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The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.

A major barrier to successful use of allogeneic hematopoietic cell transplantation is acute graft-versus-host disease (aGVHD), a devastating condition that arises when donor T cells attack host tissues. With current technologies, aGVHD diagnosis is typically made after end-organ injury and often requires invasive tests and tissue biopsies. This affects patient prognosis as treatments are dramatically less effective at late disease stages. Here, we show that a novel PET radiotracer, 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG), targeted toward two salvage kinase pathways preferentially accumulates in activated primary T cells. [18F]F-AraG PET imaging of a murine aGVHD model enabled visualization of secondary lymphoid organs harboring activated donor T cells prior to clinical symptoms. Tracer biodistribution in healthy humans showed favorable kinetics. This new PET strategy has great potential for early aGVHD diagnosis, enabling timely treatments and improved patient outcomes. [18F]F-AraG may be useful for imaging activated T cells in various biomedical applications. Cancer Res; 77(11); 2893-902. ©2017 AACR.

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]

Unresectable anaplastic thyroid cancer (ATC) has a poor prognosis. Chemotherapy and radiotherapy have limited effects on it. Here, we present four cases who underwent immunotherapy for ATC. The patients were aged between 58 and 70 years. Two male patients with pulmonary metastases received pembrolizumab and lenvatinib. However, they died of septic shock and respiratory failure in 2.7 and 1 months, respectively, after the initiation of combination therapy. Another male patient with stage IVB disease was treated with spartalizumab. The tumor remained stable after surgical debulking but slightly progressed after 23 months. He survived for 45.5 months after spartalizumab initiation. A female patient with BRAF-mutant ATC and lung metastases was treated with a combination of pembrolizumab and lenvatinib, which was complicated with grade 4 transaminitis. The patient subsequently received dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) treatment, which was continued for 10.2 months with a best response of partial remission. She died 18 months after the initial diagnosis (11.4 months after treatment with dabrafenib and trametinib). In conclusion, the treatment responses of immunotherapy, either alone or in combination with other therapies, were highly variable in patients with ATC and should be carefully monitored along with the side effects. [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]

Background: The clinical characteristics of central‐compartment‐type chronic rhinosinusitis (CRS) in East Asian individuals are not clear. We sought to investigate the clinical features and the cytokine profiles of central‐compartment‐type CRS in our patient group. Methods: Adult patients diagnosed with bilateral CRS were recruited, and patients who had previously undergone sinus surgery and pansinusitis (Lund‐Mackay scores >23) were excluded. Central‐compartment‐type CRS was defined by both endoscopic and radiological features. The symptoms, inhalant allergen sensitization status, endoscopic findings, and radiological assessments were recorded and compared between patients with central‐compartment‐type CRS and other types of CRS. We also examined the extent of tissue eosinophilia and specific cytokine protein levels (eosinophil cationic protein [ECP], myeloperoxidase [MPO], immunoglobulin E [IgE], interleukin [IL]‐4, IL‐5, and IL‐13) in the sinonasal tissues. Results: Central‐compartment‐type CRS was found in 16 (23.9%) patients, and non–central‐compartment‐type CRS was found in 51 (76.1%) patients. Hyposmia or anosmia as the major symptom was more common in the central‐compartment‐type CRS group. The numbers of eosinophils in tissue and serum were significantly higher in the central‐compartment‐type CRS patients. The presence of allergen sensitization was not significantly different between groups. The levels of IL‐5 and IL‐13 were increased in middle turbinate tissues of patients with central‐compartment‐type CRS. Conclusion: Central‐compartment‐type CRS was associated with hyposmia or anosmia, eosinophilic subtypes, and elevated levels of IL‐5 and IL‐13 in middle turbinate tissues but not necessarily correlated with allergic disease in our patients. [ABSTRACT FROM AUTHOR]

