Identifying Features of a System of Practice to Inform a Contemporary Competency Framework for Paramedics in Canada.

INTRODUCTION: Paramedic practice is highly variable, occurs in diverse contexts, and involves the assessment and management of a range of presentations of varying acuity across the lifespan. As a result, attempts to define paramedic practice have been challenging and incomplete. This has led to inaccurate or under-representations of practice that can ultimately affect education, assessment, and the delivery of care. In this study, we outline our efforts to better identify, explore, and represent professional practice when developing a national competency framework for paramedics in Canada. METHODS: We used a systems-thinking approach to identify the settings, contexts, features, and influences on paramedic practice in Canada. This approach makes use of the role and influence of system features at the microsystem, mesosystem, exosystem, macrosystem, supra-macrosystem, and chronosystem levels in ways that can provide new insights. We used methods such as rich pictures, diagramming, and systems mapping to explore relationships between these contexts and features. FINDINGS: When we examine the system of practice in paramedicine, multiple layers become evident and within them we start to see details of features that ought to be considered in any future competency development work. Our exploration of the system highlights that paramedic practice considers the person receiving care, caregivers, and paramedics. It involves collaboration within co-located and dispersed teams that are composed of other health and social care professionals, public safety personnel, and others. Practice is enacted across varying geographical, cultural, social, and technical contexts and is subject to multiple levels of policy, regulatory, and legislative influence. CONCLUSION: Using a systems-thinking approach, we developed a detailed systems map of paramedic practice in Canada. This map can be used to inform the initial stages of a more representative, comprehensive, and contemporary national competency framework for paramedics in Canada.

Quantitative retinal protein analysis after optic nerve transection reveals a neuroprotective role for hepatoma-derived growth factor on injured retinal ganglion cells.

PURPOSE: Retinal ganglion cell (RGC) degeneration is an important cause of visual impairment and can be modeled by optic nerve transection, which causes the death of 90% of RGCs within 14 days postaxotomy. We performed a proteomic study to identify and quantify proteins in the rat retina after optic nerve transection. Our goal was to isolate potential targets for therapeutic intervention to prevent RGC degeneration. METHODS: iTRAQ proteomics was used to analyze adult rat retinas at 1, 3, 4, 7, 14, and 21 days postaxotomy. Hepatoma-derived growth factor (HDGF), a target identified by iTRAQ, was delivered by intraocular injections. Wortmannin or PD98059 were coadministered with HDGF to determine if the protective effects of HDGF are dependent on PI3 kinase or MAP kinase activity, respectively. RESULTS: At a false-discovery rate of 5%, 216 proteins were identified by iTRAQ proteomics, 71 of which showed changes in expression (<0.7× or >1.3×) at one time point after injury: 52 proteins had expression peaks, whereas 19 showed downward expression spikes. Levels of GAPDH did not change after axotomy. Among these differentially expressed proteins was HDGF. HDGF delivery significantly increased RGC survival compared with control treatments, and increased Akt phosphorylation in the retina at 24 hours after intraocular injection. RGC rescue by HDGF was dependent on both MAP kinase and PI3 kinase activity in the retina. CONCLUSIONS: We have identified numerous proteins that are differentially regulated at key time points after axotomy, and how the temporal profiles of their expression parallel RGC death. Using these data, we showed that HDGF is a potent neuroprotective factor for injured adult RGCs.

Gene therapy for traumatic central nervous system injury and stroke using an engineered zinc finger protein that upregulates VEGF-A.

Recent studies have identified anti-apoptotic functions for vascular endothelial growth factor (VEGF) in the central nervous system (CNS). However, VEGF therapy has been hampered by a tendency to promote vascular permeability, edema, and inflammation. Recently, engineered zinc finger proteins (ZFPs) that upregulate multiple forms of VEGF in their natural biological ratios, have been developed to overcome these negative side effects. We used retinal trauma and ischemia models, and a cortical pial strip ischemia model to determine if VEGF upregulating ZFPs are neuroprotective in the adult CNS. Optic nerve transection and ophthalmic artery ligation lead to the apoptotic degeneration of retinal ganglion cells (RGCs) and are, respectively, two highly reproducible models for CNS trauma or ischemia. Adeno-associated vectors (AAV) vectors encoding VEGF-ZFPs (AAV-VEGF-ZFP) significantly increased RGC survival by ∼twofold at 14 days after optic nerve transection or ophthalmic artery ligation. Furthermore, AAV-VEGF-ZFP enhanced recovery of the pupillary light reflex. RECA-1 immunostaining demonstrated no appreciable differences between retinas treated with AAV-VEGF-ZFP and controls, suggesting that AAV-VEGF-ZFP treatment did not affect retinal vasculature. Following pial strip of the forelimb motor cortex, brains treated with an adenovirus encoding VEGF ZFPs (AdV-ZFP) showed higher neuronal survival, accelerated wound contraction, and reduced lesion volume between 1 and 6 weeks after injury. Behavioral testing using the cylinder test for vertical exploration showed that AdV-VEGF-ZFP treatment enhanced contralateral forelimb function within the first 2 weeks after injury. Our results indicate that VEGF ZFP therapy is neuroprotective following traumatic injury or stroke in the adult mammalian CNS.