Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Introduction: looking beyond the walls

In its consideration of the remarkable extent and variety of non-university researchers, this book takes a broader view of ‘knowledge’ and ‘research’ than in the many hot debates about today’s knowledge society, ‘learning age’, or organisation of research. It goes beyond the commonly held image of ‘knowledge’ as something produced and owned by the full-time experts to take a look at those engaged in active knowledge building outside the university walls

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Paradoxical effects of Worrisome Thoughts Suppression: the influence of depressive mood

Thought suppression increases the persistence of unwanted idiosyncratic worries thoughts when individuals try to suppress them. The failure of suppression may contribute to the development and maintenance of emotional disorders. Depressive people seem particulary prone to engage in unsuccessful mental control strategies such as thought suppression. Worry has been reported to be elevated in depressed individuals and a dysphoric mood may also contribute for the failure of suppression. No studies examine, however, the suppression of worisome thoughts in individuals with depressive symptoms. To investigate the suppression effects of worrisome thoughts, 46 participants were selected according to the cut-off score of a depressive symptomatology scale and they were divided in two groups (subclinical and nonclinical group). All the individuals took part in an experimental paradigm of thought suppression. The results of the mixed factorial analysis of variance revealed an increased frequency of worrisome thoughts during the suppression phase on depending of the depressive symptoms. These findings confirm that depressive mood can reduce the success of suppression.info:eu-repo/semantics/publishedVersio

Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?

LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20–100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering

Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development

Variable strength of forest stand attributes and weather conditions on the questing activity of Ixodes ricinus ticks over years in managed forests

Given the ever-increasing human impact through land use and climate change on the environment, we crucially need to achieve a better understanding of those factors that influence the questing activity of ixodid ticks, a major disease-transmitting vector in temperate forests. We investigated variation in the relative questing nymph densities of Ixodes ricinus in differently managed forest types for three years (2008–2010) in SW Germany by drag sampling. We used a hierarchical Bayesian modeling approach to examine the relative effects of habitat and weather and to consider possible nested structures of habitat and climate forces. The questing activity of nymphs was considerably larger in young forest successional stages of thicket compared with pole wood and timber stages. Questing nymph density increased markedly with milder winter temperatures. Generally, the relative strength of the various environmental forces on questing nymph density differed across years. In particular, winter temperature had a negative effect on tick activity across sites in 2008 in contrast to the overall effect of temperature across years. Our results suggest that forest management practices have important impacts on questing nymph density. Variable weather conditions, however, might override the effects of forest management practices on the fluctuations and dynamics of tick populations and activity over years, in particular, the preceding winter temperatures. Therefore, robust predictions and the detection of possible interactions and nested structures of habitat and climate forces can only be quantified through the collection of long-term data. Such data are particularly important with regard to future scenarios of forest management and climate warming

Evidence for phonon skew scattering in the spin Hall effect of platinum

\u3cp\u3eWe measure and analyze the effective spin Hall angle of platinum in the low-residual resistivity regime by second-harmonic measurements of the spin-orbit torques for a multilayer of Pt|Co|AlOx. An angular-dependent study of the torques allows us to extract the effective spin Hall angle responsible for the damping-like torque in the system. We observe a strikingly nonmonotonic and reproducible temperature dependence of the torques. This behavior is compatible with recent theoretical predictions which include both intrinsic and extrinsic (impurities and phonons) contributions to the spin Hall effect at finite temperatures.\u3c/p\u3

Prescribing practices of primary-care veterinary practitioners in dogs diagnosed with bacterial pyoderma

Concern has been raised regarding the potential contributions of veterinary antimicrobial use to increasing levels of resistance in bacteria critically important to human health. Canine pyoderma is a frequent, often recurrent diagnosis in pet dogs, usually attributable to secondary bacterial infection of the skin. Lesions can range in severity based on the location, total area and depth of tissue affected and antimicrobial therapy is recommended for resolution. This study aimed to describe patient signalment, disease characteristics and treatment prescribed in a large number of UK, primary-care canine pyoderma cases and to estimate pyoderma prevalence in the UK vet-visiting canine population

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies