bluuebunny/crossref_metadata_2025 huggingface dataset:
Myoinjury transiently activates muscle antigen–specific CD8+ T cells in lymph nodes in a mouse model
Authors: Liao Hua , Franck Emilie , Fréret Manuel , Adriouch Sahil , Baba‐Amer Yasmine , Authier Francois‐Jerome , Boyer Olivier , Gherardi Romain K.
Published: September 2012

Objective

To investigate the influence of myoinjury on antigen presentation to T cells in draining lymph nodes (LNs).

Methods

Muscle crush was performed in mice injected with exogenous ovalbumin (OVA) and in transgenic SM‐OVA mice expressing OVA as a muscle‐specific self antigen. Antigen exposure and the resulting stimulation of T cell proliferation in draining LNs was assessed by transferring carboxyfluorescein succinimidyl ester (CFSE)–labeled OVA‐specific CD8+ and CD4+ T cells from OT‐I and OT‐II mice and by measuring the dilution of CFSE, which directly reflects their proliferation. The role of monocyte‐derived dendritic cells (DCs) in T cell priming was assessed using pharmacologic blockade of DC migration. Immunofluorescence was used to detect CD8+ T cells, inflammatory monocyte‐derived DCs, and type I major histocompatibility complex (MHC)–expressing myofibers in crushed muscle, and to assess expression of perforin, interferon‐γ (IFNγ), interleukin‐2 (IL‐2), IL‐10, and transforming growth factor β1 (TGFβ1).

Results

OVA injection into intact muscle induced strong proliferation of CD4+ and CD8+ T cells, indicating efficient exposure of soluble antigens in draining LNs. OVA‐specific CD8+ T cell proliferation in draining LNs of SM‐OVA mice required myoinjury and was unaffected by pharmacologic inhibition of monocyte‐derived DC migration. On day 7 postinjury, activated CD8+ T cells expressing perforin, IFNγ and IL‐2 were transiently detected in crushed muscle, and these cells were in close contact with class I MHC–positive regenerating myofibers. Beginning on day 7, the immunosuppressive cytokines IL‐10 and TGFβ1 were conspicuously expressed by CD11b+ cells, and CD8+ T cells rapidly disappeared from the healing muscle.

Conclusion

Myofiber damage induces an episode of muscle antigen–specific CD8+ T cell proliferation in draining LNs. Activated CD8+ T cells transiently infiltrate the injured muscle, with prompt control by immunosuppressive cues. Inadequate control might favor sustained autoimmune myositis.
Coagulation aggravates blood‐induced joint damage in dogs
Authors: van Meegeren Monique E. R. , Roosendaal Goris , Barten‐van Rijbroek Angelique D. , Schutgens Roger E. G. , Lafeber Floris P. J. G. , Mastbergen Simon C.
Published: September 2012

Objective

Joint bleeding due to trauma, major joint surgery, or hemophilia leads to joint damage. It is unclear if there are differences between coagulating blood and anticoagulated blood with respect to joint degeneration, especially in vivo. Therefore, we undertook this study to evaluate in a canine in vivo model whether intraarticular exposure to coagulating blood is more destructive than exposure to anticoagulated blood, and whether inflammation plays a role in the cartilage‐ damaging process.

Methods

In 7 dogs the left knees were injected with coagulating blood 4 times a week during weeks 1 and 4, and the right knees were injected with saline. In 7 other dogs, anticoagulated heparinized blood was injected, and heparinized saline was used as control. Ten weeks after the last injection, cartilage matrix turnover and synovial inflammation were analyzed. To study inflammation‐independent cartilage damage, explants of cartilage from at least 6 human donors per group were exposed in vitro to coagulating and anticoagulated blood, plasma, and serum for 4 days. Cartilage matrix turnover was determined after a recovery period of 12 days.

Results

Canine knees injected with coagulating blood showed more disturbed proteoglycan turnover than knees injected with anticoagulated blood. Synovial inflammation was present only after intraarticular injections with coagulating blood. In in vitro experiments, exposure of human cartilage explants to coagulating blood resulted in more damage than did exposure to anticoagulated blood, while exposure to plasma and serum did not alter cartilage matrix turnover.

Conclusion

This study shows that coagulating blood causes more long‐lasting in vivo joint damage than anticoagulated blood, thereby suggesting that along with joint bleeding in hemophilia, exposure to intraarticular blood should also be avoided during surgery and trauma to prevent joint damage.
The mesenchymal stem cell marker CD248 (endosialin) is a negative regulator of bone formation in mice
Authors: Naylor Amy J. , Azzam Eman , Smith Stuart , Croft Adam , Poyser Callum , Duffield Jeremy S. , Huso David L. , Gay Steffen , Ospelt Caroline , Cooper Mark S. , Isacke Clare , Goodyear Simon R. , Rogers Michael J. , Buckley Christopher D.
Published: September 2012

Objective

CD248 (tumor endothelial marker 1/endosialin) is found on stromal cells and is highly expressed during malignancy and inflammation. Studies have shown a reduction in inflammatory arthritis in CD248‐knockout (CD248−/−) mice. The aim of the present study was to investigate the functional effect of genetic deletion of CD248 on bone mass.

Methods

Western blotting, polymerase chain reaction, and immunofluorescence were used to investigate the expression of CD248 in humans and mice. Micro–computed tomography and the 3‐point bending test were used to measure bone parameters and mechanical properties of the tibiae of 10‐week‐old wild‐type (WT) or CD248−/− mice. Human and mouse primary osteoblasts were cultured in medium containing 10 mM β‐glycerophosphate and 50 μg/ml ascorbic acid to induce mineralization, and then treated with platelet‐derived growth factor BB (PDGF‐BB). The mineral apposition rate in vivo was calculated by identifying newly formed bone via calcein labeling.

