bluuebunny/crossref_metadata_2025 huggingface dataset:
Can serum white birch (Betula verrucosa) pollen antigen (Bet v 1) immunoglobulin E measurement distinguish between sensitization and allergy?
Authors: Ciprandi Giorgio , Comite Paola , Ferrero Francesca , Minale Paola , Voltolini Susanna , Bignardi Donatella , Fontana Vincenzo , Bruzzone Marco , Troise Costantino , Mussap Michele
Published: August 2015

Background

In clinical practice, it is fundamental to distinguish between sensitization and allergy, mainly with respect to polysensitized patients. The aim of this study was to evaluate whether serum immunoglobulin E (IgE) to white birch (Betula verrucosa) pollen antigen (Bet v 1) assessment might be able to differentiate simple sensitization from true allergy.

Methods

In total, 197 subjects (100 females; mean age 44.9 years) with serum Bet v 1 IgE positivity and history of nasal symptoms were evaluated. Subjects were subdivided in 2 groups: allergic and sensitized.

Results

Allergic patients were 58.4% of the total; they had higher serum Bet v 1 IgE levels than sensitized subjects (p < 0.001). A serum IgE to Bet v 1 value >8.94 kilo units of allergen per liter (kUA/L) was able to differentiate between sensitization and allergy (area under the receiver operating characteristic curve [AUC] = 0.76; diagnostic odds ratio, ie, degree of agreement between health status and dichotomized IgE levels [DOR] = 6.5). Gender and season when the blood was drawn influenced IgE levels.

Conclusion

Serum Bet v 1 IgE measurement may be able to differentiate sensitization from allergy in subjects with sensitization to Betulaceae pollen allergens. Thus, Bet v 1 IgE measurement should be considered a useful step in the management of patients with allergic rhinitis due to Betulaceae pollen allergens.
Multi‐institutional study of risk factors for perioperative morbidity following transnasal endoscopic pituitary adenoma surgery
Authors: Boling Caitlin C. , Karnezis Tom T. , Baker Andrew B. , Lawrence Lauren A. , Soler Zachary M. , Vandergrift W. Alexander , Wise Sarah K. , DelGaudio John M. , Patel Zara M. , Rereddy Shruthi K. , Lee John M. , Khan Mohemmed N. , Govindaraj Satish , Chan Chun , Oue Sakiko , Psaltis Alkis J. , Wormald Peter‐John , Trosman Samuel , Stokken Janalee , Woodard Troy , Sindwani Raj , Schlosser Rodney J.
Published: August 2015

Background

The goal of this study was to identify preoperative risk factors associated with increased perioperative morbidity after endoscopic pituitary surgery.

Methods

A retrospective review of patients undergoing endoscopic pituitary adenoma surgery between 2002 and 2014 at 6 international centers was performed. Standard demographic and comorbidity data, as well as information regarding tumor extent and treatment were collected. Logistic regression was used to examine risk factors for the following 30‐day outcomes: systemic complications, intracranial complications, postoperative cerebrospinal fluid (CSF) leaks, length of hospital stay, readmission, and reoperation.

Results

Data was collected on 982 patients with a mean age of 52 years. The median body mass index (BMI) for all patients was 30.9 kg/m2 with 56% female. The median hospital stay was 5 days and 23.8% of patients suffered a postoperative adverse event. Systemic complications occurred in 3.2% of patients and intraventricular extension was a risk factor (odds ratio [OR] 8.9). Intracranial complications occurred in 7.3% of patients and risk factors included previous radiation (OR 8.6) and intraventricular extension (OR 7.9). Reoperation occurred in 6.5% of patients and intraventricular extension (OR 7.3) and age (<40 years, OR 3.5; 40 to 64 years, OR 3.2) were risk factors. Postoperative CSF leaks occurred in 5.5% of patients and risk factors included female gender (OR 2.4), BMI ≥ 30 (OR 2.1), age (<40 years, OR 5.3; 40 to 64 years, OR, 7.9), and intraventricular extension (OR, 9.5).

Conclusion

Postoperative endoscopic pituitary adenoma surgery complications are associated with tumors with intraventricular extension, preoperative radiation, as well as common patient comorbidities. Identification of these factors may permit implementation of strategies to reduce postoperative complications.
Quadripartite entanglement from coupled type I second harmonic generation
Authors: Juan Guo , Shu‐qin Zhai , Ze‐hui Zhai
Published: August 2015

We present a feasible protocol of continuous variable quadripartite entanglement from the coupled type I second harmonic generation (SHG) below threshold. According to the sufficient inseparability criteria for multipartite continuous variable (CV) entanglement, the four output fields are proved to be multicolored entangled beams in separable locations with four‐mode amplitude quadratures correlation and relative phase quadratures correlation. It shows that the coupled system can produce a compact tunable multimode entangled source that can be applied into the quantum communication.

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A Family of Molecular Sieves Containing Framework‐Bound Organic Structure‐Directing Agents
Authors: Lee Jun Kyu , Shin Jiho , Ahn Nak Ho , Turrina Alessandro , Park Min Bum , Byun Youngchul , Cho Sung June , Wright Paul A. , Hong Suk Bong
Published: August 2015

Organic structure‐directing agents (OSDAs), such as quaternary ammonium cations and amines, used in the synthesis of zeolites and related crystalline microporous oxides usually end up entrapped inside the void spaces of the crystallized inorganic host lattice. But none of them is known to form direct chemical bonds to the framework of these industrially important catalysts and adsorbents. We demonstrate that ECR‐40, currently regarded as a typical silicoaluminophosphate molecular sieve, constitutes instead a new family of inorganic‐organic hybrid networks in which the OSDAs are covalently bonded to the inorganic framework. ECR‐40 crystallization begins with the formation of an Al–OSDA complex in the liquid phase in which the Al is octahedrally coordinated. This unit is incorporated in the crystallizing ECR‐40. Subsequent removal of framework‐bound OSDAs generates Al‐O‐Al linkages in a fully tetrahedrally coordinated framework.
Phosphothreonine as a Catalytic Residue in Peptide‐Mediated Asymmetric Transfer Hydrogenations of 8‐Aminoquinolines
Authors: Shugrue Christopher R. , Miller Scott J.
Published: August 2015