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

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: The endoscopic endonasal prelacrimal recess approach to the maxillary sinus provides wide access to the walls and recesses of the maxillary sinus, and its use has been reported in many maxillary sinus and skull base diseases. The objective of this study was to determine the indication and feasibility of endoscopic sinus surgery using the prelacrimal recess approach in unilateral maxillary sinus diseases. Methods: We reviewed 192 cases of unilateral maxillary sinus diseases; over 2 years, 15 cases underwent endoscopic surgery via the prelacrimal recess approach. Data regarding preoperative computed tomography scans, operative findings, postoperative pathological diagnoses, postoperative complications, and disease recurrences were obtained from medical records. Results: Patients who underwent surgery via the prelacrimal recess approach did so mostly because tumors were present in the maxillary sinuses (12/15; 80%), while most of the patients in this study underwent surgery because of chronic inflammation (122/177; 68.9%) and fungal infections (40/177; 22.6%). Among 15 patients undergoing surgery via the prelacrimal recess approach, 9 were cases of inverted papilloma. The mean follow‐up period was 16.5 months (range, 6 to 28 months). No postoperative complications occurred after the prelacrimal recess approach. One out of the 15 cases undergoing the prelacrimal recess approach had tumor recurrence Conclusion: Most chronic inflammation and fungal infections of the unilateral maxillary sinuses can be managed through a middle meatal antrostomy. The endoscopic prelacrimal recess approach is a reliable and effective method used to approach maxillary sinus diseases. [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]

Abstract: Objectives: To determine the immediate effects of applied forearm Kinesio taping on maximal grip strength and force sense of healthy collegiate athletes. Design: Single group, repeated measures study. Setting: Clinical sports medicine laboratory at a university hospital. Participants: Twenty-one healthy collegiate athletes voluntarily participated in this study. All subjects were male (average height: 181.24 ± 7.60 cm; average body weight: 72.86 ± 7.03 kg; average age: 20.86 ± 2.59 years). Main Outcome Measures: First, maximal grip strength of the dominant hand was assessed by hand-held dynamometer. Then, 50% of maximal grip strength was established as the reference value of force sense. Absolute and related force sense errors and maximal grip strength were measured under three conditions: (1) without taping; (2) with placebo taping; and (3) with Kinesio taping. Results: Results revealed no significant differences in maximal grip strength between the three conditions (p = 0.936). Both related and absolute force sense errors in grip strength measurements significantly increased the accuracy of the results under the three conditions (related force sense errors: p < 0.05; absolute force sense errors: p < 0.05). Conclusion: Forearm Kinesio taping may enhance either related or absolute force sense in healthy collegiate athletes. However, Kinesio taping did not result in changes in maximal grip strength in healthy subjects. [Copyright &y& Elsevier]

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]

The objective of the research was to examine the effects of loading and posture on motoneuronal excitability of the triceps surae (TS) for patients with hemiplegia. Twelve healthy subjects and 12 patient subjects with post-stroke hemiparesis (onset period: 3–60 months) were enrolled in this study. The subjects were instructed to remain in quiet sitting with the test knee straight and three standing conditions of different superincumbent loads by shifting body weight to the test leg (10%, 50%, and 90% of body weight), while the H reflexes and M waves of the TS were measured. The results clearly indicated that H reflex amplitudes were not affected by different loading conditions in standing for both healthy subjects and patients who had a previous stroke. In addition, the H reflex amplitude in quiet standing for healthy subjects was significantly downward modulated relative to that in relaxed sitting with the test knee straight, but this posturally driven modulation was impaired in patients following stroke. Current electrophysiological findings imply that body weight as a means for rehabilitation facilitation had little immediate effect on paretic TS, and absence in postural gating of reflex excitability appeared to be an incentive for postural instability resulting from post-stroke hemiparesis. [Copyright &y& Elsevier]

To address the effect of electroacupuncture (Ea) on the autonomic nerve activity, responses of arteriole blood pressure (BP), intragastric pressure (IGP) and parasympathetic vagal nerve activity (VNA) to Ea were investigated in alpha-chloralose anesthetized rats. The acupoint: Hoku (Li-4) was tested with two different stimulation frequencies (2 and 20 Hz). Decrease in VNA and basal IGP associated with elevation of BP were elicited during Ea at Hoku with stimulation intensity of 20 times of motor threshold. The pattern of response induced by the low frequency Ea (LFEa) was different from that by the high frequency Ea (HFEa), i.e. a tonic effect was elicited by the LFEa, while a phasic one was induced by the HFEa. All the results in this study implicated that: (1) Ea at Hoku may activate the sympathetic and simultaneously inhibit the gastric parasympathetic nerve; (2) Ea at Hoku with different stimulation frequencies may elicit distinct mechanism to induce therapeutic effect; (3) Ea at Hoku may ameliorate the hyperactive stomach in clinical therapy. [Copyright &y& Elsevier]

