We have developed a versatile, potent technique for imaging cells in culture and in vivo by expressing a metabolically biotinylated cell-surface receptor and visualizing it with labeled streptavidin moieties. The recombinant reporter protein, which incorporates a biotin acceptor peptide (BAP) between an N-terminal signal sequence and a transmembrane domain, (BAP-TM) was efficiently biotinylated by endogenous biotin ligase in mammalian cells with the biotin displayed on the cell surface. Tumors expressing the BAP-TM have high sensitivity for magnetic resonance and fluorescence tomographic imaging in vivo after intravascular injection of streptavidin conjugated to magnetic nanoparticles or fluorochromes, respectively. Moreover, streptavidin-horseradish peroxidase conjugates in conjunction with a peroxidase-sensitive gadolinium agent further increased and prolonged the magnetic resonance signal. This BAP-TM allows noninvasive real-time imaging of any cell type transduced to express this reporter protein in culture or in vivo.
Increased awareness, interest and use of assistive technology (AT) presents substantial opportunities for many citizens to become, or continue being, meaningful participants in society. However, there is a significant shortfall between the need for and provision of AT, and this is patterned by a range of social, demographic and structural factors. To seize the opportunity that assistive technology offers, regional, national and sub-national assistive technology policies are urgently required. This paper was developed for and through discussion at the Global Research, Innovation and Education on Assistive Technology (GREAT) Summit; organized under the auspices of the World Health Organization's Global Collaboration on Assistive Technology (GATE) program. It outlines some of the key principles that AT polices should address and recognizes that AT policy should be tailored to the realities of the contexts and resources available. AT policy should be developed as a part of the evolution of related policy across a number of different sectors and should have clear and direct links to AT as mediators and moderators for achieving the Sustainable Development Goals. The consultation process, development and implementation of policy should be fully inclusive of AT users, and their representative organizations, be across the lifespan, and imbued with a strong systems-thinking ethos. Six barriers are identified which funnel and diminish access to AT and are addressed systematically within this paper. We illustrate an example of good practice through a case study of AT services in Norway, and we note the challenges experienced in less well-resourced settings. A number of economic factors relating to AT and economic arguments for promoting AT use are also discussed. To address policy-development the importance of active citizenship and advocacy, the need to find mechanisms to scale up good community practices to a higher level, and the importance of political engagement for the policy process, are highlighted. Policy should be evidence-informed and allowed for evidence-making; however, it is important to account for other factors within the given context in order for policy to be practical, authentic and actionable. Implications for Rehabilitation The development of policy in the area of asssitive technology is important to provide an overarching vision and outline resourcing priorities. This paper identifies some of the key themes that should be addressed when developing or revising assistive technology policy. Each country should establish a National Assistive Technology policy and develop a theory of change for its implementation.
Research is needed so that physicians may more accurately inform women about the relative risks of using antipsychotic medications during pregnancy and lactation. Increased knowledge about the risks of medication exposure will allow clinicians to limit treatment to situations in which the risk of untreated maternal illness outweighs the risk of exposing a developing infant to medications.
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by neurodegeneration, immunodeficiency, cancer predisposition, genome instability, and sensitivity to ionizing radiation (IR). We have previously shown that a herpes simplex virus type 1 (HSV-1) amplicon vector carrying the human ataxia-telangiectasia mutated (ATM) complementary DNA (cDNA) is able to correct aspects of the cellular phenotype of human A-T cells in culture, and is also able to transfer the ATM cDNA to the Atm(-/-) mouse cerebellum. In order to achieve stable gene replacement, we have generated an HSV/adeno-associated virus (AAV) hybrid amplicon vector carrying the expression cassettes for the ATM cDNA [(9.2 kilobases (kb)] and enhanced green fluorescent protein (EGFP), flanked by AAV inverted terminal repeats (ITRs). This hybrid vector, in the presence of AAV Rep proteins, mediates site-specific integration into the AAVS1 site on chromosome 19 in human cells and in Atm(-/-) mice carrying that human locus. The functional activity of the vector-derived ATM was confirmed in vitro and in vivo by ATM autophosphorylation at Ser-1981 after IR. This proof-of-principle study establishes the ability of HSV/AAV hybrid amplicon vectors to mediate functional targeted integration of the ATM cDNA into A-T cells in culture and in Atm(-/-) mice in vivo, thus laying a foundation for possible gene therapy approaches in the treatment of A-T patients.
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