Phosphothreonine (pThr) was found to constitute a new class of chiral phosphoric acid (CPA) catalyst upon insertion into peptides. To demonstrate the potential of these phosphopeptides as asymmetric catalysts, enantioselective transfer hydrogenations of a previously underexplored substrate class for CPA‐catalyzed reductions were carried out. pThr‐containing peptides lead to the observation of enantioselectivities of up to 94:6 e.r. with 2‐substituted quinolines containing C8‐amino functionality. NMR studies indicate that hydrogen‐bonding interactions promote strong complexation between substrates and a rigid β‐turn catalyst.
A Gallium‐Substituted Distibene and an Antimony‐Analogue Bicyclo[1.1.0]butane: Synthesis and Solid‐State Structures
Authors: Tuscher Lars , Ganesamoorthy Chelladurai , Bläser Dieter , Wölper Christoph , Schulz Stephan
Published: August 2015

RGa {R=HC[C(Me)N(2,6‐iPr2C6H3)]2} reacts with Sb(NMe2)3 with insertion into the SbN bond and elimination of RGa(NMe2)2 (2), yielding the Ga‐substituted distibene R(Me2N)GaSbSbGa(NMe2)R (1). Thermolysis of 1 proceeded with elimination of RGa and 2 and subsequent formation of the bicyclo[1.1.0]butane analogue [R(Me2N)Ga]2Sb4 (3).
An A‐Site Mixed‐Ammonium Solid Solution Perovskite Series of [(NH2NH3)x(CH3NH3)1−x][Mn(HCOO)3] (x=1.00–0.67)
Authors: Chen Sa , Shang Ran , Wang Bing‐Wu , Wang Zhe‐Ming , Gao Song
Published: August 2015

The A‐site mixed‐ammonium solid solutions of metal–organic perovskites [(NH2NH3)x(CH3NH3)1−x][Mn(HCOO)3] (x=1.00–0.67) exhibit para‐ to ferroelectric diffuse phase transitions with lowered transition temperatures from x=1.00 to 0.67. These properties are due to the decreased framework distortion and polarization in their low temperature ferroelectric phases caused by the increased CH3NH3+ concentration.
A Cell‐Penetrating Foldamer with a Bioreducible Linkage for Intracellular Delivery of DNA
Authors: Douat Céline , Aisenbrey Christopher , Antunes Stéphanie , Decossas Marion , Lambert Olivier , Bechinger Burkhard , Kichler Antoine , Guichard Gilles
Published: August 2015

Despite significant advances in foldamer chemistry, tailored delivery systems based on foldamer architectures, which provide a high level of control over secondary structure, are curiously rare among non‐viral technologies for transporting nucleic acids into cells. A potent pH‐responsive, bioreducible cell‐penetrating foldamer (CPF) was developed through covalent dimerization of a short (8‐mer) amphipathic oligourea sequence bearing histidine‐type units. This CPF exhibits a high capacity to assemble with pDNA and mediates efficient delivery of nucleic acids into the cell. Furthermore, it does not adversely affect cellular viability and was shown to compare favorably with a cognate peptide transfection agent based on His‐rich sequences.
Synthesis and properties of PMMA‐ZrO2 organic–inorganic hybrid films
Authors: Alvarado‐Beltrán Clemente Guadalupe , Almaral‐Sánchez Jorge Luis , Ramírez‐Bon Rafael
Published: August 2015

In this work we report the synthesis process and properties of PMMA‐ZrO2 organic–inorganic hybrid films. The hybrid films were deposited by a modified sol‐gel process using zirconium propoxide (ZP) as the inorganic (zirconia) source, methyl methacrylate (MMA) as the organic source, and 3‐trimetoxy‐silyl‐propyl‐methacrylate (TMSPM) as the coupling agent between organic and inorganic phases. The films were deposited by dip coating on glass slide substrates from a hybrid precursor solution containing the three precursors with molar ratio 1 : 0.25 : 0.25 for ZP, TMSPM, and MMA, respectively. After deposition, the hybrid thin films were heat‐treated at 100°C for 24 h. The macroscopic characteristics of the hybrid films such as high homogeneity and high optical transparence evidenced the formation of a cross‐linked, interpenetrated organic–inorganic network. The deposited PMMA‐ZrO2 hybrid films were homogeneous, highly transparent and very well adhered to substrates. Fourier Transform Infra‐Red measurements of the hybrid films display absorption bands of chemical groups associated with both PMMA and ZrO2 phases. The amounts of organic and inorganic phases in the hybrid films were determined from thermogravimetric measurements. The surface morphology and homogeneity of the hybrid films at microscopic level were analyzed by scanning electron microscopy and atomic force microscopy images. From the analysis of optical transmission and reflection spectra, the optical constants (refraction index and extinction coefficient) of the hybrid films were determined, employing a physical model to simulate the hybrid optical layers. The refraction index of the hybrid films at 532 nm was 1.56. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42738.
Highly crystalline and oriented high‐strength poly(ethylene terephthalate) fibers by using low molecular weight polymer
Authors: Avci Huseyin , Najafi Mesbah , Kilic Ali , Kotek Richard
Published: August 2015