Abstract Background A nasal influenza vaccine has been available only in a live attenuated form, which limits the range of recipients to immune-competent individuals. The present study evaluated a newly developed intranasal inactivated influenza vaccine with a novel adjuvant, heat-labile enterotoxin (LT) derived from E. coli (LTh(αK)). Methods The study was a randomized, double-blind, controlled phase I trial to evaluate the safety and immunogenicity of an intranasal vaccine containing the trivalent influenza HA antigen (7.5 µg each of A/California/7/09 (H1N1)-like virus, A/Victoria/210/2009 (H3N2) virus, and B/Brisbane/60/2008-like virus) in combination with 4 different doses of adjuvant LTh(αK) (7.5, 15, 30 or 45 μg) and 22.5 μg of influenza HA antigen alone (control vaccine). The vaccine was intranasally administered on Days 0 and 7. A safety evaluation commenced for 180 days, and hemagglutination inhibition (HI) antibody titers and nasal HA-specific IgA titers on Day 0 and Day 28 were assessed to determine whether an immunogenic response was elicited. Results From November 2012 to September 2013, a total of 36 subjects were enrolled. Twenty-four subjects received an adjuvanted vaccine, and 12 subjects received a control vaccine. The most common adverse event (AE) was mild nasal discomfort, and systemic AEs were mild fatigue and headache. Only two subjects discontinued the study because of an AE (one had grade 3 fever, and one had nodal arrhythmia). In the group with 45 μg of LTh(αK), the seroprotection rates were 100%, 100% and 80%, and the nasal IgA conversion factors were 7.90, 7.46 and 12.27 for the A/H3N2, A/H1N1 and split B strains, respectively. Adjuvant LTh(αK) vaccine showed a significant enhancement in mucosal immunity in split B -specific IgA. Conclusion The intranasal inactivated influenza vaccine is generally safe, and the LTh(αK)-adjuvanted vaccine is more immunogenic than non-adjuvanted control vaccine. ClinicalTrials.gov Identifier: NCT03293732. [ABSTRACT FROM AUTHOR]

The neural mechanism underlying the effect of electroacupuncture (Ea) on arterial blood pressure (BP) and renal nerve activity (RNA) in the intact state and during acute hemorrhage was investigated in anesthetized rats. Two acupoints, Hoku (Li-4, at the junction of the first and the second metacarpal bone) and Tsusanli (St-36, at the lateral upper tibia bone), were tested using Ea of two different frequencies (2 and 20 Hz). In the intact state, Ea at Hoku elicited an elevation of BP in parallel with RNA, while Ea found no response with identical parameters at Tsusanli. The pattern of the pressor response caused by a low frequency Ea (2 Hz) at Hoku was different than a high frequency one (20 Hz), i.e. a tonic effect was elicited with 2 Hz, while a phasic one was induced with 20 Hz. In mild hemorrhage conditions (10% of BP decrease), similar pressor effects, as in intact rats, were also elicited by Ea. However, in severe hemorrhage conditions (20 and 30% BP decrease), Ea induced a pressor effect on RNA and an attenuated effect on BP. BP and RNA showed a significant correlation in intact and mild hemorrhage conditions, but not in severe hemorrhage conditions. All the results suggested that Ea at Hoku with appropriate stimulation parameters can increase and maintain BP in normal and hemorrhage conditions, and such a therapeutic technique has potential in clinical practice. [Copyright &y& Elsevier]

