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Purpose: Endotype-driven treatment has been introduced in the management of chronic rhinosinusitis with nasal polyps (CRSwNP), and an understanding of the associations between phenotypes and endotypes of CRSwNP will be beneficial in identifying responders. We aimed to determine the correlations between clinical manifestations and type 2 inflammatory mediators of sinonasal tissues. Methods: Adult patients undergoing endoscopic sinus surgery for bilateral CRSwNP were prospectively enrolled. Tissue eosinophilia and type 2 mediator expression in tissue homogenates were assessed and correlated with clinical features, including symptoms, comorbidities, blood eosinophil counts, specific allergen immunoglobulin (IgE) testing, computed tomography (CT) scan findings, and Sino-Nasal Outcome Test-22 scores. Results: A total of 93 subjects were recruited in our study. Fifty-nine (63.4%) cases were identified as the eosinophilic endotype, demonstrating with higher rates of comorbidity of asthma, blood eosinophilia and a high ethmoid-maxillary ratio on CT images. To correlate of phenotypes with the inflammatory mediator profile, multivariate analyses revealed the associations of IgE expression in nasal polyp tissues with allergen sensitization (p = 0.042), CT ethmoid-maxillary ratio (p = 0.001) and tissue eosinophil counts (p = 0.022); the association of interleukin (IL-5) expression with the blood eosinophil percentage (p = 0.020); and the association of IL-13 expression with white blood cell count (p = 0.002) and central compartment-type inflammation (p < 0.001). Conclusion: We demonstrated associations of IgE and IL-5 expression with clinical features of eosinophilic-type inflammation and a significantly elevated level of IL-13 in patients with central-compartment-type CRSwNP. These observations may be useful when considering the use of type 2 biologic treatment and require further validation studies. [ABSTRACT FROM AUTHOR]

Objectives: Endoscopic endonasal transsphenoidal adenomectomy (TSA) is the most frequently performed skull base surgery, and researchers have recently focused on preserving nasal function. The endoscopic transseptal approach is a promising procedure due to its reduced injury to the nasal mucosa; however, there are no studies comparing rhinological and neurosurgical outcomes concurrently with the standard endoscopic transnasal approach. Therefore, we conducted this study to investigate whether the transseptal approach could reduce nasal morbidities with comparable neurosurgical outcomes. Methods: We retrospectively reviewed 25 patients who underwent endoscopic endonasal transseptal TSA for pituitary adenoma without encasement of internal carotid artery from January 2019 to December 2020. Another 25 patients who received transnasal approach from January 2017 to December 2018 were selected as controls. Patients with diseases affecting the nasal cavity/olfaction or usage of a nasoseptal flap were excluded for a better comparison of the two procedures. We collected data from radiological studies, endocrine studies, endoscopic evaluations, 22‐item sinonasal outcome tests (SNOT‐22) and Top International Biotech Smell Identification Test (TIBSIT) for comparison. Results: Lower postoperative SNOT‐22 and Lund‐Kennedy endoscopic scores were observed in the transseptal group. The effect size of differences were classified as large effect (The absolute value of Cohen's d > 0.8). Nevertheless, the TIBSIT scores were not significantly different. The rates of gross total resection, recovery of hormonal abnormalities, and complications were not significantly different. After controlling possible confounding factors using multivariate analysis, the endoscopic transseptal approach remained an independent factor for lower SNOT‐22 scores and Lund‐Kennedy endoscopic scores. Conclusions: The endoscopic transseptal approach provides improved recovery of nasal mucosa and intact olfaction without compromising neurosurgical outcomes. Level of Evidence: 2b. [ABSTRACT FROM AUTHOR]

The purpose of this study is to maintain the proliferation capability of human parotid gland acinar cells (ACs) in vitro to extend passage number and to study the mechanism that regulates AC stemness. N‐acetylglucosaminyltransferase V (GnT‐V) is the Golgi enzyme, and it has been reported that the β1,6GlcNAc‐branched N‐linked glycans are associated with various cell behaviors. Therefore, we modify the gene expression of ACs by transfection of the GnT‐V‐overexpression plasmid, and we found that upregulation of GnT‐V extensively increased ACs proliferation and stemness properties in ACs/GnT‐V compared to ACs transfected with Mock plasmid. More importantly, we observed that high levels of GnT‐V positively correlated with ALDH1A3 expression via increasing phosphorylation of cell surface receptors and activating the downstream signaling transduction. Hence, the current study suggested that GnT‐V is a significant factor for cell immortalization in the ACs model by activating the EGFR/ERK/ALDH1A3 signaling pathway. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