High‐strength poly(ethylene terephthalate) (PET) fibers were obtained using low molecular weight (LMW) polymervia horizontal isothermal bath (hIB), followed by postdrawing process. We investigated the unique formations of different precursors, which differentiated in its molecular orientation and crystalline structures from traditional high‐speed spinning PET fibers. Sharp increase in crystallinity was observed after drawing process even though the fibers showed almost no any crystallinity before the drawing. Properties of as‐spun and drawn hIB and control filaments at different process conditions were compared. As would be expected, performances of resulted treated undrawn and drawn fibers have dramatically improved with developing unique morphologies. Tenacities more than 8 g/d for as‐spun and 10 g/d for drawn treated fibers after just drawn at 1.279 draw ratio were observed. These performances are considerably higher than that of control fibers. An explanation of structural development of high‐strength fibers using LMW polymer spun with hIB is proposed. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42747.
Crosslinking and ozone degradation of thermosetting resins based on maleic anhydride/diene copolymer and polyfunctional alcohols
Authors: Lou Limin , Nagashima Mika , Okamura Haruyuki , Matsumoto Akikazu
Published: August 2015

Crosslinking and de‐crosslinking reactions of an alternating copolymer of maleic anhydride (MAn) and 2,4‐dimethyl‐1,3‐pentadiene (DMPD) by thermal curing with polyfunctional alcohols as the crosslinkers and subsequent ozone degradation are reported in this article. The ring‐opening reaction of an anhydride group by polyfunctional alcohols produces network polymers with an ester linkage. The rate of crosslinking reaction depends on the curing conditions, i.e. the structure of the used alcohols and the curing temperature and time. The crosslinking density of the alcohol‐cured copolymers is low due to a slow reaction between the anhydride and hydroxy groups, being different from the corresponding epoxy‐cured copolymer with a dense network structure reported in a previous article. The insoluble resins are readily de‐crosslinked and solubilized by ozone degradation. The polymer surface modification by ozone is also investigated. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42763.
Synthesis and Analgesic Activity of Annelated Xanthine Derivatives in Experimental Models in Rodents
Authors: Zygmunt Małgorzata , Sapa Jacek , Drabczyńska Anna , Karcz Tadeusz , Müller Christa , Köse Meryem , Latacz Gniewomir , Schabikowski Jakub , Bednarski Marek , Kieć‐Kononowicz Katarzyna
Published: August 2015

A series of annelated derivatives of xanthine were synthesized and assayed as potential analgesic agents. All synthesized xanthine derivatives were tested in the writhing test and hot‐plate test. The pharmacological assays demonstrated that all the compounds prepared, without exception, displayed a significant activity in the mouse writhing assay. The analgesic action of the most active compounds, expressed as ED50 was found to be 1.4–4.3 times more potent than that of acetylsalicylic acid used as the reference compound. However, only some of the compounds demonstrated analgesic activity in the hot‐plate test. The analgesic effect of some compounds is probably related to their agonistic, antagonistic, or partial agonistic activity at the adenosine receptors.
Inhibition of Natural Killer Cell Cytotoxicity by Interleukin‐6: Implications for the Pathogenesis of Macrophage Activation Syndrome
Authors: Cifaldi Loredana , Prencipe Giusi , Caiello Ivan , Bracaglia Claudia , Locatelli Franco , De Benedetti Fabrizio , Strippoli Raffaele
Published: August 2015

Objective

Systemic juvenile idiopathic arthritis (JIA) is associated with high levels of interleukin‐6 (IL‐6) in the serum and synovial fluid, and impairment of natural killer (NK) cell function is often observed. This study was undertaken to evaluate a possible link between these 2 biologic findings and whether they may be associated with the development of macrophage activation syndrome, a condition frequently observed in systemic JIA.

Methods

Splenocytes from wild‐type (WT) or IL‐6–transgenic (Tg) mice were evaluated for NK cell cytotoxicity using a 51Cr‐release assay. Numbers of NK cells and expression of perforin, granzyme B, CD69, and CD107a were evaluated by flow cytometry. Human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors were treated with IL‐6 and cultured in the presence or absence of tocilizumab (TCZ), an IL‐6 receptor blocker. Human polyclonal NK cells from healthy donor PBMCs were evaluated for cell cytotoxicity and expression of perforin, granzyme B, and CD107a. PBMCs harvested from patients with systemic JIA during periods of active or inactive disease were left untreated or treated with IL‐6 in combination with soluble IL‐6 receptor and analyzed for the expression of perforin and granzyme B.

Results

Splenic NK cell cytotoxicity was reduced in IL‐6–Tg mice compared to WT mice. Levels of CD69 and CD107a showed no significant differences, whereas expression of perforin and granzyme B was impaired in NK cells from IL‐6–Tg mice. Exposure of human peripheral blood NK cells to IL‐6 led to reduced expression of perforin and granzyme B. Culturing human polyclonal NK cells in the presence of TCZ significantly increased cell cytotoxicity, and also increased expression of perforin and granzyme B. In patients with systemic JIA, a reduction in IL‐6 plasma levels during disease remission correlated with the rescue of perforin and granzyme B expression in NK cells from these patients.

Conclusion

In both mice and humans, IL‐6 down‐modulated the cytotoxic activity of NK cells. This decrease was associated with reduced perforin and granzyme B levels in the absence of altered granule exocytosis.
Autoantibodies in Prediction of the Development of Rheumatoid Arthritis Among Healthy Relatives of Patients With the Disease
Authors: Ramos‐Remus Cesar , Castillo‐Ortiz Jose Dionisio , Aguilar‐Lozano Luis , Padilla‐Ibarra Jorge , Sandoval‐Castro Carlos , Vargas‐Serafin Cesar Omar , de la Mora‐Molina Hector , Ramos‐Gomez Ariadna , Sanchez‐Ortiz Adriana , Avila‐Armengol Hilario , Aceves‐Avila Francisco Javier
Published: August 2015

Objective

Although blood bank–based studies have shown that rheumatoid arthritis (RA)–related autoantibodies are present before the onset of RA, information on their positive predictive value (PPV) for development of RA in healthy individuals is scarce. This study was undertaken to assess the 5‐year PPV of serum IgM rheumatoid factor (IgM‐RF) and anti–cyclic citrullinated peptide (anti‐CCP) for the development of RA among healthy relatives of patients with RA.