Results

Expression of CD248 was seen in human and mouse osteoblasts, but not osteoclasts. CD248−/− mouse tibiae had higher bone mass and superior mechanical properties (increased load required to cause fracture) compared to WT mice. Primary osteoblasts from CD248−/− mice induced increased mineralization in vitro and produced increased bone over 7 days in vivo. There was no decrease in bone mineralization and no increase in proliferation of osteoblasts in response to stimulation with PDGF‐BB, which could be attributed to a defect in PDGF signal transduction in the CD248−/− mice.

Conclusion

There is an unmet clinical need to address rheumatoid arthritis–associated bone loss. Genetic deletion of CD248 in mice results in high bone mass due to increased osteoblast‐mediated bone formation, suggesting that targeting CD248 in rheumatoid arthritis may have the effect of increasing bone mass in addition to the previously reported effect of reducing inflammation.
Rituximab mediates loss of CD19 on B cells in the absence of cell death
Authors: Jones Jonathan D. , Hamilton B. JoNell , Rigby William F. C.
Published: September 2012

Objective

To evaluate loss of the B cell–specific marker CD19 after the addition of rituximab (RTX) to healthy donor blood and to determine the role of complement‐mediated cytotoxicity in these cells.

Methods

Whole blood and peripheral blood mononuclear cells (PBMCs) from healthy donors were evaluated for the loss of CD19 in the presence of RTX using flow cytometry. The effect of complement on CD19 loss was examined using serum‐free media, C3‐ and C5‐deficient sera, and a C5‐blocking antibody. Evidence of B cell death was evaluated by measuring messenger RNA (mRNA) levels as well as by flow cytometry. Transfer of CD19 antigen to monocytes and neutrophils was evaluated by flow cytometry and confocal microscopy.

Results

RTX induced a rapid decrease in CD19 count (mean 51%; n = 37) in PBMCs. This reduction occurred in the absence of complement. Despite the decrease in CD19 expression, B cell death did not occur, as evidenced by a lack of change in CD19 or CD20 mRNA levels and a lack of change in CD19 levels determined by intracellular staining and through the use of viability dyes. The CD19 antigen was shown to be transferred to monocytes and neutrophils in an Fc‐dependent manner.

Conclusion

Our findings indicate that the addition of RTX to healthy donor PBMCs in vitro results in complement‐independent loss of CD19 without causing B cell death. CD19 is transferred from B cells to monocytes and neutrophils during shaving of the RTX–CD20 complex in an Fc‐dependent manner. These data suggest that monitoring the effect of RTX by measuring the CD19+ cell count may be compromised by this activity.
Th17 cells are restrained by Treg cells via the inhibition of interleukin‐6 in patients with rheumatoid arthritis responding to anti–tumor necrosis factor antibody therapy
Authors: McGovern Jenny L. , Nguyen Dao X. , Notley Clare A. , Mauri Claudia , Isenberg David A. , Ehrenstein Michael R.
Published: September 2012

Objective

The importance of interleukin‐17 (IL‐17) is underscored both by its resistance to control by Treg cells and the propensity of Treg cells to produce this highly inflammatory cytokine. This study sought to address whether Th17 cells are inhibited by Treg cells in rheumatoid arthritis (RA) patients responding to anti–tumor necrosis factor (anti‐TNF) therapy, and if so defining the underlying mechanisms of suppression.

Methods

Inhibition of Th17 cell responses was determined by Treg cell suppression assays. The Treg cell phenotype was analyzed using flow cytometry and enzyme‐linked immunosorbent assay. Mechanisms of suppression were tested by cytokine addition or antibody blockade.

Results

Th17 responses were inhibited by Treg cells from RA patients responding to the anti‐TNF antibody adalimumab (Tregada), but not by Treg cells from healthy individuals or patients with active RA. Furthermore, Tregada cells secreted less IL‐17, even when exposed to proinflammatory monocytes from patients with active RA. Tregada cells suppressed Th17 cells through the inhibition of monocyte‐derived IL‐6, but this effect was independent of IL‐10 and transforming growth factor β, which mediated the suppression of Th1 responses. Adalimumab therapy led to a reduction in retinoic acid receptor–related orphan nuclear receptor C–positive Th17 cells and an increase in FoxP3+ Treg cells lacking expression of the transcription factor Helios. However, this acquisition of IL‐17–suppressor function was not observed in RA patients responding to treatment with etanercept, a modified TNF receptor–Fc fusion protein. Indeed, there was no alteration in Treg cell number, function, or phenotype in etanercept‐treated patients, and Th17 responses remained unchecked.

Conclusion

Th1 and Th17 responses are controlled through distinct mechanisms by Treg cells from patients responding to anti‐TNF antibody therapy. Adalimumab therapy, but not etanercept therapy, induces a potent and stable Treg cell population with the potential to restrain the progression of IL‐17–associated inflammation in RA via regulation of monocyte‐derived IL‐6.
European genetic ancestry is associated with a decreased risk of lupus nephritis
Authors: Richman Ilana B. , Taylor Kimberly E. , Chung Sharon A. , Trupin Laura , Petri Michelle , Yelin Edward , Graham Robert R. , Lee Annette , Behrens Timothy W. , Gregersen Peter K. , Seldin Michael F. , Criswell Lindsey A.
Published: September 2012

Objective

African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than are SLE patients of European descent. This study was undertaken to investigate whether European genetic ancestry protects against the development of lupus nephritis, with the aim of exploring the genetic and socioeconomic factors that might explain this effect.