Objectives: Given the lack of consensus on the screening and treatment for chronic rhinosinusitis (CRS) in the patients undergoing hematopoietic stem cell transplantation (HSCT), we reviewed the risk factors for CRS to improve the efficiency of sinonasal screening and analyzed the effect of treating CRS in search of guidance for modifying current management strategies for rhinosinusitis in HSCT patients., Methods: We conducted a nested case-control study in a retrospective cohort of hematologic patients receiving HSCT from April 2011 to April 2021 and collected data on demographics, smoking/atopic status, hematological diseases, and features of rhinosinusitis for analysis. The associated factors for control of rhinosinusitis and survival were analyzed., Results: Fifty-eight CRS patients were identified, and another 116 age- and sex-matched controls were selected from HSCT patients without CRS. Allergy and smoking were risk factors for CRS in HSCT patients. The multivariable logistic analysis indicated that endoscopic sinus surgery (ESS) was an independent factor for better control of CRS. However, survival was not associated with rhinosinusitis-related factors, but only with hematologic-related factors, including allogenic HSCT, reduced-intensity conditioning, and remission., Conclusions: Sinonasal evaluation should be targeted to the high-risk group. ESS is effective in managing CRS, while control of CRS is not determinant of overall survival in patients receiving HSCT., Competing Interests: Declaration of competing interest nil., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background/aim: Nosocomial infection is a substantial clinical, societal and economic burden, especially during the COVID-19 pandemic. Patients with cancer are required to change into patient gowns before receiving radiotherapy. To improve efficiency and infection control, we designed novel intelligent devices for both gown distribution and recycling. We conducted a pilot study to provide evidence for the device in healthcare quality improvement., Materials and Methods: We designed and set up intelligent machines with an infrared sensor for patient gown distribution and recycling. The performance of these machines was assessed by questionnaire survey of patients' perceptions and handling by laundry personnel., Results: We composed a questionnaire to measure patient/personnel satisfaction upon gown handling based on the existing data of our hospital. Two generations of patient gown distribution machines were introduced. One was the novel automated device for both gown distribution and recycling. The other one was the conventional wooden cabinets and/or hamper stands with foot pedals. Survey results showed that approximately 90% satisfaction was achieved with the automated machines. Overall satisfaction with the new soiled gown recycling machines was significantly higher than that with the conventional receptacles (p<0.01)., Conclusion: The automated patient gown distribution machines safely and efficiently provide patients with suitable gowns. The automated patient gown recycling machine reduces contamination of the gown recycling area. Using these machines improves infection control in the hospital environment and effectively reduces the risk of nosocomial infection., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The purpose of this study was to investigate the efficacy of targeting peptides chemotherapy to overcome adverse event in the conventional chemotherapy for human hepatocellular carcinoma. Previously we reported several cancer-targeting peptides that bind specifically to cancer cells and their vascular endothelia: L-peptide (anti-cancer cell membrane), RLLDTNRPLLPY; SP-94-peptide (anti-hepatoma cell membrane), SFSHHTPILP; PC5-52-peptide (anti-tumor endothelia), SVSVGMKPSPRP; and control peptide, RLLDTNRGGGGG. In this study, these peptides were linked to liposomal iron oxide nanoparticles to localize the targeted tumor cells and endothelia, and to dextran-coated liposomal doxorubicin (L-D) to treat nonobese diabetic severe combined immunodeficient mice bearing hepatoma xenografts. Our results showed that L-peptide-linked liposomal doxorubicin could inhibit tumor growth with very mild adverse events. Use of the control peptide led to a decrease in the xenograft size but also led to marked apoptotic change in the visceral organ. In conclusion, L-peptide-linked liposomal doxorubicin, SP-94-peptide, and PC5-52-peptide can be used for the treatment of hepatoma xenografts in nonobese diabetic severe combined immunodeficient mice with minimal adverse events., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Background: Olfactory dysfunction significantly influences patients' quality of life. Chitosan has been reported to support neuron and Schwann cell growth and even leads to orient axonal growth. However, researchers have yet to explore whether chitosan solution can promote differentiation of olfactory receptor neurons of the olfactory neuroepithelium and be used for treating olfactory dysfunction., Objective: To evaluate the effect of chitosan solution on the differentiation of olfactory neuroepithelial cells., Method: Olfactory neuroepithelial cells were isolated from embryonic day 17 of Wistar rats and then cultured with and without soluble chitosan for 9 days. The concentration of chitosan solution was set at 0.1 mg/mL. The effects of treatment were assessed by immunocytochemistry and Western blot after culturing., Results: The morphologic analysis indicated that olfactory neuroepithelial cells treated with chitosan exhibited bipolar shape with asymmetric processes. In addition, from days 3 to 9, the expression level of βIII tubulin gradually reduced, but the expression level of olfactory marker protein significantly rose at day 9 in the chitosan groups (p < 0.05). Importantly, chitosan-treated olfactory neuroepithelial cells expressed more signal transduction apparatuses, olfactory neuron specific-G protein and adenylate cyclase 3, than those without chitosan treatment at day 9. Western blot analysis also further confirmed the results (p < 0.05)., Conclusion: Experimental results revealed that soluble chitosan promoted differentiation of olfactory neuroepithelial cells based on its role in olfactory receptor neuron differentiation, neurite outgrowth, and signal transduction apparatus expressions.