Methods

Healthy relatives of RA patients were invited to participate in a cohort study. At baseline, information on participants’ medical history was obtained, and serum levels of IgM‐RF and anti‐CCP antibodies were determined (by nephelometry and second‐generation anti‐CCP enzyme‐linked immunosorbent assay, respectively). The subjects were followed up every 4 months via a structured interview (Community Oriented Program for Control of Rheumatic Diseases [COPCORD] questionnaire). When the COPCORD questionnaire indicated possible arthritis, subjects underwent an in‐office rheumatology assessment including joint count. The study end point was defined as fulfillment of the American College of Rheumatology criteria for RA.

Results

Eight hundred nineteen initially healthy relatives of 252 patients with RA were included (69% female, 41% offspring, mean ± SD age 35 ± 12 years). Eleven (1.3%) were positive for both anti–CCP‐2 and RF, 12 (1.5%) only for anti–CCP‐2, and 16 (2%) only for RF. RA developed in 17 (2.1%) of the relatives during the 5‐year followup (3,313 person‐years for the seronegative group and 60.8 person‐years for the anti–CCP‐2–positive group). The PPV was 64% when both anti–CCP‐2 and RF were positive and 58% when only anti–CCP‐2 was positive. Offspring of patients with RA had an independent 3‐fold increased risk of developing RA.

Conclusion

Results of the present study indicate that the magnitude of risk for developing RA in healthy relatives of patients with RA can be estimated using simple routine laboratory tests.
Autoimmune Disease–Associated Haplotypes of BLK Exhibit Lowered Thresholds for B Cell Activation and Expansion of Ig Class‐Switched B Cells
Authors: Simpfendorfer Kim R. , Armstead Brandon E. , Shih Andrew , Li Wentian , Curran Mark , Manjarrez‐Orduño Nataly , Lee Annette T. , Diamond Betty , Gregersen Peter K.
Published: August 2015

Objective

B lymphoid kinase (BLK) is associated with rheumatoid arthritis (RA) and several other B cell–associated autoimmune disorders. BLK risk variants are consistently associated with reduced BLK expression, but the mechanisms by which reduced expression alters human B cell function to confer autoimmune disease susceptibility are unknown. This study was undertaken to characterize the BLK risk haplotype and to determine associated B cell functional phenotypes involved in autoimmunity.

Methods

The BLK risk haplotype association with RA (determined using whole‐genome sequencing data) was confirmed in 2,526 RA cases and 2,134 controls. Peripheral blood mononuclear cells (PBMCs) from RA patients, healthy adults, and umbilical cord blood were used to study B cell functional phenotypes associated with the BLK risk genotype. Association of the BLK haplotype with B cell phenotypes was analyzed using cell culture and flow cytometry.

Results

Two insertion/deletions were found on the RA risk haplotype in BLK, and the reduction in BLK expression associated with the risk haplotype was confirmed in primary B lymphocytes. Carriers of the RA‐associated haplotype had evidence of lower basal B cell receptor (BCR) signaling activity, yet their B cells were hyperactivatable, with enhanced up‐regulation of CD86 after BCR crosslinking and greater T cell stimulatory capacity. The number of isotype‐switched memory B cells was also significantly increased in subjects carrying the risk haplotype.

Conclusion

A major mechanism underlying the BLK association with autoimmune disease involves lowered thresholds for BCR signaling, enhanced B cell–T cell interactions, and altered patterns of isotype switching.
Rheumatoid Factor Is Associated With the Distribution of Hand Joint Destruction in Rheumatoid Arthritis
Authors: Terao Chikashi , Yamakawa Noriyuki , Yano Koichiro , Markusse Iris M. , Ikari Katsunori , Yoshida Shinji , Furu Moritoshi , Hashimoto Motomu , Ito Hiromu , Fujii Takao , Ohmura Koichiro , Murakami Kosaku , Takahashi Meiko , Hamaguchi Masahide , Tabara Yasuharu , Taniguchi Atsuo , Momohara Shigeki , Raychaudhuri Soumya , Allaart Cornelia F. , Yamanaka Hisashi , Mimori Tsuneyo , Matsuda Fumihiko
Published: August 2015

Objective

Rheumatoid arthritis (RA) is a chronic disease leading to joint destruction. Although many studies have addressed factors potentially correlated with the speed of joint destruction, less attention has been paid to the distribution of joint destruction in patients with RA. In this study, destruction of the hand bones in patients with RA was classified into 2 anatomic subgroups, the fingers and the non‐fingers, with the aim of analyzing which factors are associated with destruction of the finger joints.

Methods

A total of 1,215 Japanese patients with RA were recruited from 2 different populations. The degree of joint destruction was assessed using the total modified Sharp/van der Heijde score (SHS) of radiographic joint damage. The SHS score of joint damage in the finger joints was used as the dependent variable, and the SHS score in the non‐finger joints was used as a covariate. Age, sex, disease duration, smoking, C‐reactive protein level, treatment for RA, and positivity for and levels of anti–citrullinated protein antibodies and rheumatoid factor (RF) were evaluated as candidate correlates. Overall effect sizes were assessed in a meta‐analysis. In addition, associations observed in the Japanese patients were compared to those in a cohort of 157 Dutch RA patients in the BeSt study (a randomized, controlled trial involving 4 different strictly specified treatment strategies for early RA).

Results

Not surprisingly, disease duration in Japanese patients with RA was associated with the finger SHS score (P ≤ 0.00037). Both positivity for and levels of RF showed significant associations with the finger SHS score after adjustment for covariates (P = 0.0022 and P = 8.1 × 10−7, respectively). These associations were also true in relation to the time‐averaged finger SHS score. An association between RF positivity and the finger SHS score was also observed in Dutch patients with RA in the BeSt study (P = 0.049).