Background: To elucidate the interaction between hypoxia-induced autophagy and glycolysis in nasal polyp fibroblasts, and the regulatory role of Sirtuin 6 (SIRT6) in the pathogenesis of nasal polyp. Objective: Through examining the expressions of lactate dehydrogenase (LDH), microtubule-associated protein II light chain 3 (LC3II) (an autophagy marker), and production of lactate under hypoxia, the interaction between autophagy and glycolysis was investigated. The role of SIRT6 on the hypoxia-induced autophagy and glycolysis was also examined. Methods: Nasal polyp specimens were used to examine the expressions of hypoxia-inducible factor (HIF) 1α, LDH, and LC3II by Western blot analysis, and primary cultures of nasal polyp fibroblasts were established from resected nasal polyps to measure hypoxia-induced LDH and LC3II expression by Western blot analysis and lactate production by colorimetry. Forced expression of SIRT6 with a lentiviral-based technique was used to evaluate its suppressive effect on autophagy and glycolysis. Immunohistochemical staining was performed to detect the expressions of SIRT6, LDH, and beclin (another autophagy marker) in nasal polyps. Results: Expression of HIF-1α, LDH, and an autophagy marker, LC3II, are increased in nasal polyp specimens, and forced expression of SIRT6 in nasal polyp fibroblasts inhibited LDH expression, lactate production under hypoxia, and SIRT6. An immunohistochemistry study of nasal polyp showed that SIRT6 expression was reduced and LDH and beclin were enhanced. Conclusion: Analysis of these data indicated that hypoxia may contribute to the formation of nasal polyp by promoting autophagy in nasal polyp fibroblasts. Through the antiglycolytic activity of SIRT6, the autophagy was suppressed, which was beneficial to nasal polyp formation. Modulation of glucose metabolism through SIRT6-based strategy may possess therapeutic potential for nasal polyposis in the future. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study is to investigate the role of Caveolin-1 (Cav-1) in nasopharyngeal carcinoma (NPC) progression and correlated with clinical outcomes. Methods We used quantitative real-time PCR (qPCR) to detect the difference in the expression of mRNA level of Cav-1 mRNA in NPC, non-NPC cell lines, and 74 NPC and 29 nontumorous nasopharyngeal mucosa biopsies. Western blotting and immunohistochemistry staining were used to detect the protein expression of Cav-1 in cell lines and biopsy tissues. We collected clinical follow-up data to investigate the association with expression of Cav-1 mRNA. Also, transfection of Cav-1 and suppression by delivery of shRNA against Cav-1 into NPC derived cell lines to analyze its influence in Akt signaling. Results By use of qPCR, immunohistochemical staining, and western blotting, we found that not only is Cav-1 overexpressed in human NPC tumor cells and NPC-derived cell lines but high Cav-1 mRNA expression is associated with poor overall survival time of NPC patients. Furthermore, phosphorylated Akt expression was enhanced by Cav-1 transfection and suppressed by delivery of shRNA against Cav-1. These data suggested a possible regulatory mechanism of Cav-1 on Akt signaling pathway. We also transfected the Cav-1 construct and shRNA in TW01 cells to prove the effect on Akt protein expression. Conclusions Overexpression of Cav-1 is related to poor prognosis in NPC patients, which correlated with Akt signaling pathway. Abrogation of Akt signaling by shRNA-mediated knockdown of Cav-1 decreased malignant properties of tumor cells. These data suggest the potential for Cav-1 as a possible novel therapeutic target in NPC treatment. Level of Evidence N/A. Laryngoscope, 125:E231-E238, 2015 [ABSTRACT FROM AUTHOR]

