bluuebunny/crossref_metadata_2025_split huggingface dataset:
Injection Force Comparison of the Old and New Dexamethasone Implant Insertion Needles in Porcine Eyes and Synthetic Sclera
Authors: Eaton Alexander M. , Gordon Gabriel M. , Booth Dave , Wafapoor Hussein , Avery Robert L. 
Published: May 2014

BACKGROUND AND OBJECTIVE:
Determine whether the new dexamethasone intravitreal implant (Ozurdex; Allergan, Irvine, CA) injector needle design can reduce the force needed for insertion when compared to the original needle design.

MATERIALS AND METHODS:
In vitro testing assessed the force required for insertion from five new-design and five old-design Ozurdex needles on a synthetic test medium and explanted porcine eyes. Maximum penetration force was measured in grams-force, while the total work of the needle was measured in joules.

RESULTS:

The new design required 29% and 68% less overall work to perform an injection in the synthetic medium (
P
= .0002) and porcine eyes (
P
= .009), respectively. The maximum force required to insert the new needle was 25% and 61% that of the old needle in the synthetic medium (
P
= .001) and porcine eyes (
P
= .007), respectively.

CONCLUSION:
The new needle design significantly reduces the force and work needed for insertion, which should improve physician control as well as patient safety and comfort.

[
Ophthalmic Surg Lasers Imaging Retina
. 2014;45:232–238.]
Human Dendritic Cells Exhibit a Pronounced Type I IFN Signature following Leishmania major Infection That Is Required for IL-12 Induction
Authors: Favila Michelle A. , Geraci Nicholas S. , Zeng Erliang , Harker Brent , Condon David , Cotton Rachel N. , Jayakumar Asha , Tripathi Vinita , McDowell Mary Ann 
Published: May 2014

Abstract
Leishmania major–infected human dendritic cells (DCs) exhibit a marked induction of IL-12, ultimately promoting a robust Th1-mediated response associated with parasite killing and protective immunity. The host cell transcription machinery associated with the specific IL-12 induction observed during L. major infection remains to be thoroughly elucidated. In this study, we used Affymetrix GeneChip (Affymetrix) to globally assess the host cell genes and pathways associated with early L. major infection in human myeloid-derived DCs. Our data revealed 728 genes were significantly differentially expressed and molecular signaling pathway revealed that the type I IFN pathway was significantly enriched. Addition of a neutralizing type I IFN decoy receptor blocked the expression of IRF7 and IL-12p40 during DC infection, indicating the L. major–induced expression of IL-12p40 is dependent upon the type I IFN signaling pathway. In stark contrast, IL-12p40 expression is not elicited by L. donovani, the etiological agent of deadly visceral leishmaniasis. Therefore, we examined the gene expression profile for several IFN response genes in L. major versus L. donovani DC infections. Our data revealed that L. major, but not L. donovani, induces expression of IRF2, IRF7, and IFIT5, implicating the regulation of type I IFN–associated signaling pathways as mediating factors toward the production of IL-12.
Intravenous Immunoglobulin Treatment in Humans Suppresses Dendritic Cell Function via Stimulation of IL-4 and IL-13 Production
Authors: Tjon Angela S. W. , van Gent Rogier , Jaadar Haziz , Martin van Hagen P. , Mancham Shanta , van der Laan Luc J. W. , te Boekhorst Peter A. W. , Metselaar Herold J. , Kwekkeboom Jaap 
Published: May 2014