Conclusion

Positivity for and levels of RF are associated with finger joint destruction independent of non‐finger joint destruction and other covariates. Our findings suggest that there are different mechanisms of joint destruction operating in the finger joints of patients with RA.
Identification of Interleukin‐1β–Producing Monocytes That Are Susceptible to Pyronecrotic Cell Death in Patients With Neonatal‐Onset Multisystem Inflammatory Disease
Authors: Edwan Jehad H. , Goldbach‐Mansky Raphaela , Colbert Robert A.
Published: August 2015

Objective

Spontaneous inflammatory responses initiated by NLRP3 mutations promote inflammasome‐mediated interleukin‐1β (IL‐1β) processing and release and can induce rapid necrotic cell death. The cells that produce IL‐1β in neonatal‐onset multisystem inflammatory disease (NOMID) have not been clearly identified, nor have the mechanisms mediating IL‐1β release and cell death been completely elucidated.

Methods

Whole blood cells were stimulated with lipopolysaccharide (LPS) in the presence of cathepsin B and caspase 1 inhibitors, followed by ATP treatment. Supernatants were collected and incubated with IL‐1β–capturing beads. Cells were fixed, permeabilized, and stained for a combination of cell surface and intracellular markers, and a novel flow cytometry bead‐based assay was used to measure secreted IL‐1β. LPS‐stimulated cells were also evaluated using immunofluorescence microscopy.

Results

Monocytes characterized by CD14high‐CD16low expression and intracellular CD83 were increased in NOMID patients and were responsible for the majority of IL‐1β production in response to LPS stimulation. This population of monocytes also underwent a rapid death response with LPS alone that is temporally associated with IL‐1β and ASC release and has characteristic features of pyronecrotic but not pyroptotic cell death. Inhibition of cell death reduced IL‐1β production from NOMID patient cells. In addition, IL‐1 triggered cell death in monocytes from NOMID patients.

Conclusion

Our findings indicate that monocytes are the predominant IL‐1β–producing cell population in the peripheral blood of NOMID patients. Furthermore, they suggest that IL‐1 receptor blockade may work in part by preventing pyronecrotic cell death, which may be an important target in NOMID and other forms of cryopyrin‐associated periodic syndromes.
Brief Report: Endothelial‐Specific X‐Box Binding Protein 1 Deficiency Limits Tumor Necrosis Factor–Induced Leukocyte Recruitment and Vasculitis
Authors: Ziogas Athanasios , Muders Michael H. , Economopoulou Matina , Sprott David , Grossklaus Sylvia , Siegert Gabriele , Baretton Gustavo B. , Mitroulis Ioannis , Chavakis Triantafyllos
Published: August 2015

Objective

Endothelial cell activation by tumor necrosis factor (TNF) and associated leukocyte infiltration are hallmarks of vasculitis. The aim of this study was to investigate the potential role of the cellular stress–associated endothelial X‐box binding protein 1 (XBP‐1) transcription factor in TNF‐induced endothelial cell inflammation and vasculitis.

Methods

Mice with an endothelial cell–specific XBP‐1 deficiency were used in a modified local Shwartzman reaction (LSR) model of TNF‐induced small vessel vasculitis. To address the contribution of XBP‐1 to the TNF‐mediated inflammatory response in endothelial cells, we examined the activation of XBP‐1 expression by TNF as well as the effect of XBP‐1 knockdown in endothelial cells on TNF‐induced signaling, proinflammatory gene expression, and leukocyte–endothelial cell adhesion.

Results

The active spliced form of XBP‐1 in endothelial cells was triggered by TNF. In addition, endothelial XBP‐1 contributed to the sustained TNF‐triggered NF‐κB−dependent transcriptional activation of proinflammatory molecules, which was associated with leukocyte–endothelial cell adhesion. In the LSR model, endothelial cell–specific XBP‐1–deficient mice displayed significantly less vascular damage, accompanied by reduced perivascular neutrophil infiltration, as compared with wild‐type mice.

Conclusion

Endothelial XBP‐1 is activated by TNF and regulates leukocyte–endothelial cell adhesion in vitro as well as neutrophil infiltration and vascular damage in murine vasculitis.
Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid
Authors: Spengler Julia , Lugonja Božo , Jimmy Ytterberg A. , Zubarev Roman A. , Creese Andrew J. , Pearson Mark J. , Grant Melissa M. , Milward Michael , Lundberg Karin , Buckley Christopher D. , Filer Andrew , Raza Karim , Cooper Paul R. , Chapple Iain L. , Scheel‐Toellner Dagmar
Published: August 2015

Objective

In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PADs). Neutrophils express high levels of PAD and accumulate in the synovial fluid (SF) of RA patients during disease flares. This study was undertaken to test the hypothesis that neutrophil cell death, induced by either NETosis (extrusion of genomic DNA–protein complexes known as neutrophil extracellular traps [NETs]) or necrosis, can contribute to production of autoantigens in the inflamed joint.

Methods

Extracellular DNA was quantified in the SF of patients with RA, patients with osteoarthritis (OA), and patients with psoriatic arthritis (PsA). Release of PAD from neutrophils was investigated by Western blotting, mass spectrometry, immunofluorescence staining, and PAD activity assays. PAD2 and PAD4 protein expression, as well as PAD enzymatic activity, were assessed in the SF of patients with RA and those with OA.

Results

Extracellular DNA was detected at significantly higher levels in RA SF than in OA SF (P < 0.001) or PsA SF (P < 0.05), and its expression levels correlated with neutrophil concentrations and PAD activity in RA SF. Necrotic neutrophils released less soluble extracellular DNA compared to NETotic cells in vitro (P < 0.05). Higher PAD activity was detected in RA SF than in OA SF (P < 0.05). The citrullinated proteins PAD2 and PAD4 were found attached to NETs and also freely diffused in the supernatant. PAD enzymatic activity was detected in supernatants of neutrophils undergoing either NETosis or necrosis.

