, Duox2-derived ROS enhancement significantly suppressed IAV infection in nasal epithelium. In particular, Duox2-derived ROS were required for the induction of retinoic acid–inducible gene (RIG)-I and melanoma differentiation–associated protein 5 (MDA5) transcription. After intranasal IAV inoculation into mice, viral infection was significantly aggravated from 3 days postinoculation (dpi) in the nasal mucosa, and the IAV viral titer was highest at 7 dpi. Both RIG-I and MDA5 messenger RNA levels increased dominantly in mouse nasal mucosa from 3 dpi; consistent with this, RIG-I and MDA5 proteins were also induced after IAV infection. RIG-I and MDA5 messenger RNA levels were induced to a lower extent in the nasal mucosa of the mice that were inoculated with Duox2 short hairpin RNA, and the IAV viral titer was significantly higher in nasal lavage. Taken together, Duox2-derived ROS are necessary for the innate immune response and trigger the induction of RIG-I and MDA5 to resist IAV infection in human nasal epithelium and mouse nasal mucosa.

Purpose: Although differentiated normal human nasal epithelial (NHNE) cells can be used to study the role of human nasal epithelium, there is a need for effective culture models of nasal epithelium in sinonasal disease status, including allergic rhinitis (AR). We aimed to examine the feasibility of intranasal brushing for culture of nasal epithelial cells in AR patients and to verify the hypothesis that allergic nasal epithelial (ARNE) cells differ in histologic and physiologic characteristics. Methods: We established a system for isolating (via intranasal brushing) and culturing (with air-liquid interface, ALI) nasal epithelial cells from healthy volunteers (n=8) and AR patients (n=8). We used this system to compare the histologic findings and physiologic characteristics of NHNE and ARNE. Results: The histology results showed that fully differentiated ALI culture was obtained at least 14 days after confluence and that both ciliated and secretory cells were well differentiated in ALI culture using nasal brushing. The histology results of ARNE culture were significantly different from NHNE. The number of ciliated cells was lower, and secretory cells were more dominant in ARNE cell culture compared to NHNE cells. We also observed, by electron microscopy, loose tight junctions and short cilia in cultured ARNE cells. In addition, the mRNA level of TSLP which was one of the epithelial-derived allergic cytokines was significantly higher, and the expressions of genes involved in ciliogenesis were lower in cultured ARNE cells without allergen stimulation. Conclusions: Our findings suggest that ALI culture of ARNE cells using intranasal brushing may be an alternative method for epithelial cell culture in AR patients and that cultured ARNE cells will be useful for in vitro studies of the mechanisms at play during AR because they maintain unique allergic characteristics.

Purpose The nasal mucosa is the first site to encounter pathogens, and it forms continuous barriers to various stimuli. This barrier function is very important in the innate defense mechanism. Additionally, inflammation of the nasal sinus is known to be a hypoxic condition. Here, we studied the effect of hypoxia on barrier function in normal human nasal epithelial (NHNE) cells. Materials and methods The expression levels of various junction complex proteins were assessed in hypoxia-stimulated NHNE cells and human nasal mucosal tissues. We performed real-time polymerase chain reaction analysis, western blotting, and immunofluorescence assays to examine differences in the mRNA and protein expression of ZO-1, a tight junction protein, and E-cadherin in NHNE cells. Moreover, we evaluated the trans-epithelial resistance (TER) of NHNE cells under hypoxic conditions to check for changes in permeability. The expression of ZO-1 and E-cadherin was measured in human nasal mucosa samples by western blotting. Results Hypoxia time-dependently decreased the expression of ZO-1 and E-cadherin at the gene and protein levels. In addition, hypoxia decreased the TER of NHNE cells, which indicates increased permeability. Human nasal mucosa samples, which are supposed to be hypoxic, showed significantly decreased levels of ZO-1 and E-cadherin expression compared with control. Conclusion Our results demonstrate that hypoxia altered the expression of junction complex molecules and increased epithelial permeability in human nasal epithelia. This suggests that hypoxia causes barrier dysfunction. Furthermore, it may be associated with innate immune dysfunction after encountering pathogens.

This study that had been conducted two months by a research team of Pusan National University at the request of Korea Manwha Contents Agency in Dec. 2013 is about the statistical analysis on `Korean Webtoon DB and its Flow Report` which resulted from the complete survey of Korean webtoons which had been published with payment in official media from early 2000 to 2013. Webtoon which means the cartoons published on web has become a typical type of Korean cartoons and has developed into a main industry since 2000s when traditional published cartoons had declined and social environments had changed. Today, it represents cultural contents in Korea. This study collected the webtoons officially published in media with payment, among Korean webtoons having been published from the early 2000s to Jan. Based on the collected data, it analyzed the general characteristics of webtoons, including cartoonists, the number of cartoons, distribution chart of each media, genre, and publication cycle. According to the data analysis and statistics, a great deal of Korean webtoons are still published in main portal websites, but their platform is being diversified and a webtoon`s publication cycle tends to be shortened. In terms of genre, traditional popular genres, such as drama, comic, fantasy, and action, are still popular, and the genres of history, sports, and food are on the rise along with a social trend. Regarding webtoon application, such events as relay webtoon and brand webtoon, and a new type of webtoon featuring PPL commercialism appear. Such phenomena can realize the common profits of cartoonists, media, and ordering bodies, and are various trials to test the possibility of webtoons. In addition, what needs to pay attention on in the expansion of webtoons is increasing webtoons for adults. The study subjects are the webtoons published with payment, excluding free webtoons. However, this study failed to collect the webtoons published on the online websites already closed, and the lost information on cartoonists and their lost webtoons, and it is necessary to conduct a complete survey on all webtoons including free ones. Despite the limitations, this study is meaningful in the points that it categorized and analyzed Korean webtoons accoridng to official media, webtoons, cartoonists, and genres and that it provided a fundamental material to understand the current conditions of webtoons. It is expected that this study will be able to contribute to activating more research on webtoons and producing more supplementary data which will be used for the Korean cartoon industry and academia.

Mucin hypersecretion and overproduction are frequent manifestations of respiratory disease. Determining the physiological function of airway mucin is presently considered more important than identifying the relevant signaling pathways. The lack of a full-length human mucin 8 (MUC8) cDNA sequence has hindered the generation of a Muc8 knockout mouse line. Thus, the precise physiological functions of MUC8 are unclear. Herein, we investigated the function of MUC8 using a small-interfering RNA (siRNA)-mediated genetic silencing approach in human airway epithelial cells. Herein, intracellular IL-1α production was stimulated by an ATP/P2Y2 complex. While ATP/P2Y2 increased IL-1α secretion in a time-dependent manner, treatment with P2Y2-specific siRNA significantly decreased IL-1α secretion. Moreover, ATP increased P2Y2-mediated upregulation of MUC8 expression; however, IL-1α significantly decreased the extent to which ATP/P2Y2 upregulated MUC8 expression. Interestingly, treatment with MUC8-specific siRNA decreased the production of anti-inflammatory cytokines (TGF-β and IL-1 receptor antagonist) and increased the production of inflammatory cytokines (IL-1α and IL-6) in our system. In addition, siRNA-mediated knockdown of MUC8 expression dramatically increased the secretion of inflammatory chemokines and resulted in an approximately threefold decrease in cell chemotaxis. We propose that MUC8 may function as an anti-inflammatory mucin that participates in inflammatory response by attracting immune cells/cytokines to the site of inflammation. Our results provide new insight into the physiological function of MUC8 and enhance our understanding of mucin overproduction during airway inflammation.

Stereotactic ablative radiotherapy is a newly emerging radiotherapy treatment method that, compared with conventionally fractionated radiation therapy (CFRT), allows an ablative dose of radiation to be delivered to a confined area around a tumor. The aim of the present study was to investigate the changes of various cytokines that may be involved in ablative radiation-induced lung injury in vitro and in vivo. In the in vivo study, ablative-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal irradiator. The levels of 24 cytokines in the peripheral blood were tested at several time points after irradiation. For the in vitro study, three mouse cell types (type II pneumocytes, alveolar macrophages, and fibroblasts) known to play important roles in radiation-induced pneumonitis and lung fibrosis were analyzed using a co-culture system. In the in vivo study, we found obvious patterns of serum cytokine changes depending on the volume of tissue irradiated (2-mm vs. 3.5-mm collimator). Only the levels of 3 cytokines increased with the 2-mm collimator at the acute phase (1–2 weeks after irradiation), while the majority of cytokines were elevated with the 3.5-mm collimator. In the in vitro co-culture system, after the cells were given an ablative dose of irradiation, the levels of five cytokines (GM-CSF, G-CSF, IL-6, MCP-1, and KC) increased significantly in a dose-dependent manner. The cytokine levels in our radiation-induced lung injury model showed specific changes, both in vivo and in vitro. These results imply that biological studies related to ablative-dose small-volume irradiation should be investigated using the corresponding experimental models rather than on those simulating large-volume CFRT.

In the inner ear, endolymph fluid surrounds the organ of Corti, which is important for auditory function, and even slight environmental changes mediated by trauma or infection can have significant consequences. However, it is unclear how the immune response is modulated in these tissues. Here, we report the local immune-surveillance role of cleaved cochlin LCCL (Limulus factor C, Cochlin, and Lgl1) during pseudomonal infection in the cochlea. Upon infection, the LCCL domain is cleaved from cochlin and secreted into the perilymph space. This cleaved fragment then induced bacterial aggregation in the scala tympani and subsequently recruited resident immune cells to eliminate the bacteria. Importantly, hearing loss in a cochlin knock-out mouse model was remedied by treatment with cochlin LCCL. These findings suggest that cleaved cochlin LCCL is a critical factor in innate immunity and auditory function and could be a potential therapeutic target to treat chronic otitis media-induced hearing loss.