In vivo higher-harmonic generation microscopy (HGM) performed on healthy human oral mucosa not only provides images with a <500 nm lateral resolution at a 280 μm penetration depth, but also leaves no photodamages in the tissues. These advantages suggest that HGM could serve as an ideal virtual biopsy tool for in vivo, in situ, and immediate histopathological diagnosis of oral cancer. However, translation of such mechanism for clinical cancer diagnosis requires evidence based algorithm capable to differentiate cancerous tissues from normal. It is thus critical to investigate if the endogenous contrast provided by the HGM would be high enough to differentiate cancerous versus normal tissues in human oral mucosa. In this report, ex vivo HGM study was performed on the cancerous mucosa from 10 patients with oral squamous cell carcinoma. Compared with histology, HGM revealed histopathological features including the cytological abnormalities, loss of differentiation, interruption of basement membrane, and irregular epithelial stratification in all 10 specimens. In addition, distinct patterns of collagen fibers and increased distribution area of actin filaments in tumor cells were noted. These results indicate HGM holds great potential for the optical biopsy screening of oral cancer lesions. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Sub-sensory electrical or mechanical stimulation can enhance the sensitivity of the human somatosensory system to improve the balance control capabilities of elderly. In addition, clinical studies suggest that visual-auditory biofeedback can improve sensory compensation for the elderly. This study hypothesizes that the static balance and gait performance of single leg quiet standing and treadmill walking could be improved for providing proprioceptive neuromuscular facilitation using sub-sensory stimulation and visual-auditory biofeedback in amputee subjects. To test this, a computerized foot pressure biofeedback sensory compensation system using sub-threshold low-level electrical stimulation combined with visual-auditory biofeedback was developed. Seven unilateral trans-tibial amputees who wore prostheses over 2 years were recruited. The subjects performed multiple single leg quiet standing trials with sub-sensory electrical stimulation applied at the quadriceps muscle during half of the trials. Static balance performance was characterized by using a Zebris motion analysis system to measure the sway distance and duration of the centre of mass on the second sacral (S2) of the subjects. In addition, multiple treadmill ambulatory trials with or without visual-auditory biofeedback was performed. Dynamic gait performance was characterized with a Zebris instrumented insole to measure the temporal responses of foot pressure sensors. Experimental results showed an improvement in three balance performance indices (Holding Time Index, HTI, Maximum Sway Distance Index, MSDI, and Average Sway Distance Index, ASDI) during single leg quiet standing by applying sub-sensory stimulation. The improvement ratio of these balance performance indices across subjects for single leg quiet standing tests resulted in 132.34% in HTI, 44.61% in MSDI, and 61.45% in ASDI. With visual-auditory biofeedback as a cue for heel contact and toe push-off condition during treadmill ambulation, the improvement of four dynamic gait performance measures (Double Support Period, DSP, Constant Time Cadence, CTC, Single Support Period, SSP, and Stance/Swing Ratio, SSR) in amputees was verified. This resulted in 7.89% in DSP (affected side), 5.09% in CTC, 16.67% in SSP (sound side), 45.30% in SSR (sound side), and 40.30% in SSR (affected side) respectively. These findings suggest that sub-threshold electrical stimulation and visual-auditory biofeedback rehabilitation strategies may be effective in compensating sensory loss and improving static balance and dynamic ambulation performance for amputees. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

When considering the engineering design process, structures resembling hinges are typically encountered in final structural topology optimization. Although the topology optimization can generate the most desired outcome for layout and approximate hinges alike, their manufacturability from a practical standpoint is in question. This paper proposes an multi-objective optimum design synthesis, using the analytic single-axis flexure formulation integrated with the formal optimization, as a post design process to obtain optimum flexural specifications with locations for promoting the overall performance of a monolithic compliant structure generated by topology optimization. The result verifies that the optimum location of hinge-like structures have been produced at the end of topology optimization. Consequently, a simple alternative design process is recommended for the integration of mechanical flexure hinges into the final product. [ABSTRACT FROM AUTHOR]

In evaluating the effectiveness of further sampling in species taxonomic surveys, a practical and important problem is predicting the number of new species that would be observed in a second survey, based on data from an initial survey. This problem can also be approached by estimating the corresponding expected number of new species. A. R. Solow and S. Polasky recently proposed a predictor (or estimator), with the form of a sum of many terms, that was derived under the assumption that all unobserved species in the initial sample have equal relative abundances. We show in this paper that the summation can be expressed as only one term. We provide a direct justification for the simplified estimator and connect it to an extrapolation formula based on a special type of species accumulation curve. Using the proposed justification, we show that, for large sample sizes, the estimator is also valid under an alternative condition, i.e., species that are represented the same number of times in the initial sample have equal relative abundances in the community. This condition is statistically justified from a Bayesian approach, although the estimator exhibits moderate negative bias for predicting larger samples in highly heterogeneous communities. In such situations, we recommend the use of a modified estimator that incorporates a measure of heterogeneity among species abundances. An example using field data from the extant rare vascular plant species patterns in the southern Appalachians is presented to compare the various methods. [ABSTRACT FROM AUTHOR]

Traumatic cerebral contusion and intracerebral hemorrhages (ICH) commonly result from traumatic brain injury and are associated with high morbidity and mortality rates. Current animal models require craniotomy and provide less control over injury severity. This study proposes a highly reproducible and controllable traumatic contusion and ICH model using non-invasive extracorporeal shockwaves (ESWs). Rat heads were exposed to ESWs generated by an off-the-shelf clinical device plus intravenous injection of microbubbles to enhance the cavitation effect for non-invasive induction of injury. Results indicate that injury severity can be effectively adjusted by using different ESW parameters. Moreover, the location or depth of injury can be purposefully determined by changing the focus of the concave ESW probe. Traumatic contusion and ICH were confirmed by H&E staining. Interestingly, the numbers of TUNEL-positive cells (apoptotic cell death) peaked one day after ESW exposure, while Iba1-positive cells (reactive microglia) and GFAP-positive cells (astrogliosis) respectively peaked seven and fourteen days after exposure. Cytokine assay showed significantly increased expressions of IL-1β, IL-6, and TNF-α. The extent of brain edema was characterized with magnetic resonance imaging. Conclusively, the proposed non-invasive and highly reproducible preclinical model effectively simulates the mechanism of closed head injury and provides focused traumatic contusion and ICH. [ABSTRACT FROM AUTHOR]