bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Oral Flora with Orbital Complications of Acute Sinusitis
Authors: Flam Juliette O. , Platt Michael P. , Sobel Rachel , Devaiah Anand K. , Brook Christopher D. 
Published: July 2016

Background Acute and chronic sinusitis in children and adults can spread to the orbit. Oral flora has been seen in orbital infections, but the extent of synergy between pathogens in such infections remains unknown. Methods A retrospective case series of patients with complicated sinusitis that involved the orbit from acute sinusitis who were admitted to a tertiary care hospital from January 2000 to December 2014 and who had surgical cultures obtained. Patients were identified by the International Classification of Diseases, Ninth Revision code for periorbital cellulitis, subperiosteal abscess, or orbital abscess. Results Sixteen patients underwent surgical drainage via external drainage or endoscopic sinus surgery of an orbital infection associated with sinusitis and had cultures obtained. Nine patients (56%) grew organisms that exist in oral flora, whereas seven patients (44%) grew common respiratory pathogens. The most common organisms recovered were viridans group streptococcus (VGS) (50%), Staphylococcus aureus (31%), Eikenella corrodens (25%), and Prevotella species (19%). Oral flora anaerobes were cultured alongside a VGS species in seven of eight patients (88%) as opposed to the respiratory pathogens, which were less frequently associated with concomitant VGS infection (29%) (p = 0.04). Conclusion There are two main sources for infectious orbital complications from acute sinusitis: respiratory pathogens and oral flora. The high prevalence of concurrent anaerobic oral flora and VGS infection supports a suspected synergy between VGS and other oral organisms.
Wogonin Inhibits Transforming Growth Factor β1–induced Extracellular Matrix Production via the p38/activator Protein 1 Signaling Pathway in Nasal Polyp–derived Fibroblasts
Authors: Ryu Nam Hyoung , Shin Jae-Min , Um Ji-Young , Park Il-Ho , Lee Heung-Man 
Published: July 2016

Background Wogonin has been shown to have antifibrotic and anti-inflammatory effects in the lower airway. The purpose of this study was to evaluate the effects of wogonin on transforming growth factor (TGF) β1–induced myofibroblast differentiation, extracellular matrix production, migration, and collagen contraction, and to determine the molecular mechanisms of wogonin in nasal polyp–derived fibroblasts (NPDF). Methods NPDFs were isolated from nasal polyps from eight patients. TGF-β1–induced NPDFs were treated with wogonin. Cytotoxicity was evaluated by using a 3-(4,5- dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. Fibroblast migration was evaluated with transwell and scratch migration assays. The expression levels of α-smooth muscle actin, fibronectin, phosphorylated-p38, and c-Fos were determined by Western blot and/or reverse transcription–polymerase chain reaction. The total collagen amount was analyzed with the Sircol collagen assay, and contractile activity was measured by a collagen gel contraction assay. Results Wogonin (0–60 μM) had no significant cytotoxic effects on TGF-β1–induced NPDFs. Migration of NPDFs was significantly inhibited by wogonin treatment. The expression levels of α-smooth muscle actin and fibronectin were significantly reduced in wogonin-treated NPDFs. Collagen production and contraction were also significantly decreased by wogonin treatment. Wogonin markedly inhibited activation of the p38/activator protein 1 pathway in TGF-β1–induced NPDFs. Conclusion These results indicated that wogonin may inhibit TGF-β–induced myofibroblast differentiation, extracellular matrix production, migration, and collagen contraction through the p38/activator protein-1 pathway in NPDFs.
Intact Soluble P-Glycoprotein is Secreted by Sinonasal Epithelial Cells
Authors: Nocera Angela L. , Meurer Ana T. , Singleton Amy , Simons Christopher , BuSaba Joseph , Gass Nicole Tara , Han Xue , Bleier Benjamin S. 
Published: July 2016

