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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.

Supplementary Figure 1 shows [18F]F-AraG Structure and Schematic of AraG Uptake into T Cells Supplementary Figure 2 shows [18F]F-AraG and [3H]F-AraC Uptake and Retention Across Various Immune Cell Lines Supplementary Figure 3 shows AraG Competitive Inhibition of [18F]F-AraG Uptake Across Various Immune Cell Lines Supplementary Figure 4 shows Comparison of [18F]F-AraG and [3H]F-AraC Uptake and Retention Across Various Solid Tumor Cell Lines Supplementary Figure 5 shows Western Blot Analysis of dCK Expression in Wild-type and Mutant CCRF-CEM cells Supplementary Figure 6 shows dGK overexpression in CHO-K1 cells leads to increased [18F]F-AraG uptake and retention Supplementary Figure 7 shows [3H]F-AraC Accumulates in Cells via dCK Activity Supplementary Figure 8 shows Uptake of [18F]F-AraG in Activated Versus Resting Murine T Cells Supplementary Figure 9 shows Isolation and Activation of Primary Human T Cells Supplementary Figure 10 shows Uptake and Retention of [3H]AraG and [3H]F-AraC in Resting and Activated Human Primary T Cells Supplementary Figure 11 shows Evaluation of GFP+ Donor T cells in Spleens and Cervical Lymph Nodes (CLNs) at Day 3 and Day 10 of Acute GVHD Supplementary Figure 12 shows Evaluation of Proliferation of Donor T Cells in Cervical Lymph Nodes

CHO Cell Transfection Tracer Uptake and Efflux Assays for Adherent Cells Western Blot Immunofluorescence Staining of Lymphoid Organs Ex Vivo Donor T Cell Proliferation Analysis Automated preparation of [18F]FAraG for human imaging using the Neptis perform PET synthesizer Imaging Studies in Humans Statistics

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.

Background Isolated sphenoid sinus disease (ISSD) is a rare clinical entity with potentially serious complications. The etiological distribution of ISSD varies among different areas and ethnicities. We aimed to investigate the clinical features of patients with endoscopic treated ISSD. Methods We retrospectively reviewed all patients with ISSD who had undergone endoscopic surgery between April 2013 and May 2019. The patient records were reviewed for demographic data, clinical presentations, endoscopic and imaging study findings, surgical outcomes and complications. Results A total of 37 patients with ISSD who underwent surgery were recruited. We divided patients into three groups according to etiology, including inflammatory diseases (78.4%), neoplasms (13.5%) and spontaneous cerebrospinal fluid (CSF) leaks (8.1%); fungal ball (62.2%) constituted the major cause of ISSD. Overall, the most common presenting symptom was headache or facial pain (65.5%). The endoscopic findings of bloody discharge and tumor lesions were mainly from the neoplasm group. Bony defects were more obvious on computed tomography in the neoplasm and CSF leak groups. Magnetic resonance imaging revealed a higher rate of involvement of the cavernous sinus (40.0%) and intracranial extensions (40.0%) in the neoplasm group. To summarize the surgical outcomes, the success rate was 97.1%, and the major complication rate was 5.4%. Conclusion ISSD represents a variety of etiologies, mostly comprising fungal ball in our area, while there is still a considerable proportion of ISSDs attributed to neoplasm and CSF leak. Untreated ISSD can result in serious complications. We recommend early surgical intervention for all patients with ISSD.