Conclusion

Release of active PAD isoforms into the SF by neutrophil cell death is a plausible explanation for the generation of extracellular autoantigens in RA.
Incidence of Malignancies in Patients With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Diagnosed Between 1991 and 2013
Authors: Rahmattulla Chinar , Berden Annelies E. , Wakker Sophie‐Charlotte , Reinders Marlies E. J. , Hagen Ernst C. , Wolterbeek Ron , Bruijn Jan A. , Bajema Ingeborg M.
Published: August 2015

Objective

To investigate the incidence of malignancies during longitudinal followup of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and to examine the effect of immunosuppressive therapy on malignancy risk in these patients.

Methods

The study population consisted of patients with histopathologically confirmed AAV, diagnosed between 1991 and 2013 at a large university hospital. The mean duration of followup was 10 years. Malignancy incidence was assessed using the Dutch National Pathology Database. Incidence rates from the Netherlands Cancer Registry were used to compare malignancy incidence in the AAV cohort to that in the general Dutch population.

Results

Thirty‐six of 138 patients with AAV developed a total of 85 malignancies during a mean followup of 9.7 years. The sex‐, age‐, and calendar year–adjusted malignancy risk was 2.21‐fold higher (95% confidence interval [95% CI] 1.64–2.92) than that in the general population. Non‐melanoma skin cancers occurred most frequently (standardized incidence ratio 4.23 [95% CI 2.76–6.19]). The incidence rates of other malignancies were not significantly increased. Malignancy risk was associated with the duration of cyclophosphamide (CYC) therapy and, interestingly, was not increased in patients who had received CYC for <1 year.

Conclusion

Patients with AAV have a higher risk of malignancy than the general population, but this risk is accounted for solely by non‐melanoma skin cancers. Over the years, the risk of other malignancies—specifically bladder and hematologic malignancies—has decreased in patients with AAV. This finding reflects ongoing efforts to reduce CYC exposure by developing new treatment regimens.
Gout Is a Chronic Inflammatory Disease in Which High Levels of Interleukin‐8 (CXCL8), Myeloid‐Related Protein 8/Myeloid‐Related Protein 14 Complex, and an Altered Proteome Are Associated With Diabetes Mellitus and Cardiovascular Disease
Authors: Kienhorst Laura B. E. , van Lochem Ellen , Kievit Wietske , Dalbeth Nicola , Merriman Marilyn E. , Phipps‐Green Amanda , Loof Arnoud , van Heerde Waander , Vermeulen Sita , Stamp Lisa K. , van Koolwijk Elly , de Graaf Jacqueline , Holzinger Dirk , Roth Johannes , Janssens Hein J. E. M. , Merriman Tony R. , Broen Jasper C. A. , Janssen Matthijs , Radstake Timothy R. D. J.
Published: August 2015

Objective

The frequent association of gout with metabolic syndrome and cardiovascular disease (CVD) suggests that it has a systemic component. Our objective was to study whether circulating proinflammatory cytokines are associated with comorbidities in gout patients.

Methods

We studied 330 gout patients from 3 independent cohorts and compared them with 144 healthy individuals and 276 disease controls. We measured circulating levels of interleukin‐8 (IL‐8)/CXCL8, IL‐1β, IL‐6, IL‐10, IL‐12, and tumor necrosis factor, after which we performed proteome‐wide analysis in a selection of samples to identify proteins that were possibly prognostic for the development of comorbidities. Replication analysis was performed specifically for myeloid‐related protein 8 (MRP‐8)/MRP‐14 complex.

Results

Compared to healthy controls and disease control patients, patients with gouty arthritis (n = 48) had significantly higher mean levels of CXCL8 (P < 0.001), while other cytokines were almost undetectable. Similarly, patients with intercritical gout showed high levels of CXCL8. CXCL8 was independently associated with diabetes mellitus in patients with intercritical gout (P < 0.0001). Proteome‐wide analysis in gouty arthritis (n = 18) and intercritical gout (n = 39) revealed MRP‐8 and MRP‐14 as the proteins with the greatest differential expression between low and high levels of CXCL8 and also showed a positive correlation of MRP8/MRP14 complex with CXCL8 levels (R2 = 0.49, P < 0.001). These findings were replicated in an independent cohort. The proteome of gout patients with high levels of CXCL8 was associated with diabetes mellitus (odds ratio 16.5 [95% confidence interval 2.8–96.6]) and CVD (odds ratio 3.9 [95% confidence interval 1.0–15.3]).

Conclusion

Circulating levels of CXCL8 are increased during both the acute and intercritical phases of gout, and they coincide with a specific circulating proteome that is associated with risk of diabetes mellitus and CVD. Further research focused on the roles of CXCL8 and MRP8/MRP14 complex in patients with gout is warranted.
Chimeric RNA Oligonucleotides with Triazole and Phosphate Linkages: Synthesis and RNA Interference
Authors: Fujino Tomoko , Kogashi Kanako , Okada Koudai , Mattarella Martin , Suzuki Takeru , Yasumoto Kenichi , Sogawa Kazuhiro , Isobe Hiroyuki
Published: August 2015

Chimeric RNA oligonucleotides with an artificial triazole linker were synthesized using solution‐phase click chemistry and solid‐phase automated synthesis. Scalable synthesis methods for jointing units for the chimeric structure have been developed, and after click‐coupling of the jointing units with triazole linkers, a series of chimeric oligonucleotides was prepared by utilizing the well‐established phosphoramidite method for the elongation. The series of chimeric 21‐mer oligonucleotides that possessed the triazole linker at different strands and positions allowed for a screening study of the RNA interference to clarify the preference of the triazole modifications in small‐interfering RNA molecules.
Training Staff to Implement a Paired‐stimulus Preference Assessment using Video Modeling with Voiceover Instruction
Authors: Deliperi Prisca , Vladescu Jason C. , Reeve Kenneth F. , Reeve Sharon A. , DeBar Ruth M.
Published: August 2015