Background P-glycoprotein (P-gp) is a 170 kDa transmembrane efflux pump, which is upregulated in chronic rhinosinusitis. Studies of leukemia demonstrated that P-gp may also be secreted in an intact soluble form. The purpose of this study was to explore whether sinonasal epithelial cells were capable of secreting soluble P-gp and whether P-gp has any functional role. Methods Soluble and cytoplasmic P-gp were quantified in vehicle and lipopolysaccharide exposed cultures by enzyme-linked immunosorbent assay. The molecular weight of the soluble P-gp was determined by Western blot. Naive cultures were exposed to recombinant human P-gp at 0-2000 ng/mL. The degree of membranous interpolation was determined by quantitative fluorescent immunocytochemistry and function was determined by a calcein acetoxymethyl ester assay. Results Soluble P-gp was secreted intact at 170 kDa. Mean (standard deviation) secretion was detected within vehicle wells at 55.43 ± 26.26 ng/mL, which significantly increased to 333.27 ± 305.98 ng/mL (p < 0.001) after lipopolysaccharide stimulation. Soluble P-gp strongly and significantly correlated with cytoplasmic P-gp (r = 0.57, p = 0.000001). Exposure to 2000 ng/mL of recombinant P-gp significantly increased corrected total cell fluorescence (1.34 ± 1.85) relative to vehicle control 0.29 ± 0.26 (p = 0.01) and significantly reduced calcein acetoxymethyl ester fluorescence (82.03 ± 43.69) relative to 100 ng/mL recombinant P-gp exposed cells (123.11 ± 42.16, p = 0.001). Conclusion Cultured sinonasal epithelial cells were able to both secrete intact P-gp and could functionally interpolate soluble P-gp into their cell membrane. These in vitro findings indicated that soluble P-gp may be present in nasal mucus as a biomarker and could participate in the maintenance of P-gp overexpression in chronic rhinosinusitis and associated inflammation.
In vitro Effects of Anthocyanidins on Sinonasal Epithelial Nitric Oxide Production and Bacterial Physiology
Authors: Hariri Benjamin M. , Payne Sakeena J. , Chen Bei , Mansfield Corrine , Doghramji Laurel J. , Adappa Nithin D. , Palmer James N. , Kennedy David W. , Niv Masha Y. , Lee Robert J. 
Published: July 2016

Background T2R bitter taste receptors play a crucial role in sinonasal innate immunity by upregulating mucociliary clearance and nitric oxide (NO) production in response to bitter gram-negative quorum-sensing molecules in the airway surface liquid. Previous studies showed that phytochemical flavonoid metabolites, known as anthocyanidins, taste bitter and have antibacterial effects. Our objectives were to examine the effects of anthocyanidins on NO production by human sinonasal epithelial cells and ciliary beat frequency, and their impact on common sinonasal pathogens Pseudomonas aeruginosa and Staphylococcus aureus. Methods Ciliary beat frequency and NO production were measured by using digital imaging of differentiated air-liquid interface cultures prepared from primary human cells isolated from residual surgical material. Plate-based assays were used to determine the effects of anthocyanidins on bacterial swimming and swarming motility. Biofilm formation and planktonic growth were also assessed. Results Anthocyanidin compounds triggered epithelial cells to produce NO but not through T2R receptors. However, anthocyanidins did not impact ciliary beat frequency. Furthermore, they did not reduce biofilm formation or planktonic growth of P. aeruginosa. In S. aureus, they did not reduce planktonic growth, and only one compound had minimal antibiofilm effects. The anthocyanidin delphinidin and anthocyanin keracyanin were found to promote bacterial swimming, whereas anthocyanidin cyanidin and flavonoid myricetin did not. No compounds that were tested inhibited bacterial swarming. Conclusion Results of this study indicated that, although anthocyanidins may elicited an innate immune NO response from human cells, they do not cause an increase in ciliary beating and they may also cause a pathogenicity-enhancing effect in P. aeruginosa. Additional studies are necessary to understand how this would affect the use of anthocyanidins as therapeutics. This study emphasized the usefulness of in vitro screening of candidate compounds against multiple parameters of both epithelial and bacterial physiologies to prioritize candidates for in vivo therapeutic testing.
Comparison of the Aesthetic Results of Two Common Incisions in External Rhinoplasty: A Randomized Trial
Authors: Saedi Babak , Amali Amin , Taibnama Narges , Most Sam P. 
Published: July 2016