Objective High mobility group box 1 (HMGB1) protein is a chromatin protein that functions as a proinflammatory cytokine when secreted in response to inflammatory stimuli. The purpose of this study was to determine the relationship between the HMGB1 level in nasal secretions and the severity of inflammation in chronic rhinosinusitis. Study Design This was a cross-sectional study. Methods Nasal secretions were obtained by irrigation of the affected sinonasal cavities with normal saline. Total 63 nasal lavage fluid samples were collected from 38 patients with chronic rhinosinusitis who underwent endoscopic sinus surgery. Levels of HMGB1 and tumor necrosis factor alpha, interleukin (IL)−1β, and IL-8 were determined by enzyme-linked immunoassay. Severity of inflammation was assessed by the Lund-Mackay scoring system, which is based on preoperative computed tomography scans. Concurrent medical disorders, presence of nasal polyps, septal deviation, and allergic rhinitis were also investigated. Results The level of HMGB1 in nasal lavage fluid was positively correlated with the Lund-Mackay score. The score was the only factor associated with HMGB1 by univariate and multivariate analysis. Other cytokines, with the exception of IL-8, were not correlated with the Lund-Mackay score. Conclusion Our results showed that HMGB1 is secreted into the extracellular area space in the upper airway, and HMGB1 levels in nasal lavage fluid correlate with severity of inflammation, as assessed by the Lund-Mackay staging system for chronic rhinosinusitis. These results provide evidence for HMGB1 as an inflammatory mediator associated with the severity of chronic rhinosinusitis. Level of Evidence N/A. Laryngoscope, 125:E225–E230, 2015

Inferior turbinate hypertrophy could be a result of allergic rhinitis (AR) that leads to nasal congestion and nasal airway obstruction, which is the most bothersome complaint in patients with AR. However, evidence regarding whether patients with AR have a more hypertrophied inferior turbinate than do patients with non-AR is lacking. We aimed to evaluate the degree of inferior turbinate hypertrophy according to the presence of AR using radiological measurements of the inferior turbinate. For evaluating the inferior turbinate, which contributes to nasal obstruction in patients with AR, we enrolled 90 adult patients with septal deviation and divided them into two groups (AR group: n = 49; non-AR group: n = 41). Allergic rhinitis was diagnosed according to the presence of an allergic history, positive multiple allergen simultaneous test, and serological total immunoglobulin E level (≥ 100 kU/L). We analyzed the minimal cross-sectional area on acoustic rhinometry for both groups. The bilateral total width as well as medial mucosa and nasal cavity space in the anterior and posterior portions of the inferior turbinate were measured using computed tomography. We could not find any significant differences in the anterior and posterior dimensions of the inferior turbinate, intranasal space, and choanal spaces between the AR and non-AR groups. Instead, the anterior part of the inferior turbinate in both the groups showed significant differences between the deviated and contralateral sides. The contralateral side had a larger width than did the deviated side, but no significant difference was noted in the posterior portion of the inferior turbinate. The degree of inferior turbinate hypertrophy showed no difference between patients with and without AR. Therefore, we suggest that surgical treatment for reducing the size of the inferior turbinate hypertrophy should be considered when performing septoplasty in patients with symptoms of nasal obstruction, regardless of the presence of AR.

In this study, the far-red-emitting fluorescence probe 1, containing a rhodamine derivative and a hydrazide reactive group, was developed for peroxynitrite detection and imaging. This probe, which is cell permeable and shows high sensitivity and selectivity in fluorometric detection of peroxynitrite over other ROS/RNS, was successfully utilized to detect exogenous and endogenous peroxynitrite in HeLa and RAW 264.7 cells, respectively. More importantly, 1 can also be used to detect endogenous peroxynitrite generated in Pseudomonas aeruginosa (PAO1)-infected mouse bone marrow-derived neutrophils. We anticipate that the new probe will serve as a powerful molecular imaging tool in investigations of the role(s) played by peroxynitrite in a variety of physiological and pathological contexts.

Purpose To obtain validated clinical values suitable for developing a gustatory function test, including umami taste, in a Korean population. Materials and methods The investigation involved 297 participants with self-reported normal sense of taste and smell. Liquid solutions were used for the assessment of gustatory function. The test consisted of 30 taste solutions [six concentrations of five tastants (sweet, bitter, salty, sour, and umami)]. For evaluation of overall gustatory function, the number of detected or correctly recognized taste thresholds was combined to form a "taste score." Results Mean values of each detection and recognition threshold for the five tastes in men were consistently lower than those of women. The 10th percentile of taste score for recognition was used as the cut-off value for distinguishing normogeusia from hypogeusia. In subgroup analysis, total taste score from recognition thresholds revealed a significant negative correlation with age, indicating lower scores for increasing age. Taste score for non-smokers was significantly higher than that of smokers, in terms of detection and recognition of taste sensitivities. Conclusion This gustatory function test was easy to perform, affordable, and time-saving, with the capacity to self-produce and obtain reliable data. Gustatory function was more sensitive in young people, women, and non-smokers.

