Identification of chitinase-3-like protein 1 as a novel neutrophil antigenic target in Crohn’s disease

Background and Aims There is an increasing incidence of inflammatory bowel disease [IBD]. Autoimmune responses are involved in the pathophysiology of IBD, but their underlying pathways and target antigens have not yet been fully elucidated. Methods Autoantigenic targets in IBD were identified after separation of whole cell proteins isolated from neutrophils using two-dimensional electrophoresis and matrix assisted laser desorption ionization – time of flight mass spectrometry-based protein identification of the spots that displayed Western blotting signals with anti-neutrophil cytoplasmic antibody-positive sera. The prevalence of IgG, IgA and secretory IgA [sIgA] to chitinase 3-like protein 1 [CHI3L1] was analysed by enzyme-linked immunosorbent assays using recombinant CHI3L1 in 110 patients with Crohn’s disease [CD], 95 with ulcerative colitis [UC], 126 with coeliac disease [CeD] and 86 healthy controls [HCs]. Results The 18-glycosylhydrolase family member CHI3L1 was identified as a neutrophil autoantigenic target. CD patients displayed significantly higher levels of IgG to CHI3L1 than patients with UC and CeD (p < 0.0001, respectively). IgA and sIgA to CHI3L1 was significantly higher in CD than in UC, CeD and HCs [p < 0.0001, respectively]. IgA and sIgA to CHI3L1 demonstrated the highest prevalence in CD [25.5%, 28/110; and 41.8%%, 46/110] compared to HCs [2.3%, 2/86; and 4.7%%, 4/86; p = 0.0015 and p < 0.0001] and are associated with a more complicated progression of CD. Conclusion CHI3L1 is a novel neutrophil autoantigenic target in CD. IgA and sIgA to CHI3L1 may serve as novel markers for CD and may facilitate the serological diagnosis of IBD

Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn's disease

AIM To assess the prevalence and stability of different antiphospholipid antibodies (APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases (IBD) patients. METHODS About 458 consecutive patients [Crohn's disease (CD): 271 and ulcerative colitis (UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course (development f complicated disease phenotype and need for surgery), occurrence of thrombotic events, actual state of disease activity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up, (median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls (HC) were tested on individual anti-β2-Glycoprotein-I (anti-β2-GPI IgA/M/G), anti-cardiolipin (ACA IgA/M/G) and anti-phosphatidylserine/prothrombin (anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies (ASCA IgA/G) by enzyme-linked immunosorbent assay (ELISA). In a subgroup of CD (n = 198) and UC patients (n = 103), obtaining consecutive samples over various arbitrary time-points during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally, we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed. RESULTS Patients with CD had significantly higher prevalence of both ACA (23.4%) and anti-PS/PT (20.4%) antibodies than UC (4.8%, P < 0.0001 and 10.2%, P = 0.004) and HC (2.9%, P < 0.0001 and 15.5%, P = NS). No difference was found for the prevalence of anti-β2-GPI between different groups (7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients. Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes. Changes in antibody status were more remarkable in CD than UC (ACA IgA: 49.9% vs 23.3% and ACA IgG: 21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis. CONCLUSION The present study demonstrated enhanced formation of APLAs in CD patients. However, presence of different APLAs were not associated with the clinical phenotype or disease course

Rediscovery of the Anti-Pancreatic Antibodies and Evaluation of their Prognostic Value in a Prospective Clinical Cohort of Crohn's Patients: The Importance of Specific Target Antigens [GP2 and CUZD1].

