Virus-Like Particle-Mediated Vaccination against Interleukin-13 May Harbour General Anti-Allergic Potential beyond Atopic Dermatitis

Virus-like particle (VLP)-based anti-infective prophylactic vaccination has been established in clinical use. Although validated in proof-of-concept clinical trials in humans, no VLP-based therapeutic vaccination against self-proteins to modulate chronic disease has yet been licensed. The present review summarises recent scientific advances, identifying interleukin-13 as an excellent candidate to validate the concept of anti-cytokine vaccination. Based on numerous clinical studies, long-term elimination of IL-13 is not expected to trigger target-related serious adverse effects and is likely to be safer than combined targeting of IL-4/IL-13. Furthermore, recently published results from large-scale trials confirm that elimination of IL-13 is highly effective in atopic dermatitis, an exceedingly common condition, as well as eosinophilic esophagitis. The distinctly different mode of action of a polyclonal vaccine response is discussed in detail, suggesting that anti-IL-13 vaccination has the potential of outperforming monoclonal antibody-based approaches. Finally, recent data have identified a subset of follicular T helper cells dependent on IL-13 which selectively trigger massive IgE accumulation in response to anaphylactoid allergens. Thus, prophylactic IL-13 vaccination may have broad application in a number of allergic conditions

Seeking Environmental Stewardship One Garden at a Time

Master Gardeners and teachers in Anne Arundel County MD partnered to give hands-on educational experiences promoting environmental stewardship, how we treat the environment when nobody is watching. The partnership supports and teaches ecological reconciliation by building and caring for 4964 ft2 (1578 m2) of native plant gardens. This reproducible project encourages environmental stewardship without rhetoric, one spadeful at a time

The Synecology of Phyco-Periphyton in Oligotrophic Lakes

This study is designed to (a) demonstrate the highly productive nature of the littoral area as compared to the pelagic region, (b) the possible importance of phyco-periphyton in the diets of fish, (c) the effects of meteorological conditions on distribution of phytoplankton, and (d) a demonstration of the invalidity of using artificial substrates as a universal means of measuring productivity

Narrowband ultraviolet B treatment for psoriasis is highly economical and causes significant savings in cost for topical treatments

Background: Narrowband ultraviolet B (NB-UVB) treatment for psoriasis is considered expensive. However, existing data are based on estimates and do not consider indirect cost savings. Objectives: To define the actual costs of NB-UVB incurred by the service provider, as well as treatment-associated cost savings. Methods: We performed data linkage of (i) comprehensive treatment records and (ii) prescribing data for all NB-UVB treatment episodes spanning 6 years in a population of 420 000. We minimized data fluctuation by compiling data from four independent treatment sites, and using drug prescriptions unrelated to psoriasis as a negative control. Results: National Health Service Tayside spent an average of £257 per NB-UVB treatment course (mean 257 ± 63, range 150–286, across four independent treatment sites), contrasting sharply with the estimate of £1882 used by the U.K. National Institute for Health and Care Excellence. The cost of topical treatments averaged £128 per patient in the 12 months prior to NB-UVB, accounting for 42% of the overall drug costs incurred by these patients. This was reduced by 40% to £53 per patient over the 12-month period following NB-UVB treatment, while psoriasis-unrelated drug prescription remained unchanged, suggesting disease-specific effects of NB-UVB. The data were not due to site-specific factors, as confirmed by highly similar results observed between treatment sites operated by distinct staff. Finally, we detail all staff hours directly and indirectly involved in treatment, allowing direct translation of cost into other healthcare systems. Conclusions: NB-UVB is a low-cost treatment; cost figures currently used in health technology appraisals are an overestimate based on the data presented here. Creating or extending access to NB-UVB is likely to offer additional savings by delaying or avoiding costly third-line treatments for many patients.PostprintPeer reviewe

The Pathology of War Plans: The Lessons of 1914

The University Archives has determined that this item is of continuing value to OSU's history.The major European powers, Austria-Hungary , Britain , France , Germany , Italy , and Russia , developed war plans in the years prior to the August 1914 outbreak. These plans, all of them, proved to be seriously flawed. Six experts will present their analyses of the planning processes and the pathologies involved.Ohio State University. Mershon Center for International Security StudiesEvent webpage, streaming audio, phot

Skin-targeted inhibition of PPAR β/δ by selective antagonists to treat PPAR β/δ-mediated psoriasis-like skin disease in vivo

We have previously shown that peroxisome proliferator activating receptor ß/δ (PPAR β/δ is overexpressed in psoriasis. PPAR β/δ is not present in adult epidermis of mice. Targeted expression of PPAR β/δ and activation by a selective synthetic agonist is sufficient to induce an inflammatory skin disease resembling psoriasis. Several signalling pathways dysregulated in psoriasis are replicated in this model, suggesting that PPAR β/δ activation contributes to psoriasis pathogenesis. Thus, inhibition of PPAR β/δ might harbour therapeutical potential. Since PPAR β/δ has pleiotropic functions in metabolism, skin-targeted inhibition offer the potential of reducing systemic adverse effects. Here, we report that three selective PPAR β/δ antagonists, GSK0660, compound 3 h, and GSK3787 can be formulated for topical application to the skin and that their skin concentration can be accurately quantified using ultra-high performance liquid chromatography (UPLC)/mass spectrometry. These antagonists show efficacy in our transgenic mouse model in reducing psoriasis-like changes triggered by activation of PPAR β/δ. PPAR β/δ antagonists GSK0660 and compound 3 do not exhibit systemic drug accumulation after prolonged application to the skin, nor do they induce inflammatory or irritant changes. Significantly, the irreversible PPAR β/δ antagonist (GSK3787) retains efficacy when applied topically only three times per week which could be of practical clinical usefulness. Our data suggest that topical inhibition of PPAR β/δ to treat psoriasis may warrant further exploration

Evaluation of seismic hazard for the assessment of historical elements at risk : description of input and selection of intensity measures

The assessment of historical elements at risk from earthquake loading presents a number of differences from the seismic evaluation of modern structures, for design or retrofitting purposes, which is covered by existing building codes, and for the development of fragility curves, procedures for which have been extensively developed in the past decade. This article briefly discusses: the hazard framework for historical assets, including a consideration of the appropriate return period to be used for such elements at risk; the intensity measures that could be used to describe earthquake shaking for the analysis of historical assets; and available approaches for their assessment. We then discuss various unique aspects of historical assets that mean the characterisation of earthquake loading must be different from that for modern structures. For example, historical buildings are often composed of heterogeneous materials (e.g., old masonry) and they are sometimes located where strong local site effects occur due to: steep topography (e.g., hilltops), basin effects or foundations built on the remains of previous structures. Standard seismic hazard assessment undertaken for modern structures and the majority of sites is generally not appropriate. Within the PERPETUATE project performance-based assessments, using nonlinear static and dynamic analyses for the evaluation of structural response of historical assets, were undertaken. The steps outlined in this article are important for input to these assessments