Methods

This was a cross‐sectional study of SLE patients from a multiethnic case collection. Participants were genotyped for 126 single‐nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. Logistic regression was used to test the association between European ancestry and renal disease. Analyses were adjusted for continental ancestries, socioeconomic status (SES), and candidate genes.

Results

Participants (n = 1,906) had, on average, 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among the participants, 656 (34%) had renal disease. A 10% increase in the proportion of European ancestry estimated in each participant was associated with a 15% reduction in the odds of having renal disease, after adjustment for disease duration and sex (odds ratio 0.85, 95% confidence interval 0.82–0.87; P = 1.9 × 10−30). Adjustment for other genetic ancestries, measures of SES, or SNPs in the genes most associated with renal disease (IRF5 [rs4728142], BLK [rs2736340], STAT4 [rs3024912], and HLA–DRB1*0301 and DRB1*1501) did not substantively alter this relationship.

Conclusion

European ancestry is protective against the development of renal disease in SLE, an effect that is independent of other genetic ancestries, candidate risk alleles, and socioeconomic factors.
Association of anti–citrullinated vimentin and anti–citrullinated α‐enolase antibodies with subsets of rheumatoid arthritis
Authors: Montes Ariana , Perez‐Pampin Eva , Calaza Manuel , Gomez‐Reino Juan J. , Gonzalez Antonio
Published: September 2012

Objective

To determine whether the anti–citrullinated vimentin peptide 60–75 (anti–Cit‐vimentin) and the immunodominant anti–citrullinated α‐enolase peptide 1 (anti–CEP‐1) antibodies are associated with subsets of patients with rheumatoid arthritis (RA) independently of the associations between anti–cyclic citrullinated peptide (anti‐CCP) antibodies and clinical features of RA.

Methods

The 3 antibody types were quantified by enzyme‐linked immunosorbent assay (ELISA) in serum samples from 521 patients with RA and 173 healthy controls of Spanish ancestry. Genotypes for HLA–DRB1 alleles and rs2476601 in PTPN22 were available for these patients and controls plus an additional 106 healthy controls. A combined analysis of the 3 antibodies was conducted using stratified contingency tables and logistic regression models.

Results

A differential, particularly strong, and independent association was observed between the presence of anti–Cit‐vimentin antibodies and the presence of shared epitope (SE) alleles, specifically in patients carrying 2 SE alleles, and between the presence of anti– Cit‐vimentin antibodies and the prevalence of joint erosion. Associations were observed between anti–CEP‐1 positivity and the presence of HLA–DRB1 and PTPN22 risk alleles and their additive interaction. These associations were not accounted for by the anti‐CCP status.

Conclusion

Our results indicate that the 2 antibodies against citrullinated peptides analyzed in this study add specific information beyond that obtained with the anti‐CCP status. They define subgroups of patients with RA in which genetic factors have different weight and there is an observed difference in the prevalence of erosions.
Brief Report: IRF5 systemic lupus erythematosus risk haplotype is associated with asymptomatic serologic autoimmunity and progression to clinical autoimmunity in mothers of children with neonatal lupus
Authors: Cherian Tharian S. , Kariuki Silvia N. , Franek Beverly S. , Buyon Jill P. , Clancy Robert M. , Niewold Timothy B.
Published: September 2012

Objective

Variation in the interferon regulatory factor 5 (IRF5) gene has been associated with risk of developing systemic lupus erythematosus (SLE), and this association is largely dependent upon anti‐Ro autoantibodies. This study was undertaken to determine if the IRF5 genotype is associated with maternal diagnosis or progression of autoimmunity.

Methods

Genotyping of haplotype‐tagging polymorphisms in IRF5 was performed in 93 subjects of European ancestry who were recruited to the Research Registry for Neonatal Lupus. All subjects had high‐titer anti‐Ro autoantibodies and had a child with neonatal lupus (NL); allele frequencies were compared to those in nonautoimmune controls. The mothers had SLE, Sjögren's syndrome (SS), or undifferentiated autoimmune syndrome (UAS), or were asymptomatic.

Results

The SLE risk haplotype of IRF5 was enriched in all anti‐Ro–positive subjects except in those with SS (odds ratio [OR] 2.55, P = 8.8 × 10−4). The SLE risk haplotype was even enriched in asymptomatic individuals with anti‐Ro antibodies (OR 2.69, P = 0.019). The same haplotype was more prevalent in subjects who were initially asymptomatic but developed symptomatic SLE during followup (OR 5.83, P = 0.0024). Interestingly, SS was associated with 2 minor IRF5 haplotypes, and these same haplotypes were decreased in frequency in mothers with SLE and those with UAS.

Conclusion

The IRF5 SLE risk haplotype was associated with anti‐Ro antibody positivity in asymptomatic individuals, as well as with progression to SLE in asymptomatic anti‐Ro–positive individuals. SS in mothers of children with NL was associated with different IRF5 haplotypes. These data suggest that IRF5 polymorphisms play a role in serologic autoimmunity in humans and may promote the progression to clinical autoimmunity.
Methylation alterations of WT1 and homeobox genes in inflamed muscle biopsy samples from patients with untreated juvenile dermatomyositis suggest self‐renewal capacity
Authors: Wang Min , Xie Hehuang , Shrestha Sheela , Sredni Simone , Morgan Gabrielle A. , Pachman Lauren M.
Published: September 2012

Objective

To determine the effect of methylation alteration in inflamed muscles from children with juvenile dermatomyositis (DM) and other idiopathic inflammatory myopathies (IIMs).