Abstract
High-dose i.v. Ig (IVIg) is a prominent immunomodulatory therapy for various autoimmune and inflammatory diseases. Recent mice studies suggest that IVIg inhibits myeloid cell function by inducing a cascade of IL-33–Th2 cytokine production causing upregulation of the inhibitory FcγRIIb, as well as by modulating IFN-γ signaling. The purpose of our study was to explore whether and how these mechanisms are operational in IVIg-treated patients. We show that IVIg in patients results in increases in plasma levels of IL-33, IL-4, and IL-13 and that increments in IL-33 levels correlate with rises in plasma IL-4 and IL-13 levels. Strikingly, no upregulation of FcγRIIb expression was found, but instead a decreased expression of the activating FcγRIIa on circulating myeloid dendritic cells (mDCs) after high-dose, but not after low-dose, IVIg treatment. In addition, expression of the signaling IFN-γR2 subunit of the IFN-γR on mDCs was downregulated upon high-dose IVIg therapy. In vitro experiments suggest that the modulation of FcγRs and IFN-γR2 on mDCs is mediated by IL-4 and IL-13, which functionally suppress the responsiveness of mDCs to immune complexes or IFN-γ. Human lymph nodes and macrophages were identified as potential sources of IL-33 during IVIg treatment. Interestingly, stimulation of IL-33 production in human macrophages by IVIg was not mediated by dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin (DC-SIGN). In conclusion, high-dose IVIg treatment inhibits inflammatory responsiveness of mDCs in humans by Th2 cytokine-mediated downregulation of FcγRIIa and IFN-γR2 and not by upregulation of FcγRIIb. Our results suggest that this cascade is initiated by stimulation of IL-33 production that seems DC-SIGN independent.
Deletion of CD24 Impairs Development of Heat Shock Protein gp96–Driven Autoimmune Disease through Expansion of Myeloid-Derived Suppressor Cells
Authors: Thaxton Jessica E. , Liu Bei , Zheng Pan , Liu Yang , Li Zihai 
Published: May 2014

Abstract
CD24 binds to and suppresses inflammation triggered by danger-associated molecular patterns such as heat shock proteins (HSPs) and high-mobility group box 1. Paradoxically, CD24 has been shown to enhance autoimmune disease. In this study, we attempt to reconcile this paradox by deletion of CD24 (24KO) in a lupus-like disease model driven by forced expression of HSP gp96 at the cell surface (transgenic mice [tm]). As expected, tm24KO mice showed increased CD11c+ dendritic cell activation coupled to a significant increase in dendritic cell–specific IL-12 production compared with tm mice. However, tm24KO mice showed less CD4 T cell activation and peripheral inflammatory cytokine production in comparison with tm mice. We characterized an enhanced immune suppressive milieu in tm24KO mice distinguished by increased TGF-β and greater regulatory T cell–suppressive capacity. We found greater absolute numbers of myeloid-derived suppressor cells (MDSCs) in tm24KO mice and showed that the Ly6C+ MDSC subset had greater suppressive capacity from tm24KO mice. Deletion of CD24 in tm mice led to diminished lupus-like pathology as evidenced by anti-nuclear Ab deposition and glomerulonephritis. Finally, we show that expanded MDSC populations were mediated by increased free high-mobility group box 1 in tm24KO mice. Thus, the deletion of CD24 in an HSP-driven model of autoimmunity led to the unexpected development of regulatory T cell and MDSC populations that augmented immune tolerance. Further study of these populations as possible negative regulators of inflammation in the context of autoimmunity is warranted.
Carbonic Anhydrase IV Is Expressed on IL-5–Activated Murine Eosinophils
Authors: Wen Ting , Mingler Melissa K. , Wahl Benjamin , Khorki M. Eyad , Pabst Oliver , Zimmermann Nives , Rothenberg Marc E. 
Published: May 2014