Objectives Endoscopic endonasal transsphenoidal adenomectomy (TSA) is the most frequently performed skull base surgery and researchers have recently focused on preserving nasal function. The transseptal approach is a promising procedure owing to its less injury to nasal mucosa. Therefore, we conducted this study to investigate whether the transseptal approach could reduce nasal morbidities with comparable neurosurgical outcomes. Study design Retrospective chart review. Setting Single-institution tertiary care centre. Participants 25 patients of transseptal approach from January 2019 to December 2020 and 25 patients of transnasal approach from January 2017 to December 2018. Main outcome measures Lund-Kennedy endoscopic scores, 22-item sinonasal outcome test (SNOT-22) scores, TIB smell identification tests (TIBSIT®) scores, the rate of gross total resection, endocrine control, and postoperative complications were collected. Results The postoperative SNOT-22 (4.40 vs. 7.36, P =.005) and Lund-Kennedy endoscopic scores (2.72 vs, 5.08 at 2 weeks, 0.88 vs. 3.52 at 1 month, 0.48 vs. 2.12 at 3 months, 0.04 vs. 1.76 at 6 months, all adjusted P < .01) were significantly lower in the transseptal group, while the TIBSIT scores were not significantly different (41.6 vs. 42.4 preoperatively, P = .68; 41.6 vs. 40.2 postoperatively, P = .46). The rates of gross total resection, recovery of hormonal abnormalities, and complications were not significantly different. In multivariate analysis, the transseptal approach remained an independent factor for lower SNOT-22 scores and Lund-Kennedy endoscopic scores. Conclusion The transseptal approach provides better recovery of nasal mucosa and intact olfactory function without compromising neurosurgical outcomes.

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 m...

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.

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., Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile cilia of the human nasal and respiratory tract and is not affected by the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.

We investigated 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 healthy human donors. We detected ACE2 protein expression within the cilia organelle of ciliated airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during respiratory transmission. We further determined whether ACE2 expression in the cilia of upper respiratory cells was influenced by patient demographics, clinical characteristics, co-morbidities, or medication use, and found no evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) increases ACE2 protein expression.

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.

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.

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.

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.

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.

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

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.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.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.

The focus of this research is on the electron transfer and its reaction rate at the perovskite cathode of a photoelectrochemical cell for hydrogen production. By employing the density functional theory (DFT), the electron density, projected density of states (PDOS), electron distribution and electron transfer path between [Fe-Fe] hydrogenase and the perovskite cathode can be obtained. Simulation results show that the perovskite cathode is better than traditional cathodes for hydrogen production. Before transmission to the [Fe-Fe] hydrogenase, electron clouds mainly aggregate at the periphery of amine molecules. Simulations also show that the key to hydrogen production at the perovskite structure lies in the organic molecules. Electrons are transferred to the hydrocarbon structural chain before reaching the Fe atoms. The Rice, Ramsperger, Kassel and Marcus (RRKM) theory was used to predict the reaction rates at different temperatures. It was found that the reaction rates are in good agreement with the experimental results. This research provides more physical insight into the electron transfer mechanism during the hydrogen production process.

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.

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.

Brain damage pathology can generate an irrelevant motor program leading to abnormal posture. Given this observation, we tested the hypothesis that postural control deficits are present in individuals with postural disorders. A new trunk sway assessment protocol evaluation system using an inertial-based sensing technique combined with visual-biofeedback strategies was developed. The proposed system was used to assess the angular deviation of the center of mass and enhanced balance control in patients with stroke. Twelve participants with hemiplegia were randomly divided into a visual-biofeedback group (experimental) and a without visual-biofeedback group (control), and were asked to stand as still as possible for 30 s. Postural sway data were submitted to conventional quantitative analyses of sway magnitude using a center of mass measurement. Additionally, group means were compared using parametric tests. Parameters in both the anterior-posterior and medio-lateral directions within the stroke patients were compared using paired t-tests. The experimental group showed increased postural control, indicative of reduced postural sway. Decreased complexity in the medio-lateral direction was also observed in the experimental group, suggesting both a reduction in the dynamic range available for postural control, and that their postural corrections were dominated primarily by longer-term scales. Significant interactions between the diagnostic group and visual condition were also observed for both of these measures, suggesting that the control group participants were impaired in their ability to make corrections to their sway pattern when no visual biofeedback was available. Greater sway magnitude and reduced complexity suggest that individuals with hemiplegia have deficits in sensorimotor integration and a reduced range of timescales available within which to make postural corrections.

In vivo higher-harmonic generation microscopy (HGM) performed on healthy human oral mucosa not only provides images with a

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 p 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.

