Generation of Fel d 1 chain 2 genome-edited cats by CRISPR-Cas9 system.

Allergens from domestic cats (Felis catus) cause allergy-related health problems worldwide. Fel d 1 is a major allergen that causes severe allergic reactions in humans, including rhinitis, conjunctivitis, and life-threatening asthma. Therefore, patients with cat allergies anticipate hypoallergenic cats. We successfully generated Fel d 1 chain 2 (CH2) genome-edited cats using the CRISPR-Cas9 system in this study. T7 endonuclease 1 assay and Sanger sequencing were used to confirm the mutation in CH2 genome-edited cats. Fel d 1 level in CH2 genome-edited cats were assessed by enzyme-linked immunosorbent assay (ELISA). Remarkably, ELISA showed that the level of Fel d 1 in the CH2 homozygous genome-edited cat (Name: Alsik) was extremely low compared with that in wild type domestic cats and could be hypoallergenic cats. Additionally, we successfully cloned the CH2 homozygous genome-edited cat using cytoplasm injection clone technology. The cloned CH2 homozygous genome-edited cat was verified using microsatellite analysis. Creating hypoallergenic cats using the CRISPR-Cas9 system is a significant step forward because these cats can safely approach allergic patients.

Direct numerical simulations of long-range infrasound propagation: Implications for source spectra estimation.

The evolution of observed dominant frequencies from a high-intensity infrasonic pulse with receiver range and stratospheric temperature is investigated using direct numerical simulations of the two-dimensional unsteady compressible Navier-Stokes equations. There is a high level of uncertainty in estimating source dominant frequencies based on received signals at sparse points on the ground. Nonlinear propagation effects in the ground-level thermospheric arrivals are found to significantly alter dominant frequency measurements compared to stratospheric arrivals with smaller amplitude sources. With a larger amplitude source, variations in observations are minimized as a result of nonlinear effects being ubiquitous across all atmospheric components of received signals but have a greater offset to the source dominant frequency. An approach to determine the source dominant frequency and minimize atmospheric variability is presented by calculating a source-to-receiver spectral transfer function averaged across the atmospheric states. This method reduces atmospheric variability in source frequency estimates within the pseudo-linear propagation regime and the average error to the known source frequency with a large amplitude source. The reduction of errors in source frequency estimates demonstrates the feasibility of using remote infrasound measurements as an indicator of source frequency and, in turn, the explosive yield of clandestine nuclear weapon test explosions.

Design of mid-infrared filter array based on plasmonic metal nanodiscs array and its application to on-chip spectrometer.

Mid-infrared wavelengths are called the molecular fingerprint region because it contains the fundamental vibrational modes inherent to the substances of interest. Since the mid-infrared spectrum can provide non-destructive identification and quantitative analysis of unknown substances, miniaturized mid-infrared spectrometers for on-site diagnosis have attained great concern. Filter-array based on-chip spectrometer has been regarded as a promising alternative. In this study, we explore a way of applying a pillar-type plasmonic nanodiscs array, which is advantageous not only for excellent tunability of resonance wavelength but also for 2-dimensional integration through a single layer process, to the multispectral filter array for the on-chip spectrometer. We theoretically and experimentally investigated the optical properties of multi-periodic triangular lattices of metal nanodiscs array that act as stopband filters in the mid-infrared region. Soft-mold reverse nanoimprint lithography with a subsequent lift-off process was employed to fabricate the multispectral filter array and its filter function was successfully extracted using a Fourier transform infrared microscope. With the measured filter function, we tested the feasibility of target spectrum reconstruction using a Tikhonov regularization method for an ill-posed linear problem and evaluated its applicability to the infrared spectroscopic sensor that monitors an oil condition. These results not only verify that the multispectral filter array composed of stopband filters based on the metal nanodiscs array when combined with the spectrum reconstruction technique, has great potential for use to a miniaturized mid-infrared on-chip spectrometer, but also provide effective guidance for the filter design.

Polar and phase domain walls with conducting interfacial states in a Weyl semimetal MoTe2.

Much of the dramatic growth in research on topological materials has focused on topologically protected surface states. While the domain walls of topological materials such as Weyl semimetals with broken inversion or time-reversal symmetry can provide a hunting ground for exploring topological interfacial states, such investigations have received little attention to date. Here, utilizing in-situ cryogenic transmission electron microscopy combined with first-principles calculations, we discover intriguing domain-wall structures in MoTe2, both between polar variants of the low-temperature(T) Weyl phase, and between this and the high-T higher-order topological phase. We demonstrate how polar domain walls can be manipulated with electron beams and show that phase domain walls tend to form superlattice-like structures along the c axis. Scanning tunneling microscopy indicates a possible signature of a conducting hinge state at phase domain walls. Our results open avenues for investigating topological interfacial states and unveiling multifunctional aspects of domain walls in topological materials.

Record High-Proximity-Induced Anomalous Hall Effect in (BixSb1-x)2Te3 Thin Film Grown on CrGeTe3 Substrate.

Quantum anomalous Hall effect (QAHE) can only be realized at extremely low temperatures in magnetically doped topological insulators (TIs) due to limitations inherent with the doping process. In an effort to boost the quantization temperature of QAHE, the magnetic proximity effect in magnetic insulator/TI heterostructures has been extensively investigated. However, the observed anomalous Hall resistance has never been more than several ohms, presumably owing to the interfacial disorders caused by the structural and chemical mismatch. Here, we show that, by growing (BixSb1-x)2Te3 (BST) thin films on structurally and chemically well-matched, ferromagnetic-insulating CrGeTe3 (CGT) substrates, the proximity-induced anomalous Hall resistance can be enhanced by more than an order of magnitude. This sheds light on the importance of structural and chemical matches for magnetic insulator/TI proximity systems.

The efficacy of cotton ball packing after endoscopic sinus surgery: A prospective, randomized, controlled trial.

OBJECTIVE: The blocking of airflow into sinonasal cavity may decrease postoperative crusting and the development of adhesions. The purpose of this study was to investigate the efficacy of cotton ball packing in patients following endoscopic sinus surgery (ESS). METHODS: Thirty nine patients with chronic rhinosinusitis requiring the same extent of ESS were included. As a part of postoperative care, the patients were instructed to perform a nasal saline irrigation and apply a nasal spray in each nostril, and then informed to put a cotton ball in a one side of nostril, and the other side was kept to be empty as a control. Patients' subjective symptoms, patients' pain while receiving sinonasal cavity debridement, time required to perform debridement, and postoperative wound healing were evaluated. RESULTS: Although cotton ball packing resulted in less discomfort for postnasal drip, rhinorrhea, headache, and facial pain than no packing, there were no statistically significant differences between the groups. The cotton ball packing was associated with significantly less pain on while performing postoperative debridement, therefore less time was needed to perform debridement. The cotton ball packing appears to improve wound healing within the sinus cavities up to 1 month postoperatively. CONCLUSION: The use of the cotton ball packing after ESS results in significantly less formation of crusts and adhesions, leading to decreasing pain and time during postoperative debridement and promoting faster wound healing.

Fibroblast growth factor receptor 3-mediated reactivation of ERK signaling promotes head and neck squamous cancer cell insensitivity to MEK inhibition.

Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has been a longstanding challenge for head and neck oncologists, and current treatments still have limited efficacy. ERK is aberrantly overexpressed and activated in HNSCC. Herein, we aimed to investigate the cause of the limited therapeutic effect of selumetinib, a selective inhibitor of MEK in HNSCC, as MEK/ERK reactivation inevitably occurs. We assessed the effects of combining selumetinib with fibroblast growth factor receptor 3 (FGFR3) inhibitor (PD173074) on tumor growth. Selumetinib transiently inhibited MAPK signaling and reactivated ERK signaling in HNSCC cells. Rebound in the ERK and Akt pathways in HNSCC cells was accompanied by increased FGFR3 signaling after selumetinib treatment. Feedback activation of FGFR3 was a result of autocrine secretion of the FGF2 ligand. The FGFR3 inhibitor PD173074 prevented MAPK rebound and sensitized the response of HNSCC cells to selumetinib. These results provided rational therapeutic strategies for clinical studies of this subtype of patients that show a poor prognosis with selumetinib. Our data provide a rationale for combining a MEK inhibitor with inhibitors of feedback activation of FGFR3 signaling in HNSCC cells. ERK rebound as a result of the upregulation of FGFR3 and the ligand FGF2 diminished the antitumor effects of selumetinib, which was overcome by combination treatment with the FGFR3 inhibitor.