Objective To compare the scar outcomes of two common incisions (inverted V and stair step) by using a validated scar-outcome instrument via a randomized clinical trial. Methods Fifty-eight consecutive cases of external rhinoplasty were randomly divided into two groups according to the type of incision. These patients were followed-up for 1 year, and the columellar scar was analyzed by using the Stony Brook Scar Evaluation Scale (SBSES) and visual analog scale (VAS) scores by an independent reviewer. Results Of 58 patients, 28 received the inverted V and the rest received the stair-step incision. Thirty-four participants (58.6%) were women. The mean (standard deviation) age of the participants was 26.2 ± 6.6 years. After 1 month, the scar outcome was significantly better in patients with the stair-step incision (p = 0.001) by using the SBSES, but the same was not true after 1 year (p = 0.425). However, when the VAS instead of the SBSES was used to evaluate the scar, the inverted V received a better score after 12 months in this series (p = 0.005). Conclusion Despite the better aesthetic outcome of the stair-step incision in the first month after the surgery, there was no significant difference between the two incisions after 1 year. However, in this series, when the VAS instead of the SBSES was used to evaluate the scar, the inverted V received a better score after 12 months.
Temporal Differences in Improvement of Nasal Obstruction between Primary and Revision Septoplasty
Authors: Jeong Jong In , Hong Sang Duk , Kim Su Jin , Dhong Hun-Jong , Chung Seung-Kyu , Kim Hyo Yeol 
Published: July 2016

Background Septoplasty is one of most frequently performed surgeries in otorhinolaryngologic clinics to improve nasal obstruction by correcting nasal septal deformities. Many patients require revision surgery for persistent nasal obstruction. However, the outcomes and sources of revision septoplasty are unclear. Objective We investigated the discrepancy between patient's subjective and objective improvements after septoplasty by comparing primary and revision procedures. Methods Patients who underwent septoplasty from January 2012 to December 2014 were enrolled. All the subjects were questioned regarding subjective nasal symptoms before surgery and 1 month and every 3 months after surgery, with responses rated on a 7-point Likert scale. Nasal endoscopic evaluation and acoustic rhinometry were also performed with the same schedule. Results One hundred seventy-nine patients were analyzed. Subjective nasal obstruction scores of both the primary (n = 161) and revision (n = 18) groups were significantly improved at 1 month after surgery and showed no difference between the two groups. However, this improvement was sustained to the last follow-up only in the primary group. The symptom improvement rate of the primary group (85.5% [n = 109]) was significantly higher than that of the revision group (58.8% [n = 10]) at the last follow-up. There was no difference in the degree of improvement in objective findings between the two groups, including the difference and the ratio of the minimal cross-sectional area between the wider and narrower sides, and in endoscopic findings, even at the last follow-up. Conclusion Compared with primary septoplasty, the long-term efficacy of revision septoplasty may not be clear, and there are discrepancies between the subjective and objective outcomes.
Sinonasal Polyposis in the Elderly
Authors: Brescia Giuseppe , Barion Umberto , Pedruzzi Barbara , Cinetto Francesco , Giacomelli Luciano , Pendolino Alfonso Luca , Marino Filippo , Manzato Enzo , Martini Alessandro , Marioni Gino 
Published: July 2016

Background/Objective The main end point of this investigation was to review our experience gained from 2009 to 2015 of treating chronic rhinosinusitis with nasal polyps (CRSwNP) in elderly patients (≥65 years old) with functional endoscopic sinus surgery. Secondary aims were to analyze the prognostic variables for CRSwNP in elderly patients and to compare the demographic, clinical, laboratory, histologic, and prognostic characteristics of CRSwNP in elderly versus young adult patients (20-40 years old). Methods Forty-three consecutive elderly patients and 71 consecutive young adult patients with CRSwNP were enrolled. Results Significant associations were found in the elderly group between CRSwNP recurrence and allergy (p = 0.037), CRSwNP recurrence and asthma (p = 0.017), and CRSwNP recurrence and acetyl salicylic acid (ASA) intolerance (p = 0.032) but not between recurrence and eosinophilic/noneosinophilic CRSwNP histology. Significant associations emerged in the young adult group between CRSwNP recurrence and asthma (p = 0.009), and ASA intolerance (p = 0.016), and serum eosinophil count (p = 0.02). The recurrence rate was also significantly higher for young adult patients with eosinophilic-type CRSwNP (p = 0.001). CRSwNP recurred less often in the elderly than in the young adult patients (p = 0.05). Conclusion The present preliminary investigation found a lower recurrence rate after functional endoscopic sinus surgery for CRSwNP in elderly patients than in young adult patients. Further investigations on larger, prospective series are mandatory to support the hypothesis that, although eosinophilic-type CRSwNP is generally considered a variant at high risk of recurrence and that probably warrants stricter postoperative follow-up and adjuvant postoperative medical treatment, these considerations could not be applied to elderly patients.
Targeting T Cell Bioenergetics by Modulating P-Glycoprotein Selectively Depletes Alloreactive T Cells To Prevent Graft-versus-Host Disease
Authors: McIver Zachariah A. , Grayson Jason M. , Coe Benjamin N. , Hill Jacqueline E. , Schamerhorn Gregory A. , Ohulchanskyy Tymish Y. , Linder Michelle K. , Davies Kellie S. , Weiner Roy S. , Detty Michael R. 
Published: July 2016