Methods

Magnetic resonance imaging–directed diagnostic muscle biopsies yielded samples from 20 children with juvenile DM, which were used for genome‐wide DNA methylation profiling, as were muscle biopsy samples from 4 healthy controls. Bisulfite treatment followed by pyrosequencing confirmed methylation status in juvenile DM and other IIMs. Immunohistochemistry defined localization and expression levels of WT1.

Results

Comparison of genome‐wide DNA methylation profiling between juvenile DM muscle and normal control muscle revealed 27 genes with a significant methylation difference between the groups. These genes were enriched with transcription factors and/or cell cycle regulators and were unrelated to duration of untreated disease. Six homeobox genes were among them; ALX4, HOXC11, HOXD3, and HOXD4 were hypomethylated, while EMX2 and HOXB1 were hypermethylated. WT1 was significantly hypomethylated in juvenile DM (Δβ = –0.41,P< 0.001). Bisulfite pyrosequencing verification in samples from 56 patients with juvenile DM confirmed the methylation alterations of these genes. Similar methylation alterations were observed in juvenile polymyositis (n = 5) and other IIMs (n = 9). Concordant with the other findings, WT1 protein was increased in juvenile DM muscle, with average positive staining of 11.6%, but was undetectable in normal muscle (P< 0.001).

Conclusion

These results suggest that affected muscles of children with juvenile DM and IIMs have the capacity to be repaired, and that homeobox and WT1 genes are epigenetically marked to facilitate this repair process, potentially suggesting new avenues of therapeutic intervention.
Cherry consumption and decreased risk of recurrent gout attacks
Authors: Zhang Yuqing , Neogi Tuhina , Chen Clara , Chaisson Christine , Hunter David J. , Choi Hyon K.
Published: September 2012

Objective

To study the relationship between cherry intake and the risk of recurrent gout attacks among individuals with gout.

Methods

We conducted a case–crossover study to examine the associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed up online for 1 year. Participants were asked to provide the following information regarding gout attacks: the onset date of the gout attack, symptoms and signs, medications (including antigout medications), and exposure to potential risk factors (including daily intake of cherries and cherry extract) during the 2‐day period prior to the gout attack. We assessed the same exposure information over 2‐day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results

Our study included 633 individuals with gout. Cherry intake over a 2‐day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate OR 0.65 [95% CI 0.50–0.85]). Cherry extract intake showed a similar inverse association (multivariate OR 0.55 [95% CI 0.30–0.98]). The effect of cherry intake persisted across subgroups stratified by sex, obesity status, purine intake, alcohol use, diuretic use, and use of antigout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than during periods without either exposure (OR 0.25 [95% CI 0.15–0.42]).

Conclusion

These findings suggest that cherry intake is associated with a lower risk of gout attacks.
Enzyme Immobilization and Direct Electrochemistry Based on a New Matrix of Phospholipid‐Monolayer‐Functionalized Graphene
Authors: Liu Jiyang , Han Lei , Wang Tianshu , Hong Wei , Liu Yaqing , Wang Erkang
Published: October 2012

A new nanocomposite material for enzyme immobilization and subsequent direct electrochemistry and electrocatalysis was developed by using 1,2‐dimyristoyl‐sn‐glycero‐3‐phospho‐(1‐rac‐glycerol)‐phospholipid‐monolayer‐membrane‐modified graphene (DMPG‐G). Microperoxidase‐11 (MP11) was chosen as a model enzyme to investigate the composite system. Owing to the improved conductivity and biocompatible microenvironment, MP11 that was immobilized in the matrix of the DMPG‐G nanocomposite (DMPG‐G‐MP11) effectively retained its native structure and bioactivity. DMPG‐G‐MP11‐modified glassy carbon electrode (DMPG‐G‐MP11/GCE) exhibited a pair of well‐defined quasi‐reversible redox peaks of MP11 and showed high electrocatalytic activity towards hydrogen peroxide (H2O2). The linear response of the developed biosensor for the determination of H2O2 ranged from 2.0×10−6 to 4.5×10−4 M with a detection limit of 7.2×10−7 M. This biosensor exhibited high reproducibility and long‐term storage stability. The promising features of this biosensor indicate that these lipid–graphene nanocomposites are ideal candidate materials for the direct electrochemistry of redox proteins and that they could serve as a versatile platform for the construction of a third‐generation biosensor.
Fine Tuning the Performance of DSSCs by Variation of the π‐Spacers in Organic Dyes that Contain a 2,7‐Diaminofluorene Donor
Authors: Baheti Abhishek , Thomas K. R. Justin , Lee Chuan‐Pei , Ho Kuo‐Chuan
Published: September 2012