The Effect of Postoperative Use of Teriparatide Reducing Screw Loosening in Osteoporotic Patients.

OBJECTIVE: The loosening of pedicle screws (PS) is one of the frequent problems of spinal surgery in the patients with osteoporosis. Previous studies had revealed that intermittent injection of teriparatide could reduce PS loosening by improving bone mass and quality when their patients took parathyroid hormone for a considerable duration before surgery. However, although the teriparatide is usually used after spine surgery in most clinical situations, there was no report on the efficacy of teriparatide treatment started after spine surgery. The purpose of this retrospective study was to examine the efficacy of teriparatide treatment started immediately after lumbar spinal surgery to prevent pedicle screw loosening in patients with osteoporosis. METHODS: We included 84 patients with osteoporosis and degenerative lumbar disease who underwent transforaminal interbody fusion and PS fixation and received parathyroid hormone or bisphosphonate (BP) postoperatively. They were divided into teriparatide group (daily injection of 20 µg of teriparatide for 6 months, 33 patients, 172 screws) and BP group (weekly oral administration of 35 mg of risedronate, 51 patients, 262 screws). Both groups received calcium (500 mg/day) and cholecalciferol (1000 IU/day) together. The screw loosening was evaluated with simple radiographic exams at 6 and 12 months after the surgery. We counted the number of patients with PS loosening and the number of loosened PS, and compared them between the two groups. Clinical outcomes were evaluated using visual analog scale (VAS) and Oswestry disability index (ODI) preoperatively, and at 12 months after surgery. RESULTS: There was no significant difference in the age, sex, diabetes, smoking, bone mineral density, body mass index, and the number of fusion levels between the two groups. The number of PS loosening within 6 months after surgery did not show a significant difference between the teriparatide group (6.9%, 12/172) and the BP group (6.8%, 18/272). However, during 6-12 months after surgery, it was significantly lower in the teriparatide group (2.3%, 4/172) than the BP group (9.2%, 24/272) (p<0.05). There was no significant difference in the number of patients showing PS loosening between the teriparatide and BP groups. The teriparatide group showed a significantly higher degree of improvement of the bone mineral density (T-score) than that of BP group (p<0.05). There was no significant difference in the pre- and post-operative VAS and ODI between the groups. CONCLUSION: Our data suggest that the teriparatide treatment starting immediately after lumbar spinal fusion surgery could reduce PS loosening compared to BP.

High-Temperature Terahertz Optical Diode Effect without Magnetic Order in Polar FeZnMo_{3}O_{8}.

We present a terahertz spectroscopic study of polar ferrimagnet FeZnMo_{3}O_{8}. Our main finding is a giant high-temperature optical diode effect, or nonreciprocal directional dichroism, where the transmitted light intensity in one direction is over 100 times lower than intensity transmitted in the opposite direction. The effect takes place in the paramagnetic phase with no long-range magnetic order in the crystal, which contrasts sharply with all existing reports of the terahertz optical diode effect in other magnetoelectric materials, where the long-range magnetic ordering is a necessary prerequisite. In FeZnMo_{3}O_{8}, the effect occurs resonantly with a strong magnetic dipole active transition centered at 1.27 THz and assigned as electron spin resonance between the eigenstates of the single-ion anisotropy Hamiltonian. We propose that the optical diode effect in paramagnetic FeZnMo_{3}O_{8} is driven by single-ion terms in magnetoelectric free energy.

