Scar tissue at sites of traumatic injury in the adult central nervous system presents a combined physical and molecular impediment to axon regeneration. Of multiple known central nervous system scar associated axon growth inhibitors, semaphorin 3A has been shown to be strongly expressed by invading leptomeningeal fibroblasts. We have previously demonstrated that infusion of the small leucine-rich proteoglycan decorin results in major suppression of several growth inhibitory chondroitin sulphate proteoglycans and growth of adult sensory axons across acute spinal cord injuries. Furthermore, decorin treatment of leptomeningeal fibroblasts significantly increases their ability to support neurite growth of co-cultured adult dorsal root ganglion neurons. In the present study we show that decorin has the ability to suppress semaphorin 3A expression within adult rat cerebral cortex scar tissue and in primary leptomeningeal fibroblasts in vitro. Infusion of decorin core protein for eight days resulted in a significant reduction of semaphorin 3A messenger RNA expression within injury sites compared with saline-treated control animals. Both in situ hybridization and immunostaining confirmed that semaphorin 3A messenger RNA expression and protein levels are significantly reduced in decorin-treated animals. Similarly, decorin treatment decreased the expression of semaphorin 3A messenger RNA in cultured rat leptomeningeal fibroblasts compared with untreated cells. Mechanistic studies revealed that decorin-mediated suppression of semaphorin 3A critically depends on erythroblastic leukaemia viral oncogene homologue B4 and signal transducer and activator of transcription 3 function. Collectively, our studies show that in addition to suppressing the levels of inhibitory chondroitin sulphate proteoglycans, decorin has the ability to suppress semaphorin 3A in the injured central nervous system. Our findings provide further evidence for the use of decorin as a potential therapy for promoting axonal growth and repair in the injured adult mammalian brain and spinal cord.
Statistical theory indicates that a flexible model can attain a lower generalization error than an inflexible model, provided that the setting is appropriate. This is highly relevant in the context of mortality risk prediction for trauma patients, as researchers have focused exclusively on the use of generalized linear models for risk prediction, and generalized linear models may be too inflexible to capture the potentially complex relationships in trauma data. Due to this, we propose a machine learning model, the Trauma Severity Model (TSM), for risk prediction. In order to validate TSM's performance, this study compares TSM to three established risk prediction models: the Bayesian Logistic Injury Severity Score, the Harborview Assessment for Risk of Mortality, and the Trauma Mortality Prediction Model. Our results indicate that TSM has superior performance, and thereby provides improved risk prediction.
More than 30,000 firefighters are injured on the fireground each year. Literature suggests that injury often occurs when protective gear is not used properly. According to firefighters, failure to correctly wear protective equipment occurs for several reasons: (1) gear not used because of haste, (2) cumbersome gear can sometimes interfere with performance, and (3) cultural factors. The purpose of this study is to quantify improper gear and tactic use in a publicly available, online video repository in order to better understand unsafe firefighting. This was an Institutional Review Board-exempt study of public video records. A search for "fire fighting videos" was conducted at YouTube (www.youtube.com). The first 50 videos that contained volunteer or career firefighters at work fighting fires were selected evaluated for appropriate use of personal protective equipment and for safe behavior. The videos were evaluated by two highly experienced professional firefighters. Of the 50 videos reviewed, 25 (50%) demonstrated violations of firefighting safety principles. Of the unsafe videos, 21 (42%) displayed firefighters improperly using gear, while the other 4 (8%) were related to unsound tactics. The most common problem was failure to wear or properly secure a self-contained breathing apparatus when appropriate (14 videos or 28%). The second most common failure was lack of helmet, hood, or approved gloves (11 videos or 22%). In conclusion, firefighting as documented on YouTube is often unsafe because of failure to properly use personal protective equipment. Half of the videos reviewed contained unsafe practices. With such a shockingly high rate of unsafe firefighting, the profession is in need of additional education and reform. In response to this epidemic, a multidisciplinary educational program has been developed to improve firefighter awareness of gear limitations and burn injury risk. Effectiveness of educational programs should be documented in additional prospective studies.
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