Organic dyes that contain a 2,7‐diaminofluorene‐based donor, a cyanoacrylic‐acid acceptor, and various aromatic conjugation segments, which are composed of benzene, fluorene, carbazole, and thiophene units, as a π‐bridge have been synthesized and characterized by optical, electrochemical, and theoretical investigations. The trends in the absorption and electrochemical properties of these dyes are in accordance with the electron‐donating ability of the conjugating segment. Consequently, the dyes that contained a 2,7‐carbazole unit in the π‐spacer exhibited red‐shifted absorption and lower oxidation potentials than their corresponding fluorene‐ and phenylene‐bridged dyes. However, the enhanced power‐conversion efficiency that was exhibited by the fluorene‐bridged dyes in the DSSCs was attributed to their broader and intense absorption. Despite the longer‐wavelength absorption and reasonable optical density, carbazole‐bridged dyes exhibited lower power‐conversion efficiencies, which were ascribed to the poor alignment of the LUMO level in these dyes, thereby leading to the inhibition of electron injection into the TiO2 conduction band.
Luminescence in Li3Al2(PO4)3:Eu2+
Authors: Shinde K. N. , Park K.
Published: September 2012

A series of efficient Li3Al2(PO4)3:Eu2+ novel phosphors were synthesized by the facile combustion method. The effects of dopant on the luminescence behavior of Li3Al2(PO4)3 phosphor were also investigated. The phosphors were characterized by X‐ray diffraction, field emission scanning electron microscope and photoluminescence techniques. The result shows that all samples can be excited efficiently by near‐ultraviolet excitation under 310 nm. The emission was observed for Li3Al2(PO4)3:Eu2+ phosphor at 425 nm, which corresponded to the d → f transition. The concentration quenching of Eu2+ was observed in Li3Al2(PO4)3:Eu2+ when the Eu concentration was at 0.5 mol%. The prepared powders exhibited intense blue emission at the 425 nm owing to the Eu2+ ion by Hg‐free excitation at 310 nm (i.e., solid‐state lighting excitation). Consequently, the availability of such a phosphor will significantly help in the development of blue‐emitting solid‐state lighting applications. Copyright © 2012 John Wiley & Sons, Ltd.
Quantitative assessment of the relative contributions of steric repulsion and chemical interactions to macromolecular crowding
Authors: Minton Allen P.
Published: September 2012

The term “macromolecular crowding” denotes the combined effects of high volume fractions of nominally unrelated macromolecules upon the equilibrium and transport properties of all macrosolutes, dilute as well as concentrated, in the crowded medium. We present a formal partitioning of the total crowding effect into contributions from steric exclusion (excluded volume) and weak, nonspecific attractive interactions between a concentrated “crowding agent” and reactant and product species present at trace concentration. A numerical example of the combined effect of both steric and chemical interactions between crowder and tracer upon the reversible dimerization of tracer is presented, based upon reasonable estimates of the magnitude of both repulsive and attractive interactions between tracer and crowder species. © 2012Wiley Periodicals, Inc. Biopolymers 99: 239–244, 2013.
National audit of the use of surgery and radiological embolization after failed endoscopic haemostasis for non-variceal upper gastrointestinal bleeding
Authors: Jairath V , Kahan B C , Logan R F A , Hearnshaw S A , Dore C J , Travis S P L , Murphy M F , Palmer K R
Published: September 2012

Background

Following non-variceal upper gastrointestinal bleeding (NVUGIB), 10–15 per cent of patients experience further bleeding. Although surgery has been the traditional salvage therapy, there is renewed interest in transcatheter arterial embolization (TAE). This study examined the use, clinical characteristics and outcomes of patients receiving salvage surgery or TAE after failed endoscopic haemostasis for NVUGIB.

Methods

A UK national audit of upper gastrointestinal bleeding was undertaken in May and June 2007. A logistic regression model was used to identify clinical predictors of endoscopic failure.

Results

Data were analysed from 4478 patients involving 212 UK centres. Some 533 (11·9 per cent) experienced further bleeding, of whom 163 (30·6 per cent) proceeded to salvage therapy with surgery (97), TAE (60) or both (6). Among surgical patients (mean age 71 years), 66·0 per cent (68 of 103) had a Rockall score of at least 3 and emergency surgery was carried out between midnight and 08.00 hours in 21 per cent, with a consultant surgeon present in 89 per cent of operations. Some 9 per cent of patients had further bleeding after TAE, resulting in later surgery. The mortality rate was 29 per cent after surgery, 10 per cent after TAE and 23·2 per cent among those with further bleeding after the index endoscopy that was managed by endoscopy alone. The strongest predictors of endoscopic failure were coagulopathy (odds ratio 3·27, 95 per cent confidence interval 2·37 to 4·53) and a haemoglobin level of 10 g/dl or less (odds ratio 2·22, 1·71 to 2·87, for haemoglobin 8–10 g/dl).

Conclusion

Salvage surgery and embolization are required in fewer than 4 per cent of patients with NVUGIB. The high postoperative mortality rate, reflecting age, co-morbidity and severity of bleeding, warrants a prospective study to establish the effectiveness and safety of TAE as an alternative to surgery in the management of bleeding after failure of endoscopic therapy.
Identification of isoquercitrin metabolites produced by human intestinal bacteria using UPLC‐Q‐TOF/MS
Authors: Lu Linling , Qian Dawei , Yang Jing , Jiang Shu , Guo Jianming , Shang Er‐xin , Duan Jin‐ao
Published: September 2012