Study objectives Investigating the exact pathophysiology of obstructive sleep apnea syndrome (OSAS)-induced hearing loss is critical. We sought to verify the hypothesis that a correlation exists between mitochondrial dysfunction in inner ear hair cells and the auditory dysfunction induced by chronic intermittent hypoxia (CIH) in a murine model of sleep apnea. Methods C57BL/6J adult male mice were randomized to 4 weeks of CIH (n = 12) or normoxia (Sham) (n = 12). Hearing threshold was determined by auditory brainstem response. The activity of mitochondria was compared between CIH and Sham mice. Histological assessment and transmission electron microscopy were performed for assessing morphologic changes in mitochondria. The number of mtDNA copies as well as the levels of PGC1-α, Tfam, and VDAC (voltage-dependent anion channel) were determined in the hair cells of CIH mice. Results We observed that hearing ability in CIH mice was impaired and hair-cell mitochondria in CIH mice were fewer compared to that in Sham and also displayed an aberrant morphology. The mRNA levels of PGC-1α and Tfam were higher in the CIH group than in the Sham group. Moreover, the expression of VDAC was increased in the tectorial membrane, the basilar membrane, and especially in the inner hair cells of CIH mice. Conclusions This study using CIH mice as a model for OSAS provides evidence of an association between OSAS and auditory function alteration, as well as of mitochondria being part of the pathophysiology of hearing impairment. Further investigation is required to determine whether mitochondria could serve as a valid target for preventive or therapeutic purposes.

Study objective No studies have investigated sequential changes in the heart on magnetic resonance imaging (MRI), along with observation of functional lung phenotypes and genetics, over the duration of chronic intermittent hypoxia (CIH). We investigated chronological changes in heart and lung phenotypes after CIH using a mouse model to provide new insights into the pathophysiology of sleep apnea-induced cardiovascular disease. Methods C57BL/6J adult male mice were randomized to 4 or 8 weeks of CIH. Cardiac cine-MRI images were analyzed to assess functional parameters of right ventricle (RV). Histopathological features of myocytes and pulmonary vessels, as well as genes involved in the endothelin (ET) system, were investigated. Results Function of the RV reduced significantly at 4 weeks and continuously decreased following another 4 weeks of CIH, although the rate of decrease was attenuated. Notably, persistence of reduced ejection fraction and end-systole RV wall thickness (WT) and increases in the ET system of the lungs and blood strongly implied the development of pulmonary hypertension after 8 weeks of CIH. Conclusions RV dysfunction with reduced end-systole RV WT could be a late phenotype in long-standing CIH and possibly also in obstructive sleep apnea.

To evaluate the potential efficacy of steroid-soaked, absorbable calcium alginate nasal packing following endoscopic sinus surgery.Prospective, randomized, single-blinded, placebo-controlled trial.Twenty-two patients (44 nostrils) who had chronic rhinosinusitis with polyps underwent bilateral endoscopic sinus surgery. Only those with an intersinus difference in Lund-Mackay severity score of 1 or less were included. In each patient, one randomly selected nostril was packed with calcium alginate soaked with 2 mL of triamcinolone (40 mg/mL) (triamcinolone group), whereas the contralateral nostril received an identical packing soaked in 2 mL of normal saline (saline group). Two independent investigators blinded to the packing allocation scored the surgical field using the validated Perioperative Sinus Endoscopy (POSE) scores 1, 4, and 8 weeks after surgery.All 44 nostrils were analyzed; the Lund-Mackay scores did not differ significantly between the groups before surgery. Eight weeks after surgery, the total POSE scores were significantly lower in the triamcinolone group (P = .014). The POSE scoring parameters were then compared between groups, and the following variables were significantly different: middle turbinate synechiae with the lateral wall (P = .037), polypoid degeneration of the ethmoid cavity (P = .006), and sphenoid sinus severity (P = .036).This study demonstrated that steroid-soaked, absorbable nasal packing can be used to enhance wound healing after endoscopic sinus surgery and to prevent polypoid changes in the nasal mucosa.1b. Laryngoscope, 128:311-316, 2018.