Abstract
T lymphocytes play a central role in many human immunologic disorders, including autoimmune and alloimmune diseases. In hematopoietic stem cell transplantation, acute graft-versus-host-disease (GVHD) is caused by an attack on the recipient’s tissues from donor allogeneic T cells. Selectively depleting GVHD-causing cells prior to transplant may prevent GVHD. In this study, we evaluated 24 chalcogenorhodamine photosensitizers for their ability to selectively deplete reactive T lymphocytes and identified the photosensitizer 2-Se-Cl, which accumulates in stimulated T cells in proportion to oxidative phosphorylation. The photosensitizer is also a potent stimulator of P-glycoprotein (P-gp). Enhanced P-gp activity promotes the efficient removal of photosensitizer not sequestered in mitochondria and protects resting lymphocytes that are essential for antipathogen and antitumor responses. To evaluate the selective depletion of alloimmune responses, donor C57BL/6 splenocytes were cocultured for 5 d with irradiated BALB/c splenocytes and then photodepleted (PD). PD-treated splenocytes were infused into lethally irradiated BALB/c (same-party) or C3H/HeJ (third-party) mice. Same-party mice that received PD-treated splenocytes at the time of transplant lived 100 d without evidence of GVHD. In contrast, all mice that received untreated primed splenocytes and third-party mice that received PD-treated splenocytes died of lethal GVHD. To evaluate the preservation of antiviral immune responses, acute lymphocytic choriomeningitis virus infection was used. After photodepletion, expansion of Ag-specific naive CD8+ T cells and viral clearance remained fully intact. The high selectivity of this novel photosensitizer may have broad applications and provide alternative treatment options for patients with T lymphocyte–mediated diseases.
Prostaglandin I2 Suppresses Proinflammatory Chemokine Expression, CD4 T Cell Activation, and STAT6-Independent Allergic Lung Inflammation
Authors: Zhou Weisong , Zhang Jian , Goleniewska Kasia , Dulek Daniel E. , Toki Shinji , Newcomb Dawn C. , Cephus Jacqueline Y. , Collins Robert D. , Wu Pingsheng , Boothby Mark R. , Peebles R. Stokes 
Published: July 2016

Abstract
Allergic airway diseases are immune disorders associated with heightened type 2 immune responses and IL-5 and IL-13 production at the site of inflammation. We have previously reported that cyclooxygenase (COX) inhibition by indomethacin augmented allergic airway inflammation in a STAT6-independent manner. However, the key COX product(s) responsible for restraining indomethacin-mediated STAT6-independent allergic inflammation is unknown. In this study, using the mouse model of OVA-induced allergic airway inflammation, we identified that PGI2 receptor (IP) signaling was critical for indomethacin-induced, STAT6-independent proallergic effects. We demonstrated that IP deficiency increased inflammatory cell infiltration, eosinophilia, and IL-5 and IL-13 expression in the lung in a STAT6-independent manner. The augmented STAT6-independent allergic inflammation correlated with enhanced primary immune responses to allergic sensitization and elevated production of multiple inflammatory chemokines (CCL11, CCL17, CCL22, and CXCL12) in the lung after allergen challenge. We also showed that the PGI2 analogue cicaprost inhibited CD4 T cell proliferation and IL-5 and IL-13 expression in vitro, and IP deficiency diminished the stimulatory effect of indomethacin on STAT6-independent IL-5 and IL-13 responses in vivo. The inhibitory effects of PGI2 and the IP signaling pathway on CD4 T cell activation, inflammatory chemokine production, and allergic sensitization and airway inflammation suggest that PGI2 and its analogue iloprost, both Food and Drug Administration–approved drugs, may be useful in treating allergic diseases and asthma. In addition, inhibiting PGI2 signaling by drugs that either block PGI2 production or restrain IP signaling may augment STAT6-independent pathways of allergic inflammation.
Plasmacytoid Dendritic Cells Die by the CD8 T Cell–Dependent Perforin Pathway during Acute Nonviral Inflammation
Authors: Mossu Adrien , Daoui Anna , Bonnefoy Francis , Aubergeon Lucie , Saas Philippe , Perruche Sylvain 
Published: July 2016