In this paper, ultraperformance liquid chromatography/quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF/MS) and the MetaboLynx™ software combined with mass defect filtering were applied to identity the metabolites of isoquercitrin using an intestinal mixture of bacteria and 96 isolated strains from human feces. The human incubated samples collected for 72 h in the anaerobic incubator and extracted with ethyl acetate were analyzed by UPLC‐Q‐TOF/MS within 10 min. The parent compound and five metabolites were identified by eight isolated strains, including Bacillus sp. 17, Veillonella sp. 23 and 32 and Bacteroides sp. 40, 41, 56, 75 and 88 in vitro. The results indicate that quercetin, acetylated isoquercitrin, dehydroxylated isoquercitrin, hydroxylated quercetin and hydroxymethylated quercetin are the major metabolites of isoquercitrin. Furthermore, a possible metabolic pathway for the biotransformation of isoquercitrin was established in intestinal flora. This study will be helpful for understanding the metabolic route of isoquercitrin and the role of different intestinal bacteria in the metabolism of natural compounds. Copyright © 2012 John Wiley & Sons, Ltd.
Highly Selective Bimetallic Pt‐Cu/Mg(Al)O Catalysts for the Aqueous‐Phase Reforming of Glycerol
Authors: Boga Dilek A. , Oord Ramon , Beale Andrew M. , Chung Young‐Min , Bruijnincx Pieter C. A. , Weckhuysen Bert M.
Published: September 2012

Monometallic Pt and bimetallic Pt‐Cu catalysts supported on Mg(Al)O mixed oxides, obtained by calcination of the corresponding layered double hydroxides (LDHs), were prepared and tested in the aqueous‐phase reforming (APR) of glycerol. The effect of the Mg/Al ratio and calcination temperature of the LDH support, as well as the effect of varying Pt and Cu amounts on glycerol reforming, was investigated. The use of a basic support increases the selectivity to hydrogen and the use of a Pt‐Cu bimetallic catalyst results in a decrease in alkane formation. The 0.9 wt. % Pt‐0.4 wt. % Cu/Mg(Al)O_2.95 catalyst system with an Mg(Al)O mixed oxide support obtained by the calcination of the corresponding LDH material with Mg/Al ratio of 2.95 at 673 K, showed higher hydrogen selectivity (55.3 %) and lower methane production (1.9 %) after 5 h reaction than the benchmark Pt/Al2O3 catalyst (49.4 % and 5.6 %, respectively). Catalyst characterization by extended X‐ray absorption fine structure (EXAFS) spectroscopy showed a bimetallic interaction between Pt and Cu. The bimetallic interaction is thought to be responsible for the lowered methane formation and, ultimately, the high hydrogen selectivity observed.
Solid‐State 73Ge NMR Spectroscopy of Simple Organogermanes
Authors: Hanson Margaret A. , Sutrisno Andre , Terskikh Victor V. , Baines Kim M. , Huang Yining
Published: September 2012

Germanium‐73 is an extremely challenging nucleus to examine by NMR spectroscopy due to its unfavorable NMR properties. Through the use of an ultrahigh (21.1 T) magnetic field, a systematic study of a series of simple organogermanes was carried out. In those cases for which X‐ray structural data were available, correlations were drawn between the NMR parameters and structural metrics. These data were combined with DFT calculations to obtain insight into the structures of several compounds with unknown crystal structures.
Organocatalyzed Enantioselective Desymmetrization of Diols in the Preparation of Chiral Building Blocks
Authors: Díaz‐de‐Villegas María D. , Gálvez José A. , Badorrey Ramón , López‐Ram‐de‐Víu M. Pilar
Published: October 2012

Desymmetrization of diols is a powerful tool to the synthesis of chiral building blocks. Among the different approaches to perform discrimination between both enantiotopic hydroxyl groups, the organocatalytic approach has gained importance in the last years. A diverse range of organocatalysts has been used to efficiently promote this enantioselective transformation and this Minireview examines the different contributions in this field.
Limitation of Discharge Capacity and Mechanisms of Air‐Electrode Deactivation in Silicon–Air Batteries
Authors: Jakes Peter , Cohn Gil , Ein‐Eli Yair , Scheiba Frieder , Ehrenberg Helmut , Eichel Rüdiger‐A.
Published: October 2012

The electrocatalytical process at the air cathode in novel silicon–air batteries using the room‐temperature ionic liquid hydrophilic 1‐ethyl‐3‐methylimidazolium oligofluorohydrogenate [EMI⋅2.3 HF⋅F] as electrolyte and highly doped silicon wafers as anodes is investigated by electrochemical means, X‐ray photoelectron spectroscopy (XPS), and electron paramagnetic resonance (EPR) spectroscopy. The results obtained by XPS and EPR provide a model to describe the limited discharge capacity by means of a mechanism of air‐electrode deactivation. In that respect, upon discharge the silicon‐air battery′s cathode is not only blocked by silicon oxide reduction products, but also experiences a major modification in the MnO2 catalyst nature. The proposed modification of the MnO2 catalyst by means of a MnF2 surface layer greatly impacts the Si–air performance and describes a mechanism relevant for other metal–air batteries, such as the lithium–air. Moreover, the ability for this deactivation layer to form is greatly impacted by water in the electrolyte.
Rainfall seasonality and pest pressure as determinants of tropical tree species' distributions
Authors: Baltzer Jennifer L. , Davies Stuart J.
Published: September 2012