BACKGROUNDS Glycoprotein 2[GP2] and CUB zona pellucida-like domain 1[CUZD1] belong to protein families involved in gut innate immunity processes and have recently been identified as specific targets of anti-pancreatic autoantibodies [PAbs] in Crohn's disease[CD]. We aimed to determine the prognostic potential of novel target-specific PAbs regarding long-term disease course of an adult CD patient cohort. METHODS Sera of 458 consecutive well-characterised IBD patients from a single referral IBD centre were tested by enzyme-linked immunosorbent assay [ELISA] with isoform 4 of recombinant GP2 [anti-MZGP2 and anti-GP2 IgA/IgG] and indirect immunofluorescence test [IIFT] system with GP2 and CUZD1 expressing transfected HEK 293 cells [anti-rPAg2 and rPAg1 IgA/IgG]. Clinical data were available on complicated disease or surgical interventions as well as disease activity and medical treatment during the prospective follow-up [median, 108 months]. RESULTS Totals of 12.4% and 20.8% of CD patients were positive for IgA/IgG type of anti-GP2 and anti-CUZD1, respectively, with a significant difference compared with UC [p < 0.01]. Antibody status was stable over time. Agreement among three different anti-GP2 assays was good. Positivity for PAbs, mainly IgA subtypes, predicted a faster progression towards complicated disease course. In Kaplan-Meier analysis, time to surgery or development of perianal disease was associated with anti-GP2 IgA [pLogRank < 0.01] or anti-CUZD1 IgA [pLogRank < 0.001] positivity, respectively. Anti-CUZD1 IgA remained an independent predictor in the multivariate Cox-regression model (hazard ratio [HR]: 3.43, 95% confidence interval [CI]: 1.68-7.02, p < 0.001). CONCLUSIONS The present study has shown that specific PAbs [especially IgA subtype] predict complicated disease course including the development of perianal disease in CD

Uses of tree saps in northern and eastern parts of Europe

In this article we review the use of tree saps in northern and eastern Europe. Published accounts by travellers, ethnologists and ethnobotanists were searched for historical and contemporary details. Field observations made by the authors have also been used. The presented data shows that the use of tree sap has occurred in most north and eastern European countries. It can be assumed that tree saps were most used where there were extensive stands of birch or maple trees, as these two genera generally produce the largest amount of sap. The taxa most commonly used have been Betula pendula, B. pubescens, and Acer platanoides, but scattered data on the use of several other taxa are presented. Tree sap was used as a fresh drink, but also as an ingredient in food and beverages. It was also fermented to make light alcoholic products like ale and wine. Other folk uses of tree saps vary from supplementary nutrition in the form of sugar, minerals and vitamins, to cosmetic applications for skin and hair and folk medicinal use. Russia, Ukraine, Belarus, Estonia, Latvia and Lithuania are the only countries where the gathering and use of sap (mainly birch sap) has remained an important activity until recently, due to the existence of large birch forests, low population density and the incorporation of sap into the former Soviet economic system. It is evident that gathering sap from birch and other trees was more widespread in earlier times. There are records indicating extensive use of tree saps from Scandinavia, Poland, Slovakia and Romania, but it is primarily of a historical character. The extraction of tree sap in these countries is nowadays viewed as a curiosity carried out only by a few individuals. However, tree saps have been regaining popularity in urban settings through niche trading. © The Author(s) 2012

High discontinuation rate of azathioprine in autoimmune hepatitis, independent of time of treatment initiation

Contains fulltext : 225262.pdf (Publisher’s version ) (Open Access)BACKGROUND: Guidelines regarding treatment for autoimmune hepatitis (AIH) favour two strategies for azathioprine (AZA) introduction: concurrent with steroids at induction or delayed by 2-4 weeks. The safety and efficacy of both strategies have been unexplored. METHODS: We established a cohort of 900 AIH patients from 12 centres in 7 European countries. There were 631 patients who used AZA as part of the therapeutic regimen. We distinguished two groups: patients with early AZA (<2 weeks) or delayed AZA initiation (≥2 weeks). Primary outcome was discontinuation of AZA in the first year of treatment. Cox regression and propensity score matching was performed to determine difference in outcomes between groups. RESULTS: Patients with early AZA initiation had significantly lower transaminases and bilirubin at baseline. Discontinuation rates of AZA did not differ between early and delayed starters (16.6% vs 14.2%), which did not reach statistical significance (hazard ratio 0.97, 95% confidence interval 0.61-1.55, P = .90). Stratification according to baseline disease activity or propensity score matching did not alter the results. Main reason for AZA discontinuation was intolerance to treatment (14.0% vs 13.2%, P = .78) with nausea and vomiting as main side effects. AIH remission rates were comparable among groups. CONCLUSION: The discontinuation rate of AZA in AIH treatment is ~15% in the first year of treatment. Early or delayed AZA initiation does not differ in remission and discontinuation rates in AIH induction therapy. Our data suggest that either strategy may be used as part of AIH treatment

The Drug Candidate BGP-15 Delays the Onset of Diastolic Dysfunction in the Goto-Kakizaki Rat Model of Diabetic Cardiomyopathy