A key component of successful early intervention programming is the identification of stimuli that may function as reinforcers. One common direct method used by behavior analysts to determine preference is the paired‐stimulus (PS) preference assessment. Although effective at identifying potential reinforcers, the PS procedure is only useful if staff are trained on the steps necessary to conduct the assessment. The current study examined the effectiveness of video modeling with voiceover instruction to train staff to conduct a PS preference assessment. Three staff were trained to do the following: (i) identify items to use during the PS assessment; (ii) conduct a PS preference assessment with a simulated consumer (i.e., an adult acting as a child); and (iii) score and interpret the results of the PS assessment. Generalization was assessed with an actual consumer (i.e., a child with an autism spectrum disorder). The results demonstrated that video modeling was effective, and staff demonstrated high levels of integrity up to 2 months following training. These results support a growing body of literature supporting the use of video modeling as an approach to training. Copyright © 2015 John Wiley & Sons, Ltd.
Luminescence and energy‐transfer properties of color‐tunable Ca2Mg0.25Al1.5Si1.25O7:Ce3+/Eu2+/Tb3+ phosphors for ultraviolet light‐emitting diodes
Authors: Yuan Bo. , Song Yanhua , Sheng Ye. , Zheng Keyan , Huo Qisheng , Xu Xuechun , Zou Haifeng
Published: August 2015

A series of Ca2Mg0.25Al1.5Si1.25O7:Ce3+/Eu2+/Tb3+ phosphors was been prepared via a conventional high temperature solid‐state reaction and their luminescence properties were studied. The emission spectra of Ca2Mg0.25Al1.5Si1.25O7:Ce3+,Eu2+ and Ca2Mg0.25Al1.5Si1.25O7:Ce3+,Tb3+ phosphors show not only a band due to Ce3+ ions (409 nm) but also as a band due to Eu2+ (520 nm) and Tb3+ (542 nm) ions. More importantly, the effective energy transfer from Ce3+ to Eu2+ and Tb3+ ions was confirmed and investigated by emission/excitation spectra and luminescent decay behaviors. Furthermore, the energy level scheme and energy transfer mechanism were investigated and were demonstrated to be of resonant type via dipole–dipole (Ce3+ to Eu2+) and dipole–quadrupole (Ce3+ to Tb3+) reactions, respectively. Under excitation at 350 nm, the emitting color could be changed from blue to green by adjusting the relative doping concentration of Ce3+ and Eu2+ ions as well as Ce3+ and Tb3+ ions. The above results indicate that Ca2Mg0.25Al1.5Si1.25O7:Ce3+,Eu2+/Tb3+ are promising single‐phase blue‐to‐green phosphors for application in phosphor conversion white‐light‐emitting diodes. Copyright © 2015 John Wiley & Sons, Ltd.
A selective determination of copper ions in water samples based on the fluorescence quenching of thiol‐capped CdTe quantum dots
Authors: Nurerk Piyaluk , Kanatharana Proespichaya , Bunkoed Opas
Published: August 2015

CdTe quantum dots (QDs) capped with different stabilizers, i.e. thioglycolic acid (TGA), 3‐mercaptopropionic acid (MPA) and glutathione (GSH) were investigated as fluorescent probes for the determination of Cu2+. The stabilizer was shown to play an important role in both the sensitivity and selectivity for the determination of Cu2+. TGA‐capped CdTe QDs showed the highest sensitivity, followed by the MPA and GSH‐capped CdTe QDs, respectively. The TGA‐ and MPA‐capped CdTe QDs were not selective for Cu2+ that was affected by Ag+. The GSH‐capped CdTe QDs were insensitive to Ag+ and were used to determine Cu2+ in water samples. Under optimal conditions, quenching of the fluorescence intensity (F0/F) increased linearly with the concentration of Cu2+ over a range of 0.10–4.0 µg/mL and the detection limit was 0.06 µg/mL. The developed method was successfully applied to the determination of Cu2+ in water samples. Good recoveries of 93–104%, with a relative standard deviation of < 6% demonstrated that the developed simple method was accurate and reliable. The quenching mechanisms were also described. Copyright © 2015 John Wiley & Sons, Ltd.
Twisting Tourniquet© Technique: introducing Schnogh, a novel device and its effectiveness in treating primary and secondary lymphedema of extremities
Authors: Chanwimalueang Narumon , Ekataksin Wichai , Piyaman Parkpoom , Pattanapen Gedsuda , Hanboon Borimas K.
Published: August 2015

Twisting Tourniquet© or in Thai “Schnogh” is a new invention for compression therapy of lymphedema. Twisting Tourniquet© Technique (TTT) is totally noninvasive for lymphedema management. After the amazing successful evidence in the first series of 28 patients, we have conducted preliminary studies in lymphedema clinics. It was found that the combination of gradually increasing constriction force by Schnogh until desired pressure was reached and maintained for 15 min, followed by a 5‐min release, doing repeatedly this compression‐decompression for at least 10 sessions a day, can generate acceptable results. The aim of the study was to evaluate the scientific effectiveness and establish a treatment protocol of TTT proposed as a therapeutic approach for clinical management of lymphedema. During 2006–2013, from over 3500 patients, 647 with primary/secondary lymphedema passed inclusion criteria, 307 for upper, and 340 for lower extremity. In the 5‐day course of TTT, each day patients underwent 10 sessions of a 15‐min compression followed by a 5‐min decompression. Vegan diet was encouraged as an adjuvant therapy. Among lymphedema patients whose spectrum of edema severity ranged from mild to gigantic, TTT yielded an average volume reduction rate (VR) at 50.2% and 55.6%, making the average edema reduction volume attained at 463 and 1856 mL for upper and lower limb, respectively. The uniformed practice by Schnogh which supports a continual compression–decompression maneuver over 3.5 h daily for five consecutive days could induce an average VR at above half of the swelling in extremities of 647 patients. Schnogh is therefore effective in clinical management of lymphedema under TTT treatment of fibroblastic interstitium.
Valsartan protects HK‐2 cells from contrast media‐induced apoptosis by inhibiting endoplasmic reticulum stress
Authors: Peng Ping‐an , Wang Le , Ma Qian , Xin Yi , Zhang Ou , Han Hong‐ya , Liu Xiao‐li , Ji Qing‐wei , Zhou Yu‐jie , Zhao Ying‐xin
Published: August 2015