Drought and pests are primary abiotic and biotic factors proposed as selective filters acting on species distributions along rainfall gradients in tropical forests and may contribute importantly to species distributional limits, performance, and diversity gradients. Recent research demonstrates linkages between species distributions along rainfall gradients and physiological drought tolerance; corresponding experimental examinations of the contribution of pest pressure to distributional limits and potential interactions between drought and herbivory are limited. This study aims to quantitate differential performance and herbivory as a function of species range limits across a climatic and floristic transition in Southeast Asia. Khao Chong Botanical Garden, Thailand and Pasoh Forest Reserve, Malaysia straddle the Kangar‐Pattani Line. A reciprocal transplantation across a seasonality gradient was established using two groups of species (“widespread” taxa whose distributions include seasonally dry forests and “aseasonal” taxa whose distributions are limited to aseasonal forests). Growth, biomass allocation, survival, and herbivory were monitored for 19 months. Systematic differences in performance were a function of species distribution in relation to rainfall seasonality. In aseasonal Pasoh, aseasonal species had both greater growth and survivorship than widespread species. These differences were not a function of differential herbivory as widespread and aseasonal species experienced similar damage in the aseasonal forest. In seasonally dry Khao Chong, widespread species showed higher survivorship than aseasonal species, but these differences were only apparent during drought. We link this differential performance to physiological mechanisms as well as differential tolerance of biotic pressure during drought stress. Systematic decreases in seedling survival in aseasonal taxa during drought corresponded with previously documented physiological differences and may be exacerbated by herbivore damage. These results have important implications for tropical diversity and community composition in light of predicted increases in the frequency and severity of drought in hyperdiverse tropical forests.
Acclimation and interaction between drought and elevated UV‐B in A. thaliana: Differences in response over treatment, recovery and reproduction
Authors: Comont David , Winters Ana , Gwynn‐Jones Dylan
Published: September 2012

Here, a factorial experiment was used to investigate the interactive effects of a UV‐B episode and concurrent progressive drought on the growth, chemistry, and reproductive success of A. thaliana. Both drought and UV‐B negatively affected rosette growth, although UV‐B had the greater effect. Acclimation to UV‐B involved adjustment of leaf morphology, while drought induced accumulation of soluble sugars and phenolics. All plants recovered from treatments, but the cost of recovery was a developmental delay resulting in alteration in phenological timings. Combined treatments interacted causing additive negative effects on growth following exposure. This may be linked with inhibition of soluble sugar accumulation by UV‐B, restricting the capacity for osmotic adjustment in response to drought. Following cessation of treatments, relative growth rate (RGR) and net assimilation rate (NAR) were significantly stimulated in plants treated with combined drought and UV‐B. This interaction alleviated subsequent impacts of elevated UV‐B on silique yield and reproductive timings. This study demonstrates the potential for interaction between these two common environmental factors. Furthermore, it shows the changeable nature of these interactions over the course of exposure and recovery through to reproduction, highlighting the need for sustained assessment of such interactions over a plant's lifecycle.
Three‐dimensional invasion of macrophages is mediated by cysteine cathepsins in protrusive podosomes
Authors: Jevnikar Zala , Mirković Bojana , Fonović Urša Pečar , Zidar Nace , Švajger Urban , Kos Janko
Published: September 2012

Podosomes, specialized actin‐rich structures in macrophages (Mfs), degrade the extra‐cellular matrix (ECM) and are involved in cell migration. On two‐dimensional (2D) surfaces Mfs form spot‐like podosomes at the ventral cell surface that develop into protrusive structures in a three‐dimensional (3D) environment resembling the ECM. We have shown that the tips of these protrusive podosomes are characterized by increased accumulation of cysteine cathepsins (Cts) B, X, S, H, and L, both in human blood Mfs and in human monocytic cell line U‐937. Monocyte‐to‐Mf differentiation induces an increase in cysteine cathepsin expression and activity, promoting their translocation to the cell surface, where they interact with ECM. This group of proteases is crucial for the extracellular as well as intracellular degradation of ECM, as demonstrated by quantitative monitoring of collagen IV degradation. Furthermore, inhibiting CtsB, X, and S significantly impairs Mf invasion through the 3D matrix. Time‐lapse live‐cell imaging of CtsB activity revealed that the extracellular and the intracellular ECM degradation are associated with extensive endocytosis at the tip of protrusive podosomes. The targeting of cysteine cathepsins, as the major mediators of human Mf 3D invasion, could be an approach to the treatment of inflammatory and cancerous diseases.
Strong Organic Bases as Building Blocks of Mesoporous Hybrid Catalysts for C–C Forming Bond Reactions
Authors: Gianotti Enrica , Diaz Urbano , Velty Alexandra , Corma Avelino
Published: September 2012

1,8‐Bis(tetramethylguanidino)naphthalene (TMGN), a neutral organic base that combines the properties of guanidine and the properties of proton sponges, was used as a building block to produce organic–inorganic silica‐based mesoporous hybrids with strong basic properties. The TMGN‐based mesoporous hybrids (TMGN/SiO2) were prepared by a sol–gel route working at a neutral pH and low temperatures, which avoided the use of SDAs. TMGN has been modified in order to have two terminal reactive silyl groups able to perform co‐condensation with a conventional organosilane (TMOS) used as a silicon source. This synthesis has allowed us to directly introduce the unmodified, functionalized TMGN as part of the walls of the mesoporous silica by a one‐pot synthesis. TMGN/SiO2 hybrid materials present excellent catalytic properties for C–C bond forming reactions: Knoevenagel, Henry (nitroaldol), and Claisen–Schmidt condensations. The activity of the hybrid materials is higher than that of the counterpart homogeneous catalyst.
Cycloaddition Reactions of Propiolamidinium Salts
Authors: Weingärtner Werner , Maas Gerhard
Published: September 2012