Abstract
Eosinophilia and its cellular activation are hallmark features of asthma, as well as other allergic/Th2 disorders, yet there are few, if any, reliable surface markers of eosinophil activation. We have used a FACS-based genome-wide screening system to identify transcriptional alterations in murine lung eosinophils recruited and activated by pulmonary allergen exposure. Using a relatively stringent screen with false-positive correction, we identified 82 candidate genes that could serve as eosinophil activation markers and/or pathogenic effector markers in asthma. Carbonic anhydrase IV (Car4) was a top dysregulated gene with 36-fold induction in allergen-elicited pulmonary eosinophils, which was validated by quantitative PCR, immunohistochemistry, and flow cytometry. Eosinophil CAR4 expression was kinetically regulated by IL-5, but not IL-13. IL-5 was both necessary and sufficient for induction of eosinophil CAR4. Although CAR4-deficient mice did not have a defect in eosinophil recruitment to the lung, nor a change in eosinophil pH-buffering capacity, allergen-challenged chimeric mice that contained Car4−/− hematopoietic cells aberrantly expressed a series of genes enriched in biological processes involved in epithelial differentiation, keratinization, and anion exchange. In conclusion, we have determined that eosinophils express CAR4 following IL-5 or allergen exposure, and that CAR4 is involved in regulating the lung transcriptome associated with allergic airway inflammation; therefore, CAR4 has potential value for diagnosing and monitoring eosinophilic responses.
Dectin-1 Pathway Activates Robust Autophagy-Dependent Unconventional Protein Secretion in Human Macrophages
Authors: Öhman Tiina , Teirilä Laura , Lahesmaa-Korpinen Anna-Maria , Cypryk Wojciech , Veckman Ville , Saijo Shinobu , Wolff Henrik , Hautaniemi Sampsa , Nyman Tuula A. , Matikainen Sampsa 
Published: May 2014

Abstract
Dectin-1 is a membrane-bound pattern recognition receptor for β-glucans, which are the main constituents of fungal cell walls. Detection of β-glucans by dectin-1 triggers an effective innate immune response. In this study, we have used a systems biology approach to provide the first comprehensive characterization of the secretome and associated intracellular signaling pathways involved in activation of dectin-1/Syk in human macrophages. Transcriptome and secretome analysis revealed that the dectin-1 pathway induced significant gene expression changes and robust protein secretion in macrophages. The enhanced protein secretion correlated only partly with increased gene expression. Bioinformatics combined with functional studies revealed that the dectin-1/Syk pathway activates both conventional and unconventional, vesicle-mediated, protein secretion. The unconventional protein secretion triggered by the dectin-1 pathway is dependent on inflammasome activity and an active autophagic process. In conclusion, our results reveal that unconventional protein secretion has an important role in the innate immune response against fungal infections.
Regulatory T Cells and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment Undergo Fas-Dependent Cell Death during IL-2/αCD40 Therapy
Authors: Weiss Jonathan M. , Subleski Jeff J. , Back Tim , Chen Xin , Watkins Stephanie K. , Yagita Hideo , Sayers Thomas J. , Murphy William J. , Wiltrout Robert H. 
Published: May 2014

Abstract
Fas ligand expression in certain tumors has been proposed to contribute to immunosuppression and poor prognosis. However, immunotherapeutic approaches may elicit the Fas-mediated elimination of immunosuppressive regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) within tumors that represent major obstacles for cancer immunotherapy. Previously, we showed that IL-2 and agonistic CD40 Ab (αCD40) elicited synergistic antitumor responses coincident with the efficient removal of Tregs and MDSCs. We demonstrate in this study in two murine tumor models that Treg and MDSC loss within the tumor microenvironment after IL-2/αCD40 occurs through a Fas-dependent cell death pathway. Among tumor-infiltrating leukocytes, CD8+ T cells, neutrophils, and immature myeloid cells expressed Fas ligand after treatment. Fas was expressed by tumor-associated Tregs and immature myeloid cells, including MDSCs. Tregs and MDSCs in the tumor microenvironment expressed active caspases after IL-2/αCD40 therapy and, in contrast with effector T cells, Tregs significantly downregulated Bcl-2 expression. In contrast, Tregs and MDSCs proliferated and expanded in the spleen after treatment. Adoptive transfer of Fas-deficient Tregs or MDSCs into wild-type, Treg-, or MDSC-depleted hosts resulted in the persistence of Tregs or MDSCs and the loss of antitumor efficacy in response to IL-2/αCD40. These results demonstrate the importance of Fas-mediated Treg/MDSC removal for successful antitumor immunotherapy. Our results suggest that immunotherapeutic strategies that include exploiting Treg and MDSC susceptibility to Fas-mediated apoptosis hold promise for treatment of cancer.
First Impressions of Cardiovascular Calcification Treatment in Hemodialysis Patients with a New Dialysis Fluid Containing Sodium Thiosulphate (STS)
Authors: Yonova Diana H. , Vazelov Evgueniy S. , Trendafilov Ivan I. , Stoinova Veselka V. , Nedevska Mariya T. , Antonov Simeon A. 
Published: May 2014