Histamine is an important mediator of allergic reactions, and mucus hypersecretion is a major allergic symptom. However, the direct effect of histamine on mucus secretion from airway mucosal epithelia has not been clearly demonstrated. TMEM16A is a Ca2+-activated chloride channel, and it is closely related to fluid secretion in airway mucosal epithelia. We investigated whether histamine directly induces fluid secretion from epithelial cells or submucosal glands (SMG) and mechanisms related, therewith, in allergic airway diseases. In pig airway tissues from the nose or trachea, histamine was a potent secretagogue that directly induced strong responses. However, gland secretion from human nasal tissue was not induced by histamine, even in allergic rhinitis patients. Histamine type 1 receptor (H1R) and histamine type 2 receptor (H2R) were not noted in SMG by in situ hybridization. Cultured primary human nasal epithelial (NHE) cells were used for the measurement of short-circuit current changes with the Ussing chamber. Histamine-induced slight responses of anion secretions under normal conditions. The response was enhanced by IL-4 stimulation through TMEM16A, which might be related to fluid hypersecretion in allergic rhinitis. Pretreatment with IL-4 augmented the histamine response that was suppressed by a TMEM16A inhibitor. TMEM16A expression was enhanced by 24-h treatment of IL-4 in human nasal epithelial cells. The expression of TMEM16A was significantly elevated in an allergic rhinitis group, compared with a control group. We elucidated histamine-induced fluid secretions in synergy with IL-4 through TMEM16A in the human airway epithelium. In addition, we observed species differences between pigs and humans in terms of gland secretion of histamine.

This study is concerned with a design process for a foldable container structure using a finite element analysis. A foldable container structure consists of frames, panels and hinge systems. The main structure of a foldable container carries all the loads while a hinge system is designed to provide its foldability. In this work, finite element structural analyses for the main foldable container structure are carried out based on the ISO standard regulation, whose results are then taken for the design of a hinge system. The finite element analysis with two types of hinge systems are also performed. It is found out that the main structure of a standard 20ft container could be used for the foldable container with the same capacity if the corner edge in the side assembly is strengthened. It is also concluded that the hinge systems proposed in this work could be successfully used in a foldable 20ft container.

BackgroundPsoriasin is known to be expressed in diverse organs, where it exerts antimicrobial activity. Psoriasin is also involved in the local host defense mechanism against pathogens. We hypothesized that allergy-related T-helper cell type 2 (Th2) cytokines may regulate the expression of psoriasin.MethodsWe treated normal human nasal epithelial (NHNE) cells with IL-4 or IL-13. Using human nasal tissues, we compared the expression level of psoriasin. We performed real-time polymerase chain reaction and Western blot assays using NHNE cells. Immunohistochemical staining and Western blot assays were performed with human nasal tissues. Furthermore, we studied the antimicrobial activity of nasal secretions from normal and allergic rhinitis patients.ResultsIL-13 markedly down-regulated psoriasin expression at the gene and protein levels in NHNE cells, and it also decreased the amount of psoriasin protein that was secreted into the extracellular compartment in NHNE cells. IL-4 had no statistically significant effect. Results from immunohistochemical staining and Western blot assays showed that psoriasin expression was decreased in allergic rhinitis patients compared with control subjects. Nasal secretions of allergic rhinitis patients exhibited decreased antimicrobial activity compared with control subjects.ConclusionWe found that Th2 cytokines regulated psoriasin expression in NHNE cells, and psoriasin expression was decreased in allergic rhinitis patients compared with control subjects. The decreased expression of psoriasin may be related to the reduction in antimicrobial capacity of nasal secretions under allergic conditions, resulting in an increase in susceptibility to viruses or bacterial infections.

A planetary gear train is more compact and endures greater amounts of transmission power compared to other gear systems. Although planetary gear systems operate in small volumes, they are capable of very high efficiency due to the compact combination of their gears in the planetary gear system. They also have outstanding efficiency of only 3% for power transmission, tantamount to the power loss that occurs in each of the shift stages. Given these advantages, planetary gear systems are used in the driving systems of, which are widely used in automobile transmissions, machine tools, semiconductor equipment, and in other areas in industrial fields. Current structural equipment requires higher efficiency and greater torque levels. According to these needs, we have designed a complex planetary gear system which creates higher levels of torque. In this paper, an evaluation of strength designs for the proposed planetary gear system was conducted to ensure the stability of the gear. In addition, a durability analysis based on Miner's rule was performed using RS B 0095 device.

This work is concerned with rolling of a Teflon-Cu-SPCC steel plate, which has been used as a base material for an oilless bearing or dry bearing. Materials for an oilless bearing require special characteristics such as high wear resistance, low friction, fast heat loss, as well as structural strength. Such superior mechanical properties could be obtained by rolling the multilayer plate composed of a mixture of Teflon-Cu powder and a SPCC steel. The main objective of this research is to investigate the deformation characteristics of a Teflon-Cu-SPCC steel plate during rolling process. Especially, focus is given to the thickness changes of the Teflon-Cu powder mixture layer. An Eulerian finite element method coupled with a contact profile correction algorithm is adopted for the simulation of rolling. Validity of the proposed finite element analysis is given. The important parameters chosen in this work are the reduction ratio, roll size, and the Cu content in a Teflon-Cu mixture. Effects of the above important parameters on the deformation behavior and on the final thickness of a Teflon-Cu mixture layer are carefully studied.

