Science translational medicine
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Leber's congenital amaurosis (LCA) is a group of severe inherited retinal degenerations that are symptomatic in infancy and lead to total blindness in adulthood. Recent clinical trials using recombinant adeno-associated virus serotype 2 (rAAV2) successfully reversed blindness in patients with LCA caused by RPE65 mutations after one subretinal injection. However, it was unclear whether treatment of the second eye in the same manner would be safe and efficacious, given the potential for a complicating immune response after the first injection. ⋯ Cell-mediated immune responses were benign, with only 1 of 10 animals in the study developing a persistent T cell immune response to AAV2, a response that was mediated by CD4(+) T cells. Sequential bilateral injection caused minimal inflammation and improved visual function in affected animals. Thus, subretinal readministration of rAAV2 in animals is safe and effective, even in the setting of preexisting immunity to the vector, a parameter that has been used to exclude patients from gene therapy trials.
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The U. S. National Institutes of Health Roadmap and the U. ⋯ Clearly, the role of these networks as translational science incubators that complement industry-sponsored programs is laudable and much-needed. However, the path to success for such organizations is less clear. Here, drawing on the experiences of the Immune Tolerance Network, a multidisciplinary clinical research network founded in 1999, we discuss some of the barriers inherent in developing such consortia and offer firsthand insight into the planning, resources, and organizational infrastructure required for a successful research program.
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Research on medical education is translational science when rigorous studies on trainee clinical skill and knowledge acquisition address key health care problems and measure outcomes in controlled laboratory settings (T1 translational research); when these outcomes transfer to clinics, wards, and offices where better health care is delivered (T2); and when patient or public health improves as a result of educational practices (T3). This Commentary covers features of medical education interventions and environments that contribute to translational outcomes, reviews selected research studies that advance translational science in medical education at all three levels, and presents pathways to improve medical education translational science.
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Review
alpha2A-adrenergic receptors in the genetics, pathogenesis, and treatment of type 2 diabetes.
Insulin secretion from pancreatic islets is inhibited by the activation of beta cell alpha(2A)-adrenergic receptors (alpha(2A)ARs). Increased expression of alpha(2A)ARs, then, would depress insulin release, which is a pathogenic mechanism of type 2 diabetes. ⋯ A single-nucleotide polymorphism in the human ADRA2A gene was associated with decreased insulin secretion in normal people during glucose challenge and was also associated with type 2 diabetes. These findings offer another genetic association locus for the disease, with concordant biochemical and expression phenotypes, and also provide a potential new pathway for therapeutic intervention.
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Blood loss is the major cause of death in both civilian and battlefield traumas. Methods to staunch bleeding include pressure dressings and absorbent materials. For example, QuikClot effectively halts bleeding by absorbing large quantities of fluid and concentrating platelets to augment clotting, but these treatments are limited to compressible and exposed wounds. ⋯ The effects of these synthetic platelets surpass other treatments, including recombinant factor VIIa, which is used clinically for uncontrolled bleeding. Synthetic platelets were cleared within 24 hours at a dose of 20 mg/ml, and no complications were seen out to 7 days after infusion, the longest time point studied. These synthetic platelets may be useful for early intervention in trauma and demonstrate the role that nanotechnology can have in addressing unmet medical needs.