Background Cardiovascular calcification (CVC) in hemodialysis patients (HDP) causes cardiovascular pathology. Up until now very few drugs and therapeutic interventions have been able to reduce cardiovascular calcium deposits in hemodialysis patients and the process requires more than a year. Our idea in this study was to test 2 calcium binders – sodium thiosulfate (STS) and dinatrium ethylene diamine tetraacetic acid (DNEDTA) – for prevention and treatment of cardiovascular calcification of hemodialysis patients, using both substances not as an intravenous infusion but by adding them to the liquid bicarbonate part of the dialysis fluid. Material and Methods 6 HDPs were treated with sodium thiosulphate (STS), 6 with dinatrium ethylene diamine tetraacetic acid (DNEDTA), and 6 patients served as controls. Electrolytes, liver function, markers of inflammation, oxidative stress, bone metabolism, spiral computed tomography (SCT) of coronary CVC and bone densitometry were performed twice (start and end of the study). Results Starting blood parameters were similar to the end (STS group). No toxic or side effects from STS were observed. Initially in the DNEDTA group all the patients had vomiting so we excluded DNEDTA from the study. SCT found a significant reduction of calcification in 4 patients (STS group) and retardation in 2 patients comparatively to controls. Conclusions The first results are hopeful, but the number of the patients was small, so we are enlarging the enrollment in the expectation of corroborating our results soon.
The Dialysis Staff Workload and the Blood Volume Tracking System during the Hemodialysis Sessions of Hypotension-prone Patients
Authors: Doria Maria , Genovesi Simonetta , Biagi Fabio , Steckiph Denis , Mancini Elena , Stella Andrea , Santoro Antonio 
Published: May 2014

Purpose Intradialytic hypotension (IDH) represents a common hemodialysis (HD) complication. Blood volume tracking (BVT) is a tool regulating the relative blood volume changes and potentially reducing the occurrence of IDH. The aim of this study was to evaluate the ability of BVT to reduce the staff workload associated to IDH. Methods Ten hypotension-prone HD patients were treated each with 39 conventional HD (HD) sessions and then switched to 39 HD sessions with BVT (HD-BVT). The staff interventions related to IDH were monitored by a trained staff. Results Dialysis sessions complicated by IDH and staff interventions were affected by BVT (HD: 102 and 127 vs. HD-BVT: 57 and 59, respectively, for both p<0.001). The time consumed by staff in IDH management was decreased by HD-BVT (1416 vs. 578 min, p<0.001). Conclusions The effectiveness of BVT to reduce the frequency of IDH leads to a reduction of the dialysis staff workload with fewer staff interventions, allowing for major work-time saving.
Superior in vivo Compatibility of Hydrophilic Polymer Coated Prosthetic Vascular Grafts
Authors: Strang Aart C. , Knetsch Menno L.W. , Idu Mirza M. , Bisoendial Radjesh J. , Kramer Gertjan , Speijer Dave , Koole Leo H. , Stroes Erik S.G. , Rotmans Joris I. 
Published: May 2014