A buffer layer for PbZr x Ti 1− x O 3 (PZT) coating on nanocrystalline diamond (NCD) film was investigated to prevent the oxidation damage of NCD layer during ambient air annealing at high-temperature. As for the phase of buffer layer, metal nitride is more effective than pure metal for enhancing adhesion of PZT coating on NCD film. For the metal nitride-based buffer layer, the incorporation of Al and Si increases further the adhesive strength of PZT coating on NCD film. As a microstructural point of view, nanoscale multilayered structure was observed to contribute to the increase of adhesive strength between PZT and NCD. As a consequence, introducing thin (∼70 nm) composite buffer composed of Ti(Al)N/SiN x nanoscale multilayer with bilayer period of ∼5 nm as an intermediate layer between PZT coating and NCD film improved the high-temperature oxidation resistance of the NCD film and relevant adhesive strength of PZT coating even after the 900 °C air-annealing. The improved adhesion was attributed to the suppressed oxygen diffusion to the NCD film through the PZT layer at high temperature by the intervening nanoscale multilayer buffer.

Objective Vitamin D has immune modulatory functions, and thus its relationship with allergic disease has been evaluated in a number of studies. However, no concrete link between serum IgE level and vitamin D has been established. Thus, the purpose of study was to confirm the association of serum vitamin D level with the serum IgE (total and Dematophagoides farinae specific IgE) in Korean adolescents. Methods A total of 365 subjects between 10 and 18 years of age were enrolled through the Korea National Health and Nutrition Examination Survey (KNHANES). Serum levels of vitamin D, total IgE, and Dermatophagoides farinae (Df) specific IgE were measured, and data for potential confounding variables were collected. Multivariate regression analyses were used to determine the independent effects of these variables. Results Levels of both total and Df specific IgE were positively correlated with serum concentration of vitamin D (Spearman's rho ( R ) = 0.126, p = 0.016; R = 0.152, p = 0.004, respectively). These results were confirmed by multivariate linear regression analysis after adjusting for sex, age, and body mass index (coefficient ( B ): 10.45 95% confidence interval (CI): 0.59–20.31; B : 1.06, 95% CI: 0.31–1.80, respectively). And, the association between serum vitamin D and IgE showed the different results depending on the presence or absence of Df sensitization. Conclusions Serum concentration of vitamin D was positively associated with levels of both total IgE and Df-specific IgE in Korean adolescents.

Cartoons exhibit contents and images and deliver them to readers by repeating frames. Frames embody the cross sectional factors of space-time, and the repetition of frames makes those cross sectional factors into a continuous flow. The gutter, which exists between frames, takes the role to make the continuous flow link smoothly, and at the beginning stage of the gutter, the operating of the gutter was usually passive by the frame meanings. However, the gutter is not just a medium for linking the frames, but is an efficient participation device for creating new expression methods of cartoon organization. By producing new directing methods for cartoon organization, the distinctive functions of the gutter have been kept alive with cartoon history. The distinctive functions of the gutter can be divided largely into transition function, reminiscence function, speech balloon function, pen function, and decorative function. And those functions perform actively as direct expression method of the gutter. When those functional methods are expressed by the author`s intention and the frequency of them is generalized according to described contents, using each author`s individual differences can suggest direction for new directing organization of cartoons.

Objectives/Hypothesis The soft palate is composed of several muscles. So far, these muscles have been analyzed separately and the whole structure of the soft palate has been described very vaguely. The purpose of this study was to describe the structure of soft palate collectively. Study Design Human cadaver dissection. Methods Anatomical dissection was performed on 20 Korean, formalin-fixed cadavers (13 men and 7 women). The heads were randomly assigned to either dissection groups, medial-to-lateral (10 heads) or posterior-to-anterior (10 heads). Results Fibro-fatty layer was located in the oral side of the soft palate and became thick and dense along the midline. The levator veli palatini was distributed on the nasal side of the soft palate. The average vertical distance from the top of palatopharyngeal arch to the levator veli palatini was 12.3 ± 5.2 mm. The palatopharyngeus was also spread out widely and filled the palatopharyngeal arch. The periosteum of the hard palate became the fascia of the soft palate, which was merged with the aponeurosis of the tensor veli palatini in the midline. The Passavant's ridge was located between the levator veli palatini and palatopharyngeus, inserting onto the aponeurosis. The palatoglossus was very thin and embedded in the palatoglossal arch. Conclusion The muscles of the soft palate are intermingled with each other in the fibro-fatty layer. Comprehensive anatomical knowledge is needed to reduce unnecessary damage and obtain good surgical results for obstructive sleep apnea. Level of Evidence N/A. Laryngoscope, 123:2900–2904, 2013

