Developing a trauma-informed, emergency department-based intervention for victims of urban violence.

The Surgeon General's report on youth violence, the Centers for Disease Control and Prevention, and other national organizations are calling for public health approaches to the issue of youth violence. Hospital-based violence intervention programs have shown promise in reducing recurrent violence and decreasing future involvement in the criminal justice system. These programs seldom address trauma-related symptoms. We describe a conceptual framework for emergency department-based and hospital-based violence intervention programs that intentionally addresses trauma. The intervention described--Healing Hurt People--is a trauma-informed program designed to intervene in the lives of injured patients at the life-changing moment of violent injury. This community-focused program seeks to reduce recurrent violence among 8- to 30-year-olds through opportunities for healing and connection. Healing Hurt People considers the adversity that patients have experienced during their lives and seeks to break the cycle of violence by addressing this trauma.

DNA hypomethylation and human diseases.

Changes in human DNA methylation patterns are an important feature of cancer development and progression and a potential role in other conditions such as atherosclerosis and autoimmune diseases (e.g., multiple sclerosis and lupus) is being recognised. The cancer genome is frequently characterised by hypermethylation of specific genes concurrently with an overall decrease in the level of 5 methyl cytosine. This hypomethylation of the genome largely affects the intergenic and intronic regions of the DNA, particularly repeat sequences and transposable elements, and is believed to result in chromosomal instability and increased mutation events. This review examines our understanding of the patterns of cancer-associated hypomethylation, and how recent advances in understanding of chromatin biology may help elucidate the mechanisms underlying repeat sequence demethylation. It also considers how global demethylation of repeat sequences including transposable elements and the site-specific hypomethylation of certain genes might contribute to the deleterious effects that ultimately result in the initiation and progression of cancer and other diseases. The use of hypomethylation of interspersed repeat sequences and genes as potential biomarkers in the early detection of tumors and their prognostic use in monitoring disease progression are also examined.

Differentiation of marrow stromal cells into photoreceptors in the rat eye.

Retinal degenerations and dystrophies are the major causes of genetically inherited blindness that are characterized by the apoptotic death of the photoreceptor cell layer of the retina. To date, no treatment exists for these diseases and only recently have they been considered as candidates for gene and stem cell therapies. Here we report the ability of adult CD90+ marrow stromal cells (MSCs) to be induced by activin A, taurine, and EGF into cells (20-32%) expressing photoreceptor-specific markers rhodopsin, opsin, and recoverin in vitro. CD90+ cells were either transduced with recombinant adeno-associated virus expressing green fluorescent protein (GFP) or bromodeoxyuridine (BrdU) labeled and then injected into the subretinal space of adult Royal College of Surgeons rats. Fundus photography and angiography showed no adverse effects of CD90+ MSC transplantation. GFP-expressing cells or BrdU-positive cells covered approximately 30% of the entire retinal area. By 2 weeks after injection, CD90+ MSCs integrated into the host retina, forming structures similar to the photoreceptor layer and expressed a photoreceptor-specific marker. No teratoma formation was observed in the recipient retina. The subretinally delivered CD90+ MSCs did not stain for proliferating cell nuclear antigen, indicating that they primarily undergo differentiation rather than proliferation. In addition, we established that transplanted cells can attract synaptic vesicles and hence are potentially capable of signal transduction. This study demonstrates for the first time the partial differentiation of adult CD90+ MSCs into photoreceptors in vitro and in vivo. Our results establish a proof of concept for CD90+ MSC differentiation with autologous transplantation, which may provide a promising therapeutic strategy for the treatment of some forms of genetically inherited retinal degenerations.

Argon laser photocoagulation-induced modification of gene expression in the retina.

PURPOSE: To generate a profile of genes expressed in the retina, RPE, and choroid after laser treatment and to identify genes that may contribute to the beneficial effects of laser photocoagulation in the treatment of angiogenic retinal diseases. METHODS: Argon laser irradiation was delivered to the left eye of normal C57BL/6J mice (n = 30), with the right eye serving as the control in each animal. Three days after laser treatment, mice were culled, eyes enucleated, and the retinas dissected and pooled into respective groups. The total RNA of replicate samples was extracted, and expression profiles were obtained by microarray analysis. Data comparisons between control and treated samples were performed and statistically analyzed. RESULTS: Data revealed that the expression of 265 known genes and expressed sequence tags (ESTs) changed after laser treatment. Of those, 25 were found to be upregulated. These genes represented a number of biological processes, including photoreceptor metabolism, synaptic function, structural proteins, and adhesion molecules. Thus angiotensin II type 2 receptor (Agtr2), a potential candidate in the inhibition of VEGF-induced angiogenesis, was upregulated, whereas potential modulators of endothelial cell function, permeability factors, and VEGF inducers, such as FGF-14, FGF-16, IL-1beta, calcitonin receptor-like receptor (CRLR), and plasminogen activator inhibitor-2 (PAI2), were downregulated. CONCLUSIONS: In this study, genes were identified that both explain and contribute to the beneficial effects of laser photocoagulation in the treatment of angiogenic retinal diseases. The molecular insights into the therapeutic effects of laser photocoagulation may provide a basis for future therapeutic strategies.

The microarray: potential applications for ophthalmic research.

The microarray is a revolutionary technology combining molecular biology and computer technology in the high throughput, simultaneous analysis of global gene expression. It is emerging as a powerful and valuable research tool that holds great promise in elucidating the molecular mechanisms involved in complex diseases. The information gained may provide direction toward identifying appropriate targets for therapeutic intervention. Despite the enormous potential of this technology, however, a number of issues exist that complicate gene expression analysis and require further resolution. This paper reviews these issues as well as the conceptual, practical and statistical aspects of microarray technology, including its current use in research and clinical applications. Furthermore, the advantages and potential benefits of this technology in ophthalmic research are discussed, with particular attention to retinal diseases, and its possible application in the identification of genes involved in ocular disease progression that may serve as clinical markers or potential therapeutic targets.