Purpose Protein adsorption, cell adhesion and graft patency was compared in hydrophilic versus hydrophobic polymer-coated prosthetic vascular grafts. We hypothesize that in vivocompatibility of hydrophilic polymer-coated prosthetic vascular grafts is superior to in vivo compatibility of hydrophobic grafts. Methods A pairwise side-to-side common carotid artery interposition graft was placed eight female landrace goats (mean weight 55 kg). Protein adsorption was assessed using Western Blot in two hydrophilic and two hydrophobic grafts harvested after three days. Graft patency was monitored for 28 days in six goats with continuous wave Doppler ultrasonography. Adherence of endothelial cells, leukocytes and platelets was determined with ELISA and compared between the two graft types after 28 days. Results After three days, more ApoA-l, albumin and VEGF and less fibrin adsorbed to hydrophilic grafts. After 28 days, compared to hydrophobic grafts, higher numbers of endothelial cells were present on hydrophilic grafts (P=0.016), and less thrombocytes and leukocytes (P=0.012 and 0.024, respectively). Two out of eight hydrophobic grafts lost patency, while none of the hydrophilic grafts failed (P=0.157). Conclusions Hydrophilic polymer-coated vascular grafts have superior in vivo compatibility when compared to hydrophobic grafts as characterized by reduced platelet and leukocyte adherence as well as higher endothelialization.
Evaluation of Post-Puncture Bleeding Time of Arteriovenous Fistulas with IRIS® Bandage
Authors: Boulanger Henri , Ahriz-Saksi Salima , Flamant Martin , Vigeral Philippe 
Published: May 2014

Purpose Our aim was to evaluate the safety and effectiveness of the IRIS® bandage (Nephrokit®) on post-puncture bleeding compared to conventional manual compression. Methods Sixty-four patients, hemodialyzed with an arteriovenous fistula, were enrolled in a 3-week prospective study. Conventional manual compression was used during the first week, the IRIS® bandage during the second week and conventional manual compression again during the third week. The outcomes analyzed were the persistence or absence of bleeding 3 minutes post-puncture with IRIS® device compared to conventional manual compression. The safety of the IRIS® bandage was also evaluated. Results Rates of persistent bleeding 3 minutes post-puncture at arterial sites were 53±6% and 56±5%, respectively, during the first and third weeks (conventional compression) versus 18±5% during the second week (IRIS® bandage). Similarly, rates of persistent bleeding 3 minutes post-puncture at venous sites were 45±6% and 45±6%, respectively, with conventional compression versus 23±5% with the IRIS® bandage. The difference between the IRIS® device and conventional compression therefore proved highly statistically significant (p<0.05) for both arterial and venous puncture sites. No particular adverse events were observed with the IRIS® device. Conclusions Post-puncture bleeding time at arteriovenous fistula sites is significantly shortened by the IRIS® bandage in comparison with conventional manual compression.
Distal Ulnar-Basilic Fistula as the First Hemodialysis Access
Authors: Shintaku Sadanori , Kawanishi Hideki , Moriishi Misaki , Bansyodani Masataka , Tsuchiya Shinichiro 
Published: May 2014

Purpose A distal forearm ulnar-basilic (UB) arteriovenous fistula (AVF) can be chosen if a radial-cephalic (RC)-AVF is not suitable for a primary AVF. However, limited data are available on the feasibility of using a distal forearm UB-AVF as an option for primary AVF. Methods This retrospective analysis included 446 patients for whom AVFs (417 RC and 29 UB) had been newly created from January 2003 to December 2009, at our hospital. Patients in whom the arterial or venous anatomy precluded RC-AVF creation, UB-AVF was established as distally as possible on the forearm. Patency, defined as access survival after creation, was calculated using Kaplan-Meier analysis. The difference in patency between the two groups was examined using log-rank test. Results The primary patency of UB-AVFs was significantly lower than that of RC-AVFs (p=0.037, log-rank test). The primary patency rate at 1 year was 25.0% versus 44.7%, respectively. However, there was no significant difference in secondary patency between the two groups. The secondary patency rate at 1 year was 85.5% for UB-AVFs versus 82.9% for RC-AVFs. The incidence rate of percutaneous angioplasty until access abandonment per patient-years was 1.100 for UB-AVFs versus 0.671 for RC-AVFs. There was no difference in the time to maturation between the two groups. Conclusions The secondary patency rate of UB-AVF is similar to that of RC-AVF. We recommend the creation of an UB-AVF when an RC-AVF is not a suitable option for the primary AVF.
Efficacy of Normal Saline in the Maintenance of the Arterial Lines in Comparison to Heparin Flush: A Comprehensive Review of the Literature
Authors: Kordzadeh Ali , Austin Tomas , Panayiotopoulos Yiannis 
Published: May 2014