This paper presents a new built-in current sensor (BICS)-based I DDQ testing scheme for complementary metal-oxide semiconductor (CMOS) integrated circuits (ICs). The proposed BICS will employ short detection times and low power dissipation to effectively ensure the reliability of the BICS and reduce the impact of the circuit under test (CUT) during testing. In addition, an I DDQ testing scheme based on the proposed BICS for detecting the abnormal quiescent current is presented. A 16-kB CMOS static random access memory (SRAM) is used as the CUT in this paper to discuss the testing considerations, including fault models and the I DDQ testing strategy. The simulation results show that the proposed BICS has a much improved performance compared with that in previous works. In addition, the physical chip design of the proposed BICS-based I DDQ testing scheme for SRAM testing applications is also implemented using the Taiwan Semiconductor Manufacturing Company (TSMC) 0.18-mum CMOS technology. The test results show that 100% fault coverage can be achieved with only a 1.23% area overhead penalty.

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 out- comes. Methods. We investigated the margin status, pattern of tu- mor 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 associ- ated with overall survival. Tumor satellites occurred in 92% of tumors and were significantly associated with betel nut expo- sure. Patients with TSD 0.5 mm had significantly better overall survival. 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 me- tastasis. Conclusion. TSD is associated with local recurrence, contra- lateral neck metastasis, and the overall survival of patients with tongue cancer. V C 2008 Wiley Periodicals, Inc. Head Neck 30: 631-638, 2008

This paper presents the design and implementation of a tele-emergent system to provide constant monitoring of cardiac patients. Our system is consisted of a user integration device attached to the patient, a wireless sensor network (WSN) and a medical gateway installed in the patient's home, and a server set up in the hospital. The user integration device includes Electrocardiogram (ECG) signal acquisition and processing circuit utilizing a "Modified So and Chan" QRS detection algorithm to discriminate the R signal wave and calculate RR intervals to subsequently detect abnormal Heart Rate Variability (HRV), and a Bluetooth transmission module to communicate with WSN. The WSN which is consisted of wireless sensor nodes with power-saving scheme is used to relay the ECG data to the medical gateway for ubiquitous monitoring at home. The medical gateway includes the heart disease symptom recognition system to further analyze the ECG data and recognize the symptoms of serious heart diseases, and a General Packet Radio Service (GPRS) module with Multimedia Messaging Service (MMS) to communicate with the server in the hospital. The server in the hospital can passively process the MMS messages from the medical gateway, and actively send commands to the medical gateway to acquire the needed ECG data from the patient. With our integrated system it is possible to provide real-time and long-term monitoring of physiological data for cardiac patients which is vital for the patients' medical care.

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.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.Submerged single layer (SSL) and air-liquid interface (ALI) nasal epithelial cell cultures with or without 10(-7) M retinoid acid (+/- RA) were created.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.

Proprioceptive neuromuscular facilitation and foot sensory compensation are critical to balance control and ambulatory performance in below-knee amputees. Sub-sensory stimulation has been shown to be effective in enhancing the sensitivity of the human somatosensory system. In addition, visual-auditory biofeedback to improve foot sensory compensation for amputees was suggested in recent articles. The purpose of this study is to develop a new biofeedback proprioceptive neuromuscular facilitation system for improving balance control and foot sensory compensation in below-knee amputees. The proposed system functioned with sub-threshold electrical stimulation and visual-auditory biofeedback was developed for clinical study. Two unilateral trans-tibial amputees who consecutively wore prosthetics over 10 years were participated in this study. Subjects performed multiple single leg quite standing trails with sub-sensory electrical stimulation applied at the quadriceps muscle during half of the trails. Four static balance performance indices (i.e. Holding Time Index, HTI; Sway Length Index, SLI; Max Sway Distance Index, MSDI; Average Sway Distance Index, ASDI) were characterized using Zebris motion analysis system. The improvement ratio of these static balance performance indices across subjects for single leg quiet standing tests were resulted in a 209.7% in HTI, 39.1% in SLI, 24.3% in MSDI, and 65.4% in ASDI respectively. In addition, multiple treadmill ambulatory trails with or without visual-auditory biofeedback were evaluated. Four dynamic gait performance indices (i.e. Double Support Time Index, DSTI; Constant Time Cadence Index, CTCI; Single Support Time Index, SSTI; Stance/Swing Phase Index, SSPI) were characterized with Zebris instrumented insole and associated FMS analysis software. With visual-auditory biofeedback, the improvement of all four dynamic gait performance indices in below-knee amputees was verified. The improvement ratio of four gait performance indices across subjects resulted in a 14.81% in DSTI (sound side), 14.29% in DSTI (affected side), 14% in CTCI, 13.00% in SSTI (sound side), 6.02% in SSTI (affected side), 45.17% in SSPI (sound side), and 27.49% in SSPI (affected side) respectively. These findings suggest that sub-threshold electrical stimulation and visual-auditory biofeedback proprioceptive neuromuscular facilitation strategies may be effective in compensating foot sensory loss and improving balance control for below-knee amputees.