Does drug-induced sleep endoscopy predict surgical success of limited palatal muscle resection in patients with obstructive sleep apnea?

OBJECTIVE: The aims of this study were to determine the associated factors affecting the success rate of limited palatal muscle resection (LPMR), and to investigate whether drug-induced sleep endoscopy (DISE) could predict the therapeutic response to LPMR in patients with obstructive sleep apnea obstructive sleep apnea (OSA). METHODS: Twenty-one consecutive OSA patients underwent LPMR were enrolled. All patients received routine ENT examination, preoperative DISE, and polysomnography (PSG). Clinical, polysomnographic, cephalometric variables, and DISE findings were evaluated. The measurements were related to the success or failure of LPMR based on the results of preoperative and postoperative PSG. RESULTS: The overall success rate of LPMR was 66.6%. Postoperative AHI and minimal oxygen saturation were significantly decreased after LPMR (p<0.001). Comparison between success and failure groups revealed no significant differences in BMI, Friedman stage, preoperative AHI, minimal oxygen saturation, and all cephalometric parameters. However, the success of LPMR was significantly correlated with site, degree, and configuration of obstruction in DISE. In the velopharynx, complete obstruction (p=0.006) with anterolateral or concentric pattern (p=0.044) had significantly better success rate than partial obstruction with lateral pattern. CONCLUSION: DISE was only predictive method for identifying the success in OSA patients undergoing LPMR. Patients with anteroposterior or concentric total obstruction in the velopharynx might be suitable candidate for LPMR.

A clinical prediction score to determine surgical drainage of deep neck infection: A retrospective case-control study.

BACKGROUND: The objective of this retrospective study was to identify predictors of an abscess guaranteed to be surgically drained successfully in patients with deep neck infection (DNI). MATERIALS AND METHODS: We divided 97 consecutive patients with DNI into a drained group and a non-drained group. We then developed a clinical prediction score and validated it in 32 further patients. RESULTS: Significant predictors of successful surgical drainage (i.e., positive for pus) were rim enhancement on computed tomography, C-reactive protein, erythrocyte sedimentation rate, and the neutrophil to lymphocyte ratio. The estimated cut-off values (excluding rim enhancement, which is a yes/no parameter) were 41.25, 56.5, and 8.02, respectively, and the clinical prediction score for each of the four other factors was determined to be 2, 2, 3, and 3 points, respectively. The cut-off score for the sum of these points was 6.5 and the scoring system had an accuracy of 87.5% in the validation group. CONCLUSION: Our clinical prediction scoring system can predict whether drainage is successful in patients with DNI.

Korean survey data reveals an association of chronic laryngitis with tinnitus in men.

The association between chronic laryngitis and tinnitus is not a well-studied topic, unlike the association of these two conditions with many other disorders. Cross-sectional data of 11,347 adults (males: 4,934; females: 6,413), who completed the Korea National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2012 were used to investigate this association. Lifestyle patterns, including smoking and alcohol habits, regular exercise, physical and mental health status, socioeconomic status, nutritional status, and other chronic diseases, were analyzed. Chronic laryngitis and tinnitus were diagnosed by field survey teams, which included otolaryngologists, who conducted chronic disease surveillance using a health status interview, a nutritional status questionnaire, and a physical examination. Chronic laryngitis was significantly associated with age, education beyond high school, depressed mood, voice change, metabolic syndrome, and tinnitus in men. In women, chronic laryngitis was associated with body mass index and diabetes mellitus. Chronic laryngitis in men was significantly associated with tinnitus (odds ratio 1.671, [95% confidence interval: 1.167-2.393]) after adjusting for age, body mass index, smoking status, alcohol intake, regular exercise, metabolic syndrome, education beyond high school, and depressed mood. Additionally, the prevalence of chronic laryngitis increased with increasing severity of tinnitus in men alone (P = 0.002). The study revealed a significant association between chronic laryngitis and tinnitus.