Abstract
Regulation of the inflammatory response involves the control of dendritic cell survival. To our knowledge, nothing is known about the survival of plasmacytoid dendritic cells (pDC) in such situation. pDC are specialized in type I IFN (IFN-I) secretion to control viral infections, and IFN-I also negatively regulate pDC survival during the course of viral infections. In this study, we asked about pDC behavior in the setting of virus-free inflammation. We report that pDC survival was profoundly reduced during different nonviral inflammatory situations in the mouse, through a mechanism independent of IFN-I and TLR signaling. Indeed, we demonstrated that during inflammation, CD8+ T cells induced pDC apoptosis through the perforin pathway. The data suggest, therefore, that pDC have to be turned down during ongoing acute inflammation to not initiate autoimmunity. Manipulating CD8+ T cell response may therefore represent a new therapeutic opportunity for the treatment of pDC-associated autoimmune diseases, such as lupus or psoriasis.
Extensive Citrullination Promotes Immunogenicity of HSP90 through Protein Unfolding and Exposure of Cryptic Epitopes
Authors: Travers Timothy S. , Harlow Lisa , Rosas Ivan O. , Gochuico Bernadette R. , Mikuls Ted R. , Bhattacharya Sanjoy K. , Camacho Carlos J. , Ascherman Dana P. 
Published: July 2016

Abstract
Post-translational protein modifications such as citrullination have been linked to the breach of immune tolerance and clinical autoimmunity. Previous studies from our laboratory support this concept, demonstrating that autoantibodies targeting citrullinated isoforms of heat shock protein 90 (HSP90) are associated with rheumatoid arthritis complicated by interstitial lung disease. To further explore the relationship between citrullination and structural determinants of HSP90 immunogenicity, we employed a combination of ELISA-based epitope profiling, computational modeling, and mass-spectrometric sequencing of peptidylarginine deiminase (PAD)-modified protein. Remarkably, ELISAs involving selected citrullinated HSP90β/α peptides identified a key epitope corresponding to an internal Arg residue (R502 [HSP90β]/R510 [HSP90α]) that is normally buried within the crystal structure of native/unmodified HSP90. In vitro time/dose-response experiments reveal an ordered pattern of PAD-mediated deimination events culminating in citrullination of R502/R510. Conventional as well as scaled molecular dynamics simulations further demonstrate that citrullination of selected Arg residues leads to progressive disruption of HSP90 tertiary structure, promoting exposure of R502/R510 to PAD modification and subsequent autoantibody binding. Consistent with this process, ELISAs incorporating variably deiminated HSP90 as substrate Ag indicate a direct relationship between the degree of citrullination and the level of ex vivo Ab recognition. Overall, these data support a novel structural paradigm whereby citrullination-induced shifts in protein structure generate cryptic epitopes capable of bypassing B cell tolerance in the appropriate genetic context.
Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells
Authors: Provine Nicholas M. , Larocca Rafael A. , Aid Malika , Penaloza-MacMaster Pablo , Badamchi-Zadeh Alexander , Borducchi Erica N. , Yates Kathleen B. , Abbink Peter , Kirilova Marinela , Ng’ang’a David , Bramson Jonathan , Haining W. Nicholas , Barouch Dan H. 
Published: July 2016

Abstract
CD4+ T cell help is critical for optimal CD8+ T cell memory differentiation and maintenance in many experimental systems. In addition, many reports have identified reduced primary CD8+ T cell responses in the absence of CD4+ T cell help, which often coincides with reduced Ag or pathogen clearance. In this study, we demonstrate that absence of CD4+ T cells at the time of adenovirus vector immunization of mice led to immediate impairments in early CD8+ T cell functionality and differentiation. Unhelped CD8+ T cells exhibited a reduced effector phenotype, decreased ex vivo cytotoxicity, and decreased capacity to produce cytokines. This dysfunctional state was imprinted within 3 d of immunization. Unhelped CD8+ T cells expressed elevated levels of inhibitory receptors and exhibited transcriptomic exhaustion and anergy profiles by gene set enrichment analysis. Dysfunctional, impaired effector differentiation also occurred following immunization of CD4+ T cell–deficient mice with a poxvirus vector. This study demonstrates that following priming with viral vectors, CD4+ T cell help is required to promote both the expansion and acquisition of effector functions by CD8+ T cells, which is accomplished by preventing immediate dysfunction.