Thermal and microwave‐assisted [3+2] cycloadditions between differently substituted propiolamidinium tetraphenylborates 3a–d and N‐methyl‐C‐phenylnitrone, benzyl azide, and N‐(3‐azidopropyl)phthalimide were studied. The activation parameters of the [3+2] cycloaddition between alkyne 3a and benzyl azide were determined. A Diels–Alder reaction between the terminal alkyne 3a and cyclopentadiene could be achieved with the aid of microwave activation. The reaction between 3a and triphenylphosphorane imine provides the β,β‐bis(dimethylamino)vinylphosphonium salt 21, which might or might not have been formed through an initial [2+2] cycloaddition reaction.
Hydrogen and methane production from desugared molasses using a two‐stage thermophilic anaerobic process
Authors: Kongjan Prawit , O‐Thong Sompong , Angelidaki Irini
Published: September 2012

Hydrogen and methane production from desugared molasses by a two‐stage thermophilic anaerobic process was investigated in a series of two up‐flow anaerobic sludge blanket (UASB) reactors. The first reactor that was dominated with hydrogen‐producing bacteria of Thermoanaerobacterium thermosaccharolyticum and Thermoanaerobacterium aciditolerans could generate a high hydrogen production rate of 5600 mL H2/day/L, corresponding to a yield of 132 mL H2/g volatile solid (VS). The effluent from the hydrogen reactor was further converted to methane in the second reactor with the optimal production rate of 3380 mL CH4/day/L, corresponding to a yield of 239 mL CH4/g VS. Aceticlastic Methanosarcina mazei was the dominant methanogen in the methanogenesis stage. This work demonstrates that biohydrogen production can be very efficiently coupled with a subsequent step of methane production using desugared molasses. Furthermore, the mixed gas with a volumetric content of 16.5% H2, 38.7% CO2, and 44.8% CH4, containing approximately 15% energy by hydrogen is viable to be bio‐hythane.
Geotechnical experience from the hydroshield drives on contracts H 3‐4 and H 8 in the Lower Inn Valley / Geotechnische Erkenntnisse aus den Hydroschildvortrieben der Baulose H 3‐4 und H 8 im Unterinntal
Authors: Köhler Manfred , Maidl Ulrich , Scholz Marcus , Wendl Katharina
Published: October 2012

Two tunnels were driven in the Lower Inn valley in the years 2007 to 2009 using almost identical mixshields (∅︁ 13.03 m) under difficult geotechnical conditions. The tunnelling works were monitored and recorded permanently in real time, from which information can be gained about the system of shield machine and surrounding ground. The documentation of the ground conditions was undertaken by geologists working for the client. The continuous documentation of tunnelling included reporting on the excavated material as the drive was underway and the documentation of face conditions during compressed air interruptions. The combination of recorded machine data and the geological documentation of the tunnel drive provides an extensive data basis, whose evaluation shows the complex relationships of the various tunnelling parameters.

Im Unterinntal wurden in den Jahren 2007 bis 2009 zwei Tunnel mit fast baugleichen Mixschilden (∅︁ 13, 03 m) unter schwierigen geotechnischen Randbedingungen aufgefahren. Die Vortriebsarbeiten wurden permanent in Echtzeit überwacht und aufgezeichnet, aus den gesammelten Daten ergaben sich Einblicke in das Systemverhalten Schildmaschine/Baugrund. Die Dokumentation der Baugrundverhältnisse wurde von Geologen des Bauherrn vorgenommen. Die kontinuierliche Vortriebsdokumentation umfasste die Begutachtung des Ausbruchmaterials während des laufenden Vortriebs sowie die Dokumentation der Ortsbrustverhältnisse während der Drucklufteinstiege. Die Kombination aus aufgezeichneten Maschinendaten und der geologischen Vortriebsdokumentation ergibt eine umfassende geotechnische Datenbasis, deren Auswertung die komplexen Zusammenhänge der verschiedenen Vortriebsparameter aufzeigt.
Performance of Compliance and Persistence Measures in Predicting Clinical and Economic Outcomes Using Administrative Data from German Sickness Funds
Authors: Frey Simon , Stargardt Tom
Published: October 2012

Study Objective

To compare the performance of various compliance and persistence measures in predicting schizophrenia‐related hospitalization rates and inpatient costs.

Design

Retrospective, nonrandomized cohort study.

Data Source

Prescription claims databases from three German sickness funds (public health insurance programs).

Patients

A total of 1484 patients who were hospitalized in 2003 for a schizophrenia‐related episode and subsequently received long‐term antipsychotic pharmacotherapy.

Measurements and Main Results

Data on age, sex, schizophrenia, prescription drugs, hospitalizations, and inpatient expenditures were collected for each patient from the three German sickness funds. Refill compliance measures based on single‐interval availability and multiple‐interval availability, as well as refill persistence, were calculated for each patient over 1 year. Ten measurement variables were compared with respect to their performance in predicting disease‐related hospitalization and inpatient expenditure, using multivariate logistic regression and gamma regression, respectively. C‐statistics were calculated to determine each measure's predictive performance. Likelihood ratio tests showed that inclusion of compliance and persistence measures significantly improved (p<0.05) outcomes prediction in 6 of 10 hospitalization models and in 3 of 10 inpatient cost models compared with a baseline model that included only age, sex, and disease severity covariates. Refill compliance as a continuous variable of drug persistence, including transfer of oversupplies into subsequent periods, performed best in predicting hospitalization (C = 0.669). Availability ratios, capped at 100%, were superior to default availability ratios in predicting hospitalization. Allowing for cross‐period carryover improved the discriminatory performance of the persistence models.

Conclusion

Refill persistence measures appear sufficiently flexible to account for hospitalizations common in schizophrenia and other psychiatric diseases. A continuous refill persistence measure should be used to assess compliance in psychiatric conditions when working with administrative data.