An Unruptured Anterior Communicating Artery Aneurysm Presenting with Left Homonymous Hemianopsia: A Case Report.

Unruptured cerebral aneurysms sometimes present with visual symptomsdue to compression of the visual pathways. However, until now, unruptured anterior communicating artery (ACoA) aneurysms presenting visual field defects have been extremely rare. The authors report the case of a 51-year-old woman who presented with left homonymous hemianopsia. Radiological findings demonstrated an ACoA aneurysm filled with thrombus, that was compressing the optic chiasm and post-chiasmal tract. The patient underwent clipping of the aneurysm, which resolved the visual field defect. In cases of visual field defects, an ACoA aneurysm should be included in the differential diagnosis.

Guidelines for the Antibiotic Use in Adults with Acute Upper Respiratory Tract Infections.

These guidelines were developed as part of the 2016 Policy Research Servicing Project by the Korea Centers for Disease Control and Prevention. A multidisciplinary approach was taken to formulate this guideline to provide practical information about the diagnosis and treatment of adults with acute upper respiratory tract infection, with the ultimate aim to promote the appropriate use of antibiotics. The formulation of this guideline was based on a systematic literature review and analysis of the latest research findings to facilitate evidence-based practice, and focused on key questions to help clinicians obtain solutions to clinical questions that may arise during the care of a patient. These guidelines mainly cover the subjects on the assessment of antibiotic indications and appropriate selection of antibiotics for adult patients with acute pharyngotonsillitis or acute sinusitis.

Epidemiological association of olfactory dysfunction with hearing loss and dysphonia in the Korean population: A cross-sectional study.

The aim of the study is to investigate the association between olfactory dysfunction (OD), hearing loss, and dysphonia.The cross-sectional data for 17,984 adults who completed the Korea National Health and Nutrition Examination Surveys (2010-12) were analyzed. OD, hearing loss, and dysphonia were assessed using self-reporting questionnaires. The association of OD with hearing loss and dysphonia was evaluated.Hearing loss and dysphonia were significantly more prevalent in patients with OD than in those without OD (hearing loss, 28.1% vs 11.3%; dysphonia, 11.1% vs 5.9%; both P < .0001). After adjusting for confounders, including mental stress and metabolic syndrome, the risk of OD was significantly associated with hearing loss and dysphonia, and was greater in those with combined hearing loss and dysphonia than in both patients without these dysfunctions and in those with a single dysfunction (odds ratio 3.115, 95% confidence interval 1.973-4.917).OD was significantly associated with hearing loss and dysphonia.

The Efficacy of Fibroblast Growth Factor for the Treatment of Chronic Vocal Fold Scarring: From Animal Model to Clinical Application.

OBJECTIVES: This study assessed the regenerative efficacy of basic fibroblast growth factor (FGF) in a rabbit model of chronic vocal fold scarring and then confirmed its utility and safety in a prospective trial of patients with this condition. METHODS: FGF was injected three times, at 1-week intervals, into a chronic vocal fold scar created in a rabbit model. After 1 month, mRNA level of procollagen I, hyaluronic acid synthetase 2 (HAS 2), and matrix metalloproteinase 2 (MMP 2) were analyzed by real-time polymerase chain reaction. The relative densities of hyaluronic acid (HA) and collagen were examined 3 months post-injection. From April 2012 to September 2014, a prospective clinical trial was conducted at a tertiary hospital in Korea. FGF was injected into the mild vocal fold scar of 17 consecutive patients with a small glottic gap. The patients underwent perceptual, stroboscopic, acoustic aerodynamic test, and Voice Handicap Index (VHI) survey prior to and 3, 6, and 12 months after FGF injection. RESULTS: FGF injection of the vocal fold scar decreased the density of collagen and increased mRNA level of HAS 2 and MMP 2 expression significantly compared to the control group injected with phosphate buffered solution in a rabbit model (P<0.05). In the clinical trial, significant improvements in the majority of the subjective and objective voice parameters were registered 3 months after FGF injection and were maintained at 12 months. Complications associated with the FGF injections, such as granuloma, were not observed during the follow-up period. CONCLUSION: Based on the animal model and the prospective clinical trial, vocal fold injections of FGF in patients with mild chronic vocal fold scarring can significantly improve voice quality for as long as 1 year and without side effects. Our results recommend the use of FGF vocal fold injection as an alternative treatment modality for mild chronic vocal fold scarring.