Purpose The aim of this study is to examine the efficacy of normal saline (0.9% sodium chloride) as a flush solution on patency of arterial lines in comparison to heparin flush. Data have been examined in various categories of specialty (medical, surgical, cardiac, burns, gynecology), frequency of flushes, strength and volume of flushes, continuous versus bolus, duration of each flush and patency incidence (range, ≤24 to ≥96 hours). The secondary aim focused on the incidences of reported heparin-induced thrombocytopenia (HIT type I and II). Methods A comprehensive review of the literature from 1951 to 2012. An electronic search of OVID, Medline, Embase, Cochrane, Scopus and CINAHL database in English language was conducted. The search was limited to adult subjects only. The following keywords were used: heparin flush, saline flush, 0.9% sodium chloride flush, arterial line and indwelling vascular line. A total of ten papers (n=10) were found eligible. Results The evidence suggests patency is feasible with both solutions but if longer duration of use (arterial line) is advocated, heparin is superior in the long term. Furthermore, heparin flush effects are dose dependent and require fewer numbers of flushes. In addition, no adverse effects were found with heparin flush solution. Conclusion There is level 1 evidence to support heparin as a flush solution once the time frame exceeds 48 hours. In addition, there is level 1 evidence to suggest that heparin at higher doses and in continuous infusion has better patency incidence with no reports of HIT type II or I.
Translesional Pressure Ratio Predicts Technical Outcome and Patency in Angioplasty on Outflow Stenosis of Hemodialysis Graft
Authors: Lai Chi-Cheng , Fang Hua-Chang , Tsai Han-Lin , Mar Guang-Yuan , Tseng Ching-Jiunn , Liu Chun-Peng , Liou Jau-Cheng 
Published: May 2014

Purpose Translesional pressure ratio (TLPR) indicating fractional flow reserve has been applied to physiological assessment of moderate coronary stenosis. The role of TLPR in hemodialysis (HD) patients with arteriovenous graft (AVG) outflow stenosis undergoing percutaneous transluminal angioplasty (PTA) is unclear. The purpose of the study was to assess the validation of TLPR in such patients undergoing PTA. Methods Patients with pure AVG outflow stenosis confirmed by angiography were prospectively enrolled. A TLPR defined as a ratio of the mean pressure downstream to the lesion(s) to the vein-sided intragraft pressure was measured using a catheter pullback method. Relationship among TLPR, angiographic result and clinical outcome within 6 months was detected. Results Of 65 PTAs, the post-PTA TLPR significantly increased (from 0.28±0.10 to 0.50±0.11; p<0.0001). A significantly greater pre-PTA TLPR was observed in the simple lesions at baseline compared with the complex lesions (0.32±0.09 vs. 0.20±0.06; p<0.0001). Post-PTA TLPR ≥0.5 was powerfully related to angiographic success (p<0.0001). The group with angiographic success plus post-PTA TLPR ≥0.5 had a longer PTA-free patency (208.7±188.7 vs. 109.8±67.7 days; p=0.013) compared with that with angiographic nonsuccess plus post-PTA TLPR <0.5. Conclusions Our data show that TLPR correlates well with lesion properties and angiographic results, and helps predict following unassisted patency. The study suggests TLPR as a hemodynamic indicator during PTA.