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Of the importance of a leaf: the ethnobotany of sarma in Turkey and the Balkans

BACKGROUND: Sarma - cooked leaves rolled around a filling made from rice and/or minced meat, possibly vegetables and seasoning plants - represents one of the most widespread feasting dishes of the Middle Eastern and South-Eastern European cuisines. Although cabbage and grape vine sarma is well-known worldwide, the use of alternative plant leaves remains largely unexplored. The aim of this research was to document all of the botanical taxa whose leaves are used for preparing sarma in the folk cuisines of Turkey and the Balkans. Methods: Field studies were conducted during broader ethnobotanical surveys, as well as during ad-hoc investigations between the years 2011 and 2014 that included diverse rural communities in Croatia, Bosnia and Herzegovina, Serbia, Kosovo, Albania, Macedonia, Bulgaria, Romania, and Turkey. Primary ethnobotanical and folkloric literatures in each country were also considered. Results: Eighty-seven botanical taxa, mainly wild, belonging to 50 genera and 27 families, were found to represent the bio-cultural heritage of sarma in Turkey and the Balkans. The greatest plant biodiversity in sarma was found in Turkey and, to less extent, in Bulgaria and Romania. The most commonly used leaves for preparing sarma were those of cabbage (both fresh and lacto-fermented), grape vine, beet, dock, sorrel, horseradish, lime tree, bean, and spinach. In a few cases, the leaves of endemic species (Centaurea haradjianii, Rumex gracilescens, and R. olympicus in Turkey) were recorded. Other uncommon sarma preparations were based on lightly toxic taxa, such as potato leaves in NE Albania, leaves of Arum, Convolvulus, and Smilax species in Turkey, of Phytolacca americana in Macedonia, and of Tussilago farfara in diverse countries. Moreover, the use of leaves of the introduced species Reynoutria japonica in Romania, Colocasia esculenta in Turkey, and Phytolacca americana in Macedonia shows the dynamic nature of folk cuisines. Conclusion: The rich ethnobotanical diversity of sarma confirms the urgent need to record folk culinary plant knowledge. The results presented here can be implemented into initiatives aimed at re-evaluating folk cuisines and niche food markets based on local neglected ingredients, and possibly also to foster trajectories of the avant-garde cuisines inspired by ethnobotanical knowledge

Taxonomy based on science is necessary for global conservation

Peer reviewe

Mechanical design of the optical modules intended for IceCube-Gen2

IceCube-Gen2 is an expansion of the IceCube neutrino observatory at the South Pole that aims to increase the sensitivity to high-energy neutrinos by an order of magnitude. To this end, about 10,000 new optical modules will be installed, instrumenting a fiducial volume of about 8 km3. Two newly developed optical module types increase IceCube’s current sensitivity per module by a factor of three by integrating 16 and 18 newly developed four-inch PMTs in specially designed 12.5-inch diameter pressure vessels. Both designs use conical silicone gel pads to optically couple the PMTs to the pressure vessel to increase photon collection efficiency. The outside portion of gel pads are pre-cast onto each PMT prior to integration, while the interiors are filled and cast after the PMT assemblies are installed in the pressure vessel via a pushing mechanism. This paper presents both the mechanical design, as well as the performance of prototype modules at high pressure (70 MPa) and low temperature (−40∘C), characteristic of the environment inside the South Pole ice

The next generation neutrino telescope: IceCube-Gen2

The IceCube Neutrino Observatory, a cubic-kilometer-scale neutrino detector at the geographic South Pole, has reached a number of milestones in the field of neutrino astrophysics: the discovery of a high-energy astrophysical neutrino flux, the temporal and directional correlation of neutrinos with a flaring blazar, and a steady emission of neutrinos from the direction of an active galaxy of a Seyfert II type and the Milky Way. The next generation neutrino telescope, IceCube-Gen2, currently under development, will consist of three essential components: an array of about 10,000 optical sensors, embedded within approximately 8 cubic kilometers of ice, for detecting neutrinos with energies of TeV and above, with a sensitivity five times greater than that of IceCube; a surface array with scintillation panels and radio antennas targeting air showers; and buried radio antennas distributed over an area of more than 400 square kilometers to significantly enhance the sensitivity of detecting neutrino sources beyond EeV. This contribution describes the design and status of IceCube-Gen2 and discusses the expected sensitivity from the simulations of the optical, surface, and radio components