Prevention of Birch Pollen-Related Food Allergy by Mucosal Treatment with Multi-Allergen-Chimers in Mice

Among birch pollen allergic patients up to 70% develop allergic reactions to Bet v 1-homologue food allergens such as Api g 1 (celery) or Dau c 1 (carrot), termed as birch pollen-related food allergy. In most cases, specific immunotherapy with birch pollen extracts does not reduce allergic symptoms to the homologue food allergens. We therefore genetically engineered a multi-allergen chimer and tested if mucosal treatment with this construct could represent a novel approach for prevention of birch pollen-related food allergy.BALB/c mice were poly-sensitized with a mixture of Bet v 1, Api g 1 and Dau c 1 followed by a sublingual challenge with carrot, celery and birch pollen extracts. For prevention of allergy sensitization an allergen chimer composed of immunodominant T cell epitopes of Api g 1 and Dau c 1 linked to the whole Bet v 1 allergen, was intranasally applied prior to sensitization.Intranasal pretreatment with the allergen chimer led to significantly decreased antigen-specific IgE-dependent β-hexosaminidase release, but enhanced allergen-specific IgG2a and IgA antibodies. Accordingly, IL-4 levels in spleen cell cultures and IL-5 levels in restimulated spleen and cervical lymph node cell cultures were markedly reduced, while IFN-γ levels were increased. Immunomodulation was associated with increased IL-10, TGF-β and Foxp3 mRNA levels in NALT and Foxp3 in oral mucosal tissues. Treatment with anti-TGF-β, anti-IL10R or anti-CD25 antibodies abrogated the suppression of allergic responses induced by the chimer.Our results indicate that mucosal application of the allergen chimer led to decreased Th2 immune responses against Bet v 1 and its homologue food allergens Api g 1 and Dau c 1 by regulatory and Th1-biased immune responses. These data suggest that mucosal treatment with a multi-allergen vaccine could be a promising treatment strategy to prevent birch pollen-related food allergy

Secretogranin II; a Protein Increased in the Myocardium and Circulation in Heart Failure with Cardioprotective Properties

Background: Several beneficial effects have been demonstrated for secretogranin II (SgII) in non-cardiac tissue. As cardiac production of chromogranin A and B, two related proteins, is increased in heart failure (HF), we hypothesized that SgII could play a role in cardiovascular pathophysiology. Methodology/Principal Findings: SgII production was characterized in a post-myocardial infarction heart failure (HF) mouse model, functional properties explored in experimental models, and circulating levels measured in mice and patients with stable HF of moderate severity. SgII mRNA levels were 10.5 fold upregulated in the left ventricle (LV) of animals with myocardial infarction and HF (p<0.001 vs. sham-operated animals). SgII protein levels were also increased in the LV, but not in other organs investigated. SgII was produced in several cell types in the myocardium and cardiomyocyte synthesis of SgII was potently induced by transforming growth factor-beta and norepinephrine stimulation in vitro. Processing of SgII to shorter peptides was enhanced in the failing myocardium due to increased levels of the proteases PC1/3 and PC2 and circulating SgII levels were increased in mice with HF. Examining a pathophysiological role of SgII in the initial phase of post-infarction HF, the SgII fragment secretoneurin reduced myocardial ischemia-reperfusion injury and cardiomyocyte apoptosis by 30% and rapidly increased cardiomyocyte Erk1/2 and Stat3 phosphorylation. SgII levels were also higher in patients with stable, chronic HF compared to age-and gender-matched control subjects: median 0.16 (Q1-3 0.14-0.18) vs. 0.12 (0.10-0.14) nmol/L, p<0.001. Conclusions: We demonstrate increased myocardial SgII production and processing in the LV in animals with myocardial infarction and HF, which could be beneficial as the SgII fragment secretoneurin protects from ischemia-reperfusion injury and cardiomyocyte apoptosis. Circulating SgII levels are also increased in patients with chronic, stable HF and may represent a new cardiac biomarker

Intel Compiler C Software and Solutions Group

Recently, a number of thread-based prefetching techniques have been proposed. These techniques aim at improving the latency of single-threaded applications by leveraging multithreading resources to do memory prefetching via speculative prefetch threads. Software-based speculative precomputation (SSP) is one such technique, proposed for multithreaded Itanium models. SSP does not require expensive hardware support—instead it relies on the compiler to adapt binaries to perform prefetching on otherwise idle hardware threads at run time. This paper presents a post-pass compilation tool for generating SSP-enhanced binaries. The tool is able to: (1) analyze a single-threaded application to generate prefetch threads; (2) identify and embed trigger points in the original binary; and (3) produce a new binary that has the prefetch threads attached. The execution of the new binary spawns the speculative prefetch threads, which are executed concurrently with the main thread. Our results indicate that for a set of pointer-intensive benchmarks, the prefetching performed by the speculative threads achieves an average of 87 % speedup on an in-order processor and 5 % speedup on an out-of-order processor. 1

International importance of robust breast device registries

BACKGROUND: Breast implants are high-risk devices that have been at the epicenter of much debate and controversy. In light of the Poly Implant Prothèse crisis, data registries among 11 national societies around the world are cooperatively calling for the urgent need to establish robust national clinical quality registries based on international best practice within a framework of international collaboration. METHODS: A survey was conducted on the historic and current status of national breast device registries. Eleven countries participated in the study, illustrating different data collection systems and registries around the world. Data collection was designed to illustrate the capabilities of current national registries, with particular focus on capture rate and outcome reporting mechanisms. RESULTS: A study of national breast implant registries revealed that less than half of the participating countries had operational registries and that none of these had adequately high data capture to enable reliable outcome analysis. The study revealed that the two most common problems that discouraged participation are the complexity of data sets and the opt-in consent model. CONCLUSIONS: Recent implant crises have highlighted the need for robust registries. This article argues the importance of securing at least 90 percent data capture, which is achievable through the opt-out consent model. Since adopting this model, the Australian Breast Device Registry has increased data capture from 4 percent to over 97 percent. Simultaneously, it is important to foster international collaboration from the outset to avoid duplication of efforts and enable the development of effective international early warning systems.Rodney D. Cooter, Shane Barker, Sean M. Carroll, Gregory R. D. Evans, Uwe von Fritschen, . Helmut Hoflehner, . Claude Le Louarn, . David B. Lumenta, Irene M. J. Mathijssen, John McNeil, Stephen Mulgrew, Marc A. M. Mureau, Graeme Perks, Hinne Rakhorst, Charles Randquist, Moris Topaz, Charles Verheyden, John de Waa