Acquired resistance to BRAF inhibition induces epithelial-to-mesenchymal transition in BRAF (V600E) mutant thyroid cancer by c-Met-mediated AKT activation.

Previously, the authors have identified that c-Met mediates reactivation of the PI3K/AKT pathway following BRAF inhibitor treatment in BRAF (V600E) mutant anaplastic thyroid cancer, thereby contributing to the acquired drug resistance. Therefore dual inhibition of BRAF and c-Met led to sustained treatment response, thereby maximizing the specific anti-tumor effect of targeted therapy. The present study goes one step further and aims to investigate the effect of acquired resistance of BRAF inhibitor on epithelial-to-mesenchymal transition (EMT) in BRAF mutant thyroid cancer cells and the effect of dual inhibition from combinatorial therapy. Two thyroid cancer cell lines, 8505C and BCPAP were selected and treated with BRAF inhibitor, PLX4032 and its effect on EMT were examined and compared. Further investigation was carried out in orthotopic xenograft mouse models. Unlike BCPAP cells, the BRAF inhibitor resistant 8505C cells showed increased expressions of EMT related markers such as vimentin, ß-catenin, and CD44. The combinatorial treatment of PLX4032 and PHA665752, a c-Met inhibitor reversed EMT. Similar results were confirmed in vivo. c-Met-mediated reactivation of the PI3K/AKT pathway contributes to the drug resistance to PLX4032 in BRAF (V600E) mutant anaplastic thyroid cancer cells and further promotes tumor cell migration and invasion by upregulated EMT mechanism. Dual inhibition of BRAF and c-Met leads to reversal of EMT, suggesting a maximal therapeutic response.

Septochoanal Polyp with Metaplastic Ossification Mimicking Sinonasal Tumor: A Case Report.

Choanal polyps are a form of nasal polyps that grow toward the choana with a single stalk. Septochoanal polyp is a rare entity that originates from the mucosa of the nasal septum with choanal extension. The most common site of its origin is mainly the superior aspect of the posterior portion of the nasal septum. However, metaplastic ossification is a rare event in nasal polyp and to the best of our knowledge, septochoanal polyp with metaplastic ossification has not been reported in the literature. Herein, we report a case of huge septochoanal polyp with metaplastic ossification obstructing both the nasal cavity and nasopharynx, which was successfully removed via transnasal endoscopic approach.

Anti-Proliferative and Apoptotic Activities of Müllerian Inhibiting Substance Combined with Calcitriol in Ovarian Cancer Cell Lines.

PURPOSE: This study aimed to investigate whether Müllerian inhibiting substance (MIS) in combination with calcitriol modulates proliferation and apoptosis of human ovarian cancer (OCa) cell lines (SKOV3, OVCAR3, and OVCA433) and identify the signaling pathway by which MIS mediates apoptosis. MATERIALS AND METHODS: OCa cell lines were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay. Western blot and enzyme-linked immunosorbent assay were used to determine the signaling pathway. RESULTS: The cells showed specific staining for the MIS type II receptor. Treatment of OCa cells with MIS and calcitriol led to dose- and time-dependent inhibition of cell growth and survival. The combination treatment significantly suppressed cell growth, down-regulated the expression of B-cell lymphoma 2 (Bcl-2), and up-regulated the expressions of Bcl-2 associated X protein, caspase-3, and caspase-9 through the extracellular signal-regulated kinase signaling pathway. CONCLUSION: These results, coupled with a much-needed decrease in the toxic side effects of currently employed therapeutic agents, provide a strong rationale for testing the therapeutic potential of MIS, alone or in combination with calcitriol, in the treatment of OCa.