The effects of electroacupuncture (Ea) on circulatory dynamics were investigated in anesthetized rats. The arterial blood pressure (BP) and the heart rate (HR) in response to Ea stimulations at the Tsusanli point (St-36) and the Hoku point (Li-4) were tested by a low frequency Ea (2 Hz; LFEa) and a high frequency Ea (20 Hz; HFEa) with stimulation intensities 20 times the motor threshold. Neither the HR nor the BP was affected when the Tsusanli point was stimulated. Whereas, Ea stimulations at the Hoku point elicit chronotropic and pressor effects. The patterns of pressor responses caused by the LFEa were different from that of an HFEa, i.e., the LFEa elicited a tonic effect, while an HFEa had a phasic one. The HFEa-induced pressor and chronotropic effects were attenuated, while the LFEa induced effects were completely blocked by an intravenous infusion of an alpha-adrenergic blocker (moxisylyte 0.2 mg/min/kg, i.v., for 20 min). A co-infusion with alpha-and beta-adrenergic blockers (propanolol 0.2 mg/min/kg, i.v., for 20 min) completely blocked the HFEa-induced pressor and chronotropic effects. We concluded that Ea stimulations, at the Hoku acupoint, with appropriate stimulation parameters can increase and maintain BP. Furthermore, the LFEa stimulation activates sympathetic vasomotor tone, whereas the HFEa stimulation causes an additional potentiation on the sympathetic drive to the heart.

This paper presents the analytic flexure hinge, involved in design optimization for a compliant mechanism, as a one‐piece member. Several objective functions simultaneously arise in optimization to enhance the magnification factor in improving the mechanism's performance. A compliant micro‐gripper, after pseudo‐rigid‐body model synthesis, is adopted in the paper to illustrate the present design process. The final design shows a noticeable improvement over the initial design in previous publications.

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.

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. Corresponding Editor: A. R. Solow

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.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.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.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.

Oral cancer is one of the most frequently diagnosed human cancers and leading causes of cancer death all over the world, but the prognosis and overall survival rate are still poor because of delay in diagnosis and lack of early intervention. The failure of early diagnosis is due to insufficiency of proper diagnostic and screening tools and most patients are reluctant to undergo biopsy. Optical virtual biopsy techniques, for imaging cells and tissues at microscopic details capable of differentiating benign from malignant lesions non-invasively, are thus highly desirable. A novel multi-harmonic generation microscope, excited by a 1260 nm Cr:forsterite laser, with second and third harmonic signals demonstrating collagen fiber distribution and cell morphology in a sub-micron resolution, was developed for clinical use. To achieve invivo observation inside the human oral cavity, a small objective probe with a suction capability was carefully designed for patients’ comfort and stability. By remotely changing its focus point, the same objective can image the mucosa surface with a low magnification, illuminated by side light-emitting diodes, with a charge-coupled device (CCD) for site location selection before the harmonic generation biopsy was applied. Furthermore, the slow galvanometer mirror and the fast resonant mirror provide a 30 fps frame rate for high-speed real-time observation and the z-motor of this system is triggered at the same rate to provide fast 3D scanning, again ensuring patients’ comfort. Focusing on the special cytological and morphological changes of the oral epithelial cells, our preliminary result disclosed excellent consistency with traditional histopathology studies.