A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis

Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd) efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks) persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate—yet significant—pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease

Otherness, Discrimination, and Cats in Eugene Trivizas's The Last Black Cat

This paper examines Greek writer Eugene Trivizas's 2001 crossover animal fantasy The Last Black Cat, considering the implications of using the trope of the animal both to interrogate the construction of black cats as Other and to challenge examples of prejudice, or rather the grounds of prejudice, discrimination, and scapegoating. Extended consideration is devoted to the ways in which the narrative produces black cats as the marginalised and demonised Other of both humans and other cats, while at the same time it questions the culturally established hierarchy between humans and animals, and the paradigm of animal victim. It is argued that the focus on how the human/animal relations are articulated in Trivizas's novel makes it possible to perceive both the irrationality of the ideology behind the discrimination and the beast in humankind; in others words, by using misfortunes of animals as a tool for social criticism it subverts dominant discriminatory discourses and redefines prevailing ideas of humanity

Enhancing translational research in paediatric rheumatology through standardization.

The past decade has seen many successes in translational rheumatology, from dramatic improvements in outcomes brought about by novel biologic therapies, to the discovery of new monogenic inflammatory disorders. Advances in molecular medicine, combined with progress towards precision care, provide an excellent opportunity to accelerate the translation of biological understanding to the bedside. However, although the field of rheumatology is a leader in the standardization of data collection and measures of disease activity, it lags behind in standardization of biological sample collection and assay performance. Uniform approaches are necessary for robust collaborative research, particularly in rare diseases. Standardization is also critical to increase reproducibility between centres, a prerequisite for clinical implementation of translational research. This Perspectives article emphasizes the need for standardization and implementation of best practices, presented in the context of lessons learned from international biorepository networks