The electrical properties of Cu(In,Ga)Se2/Mo junctions were characterized with respect of MoSe2 orientation and Na doping level using an inverse transmission line method, in which the Cu(In,Ga)Se2 (CIGS)/Mo contact resistance could be measured separately from the CIGS film sheet resistance. The MoSe2 orientation was controlled by varying the Mo surface density, with the c-axis parallel and normal orientations favored on Mo surfaces of lower and higher density, respectively. The effect of Na doping was compared by using samples with and without a SiOx film on sodalime glass. The conversion of the MoSe2 orientation from c-axis normal to parallel produced a twofold reduction in CIGS/Mo contact resistance. Measurements of the contact resistances as a function of temperature showed that the difference in CIGS/Mo contact resistance between the samples with different MoSe2 orientations was due to different barrier heights at the back contact. Comparison between Na-doped and Na-reduced samples revealed that the contact resistance for the Na-reduced system was four times of that of the doped sample, which showed more pronounced Schottky-junction behavior at lower temperature, indicating that Na doping effectively reduced the barrier height at the back contact. Copyright © 2013 John Wiley & Sons, Ltd.

In various directions of cartoon, vertical stroll direction is opposite to the page direction of existing published cartoon with the popularity of webtoon and established new genre. Lots of studies on published cartoon focus on the cut direction by page, but webtoon doesn`t have any concept of page. The pivot of cartoon oriented people is changed from paper to computer monitor as times go by, characteristics of media are changed and media is gradually diversified. Like the strengthening of mobile caused by smart phone`s popularity, tablet PC`s propagation in public education, etc. cartoon is included to the environment of media which is rapidly changed. In this situation, one of cartoon`s unchanged important identities can be the direction made by harmony between picture and text. This thesis analyzed symbolic characteristics and effective value of hyogwatae, mimetic words of cartoon, focusing on works of Heo, Young Man. Hyogwatae just delivers not only sound but also shape, feeling, status, etc. and has significant characteristics by invoking the imaginary structure of literature. Strengths of modern Korean, various linguistic expressions and syllabic systems, let people feel minute feeling of language and difference of emotion and remember the memory through the direct and indirect experiences, so it makes it nuance. Because of the characteristics, representative works of Heo, Young Man have commercialization and writer characteristics, have communicated with people for a long time and have plentiful knowledge of Korean cartoon. The characteristics of hyogwatae in Heo, Young Man`s cartoon make a lot of effects for the expression and delivery of cartoon more than the general expectation. When conducting the study focusing on the symbolic process of language, uncertainty and vague standard of judgement caused by the wide factors of study on the direction of general cartoon could be endured. And, through the Heo, Young Man`s deep analysis on hyogwatae`s direction, readers enjoy the process while inferring actually and intellectually between pictures and sentences. In the process, the equipment stimulating imagination more than pictures, effects and dialogues is hyogwatae. It`s reader`s equipment of active participation and its strength is symbolic structure.

We investigated the effects of process parameters on the microstructure and compressive properties of reactive-sintered porous TiAl-based intermetallics. Different extrusion ratios were selected in order to change the as-extruded microstructure and thus obtain various types of porous structures (unidirectional and spherical pores) after reactive sintering. In addition, different environmental conditions, such as vacuum and air, were used during the reactive sintering stage. It was revealed that the compressive strength is influenced by the unidirectionalty of the pores. High unidirectionalty led to higher yield strength at room temparature and at 1073 K. The compressive properties of the porous TiAl intermetallics were also influenced by the environment where reactive sintering is carried out.

Background Allergic rhinitis (AR) and asthma are 2 entities of allergic airway diseases that frequently occur together, which is referred to as united airways . In contrast to this general concept, we hypothesized that innate immunity of the upper and lower airways is respectively distinctive, because the immunologic conditions of the nasal and lung mucosa as well as the functions of the immune cells within their epithelia are different. Objective We wanted to identify distinctive mechanisms of innate immunity in the nose and lung mucosa, which are responsible for house dust mite (HDM)–induced AR and allergic asthma (AA), respectively. Methods We constructed a mouse model of AR or AA induced by sensitization and consequent provocation with HDM extracts. Results HDM-derived β-glucans, rather than LPS, were proven to be essential to activating innate immunity in the nasal mucosa and triggering AR, which depended on Toll-like receptor 2 (TLR2), but not on TLR4; however, the LPS/TLR4 signaling axis, rather than β-glucans/TLR2, was critical to HDM-induced AA. These differences were attributed to the specific role of β-glucans and LPS in inducing the surface expression of TLR2 and TLR4 and their translocation to lipid rafts in nasal and bronchial epithelial cells, respectively. We also showed that dual oxidase 2–generated reactive oxygen species mediate both β-glucan–induced TLR2 activation and LPS-induced TLR4 activation. Conclusions We describe a novel finding of distinctive innate immunity of the nose and lungs, respectively, which trigger AR and AA, by showing the critical role of HDM-induced TLR activation via dual oxidase 2–mediated reactive oxygen species.

The endolymphatic sac (ES) is a cystic structure of the inner ear connected to the cochlea and vestibule, which plays a role in regulating ion homeostasis in inner ear fluid. Disruption of ion homeostasis can cause inner ear disorders with hearing loss and dizziness, such as Meniere’s disease. Herein, we found, for the first time, functional evidence for the involvement of β1- and β2-adrenergic receptors in apical electrogenic ion transport by human ES epithelium by using electrophysiological/pharmacological and molecular biological methods, which were dependent on K+ and Cl− ion transport. The apical electrogenic transport was absent or very weak in ES epithelia of patients with Meniere’s disease. These results suggested that adrenergic stimulation via β1- and β2-adrenergic receptors in the human ES was involved in regulation of inner ear fluid ion homeostasis and impairment of this response could be a pathological mechanism of Meniere’s disease.

Objective The mouse is the most popular animal model in olfactory research. Behavior tests with odorants are essential for determining olfactory phenotype. To the best of our knowledge, the mouse olfactory behavior test has not been standardized, making the results vulnerable to inter-observer variation. We sought to develop a new mouse olfactory behavior test assessed by an automatic video tracking system with minimal inter-observer variation. Methods A video-tracking system was used to automatically track mouse behavior in standard breeding cages with C57BL/6N mice. We tested two odorants (peanut butter for the preference test, 2MB acid for the avoidance test) and distilled water (for a control). Mouse behavior was recorded for 3 min and analyzed. For the preference test, investigation time was measured. For the avoidance test, time spent in sectors away from the odorant zone was measured. To confirm our experimental settings, we also evaluated an anosmia mouse model prepared with intranasal administration of ZnSO4. Results All strains of mice showed reproducible behavior patterns of preference or avoidance for the odorants. The anosmia mouse model, as expected, failed to show an olfactory ability for preference or avoidance, and this was well-matched by histologic changes caused by the ZnSO4 treatment. The automatic video tracking system successfully tracked and automatically calculated mouse behavior with good reproducibility. Conclusion Our olfactory behavior test offers a simple and accurate method to evaluate olfactory function in mice. This test can be utilized as a possible standard method to search for features of olfactory phenotypes in mice.

Here, we studied the IFN-regulated innate immune response against influenza A virus (IAV) infection in the mouse lung and the therapeutic effect of IFN-λ2/3 in acute IAV lung infection. For viral infections, IAV (WS/33, H1N1, PR8 H1N1, H5N1) were inoculated into wild-type mice by intranasal delivery, and IAV mRNA level and viral titer were measured. To compare the antiviral effect of IFNs in vivo in the lung, neutralizing antibodies and recombinant IFNs were used. After intranasal inoculation of IAV into mice, viral infection peaked at 7 days postinfection, and the IAV titer also reached its peak at this time. We found that IFN-β and IFN-λ2/3 were preferentially induced after IAV infection and the IFN-λ2/3-mediated innate immune response was specifically required for the induction of IFN-stimulated genes (ISGs) transcription in the mouse respiratory tract. Neutralization of secreted IFN-λ2/3 aggravated acute IAV lung infection in mice with intact IFN-β induction; consistent with this finding, the transcription of ISGs was significantly reduced. Intranasal administration of IFN-λ2/3 significantly suppressed various strains of IAV infection, including WS/33 (H1N1), PR (H1N1), and H5N1 in the mouse lung, and was accompanied by greater up-regulation of ISGs. Taken together, our data indicate that the IFN-λ2/3-mediated innate immune response is necessary to protect the lungs from IAV infection, and intranasally delivered IFN-λ2/3 has the potential to be a useful therapeutic strategy for treating acute IAV lung infection.

Background Nasal secretions include cytokines and inflammatory mediators that are involved in the pathogenesis of upper airway inflammation. Objective We tried to find unknown biomolecules that are involved in the pathogenesis of chronic rhinosinusitis (CRS). Methods We collected nasal mucosal secretions from patients who were diagnosed as having CRS and who underwent endoscopic sinus surgery. A total of 63 patients who underwent nasal secretion collection were reviewed. Enzyme-linked immunosorbent assay was performed by using nasal lavage samples to evaluate which biomolecules were associated with the severity of inflammation based on the Lund-Mackay score. By using human nasal epithelial cells, we performed Western blot, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay to evaluate the secretory mechanism of heat shock protein (HSP) 70. Results We found that the level of interleukin 8 and HSP70 were significantly associated with the Lund-Mackay score and interleukin 17C, C-X-C motif chemokine 10, and HSP27 were not significantly associated. HSP70 was also significantly associated with the surgical outcome of the enrolled patients. Furthermore, we found that exposure to hypoxia and treatment of lipoteichoic acid induced the secretion of HSP70 but that lipopolysaccharide did not induce the secretion of HSP70 in human nasal epithelial cells. Conclusion Our findings indicated that HSP70 might play a role in the pathogenesis of CRS and the possibility of HSP70 as a biomolecule that represents the severity of CRS.