Tumors of the supraclavicular fossa (SC) is clinically challenging because of anatomical complexity and tumor pathological diversity. Because of varied diseases entities and treatment choices of SC tumors, making the accurate decision among numerous differential diagnoses is imperative. Sampling by open biopsy (OB) remains the standard procedure for pathological confirmation. However, complicated anatomical structures of SC always render surgical intervention difficult to perform. Ultrasound-guided core biopsy (USCB) is a minimally invasive and office-based procedure for tissue sampling widely applied in many diseases of head and neck. This study aims to evaluate the clinical efficacy and utility of using USCB as the sampling method of SC tumors. From 2009 to 2014, consecutive patients who presented clinical symptoms and signs of supraclavicular tumors and were scheduled to receive sampling procedures for diagnostic confirmation were recruited. The patients received USCB or OB respectively in the initial tissue sampling. The accurate diagnostic rate based on pathological results was 90.2% for USCB, and 93.6% for OB. No significant difference was noted between USCB and OB groups in terms of diagnostic accuracy and the percentage of inadequate specimens. All cases in the USCB group had the sampling procedure completed within 10  minutes, but not in the OB group. No scars larger than 1  cm were found in USCB. Only patients in the OB groups had the need to receive general anesthesia and hospitalization and had scars postoperatively. Accordingly, USCB can serve as the first-line sampling tool for SC tumors with high diagnostic accuracy, minimal invasiveness, and low medical cost., Competing Interests: The authors have no conflicts of interest to disclose.

Background: The margin status is an important prognosticator for the survival of patients with tongue cancer. Although a positive margin is associated with a poor prognosis, those with clear margins do not always have good clinical outcomes., Methods: We investigated the margin status, pattern of tumor invasion (POI), and tumor satellite distance (TSD) in 119 freshly treated tongue cancers and assessed their association with the characteristics and clinical outcomes., Results: A close or clear margin and POI were not associated with overall survival. Tumor satellites occurred in 92% of tumors and were significantly associated with betel nut exposure. Patients with TSD 0.5 mm had a higher incidence of local recurrence, shorter intervals to neck recurrence, and a higher propensity to contralateral or bilateral cervical nodal metastasis., Conclusion: TSD is associated with local recurrence, contralateral neck metastasis, and the overall survival of patients with tongue cancer.

This study investigated exertion-dependent motor overflow among healthy adults when they performed isometric tasks with contralateral joints in different task directions. Twenty healthy adults (10 males and 10 females, mean age = 26.2 yrs) were instructed to complete a set of isometric contractions of various force vectors with the shoulder, elbow, and wrist joints, in a total of ten motor tasks at submaximal and maximal intensities (50%, 100% maximal voluntary contractions). The electromyographical activities from eight muscles of the unexercised upper limb were recorded to characterize intensity of motor overflow during sustained isometric contraction. Both occurrence frequency and magnitude of motor overflow in terms of standardized net excitation (SNE) increased with exertion level for all joint movements (P < 0.001). Additionally, the motor overflow magnitude depended strongly on the task direction of maximal isometric contraction (P < 0.05). Motor overflow was particularly augmented by the contralateral isometric contractions where task directions were opposed to gravity. However, such a directional effect upon SNE was not evident during submaximal contraction (P > 0.05). The difference of the net excitation between maximal and submaximal contraction (DNE(100%-50%MVC) data) indicated that the pectoralis major and triceps brachii consistently exhibited a marked recruitment in reaction to change in task direction of isometric contraction. Patterned motor overflow may be physiologically relevant to topological mapping of the ipsilateral pathways and altered effectiveness of use-dependent interhemispherical connectivity. The current observations provide better insight into gain in muscle strength due to contralateral exercise.