Contrast‐induced acute kidney injury (CI‐AKI) is associated with increasing in‐hospital and long‐term adverse clinical outcomes in high‐risk patients undergoing percutaneous coronary intervention (PCI). Contrast media (CM)‐induced renal tubular cell apoptosis is reported to participate in this process by activating endoplasmic reticulum (ER) stress. An angiotensin II type 1 receptor (AT1R) antagonist can alleviate ER stress‐induced renal apoptosis in streptozotocin (STZ)‐induced diabetic mice and can reduce CM‐induced renal apoptosis by reducing oxidative stress and reversing the enhancement of bax mRNA and the reduction of bcl‐2 mRNA, but the effect of the AT1R blocker on ER stress in the pathogenesis of CI‐AKI is still unknown. In this study, we explored the effect of valsartan on meglumine diatrizoate‐induced human renal tubular cell apoptosis by measuring changes in ER stress‐related biomarkers. The results showed that meglumine diatrizoate caused significant cell apoptosis by up‐regulating the expression of ER stress markers, including glucose‐regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), CCAAT/enhancer‐binding protein‐homologous protein (CHOP) and caspase 12, in a time‐ and dose‐dependent manner, which could be alleviated by preincubation with valsartan. In conclusion, valsartan had a potential nephroprotective effect on meglumine diatrizoate‐induced renal cell apoptosis by inhibiting ER stress.
Cross‐Linked Thiazolidine Network as Support for Palladium: A New Catalyst for Suzuki and Heck Reactions
Authors: Bivona Lucia Anna , Giacalone Francesco , Vaccaro Luigi , Aprile Carmela , Gruttadauria Michelangelo
Published: August 2015

A thiazolidine‐based material was used for the first time as support for palladium. The support was prepared by starting from a highly cross‐linked thiazolium‐based material, obtained by radical oligomerization of a bisvinylthiazolium dibromide salt in the presence of 3‐mercaptopropyl‐modified silica SBA‐15. Palladium was immobilized by treatment with tetrachloropalladate salt. Reduction with sodium borohydride afforded a thiazolidine‐based material that acted as ligands for the Pd species. The thiazolidine‐based palladium catalyst was fully characterized and, working in only 0.1 mol % amount, displayed good activity in the Suzuki–Miyaura and in the Heck reactions. Several biphenyl and alkene compounds could be prepared in high yields. The catalytic material proved to be fully recoverable and it was representatively used for three times in the Suzuki–Miyaura reaction without showing any decrease in its activity.
Glycerol/Dodecanol Double Pickering Emulsions Stabilized by Polystyrene‐Grafted Silica Nanoparticles for Interfacial Catalysis
Authors: Shi Hui , Fan Zhaoyu , Ponsinet Virginie , Sellier Remi , Liu Honglai , Pera‐Titus Marc , Clacens Jean‐Marc
Published: August 2015

Polystyrene‐grafted silica nanoparticles bearing sulfonic acid centers and with tunable amphiphilic properties were designed to perform the biphasic etherification reaction of glycerol with dodecanol at the interface of Pickering emulsions. By optimizing the hydrophobic properties of the particles, double Pickering emulsions could be generated allowing a facilitated diffusion of glycerol and dodecanol into the microenvironment near the acid centers.
Mesoporous Titania‐Iron(III) Oxide with Nanoscale Porosity and High Catalytic Activity for the Synthesis of β‐Amino Alcohols and Benzimidazole Derivatives
Authors: Roy Susmita , Banerjee Biplab , Salam Noor , Bhaumik Asim , Islam Sk. Manirul
Published: August 2015

A mesoporous TiO2‐Fe2O3 mixed oxide material (MTF‐1E) with nanoscale porosity and a high BET surface area was synthesized using sodium dodecyl sulfate (SDS) as a structure‐directing agent. The material was characterized by powder XRD, high‐resolution TEM, N2 sorption, and NH3 temperature‐programmed desorption studies. The catalyst shows an excellent regioselectivity for the ring‐opening of epoxides with amines under solvent‐free conditions at room temperature for the synthesis of a series of β‐amino alcohols. It also showed a very high catalytic efficiency for the synthesis of benzimidazole derivatives in water. The catalyst can be recovered easily from the reaction medium and reused six times without a significant decrease in its catalytic activity and selectivity.
High‐Temperature, In Situ X‐ray Absorption Study of Sr2MgMoO6 Solid‐Oxide Fuel‐Cell Anode Materials
Authors: Eigenbrodt Bryan C. , Young Anthony M. , Howell Thomas G. , Segre Carlo U. , Reitz Thomas L.
Published: August 2015

Limitations of current solid oxide fuel cell anode materials have spurred the exploration of alternative materials. Mixed ionic and electronic conducting anode materials have the potential to overcome these limitations. The mixed ionic and electronic conducting material explored in this work is Sr2MgMoO6 (SMMO). X‐ray absorption spectroscopy in conjunction with an in situ assembly was used to study the fundamental redox chemistry of SMMO at 800 °C. The X‐ray absorption spectra for the Mo K‐edge exhibited changes in the reduced and oxidized bulk SMMO samples, as evident in a shift in the Mo binding energies and in the formation of oxide vacancies. However, in situ measurements of the working devices revealed that the Mo oxidation state remained unchanged under various cell polarizations. These findings demonstrate that SMMO, as a solid oxide fuel cell anode, has the potential to provide adequate electron conduction through multivalent Mo sites and to provide fuel tolerance through oxide vacancies built into its crystal structure.